Digoxin Toxicity in a 14 Days Old Newborn: A Case Report

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İclal Sucaklı

2006-01-01

Full Text Available Digoxin is one of the most commonly used positive inotropic agent. Digitalis toxicity may occur easily because of digoxin has a narrow therapeutic window. Digitalis toxicity may result during treatment with digoxin or from accidental overdose of digoxin. An elevated serum level of digoxin (>2ng/ml is likely to be associated with toxicity, overdose of digoxin (>5ng/ml may lead to life-threatening arrhythmias. A 14-days old newborn with VSD, which had been prescribed the droplet form of digoxin but given the tablet form by the drugstore, was diagnosed as digitalis toxicity and hospitalized to our clinic. His mother expressed that she had given two tablets mashed with spoon and diluted. Bradycardia and grade 3/6 pansystolic murmur was determined in physical examination. Digoxin level in serum was >5 ng/ml and there was third degree atrioventricular block in ECG findings. The case has been presented to emphasize the importance of better evaluation of digoxin indications and making families of the patients conscious of the usage of digoxin.

Pharmacokinetics of a telmisartan, amlodipine and ...

African Journals Online (AJOL)

Conclusion: A formulated FDC tablet containing a telmisartan/amlodipine/HCTZ combination (80/10/25mg) was bioequivalent to a co-administrated commercially available telmisartan/amlodipine combination and HCTZ tablets at equivalent concentrations. Keywords: Fixed-dose combination, Hypertension, Telmisartan, ...

Tissue distribution of tritiated digoxin and quabain in mice

International Nuclear Information System (INIS)

Klopper, J.F.; Atkins, H.L.

1976-01-01

Tissue concentration of tritiated digoxin in human subjects appears to be selective in that after a single dose of the radioactive tracer a myocardial concentration of digoxin on an average 24 to 30 times higher than the serum concentration is reached. In patients studied 3.5 to 84 hours after administration of tritiated digoxin, the dose in the heart was found to vary between 1.95 to 4.83 percent. Should it be possible to label digoxin or another cardiac glycoside with a suitable gamma-emitting tracer, its use as a cardiac imaging agent should thus be feasible. This study was undertaken to determine the tissue distribution in mice of tritiated digoxin at various time intervals post injection; and to determine if these values showed any correlation to the previously determined human data. A preliminary study in mice using 3 H-digitoxin revealed no selective uptake in the heart with high uptakes in the liver and gut. Since ouabain has a more rapid clinical onset of action than digoxin, its tissue distribution was included in the study and compared to that of digoxin

Development of glycoside-bound radiopharmaceuticals; Novel radioiodination method for digoxin

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Takemura, Yasutaka; Dote, Nobuhito; Taniuchi, Hideyuki; Iijima, Naoko; Yokoyama, Akira (Kyoto Univ. (Japan). Faculty of Pharmaceutical Science); Fujibayashi, Yasuhisa; Konishi, Junji

1994-01-01

We combined 2-hydroxy-3-methylbenzoylhydrazide (HMBH) with glycosides as a novel method for the radioiodination of physiologically active glycosides. This method was tested using digoxin, which is one of the cardiac glycosides. A digoxin-HMBH conjugate was synthesized by periodate cleavage of the third sugar ring, and was readily radiolabelled with Na[[sup 125]I] by the chloramine-T method. [sup 125]I labelled digoxin-HMBH conjugate retained Na[sup +], K[sup +]-ATPase binding in vivo and in vitro, and also retained immunoreactivity to an anti-digoxin antibody. Thus, this [sup 125]I labelled digoxin-HMBH conjugate represents a potential radiopharmaceutical for Na[sup +], K[sup +]-ATPase imaging, as well as for the radioimmunoassay of digoxin. (author).

The effects of high-dose amlodipine/benazepril combination therapies on blood pressure reduction in patients not adequately controlled with amlodipine monotherapy.

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Chrysant, Steven G; Sugimoto, Daniel H; Lefkowitz, Marty; Salko, Thomas; Khan, Mahmudul; Arora, Vipin; Shi, Victor

2007-03-01

This study compared the efficacy and safety of amlodipine/benazepril (10/40 mg/day and 10/20 mg/day) with amlodipine 10 mg/day in patients whose blood pressure (BP) was not adequately controlled with amlodipine monotherapy. After a lead-in period with amlodipine monotherapy, 812 non-responder patients (mean sitting diastolic BP > or =95 mmHg) were randomized to one of three treatment groups. Ambulatory BP monitoring was conducted in 276 patients. Treatment with amlodipine/benazepril 10/40 mg/day and 10/20 mg/day resulted in a decrease of mean sitting systolic and mean sitting diastolic BP by 13.3/12.7 mmHg and 12.1/11.6 mmHg, respectively, compared with monotherapy (6.6/8.5 mmHg) (p benazepril 10/40 mg/day and 10/20 mg/day decreased ambulatory systolic and diastolic BP by 9.9/6.7 mmHg and 7.4/5.2 mmHg compared with monotherapy (p benazepril combinations compared with monotherapy (4.5%, 5.5% vs. 9.2%, respectively, p=NS). No significant metabolic side-effects were noted among the combination groups. Amlodipine/benazepril combinations were well tolerated and resulted in significant BP reductions and better BP responder rates than amlodipine monotherapy.

Lack of interaction between digoxin and quinidine in cultured heart cells

International Nuclear Information System (INIS)

Horowitz, J.D.; Barry, W.H.; Smith, T.W.

1982-01-01

Previous investigations have raised the possibility that the digoxin-quinidine interaction is associated with a reduction in the positive inotropic effect of digoxin due to displacement of digoxin from cardiac as well as skeletal muscle. To circumvent some of the complexities presented by intact animal models, this interaction was investigated in cultured chick embryo ventricular cells. Quinidine, even at relatively high concentrations (10(-4)--2 x 10(-3) M), did not significantly affect positive inotropic effects of digoxin and did not protect against cellular contracture induced by toxic digoxin concentrations, despite preincubation of cells with quinidine for 60 min. The effects of digoxin on monovalent cation transport, as judged by active uptake of the K analog 86Rb, were also not altered by 10(-4) M to 2 x 10(-3) M quinidine. These data suggest that quinidine does not displace digoxin from Na, K adenosine triphosphatase binding sites in this preparation. Although these data must be extrapolated to the intact animal with caution, our findings suggest that changes in digoxin clearance are more likely of primary importance in the digoxin-quinidine interaction, and indicate that the approximately 2-fold increase in serum digoxin concentration observed after addition of quinidine would be expected to have direct effects on myocardial cells comparable with those seen with increased digoxin concentration in the absence of quinidine

3H-digoxin distribution in the nervous system in ventricular tachycardia

International Nuclear Information System (INIS)

Frazer, G.; Binnion, P.

1981-01-01

The distribution of 3H-digoxin has been measured in a large number of tissues from the central, autonomic, and peripheral nervous system after the induction of ventricular tachycardia by infusing digoxin into anesthetized dogs. In most parts of the nervous system the tissue digoxin concentration was close to that in the cerebrospinal fluid. Digoxin accumulation in the choroid plexus probably represented a labeling of adenosine triphosphatase. There was a markedly higher concentration of digoxin in the neurohypophysis than in the adenohypophysis, and the very high levels in the neurohypophysis are hard to explain. There may be a relationship between the pituitary and the hypothalamic digoxin levels, although the concentration in the latter was unimpressive. The fornix showed a modest increase in 3H-digoxin concentration and may play a role, as its efferent discharge goes to the hypothalamus. The high concentration of digoxin in the area postrema suggests that this central nervous system structure is responsible, at least in part, for producing digoxin-induced cardiac arrhythmias. It may act as a sensing organ sensitive to blood digoxin concentration. Either it is the only central nervous structure implicated, or it is involved together with the fornix-hypothalamus-hypophysis pathways. Further proof is given for the importance of the autonomic nervous system in cardiac arrhythmias by the high digoxin levels in the superior cervical sympathetic ganglion and adrenal medulla

Digoxigenin-histamine conjugates and their use in digoxin measurement

International Nuclear Information System (INIS)

1979-01-01

A method for measuring the digoxin content of a serum comprises adding to digoxin antibody coated tubes a mixture of a radiolabelled histamine derivative of digoxegenin and a sample, incubating the mixture to bind the antibody, separating the bound, labelled digoxin and measuring the radioactivity. (U.K.)

Amlodipine-induced gingival hyperplasia in chronic renal failure: a ...

African Journals Online (AJOL)

Amlodipine is a dihydropyridine calcium channel blocker that is used in the management of both hypertension and angina. Amlodipine induced side effects are headache, dizziness, edema, flushing, palpitations, and rarely gingival hyperplasia. The exact reason of amlodipine-induced gingival hyperplasia is not known.

Comparative kinetics of serum and vitreous humor digoxin concentrations in a guinea pig model. Part I: Intravenous administration of digoxin

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Donnelly, B.; Balkon, J.; Bidanset, J.H.; Belmonte, A.; Barletta, M.; Manning, T. (Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John' s University, Jamaica, NY (USA))

1991-03-01

The pharmacokinetics of a single intravenous dose of digoxin in the guinea pig was investigated with emphasis on the penetration of digoxin into the vitreous humor. A controlled study was undertaken and data was collected which indicated that digoxin follows an open, two-compartment pharmacokinetic model with a terminal half-life of 318 minutes. The data indicated that the ratio of vitreous concentrations to serum concentrations were determined to be equal following an initial tissue distribution phase.

Comparative kinetics of serum and vitreous humor digoxin concentrations in a guinea pig model. Part I: Intravenous administration of digoxin

International Nuclear Information System (INIS)

Donnelly, B.; Balkon, J.; Bidanset, J.H.; Belmonte, A.; Barletta, M.; Manning, T.

1991-01-01

The pharmacokinetics of a single intravenous dose of digoxin in the guinea pig was investigated with emphasis on the penetration of digoxin into the vitreous humor. A controlled study was undertaken and data was collected which indicated that digoxin follows an open, two-compartment pharmacokinetic model with a terminal half-life of 318 minutes. The data indicated that the ratio of vitreous concentrations to serum concentrations were determined to be equal following an initial tissue distribution phase

Study on the correlation between serum digoxin levels and its therapeutic efficacy and toxicity and pharmacokinetics of digoxin in Thai patients using radionuclide procedures

International Nuclear Information System (INIS)

Poopyruchpong, N.

1984-02-01

The development of a radioimmunoassay procedure for the measurement of serum digoxin, using a locally raised rabbit anti-digoxin serum, tritiated digoxin from a commercial supplier and dextran-coated charcoal for the separation step, is described. Assay optimization included the determination of optimal antiserum dilution, incubation time and charcoal concentration. Assay validation included the evaluation of assay accuracy, precision and specificity. Results of measurements on sera from a preliminary group of patients undergoing digoxin medication are presented

Hypothalamic digoxin, hemispheric chemical dominance, and eating behavior.

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Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-08-01

The isoprenoid pathway produces an endogenous membrane Na+-K+ ATPase inhibitor, digoxin, which can regulate neurotransmitter and amino acid transport. Digoxin synthesis and neurotransmitter patterns were assessed in eating disorders. The patterns were compared in those with right hemispheric and left hemispheric dominance. The serum HMG CoA reductase activity, RBC membrane Na+-K+ ATPase activity, serum digoxin, magnesium, tryptophan catabolites (serotonin, quinolinic acid, strychnine, and nicotine), and tyrosine catabolites (morphine, dopamine, and noradrenaline) were measured in anorexia nervosa, bulimia nervosa, right hemispheric dominant, left hemispheric dominant, and bihemispheric dominant individuals. Digoxin synthesis was increased with upregulated tryptophan catabolism and downregulated tyrosine catabolism in those with anorexia nervosa and right hemispheric chemical dominance. Digoxin synthesis was reduced with downregulated tryptophan catabolism and upregulated tyrosine catabolism in those with bulimia nervosa and left hemispheric chemical dominance. The membrane Na+-K+ ATPase activity and serum magnesium were decreased in anorexia nervosa and right hemispheric chemical dominance while they were increased in bulimia nervosa and left hemispheric chemical dominance. Hypothalamic digoxin and hemispheric chemical dominance play a central role in the regulation of eating behavior. Anorexia nervosa represents the right hemispheric chemically dominant/hyperdigoxinemic state and bulimia nervosa the left hemispheric chemically dominant/hypodigoxinemic state.

Importance of Pharmacokinetics and Dosage in digoxin ...

African Journals Online (AJOL)

Patients diagnosed as being digitalis-toxic or as exhibiting refractory cardiac failure on clinical grounds, had digoxin serum levels significantly higher than those found in patients with satisfactorily controlled cardiac failure but without signs of digitalis toxicity. Serum digoxin levels were significantly raised in patients with ...

Study of digoxin use in a public health unit

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Felipe C. Souza

2015-06-01

Full Text Available Digoxin is used for heart failure associated to systolic dysfunction and high ventricular rate. It has a narrow therapeutic range and intoxication may occur due to drug interactions or comorbidities. The aim of this work was to study digoxin use in a public health unit delineating the profile of patients susceptible to digitalis intoxication. Medical records belonging to patients admitted to the cardiomyopathy ward of the health unit (2009-2010 and in use of digoxin were analyzed. Among 647 patients admitted, 185 individuals using digoxin and possessed records available. The registration of plasma digoxin concentration was found in 80 records and it was out of the therapeutic range in 42 patients (52.5%. This group of individuals was constituted mainly by males patients (79%, functional class III of heart failure (65%, exhibiting renal failure (33%. The evaluated sample reflects the epidemiology of heart failure in Brazil and, although pharmacotherapy had been according to Brazilian Guidelines, apparently the monitoring was not performed as recommended. This work highlighs the necessity of plasma digoxin constant monitoring during pharmacotherapy and the development of protocols that enable a safer use, especially in male patients, functional class III and with renal dysfunction.

The effect of age on digoxin pharmacokinetics in Fischer-344 rats

International Nuclear Information System (INIS)

Evans, R.L.; Owens, S.M.; Ruch, S.; Kennedy, R.H.; Seifen, E.

1990-01-01

Digoxin protein binding and pharmacokinetics were studied in 4-, 14-, and 25-month-old male Fischer-344 rats to determine if there were age-dependent changes in digoxin disposition. Serum protein binding did not differ among age groups. The average percentage unbound digoxin for all animals was 61.3 ± 5.3% (means ± SD, n = 15). For pharmacokinetic studies, [ 3 H]digoxin and 1 mg/kg unlabeled digoxin were administered as an intravenous bolus dose to animals from each age group. The [ 3 H]digoxin terminal elimination half-life was 2.0, 2.3, and 2.5 hr, respectively. The steady-state volume of distribution in the three age groups was 1.51, 1.49, and 1.27 liters/kg, respectively. Total body clearance for the three age groups was 14.2, 12.1, and 7.5 ml/min/kg, respectively. Analysis of variance of these data followed by Duncan's multiple range test indicated a significant decrease in clearance in the aged rats (25-month-old, p less than 0.05). This age-dependent decrease in clearance suggested that digoxin pharmacokinetics could be a significant factor in age-related alterations in digoxin cardiotoxicity in the rat, as it is in humans, and that the Fischer-344 rat could be a useful model for studies of digoxin pharmacokinetic changes with age

Basic evaluation of 67Ga labeled digoxin derivative as a metal-labeled bifunctional radiopharmaceutical

International Nuclear Information System (INIS)

Fujibayashi, Yasuhisa; Konishi, Junji; Takemura, Yasutaka; Taniuchi, Hideyuki; Iijima, Naoko; Yokoyama, Akira.

1993-01-01

To develop metal-labeled digoxin radiopharmaceuticals with affinity with anti-digoxin antibody as well as Na + , K + -ATPase, a digoxin derivative conjugated with deferoxamine was synthesized. The derivative had a high binding affinity with 67 Ga at deferoxamine introduced to the terminal sugar ring of digoxin. The 67 Ga labeled digoxin derivative showed enough in vitro binding affinity and selectivity to anti-digoxin antibody as well as Na + , K + -ATPase. The 67 Ga labeled digoxin derivative is considered to be a potential metal-labeled bifunctional radiopharmaceutical for digoxin RIA as well as myocardial Na + , K + -ATPase imaging. (author)

Hypothalamic digoxin, hemispheric chemical dominance, and spirituality.

Science.gov (United States)

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-03-01

The isoprenoid pathway was assessed in atheistic and spiritually inclined individuals. The pathway was also assessed in individuals with differing hemispheric dominance to assess whether hemispheric dominance has a correlation with spiritual and atheistic tendency. HMG CoA reductase activity, serum digoxin, RBC membrane Na(+)-K+ ATPase activity, serum magnesium, and tyrosine/tryptophan catabolic patterns were assessed in spiritual/atheistic individuals and in those differing hemispheric dominance. In spiritually-inclined individuals, there was increased digoxin synthesis, decreased membrane Na(+)-K+ ATPase activity, increased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and decreased tyrosine catabolites (dopamine, noradrenaline, and morphine). The pattern in spiritually-inclined individuals correlated with right hemispheric chemical dominance. In atheistic individuals there was decreased digoxin synthesis, increased membrane Na(+)-K+ ATPase activity, decreased tryptophan catabolities (serotonin, quinolinic acid, and nicotine), and increased tyrosine catabolites (dopamine, noradrenaline, and morphine). This pattern in atheistic individuals correlated with that obtained in left hemispheric chemical dominance. Hemispheric chemical dominance and hypothalamic digoxin could regulate the predisposition to spirituality or atheism.

Personalized Medicine Digoxin Theraphy in Individuals with MDR Gene Polymorphism

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Em Sutrisna

2015-06-01

Full Text Available Digoxin is one of digitalis drugs. Wider applicability to heart failure and arrhythmias (supraventricular requires fairly strict scrutiny because of its narrow therapeutic index. Digoxin is a substrate of P-glycoprotein (P-gp encoded by multi drugs resistance-1 (MDR1. MDR-1 gen located on chromosome 7q21.1. This gene contains 28 exons that encoded a protein of 1280 amino acids. This gene plays an important role in the absorption, distribution and elimination of many drugs. MDR1C3435T polymorphism occurs in exon 26. There are three types of MDR1C3435T gene namely MDR1C3435T CC, MDR1C3435T CT and MDR1C3435T TT. These polymorphisms will affect to the formation of P-gp and consequently to change the kinetic profile of digoxin. The change of kinetic profile causes changes in the digoxin blood levels. The method used in this review is data search based on pubmed, medline, and embase with keywords MDR and digoxin. There are several different studies of the influence of polymorphisms MDR1C3435T on blood digoxin levels. Increased levels of digoxin in the blood due to polymorphism of MDR1C3435T will be at risk of digitalis intoxication. Long-term digoxin treatment or large dose should consider the patient’s genetic profile. Distribution of polymorphism of MDR1C3435T in Javanese population is approximately TT (0,10, CT (0,52, and CC(0, 38.

Digoxin-induced retinal degeneration depends on rhodopsin.

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Landfried, Britta; Samardzija, Marijana; Barben, Maya; Schori, Christian; Klee, Katrin; Storti, Federica; Grimm, Christian

2017-03-16

Na,K-ATPases are energy consuming ion pumps that are required for maintaining ion homeostasis in most cells. In the retina, Na,K-ATPases are especially important to sustain the dark current in photoreceptor cells needed for rapid hyperpolarization of rods and cones in light. Cardiac glycosides like digoxin inhibit the activity of Na,K-ATPases by targeting their catalytic alpha subunits. This leads to a disturbed ion balance, which can affect cellular function and survival. Here we show that the treatment of wild-type mice with digoxin leads to severe retinal degeneration and loss of vision. Digoxin induced cell death specifically in photoreceptor cells with no or only minor effects in other retinal cell types. Photoreceptor-specific cytotoxicity depended on the presence of bleachable rhodopsin. Photoreceptors of Rpe65 knockouts, which have no measurable rhodopsin and photoreceptors of Rpe65 R91W mice that have treatment. Similarly, cones in the all-cone retina of Nrl knockout mice were also not affected. Digoxin induced expression of several genes involved in stress signaling and inflammation. It also activated proteins such as ERK1/2, AKT, STAT1, STAT3 and CASP1 during a period of up to 10 days after treatment. Activation of signaling genes and proteins, as well as the dependency on bleachable rhodopsin resembles mechanisms of light-induced photoreceptor degeneration. Digoxin-mediated photoreceptor cell death may thus be used as an inducible model system to study molecular mechanisms of retinal degeneration.

Evidence Based Digoxin Therapeutic Monitoring - A Lower and Narrower Therapeutic Range

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Amine BENLMOUDEN

2016-06-01

Full Text Available Cardiac glycosides have been used for congestive heart failure and certain cardiac arrhythmias for more than 200 years. Despite the introduction of a variety of new classes of drugs for the management of heart failure, specifically angiotensin-converting enzyme (ACE inhibitors, b-adrenergic antagonists (bblockers, and the aldosterone antagonist spironolactone, digoxin continues to have an important role in long-term outpatient management. However, a narrow margin exists between therapeutic and toxic doses of digoxin, resulting in a high incidence of digoxin toxicity in clinical practice.A wide variety of placebo-controlled clinical trials have unequivocally shown that treatment with digoxin can improve symptoms, quality of life, and exercise tolerance in patients with mild, moderate, or severe heart failure. The clinical relevance of digoxin therapeutic monitoring is also proved but the SDC (Serum Digoxin Conentrations required for optimal clinical efficacy and acceptable toxicity remains controversial. In the last years, international guidelines recommend 1.2 ng/mL as acceptable high level.In this bibliographic synthesis, we aim to collect pertinent informations from MedLine database about exposure-effect relationship in order to assess the evidence level scientific of new digoxin therapeutic monitoring. 

Digoxin serum levels with respect to some biochemical and clinical indicators

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Sedlak, J; Curilla, E [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Lekarska Fakulta

1984-10-01

Digoxin serum levels were examined in 40 patients using enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) and correlated with levels of potassium, magnesium, creatinine, urea, glomerular filtration (GF) and with clinical signs of different degrees of digitalis serum concentration. The digoxin level assessed by ELISA and RIA methods correlated fairly closely. An average dependence was found between digoxin levels and levels of creatinine, urea and GF. A correlation was observed between a high level of digoxin and clinical signs of digitalis intoxication.

Digoxin serum levels with respect to some biochemical and clinical indicators

International Nuclear Information System (INIS)

Sedlak, J.; Curilla, E.

1984-01-01

Digoxin serum levels were examined in 40 patients using enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) and correlated with levels of potassium, magnesium, creatinine, urea, glomerular filtration (GF) and with clinical signs of different degrees of digitalis serum concentration. The digoxin level assessed by ELISA and RIA methods correlated fairly closely. An average dependence was found between digoxin levels and levels of creatinine, urea and GF. A correlation was observed between a high level of digoxin and clinical signs of digitalis intoxication

Titration of digoxin through radio-immunology in the solid phase

International Nuclear Information System (INIS)

Hersh, L.S.; Yaverbaum, Sidney.

1975-01-01

The invention relates to biological titrations. It refers to a method for determining the digoxin concentration in a solution, characterized in that it comprises the steps of: causing the solution (a known amount of labelled digoxin and a composite substance constituted by anti-digoxin antibodies chemically coupled through the medium of a silane coupling agent) to react with magnetically-sensitive inorganic particles, so as to generate immuno-chemical complex; magnetically separating the composite substance from the reaction solution; measuring the radioactivity of the thus separated composite substance or of the remaining solution; and comparing the measurements of step with a reference curve so as to determine the digoxin concentration [fr

Amlodipine reduces the antimigratory effect of diclofenac in spontaneously hypertensive rats.

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Rodrigues, Stephen Fernandes; Dossantos, Rosangela Aparecida; de Oliveira, Maria Aparecida; Rastelli, Viviani Milan; Nucci, Gilberto de; Tostes, Rita de Cássia; Nigro, Dorothy; Carvalho, Maria Helena; Fortes, Zuleica B

2008-05-01

Amlodipine, an antihypertensive drug, and diclofenac, an antiinflammatory drug, may generally be combined, particularly in elderly patients; therefore, the potential for their interaction is high. We aim to determine if amlodipine interferes with the antimigratory effect of diclofenac. For this, male spontaneously hypertensive rats (SHRs) were treated with either diclofenac (1 mg.kg.d, 15 d) alone or combined with amlodipine (10 mg.kg.d, 15 d). Leukocyte rolling, adherence, and migration were studied by intravital microscopy. Diclofenac did not change (180.0 +/- 2.3), whereas amlodipine combined (163.4 +/- 5.1) or not (156.3 +/- 4.3) with diclofenac reduced the blood pressure (BP) levels in SHR (183.1 +/- 4.4). Diclofenac and amlodipine reduced leukocyte adherence, migration, and ICAM-1 expression, whereas only diclofenac reduced rolling leukocytes as well. Combined with amlodipine, the effect of the diclofenac was reduced. Neither treatment tested increased the venular shear rate or modified the venular diameters, number of circulating leukocytes, P-selectin, PECAM-1, L-selectin, or CD-18 expressions. No difference could be found in plasma concentrations of both drugs given alone or in association. In conclusion, amlodipine reduces leukocyte migration in SHR, reducing endothelial cell ICAM-1 expression. Amlodipine reduces the effect of the diclofenac, possibly by the same mechanism. A pharmacokinetic interaction as well as an effect on the other adhesion molecules tested could be discarded.

Basic evaluation of [sup 67]Ga labeled digoxin derivative as a metal-labeled bifunctional radiopharmaceutical

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Fujibayashi, Yasuhisa; Konishi, Junji (Kyoto Univ. (Japan). Faculty of Medicine); Takemura, Yasutaka; Taniuchi, Hideyuki; Iijima, Naoko; Yokoyama, Akira

1993-11-01

To develop metal-labeled digoxin radiopharmaceuticals with affinity with anti-digoxin antibody as well as Na[sup +], K[sup +]-ATPase, a digoxin derivative conjugated with deferoxamine was synthesized. The derivative had a high binding affinity with [sup 67]Ga at deferoxamine introduced to the terminal sugar ring of digoxin. The [sup 67]Ga labeled digoxin derivative showed enough in vitro binding affinity and selectivity to anti-digoxin antibody as well as Na[sup +], K[sup +]-ATPase. The [sup 67]Ga labeled digoxin derivative is considered to be a potential metal-labeled bifunctional radiopharmaceutical for digoxin RIA as well as myocardial Na[sup +], K[sup +]-ATPase imaging. (author).

Retrospective evaluation of patients with elevated digoxin levels at an emergency department

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Gulsum Limon

2016-03-01

Full Text Available Objectives: We investigated the demographic characteristics, clinical and laboratory findings, treatment strategies and clinical outcomes of patients presenting at emergency department (ED with digoxin levels at or above 1.2 ng/ml. Materials and methods: The demographic and clinical characteristics of patients with serum digoxin levels at or above 1.2 ng/ml admitted to an ED between January 2010 and July 2011 were investigated in this cross-sectional descriptive study. Patients with ECG and clinical findings consistent with digoxin toxicity and no additional explanation of their symptoms were evaluated for digoxin toxicity. Results: In this study 137 patients were included, and 68.6% of patients were women with mean age 76.1 ± 12.2. There was no significant difference between gender and digoxin intoxication. The mean age of intoxicated group was significantly higher than the non-intoxicated group (P = 0.03. The most common comorbidities were congestive heart failure (n = 91 and atrial fibrillation (n = 74. The most common symptoms were nausea, vomiting and abdominal pain. The levels of hospitalization and mortality in this group were significantly higher. Conclusion: Digoxin intoxication must be suspected in patients present in the ED, particularly those with complaints that include nausea and vomiting, as well as new ECG changes; serum digoxin levels must be determined. Keywords: Digoxin, Digoxin level, Intoxication, Emergency department

Hypothalamic digoxin, hemispheric dominance, and neurobiology of love and affection.

Science.gov (United States)

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-05-01

The human hypothalamus produces an endogenous membrane Na+-K+ ATPase inhibitor, digoxin, which can regulate neuronal transmission. The digoxin status and neurotransmitter patterns were studied in individuals with a predilection to fall in love. It was also studied in individuals with differing hemispheric dominance to find out the role of cerebral dominance in this respect. In individuals with a predilection to fall in love there was decreased digoxin synthesis, increased membrane Na+-K+ ATPase activity, decreased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and increased tyrosine catabolites (dopamine, noradrenaline, and morphine). This pattern correlated with that obtained in left hemispheric chemical dominance. Hemispheric dominance and hypothalamic digoxin could regulate the predisposition to fall in love.

The potential role of amlodipine on experimentally induced bacterial rhinosinusitis

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Arzu Tatar

Full Text Available Abstract Introduction: Antibiotics are frequently used for the treatment of rhinosinusitis. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of development of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. Objective: In this study we aimed to investigate the potential role of amlodipine in the treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. Methods: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was composed by five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione and an oxidative product (malondialdehyde were determined. Results: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline and although not superior to cefazolin, amlodipine decreased polymorphonuclear leukocyte infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. Conclusion: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.

Blood pressure control with amlodipine add-on therapy in patients with hypertension and diabetes: results of the Amlodipine Diabetic Hypertension Efficacy Response Evaluation Trial.

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Kloner, Robert A; Neutel, Joel; Roth, Eli M; Weiss, Robert; Weinberger, Myron H; Thakker, Kamlesh M; Schwartz, Brian; Shi, Harry; Gregg, Anne-Marie

2008-11-01

Attainment of blood pressure (BP) goals in patients with diabetes is critical both to reduce the risk of cardiovascular events and to delay the progression of renal disease. While therapeutic guidelines advise initial therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, monotherapy with these agents may not be sufficient to attain target BP. The ADHT (Amlodipine Diabetic Hypertension Efficacy Response Evaluation Trial) evaluated the efficacy and safety of adding amlodipine to the treatment regimen of patients with hypertension and diabetes who were already receiving either quinapril or losartan as monotherapy. ADHT was a double-blind, double-dummy, 22-week trial conducted in the US. After a washout period of 7-13 days, patients (aged 30-75 y) with hypertension and diabetes were randomized to receive quinapril 20 mg/day plus placebo or losartan 50 mg/day plus placebo for 4 weeks, titrated to 40 mg or 100 mg (if required), respectively, for an additional 4 weeks to achieve their BP goals (<130/80 mm Hg). At week 8, either amlodipine 5 mg/day or placebo was added for an additional 12 weeks, with titration to 10 mg at week 14 if the BP goal was not achieved. Efficacy of add-on therapy was evaluated in 411 patients (amlodipine 211, placebo 200). BP goal was reached by 27.5% of patients when amlodipine was added to quinapril or losartan monotherapy, compared with 12.5% when placebo was added (OR 2.73; 95% CI 1.61 to 4.64; p < 0.001). When added to quinapril or losartan monotherapy, amlodipine reduced BP by 8.1/5.4 mm Hg, compared with a 1.6/0.7 mm Hg decrease with add-on placebo (p < 0.001). Amlodipine, quinapril, and losartan were well tolerated. Amlodipine is safe and effective when added to quinapril or losartan monotherapy to help lower BP toward therapeutic targets in patients with hypertension and diabetes.

Optimizing Growth Conditions for Digoxin Production in Digitalis lanata Ehrh

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Herman A. van Wietmarschen

2016-08-01

Full Text Available Objective: Digoxin is a therapeutic cardenolide widely used to treat various heart conditions such as atrial flutter, atrial fibrillation and heart failure in both Western as well as Chinese medicine. Digoxin is extracted from cultivated Digitalis lanata Ehrh. plants, known as Mao Hua Yang Di Huang in Chinese medicine. This manuscript presents two studies that were conducted to optimize the cultivation conditions for digoxin production in the TCM Mao Hua Yan Di Huang in a greenhouse under GAP conditions.

Pharmacogenetics-Oriented Therapeutic drug monitoring of Digoxin in critically ill patients

International Nuclear Information System (INIS)

Ebid, Abdel-Hameed I.; Mokhtar, Mohammed Sherif; Abdel-Shafi, Sana'a; El-Feky, Gina Samy

2006-01-01

This study was performed to outline the different MDR-1 (Multi-Drug Resistance-1) genotypes in a sample of 37 Egyptian patients, suffering from atrial fibrillation (AF) and/or congestive heart failure (CHF) and is using digoxin, to assess the role of MDR-1 genotypes polymorphism in affecting steady state serum digoxin therapeutic levels, and studying the consequences on patient's clinical outcome. Two venous blood samples were drawn from each patient; the 1st sample was taken, on admission, for DNA extraction and genotyping and the 2nd was taken, 6 hours post dose after reaching steady state concentration, for serum digoxin assay. Serum digoxin levels were assayed using EMIT 2000 analyzer, and MDR-1 genotyping was done using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Twenty patients (54.1%) showed serum digoxin levels within the therapeutic range, 12 patients (32.4%) showed serum digoxin levels under the minimum effective concentration ( 2 ng/ml), with P value of 0.0001 among three groups. MDR-1 genotyping revealed ten patients (27%) carrying the homozygous mutant TT genotype, 27 patients (73%) carrying the heterozygous mutant CT genotype, with no patient showing the wild CC genotype Allelic distribution showed 42% for the wild type C allele while 58% for the homozygous mutant C allele. Patients carrying the homozygous mutant TT genotype showed significantly lower serum digoxin levels compared with those carrying the heterozygous mutant CT genotype (P value: 0.009). Patients with significant improvement carried the CT genotype and had serum digoxin levels within the therapeutic range. In conclusion, patients with different MDR-1 genotypes had variations in their serum digoxin levels and identification of MDR-1 variations was found useful in predicting therapy outcome. We recommend further extensive work on large samples to study the important role of MDR-1 gene in affecting the disposition of different substrates, to

Microneedle-assisted delivery of verapamil hydrochloride and amlodipine besylate.

Science.gov (United States)

Kaur, Monika; Ita, Kevin B; Popova, Inna E; Parikh, Sanjai J; Bair, Daniel A

2014-02-01

The aim of this project was to study the effect of stainless steel solid microneedles and microneedle rollers on percutaneous penetration of verapamil hydrochloride and amlodipine besylate. Verapamil, 2-(3,4-dimethooxyphenyl)-5-[2-(3,4 dimethoxyphenyl)ethyl-methyl-amino]-2-propan-2-yl-pentanenitrile is a calcium channel blocker agent that regulates high blood pressure by decreasing myocardial contractilty, heart rate and impulse conduction. Amlodipine, (R, S)-2-[(2-aminoethoxy) methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1, 4-dihydropyridine, is a calcium channel blocker that is used for the management of hypertension and ischemic heart disease. Passive penetration of verapamil and amlodipine across the skin is low. In vitro studies were performed with microneedle-treated porcine ear skin using vertical static Franz diffusion cells (PermeGear, Hellertown, PA, USA). The receiver chamber contained 5ml of PBS (pH7.4) and was constantly maintained at 37°C temperature with a water circulation jacket. The diffusion area of the skin was 1.77cm(2). The donor compartment was loaded with 1ml of the solution containing 2.5mg/ml of amlodipine besylate. The donor chamber was covered with parafilm to avoid evaporation. Passive diffusion across untreated porcine skin served as control. Aliquots were taken every 2h for 12h and analyzed by liquid chromatography-mass spectrometry. Transcutaneous flux of verapamil increased significantly from 8.75μg/cm(2)/h to 49.96μg/cm(2)/h across microneedle-roller treated porcine skin. Percutaneous flux of amlodipine besylate following the use of stainless steel microneedles was 22.39μg/cm(2)/h. Passive flux for the drug was 1.57μg/cm(2)/h. This enhancement of amlodipine flux was statistically significant. Transdermal flux of amlodipine with microneedle roller was 1.05μg/cm(2)/h in comparison with passive diffusion flux of 0.19μg/cm(2)/h. The difference in flux values was also statistically significant. Stainless

ASSESSMENT OF AMLODIPINE ANTIHYPERTENSIVE EFFECT HOMOGENEITY IN CONTROLLED TRIAL

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V. M. Gorbunov

2016-01-01

Full Text Available Aim. To compare influence of amlodipine and spirapril on ambulatory blood pressure profile, including antihypertensive effect smoothness in patients with arterial hypertension (HT.Methods. 39 patients (aged 53,7±10,0 y.o. with HT were included in the open, randomized, cross-over study, 30 patients completed study. The duration of every therapies was 4 weeks, initial control period and wash-out period between therapies lasted 1 week. The initial daily dose of amlodipine was 5 mg, standard dose of spirapril (6 mg/daily was not changed during the trial. After 1-2 weeks of treatment amlodipine dose was increased up to 10 mg/daily as well as dihydrochlorothiazide was added, if necessary. Ambulatory blood pressure monitoring (ABPM was performed initially and at the end of both therapies.Results. Both drugs demonstrated good antihypertensive effect according to ABPM data. Decrease of systolic/diastolic blood pressure was 11,2±1,8/7,6±1,2 mm Hg in amlodipine therapy and 10,0±1,8/7,1±1,2 in spirapril therapy (p<0,0001. The smoothness indexes (SI were 0,65/0,45 and 0,55/0,45, respectively, differences between two therapies were not significant. However the individual analysis of the SI distribution (with SI=0,5 as a satisfactory criterion, showed that antihypertensive effect smoothness is better in amlodipine therapy than this in spirapril one.Conclusion. Amlodipine has prominent as well as smooth antihypertensive effect, that gives it advantages in the long-term antihypertensive therapy.

Evaluation of the Effectiveness of Sugammadex for Digoxin Intoxication: An Experimental Study.

Science.gov (United States)

Ozbilgin, Sule; Yurtlu, Derya Aslan; Küçükoztaş, Beyza; Kamacı, Gonca; Korkut, Sezen; Yurtlu, Bülent Serhan; Ensari Güneli, M; Hancı, Volkan; Günerli, Ali

2018-03-16

Previous studies have shown that cyclodextrin group medicines bind to various drugs. The hypothesis of our study is to determine whether sugammadex could bind to digoxin and delay the cardiovascular toxicity of that drug. Twenty-eight sedated Wistar rats were infused with digoxin at 3 mg/h (0.25 mg/ml). Five minutes after the start of infusion, animals were treated with a bolus of either 16 mg/kg (Sgdx16), 100 mg/kg (Sgdx100), or 1000 mg/kg (Sgdx1000) sugammadex. The control group infusion did not contain sugammadex. Heart rate, electrocardiography, and respiratory rate were monitored. The primary endpoint was time to asystole. Digoxin infusion continued until the animals arrested. The time to asystole for the Sgdx1000 group was significantly longer compared to that for the control group (p sugammadex 1000 group (p sugammadex delayed digoxin cardiotoxicity in a rat model of digoxin toxicity. We conclude that further research must be conducted on the interaction between digoxin and sugammadex.

Binding of digitoxin and digoxin to normal human β-lipoproteins

International Nuclear Information System (INIS)

Brock, A.

1976-01-01

The binding of digitoxin and digoxin to purified β-lipoprotein, obtained from pooled normal human serum, was studied under equilibrium conditions. Even with as high concentrations of unbound digitoxin or digoxin as 4 μmol/l, the preparations of β-lipoproteins, containing cholesterol 1.98-3.95 mmol/l, showed no signs of saturation. The binding affinity of digitoxin was about ten times as high as that of digoxin. Gel filtration chromatography, performed on native serum after addition of 3 H-digitoxin or 3 H-digoxin, showed a minor fraction of the cardiac glycosides to be associated with te protein fraction of highest molecular weight. This phenomenon disappeared after precipitation of the β-lipoproteins. In clinical relations the contribution of protein-bound digitoxin caused by the lipoprotein interaction is immaterial compared to that caused by the albumin interaction. (author)

Efficiency of individual dosage of digoxin with calculated concentration

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Zhao L

2014-07-01

Full Text Available Li Zhao,1,* Peng Yang,2,* Pengmei Li,1 Xiaoxing Wang,1 Wangjun Qin,1 Xianglin Zhang1 1Department of Pharmacy, 2Department of Cardiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Background: Digoxin is a frequently prescribed drug, particularly in the elderly population, in which there is an increased prevalence of atrial fibrillation and cardiac failure. With its complex pharmacokinetic profile and narrow therapeutic index, use of digoxin requires regular monitoring of blood levels. Recent evidence suggests that a lower concentration range (0.4–1.0 ng/mL is preferable in patients with congestive heart failure and a higher range (0.8–2.0 ng/mL is needed in patients with atrial tachyarrhythmia. The Konishi equation is widely used to predict the serum digoxin concentration (SDC in Japan. This study assessed the correlation between SDC predicted by the Konishi equation and that actually measured in Chinese patients and investigated the impact of renal function on SDC. Methods: The study subjects comprised 72 patients with cardiac failure or/and atrial tachyarrhythmia seen at our hospital from January 2012 to December 2013. The patients were divided into five groups according to Kidney Diseases Outcome Quality Initiative guidelines. SDCs were measured using the Abbott Architect i1000 immunology analyzer. The correlations between measured SDCs and calculated SDCs and between clearance of digoxin and creatinine clearance rate were assessed retrospectively.Results: The correlation between measured and predicted SDC calculated by the Konishi equation was significant (r=0.655, P<0.001 for the 72 patients overall; however, correlations within the different stages of renal function were nonsignificant, with a correlation found only in patients with stage 3 (30 mL per minute < creatinine clearance <60 mL per minute. With regard to the correlation between clearance of

Radioimmunoassay of serum digoxin levels. Clinical exploration

International Nuclear Information System (INIS)

Galland, F.; Geslin, P.; Kerjean, J.; Six, P.; Tadei, A.; Jallet, P.

1982-01-01

This work undertakes, in a second part, the clinical exploration of 947 serum digoxin levels of 281 hospitalized patients on a cardiology ward. Our results, which coincide with those of other researchers, have led us to draw certain practical conclusions: the posology is determined first of all according to kidney function, weight and age of the patient. When the treatment is insufficient or, on the other hand, poorly tolerated, a serum digoxin level is performed permitting thus: in the case of ineffective treatment: to be sure of the patient's cooperation, to increase the posology if the serum digoxin level is not in the toxic zone, to discover an eventual pharmacokinetic problem; to establish the responsability of digitalis (when there are signs of intolerance or of intoxication), in case of arrhythmia, in patients with pacemakers, when associated drugs are capable of causing similar adverse effects; to better manage a digitalis treatment in a high risk patient (unstable renal function, advanced myocardial disease, chronic obstructive disease) [fr

Digoxin therapy in the modern management of cardiovascular disease

African Journals Online (AJOL)

β-blockers for the treatment of heart failure, supports the use of digoxin in patients with left ventricular systolic dysfunction, particularly in those with advanced symptoms.[6] There is, however, no evidence that digoxin improves survival – it may even worsen outcomes. The Digitalis Investigation Group (DIG). Trial, a study of ...

Digoxin use and risk of mortality in hypertensive patients with atrial fibrillation

DEFF Research Database (Denmark)

Okin, Peter M; Hille, Darcy A; Wachtell, Kristian

2015-01-01

, diabetes, history of ischemic heart disease, stroke, or heart failure, baseline Cornell product, QRS duration, heart rate, serum glucose, creatinine and high-density lipoprotein cholesterol, and a propensity score for digoxin use entered as standard covariates, and for in-treatment heart rate, pulse...... patients with atrial fibrillation has not been examined. METHODS AND RESULTS: All-cause mortality was examined in relation to in-treatment digoxin use in 937 hypertensive patients with ECG left ventricular hypertrophy in atrial fibrillation at baseline (n = 134) or who developed atrial fibrillation during...... fibrillation, digoxin use is not associated with a significantly increased risk of all-cause mortality after adjusting for other independent predictors of death and for the factors associated with the propensity to use digoxin in this population. These findings suggest that factors other than digoxin use may...

Propranolol and survival from breast cancer

DEFF Research Database (Denmark)

Cardwell, Chris R; Pottegård, Anton; Vaes, Evelien

2016-01-01

BACKGROUND: Preclinical studies have demonstrated that propranolol inhibits several pathways involved in breast cancer progression and metastasis. We investigated whether breast cancer patients who used propranolol, or other non-selective beta-blockers, had reduced breast cancer-specific or all......-cause mortality in eight European cohorts. METHODS: Incident breast cancer patients were identified from eight cancer registries and compiled through the European Cancer Pharmacoepidemiology Network. Propranolol and non-selective beta-blocker use was ascertained for each patient. Breast cancer-specific and all......-analysis techniques. Dose-response analyses by number of prescriptions were also performed. Analyses were repeated investigating propranolol use before cancer diagnosis. RESULTS: The combined study population included 55,252 and 133,251 breast cancer patients in the analysis of breast cancer-specific and all...

Strategy for the Prediction of Steady-State Exposure of Digoxin to Determine Drug-Drug Interaction Potential of Digoxin With Other Drugs in Digitalization Therapy.

Science.gov (United States)

Srinivas, Nuggehally R

2016-01-20

Digoxin, a narrow therapeutic index drug, is widely used in congestive heart failure. However, the digitalization therapy involves dose titration and can exhibit drug-drug interaction. Ctrough versus area under the plasma concentration versus time curve in a dosing interval of 24 hours (AUC0-24h) and Cmax versus AUC0-24h for digoxin were established by linear regression. The predictions of digoxin AUC0-24h values were performed using published Ctrough or Cmax with appropriate regression lines. The fold difference, defined as the quotient of the observed/predicted AUC0-24h values, was evaluated. The mean square error and root mean square error, correlation coefficient (r), and goodness of the fold prediction were used to evaluate the models. Both Ctrough versus AUC0-24h (r = 0.9215) and Cmax versus AUC0-24h models for digoxin (r = 0.7781) showed strong correlations. Approximately 93.8% of the predicted digoxin AUC0-24h values were within 0.76-fold to 1.25-fold difference for Ctrough model. In sharp contrast, the Cmax model showed larger variability with only 51.6% of AUC0-24h predictions within 0.76-1.25-fold difference. The r value for observed versus predicted AUC0-24h for Ctrough (r = 0.9551; n = 177; P < 0.001) was superior to the Cmax (r = 0.6134; n = 275; P < 0.001) model. The mean square error and root mean square error (%) for the Ctrough model were 11.95% and 16.2% as compared to 67.17% and 42.3% obtained for the Cmax model. Simple linear regression models for Ctrough/Cmax versus AUC0-24h were derived for digoxin. On the basis of statistical evaluation, Ctrough was superior to Cmax model for the prediction of digoxin AUC0-24h and can be potentially used in a prospective setting for predicting drug-drug interaction or lack of it.

Effect of enrofloxacin on digoxin clearance and steady-state serum concentrations in dogs.

OpenAIRE

Novotny, M J; Shaw, D H

1991-01-01

The effect of enrofloxacin on the oral clearance and steady-state concentrations of digoxin in serum was evaluated in dogs. Digoxin was administered orally to six healthy adult Beagle dogs following a multiple-dose regimen of 0.0625 mg every 12 h for 23 days. From days 14 to 23 enrofloxacin was administered orally at a dosage of 2.5 mg/kg every 12 h, with subjects receiving enrofloxacin 2 h prior to digoxin. Trough serum concentrations of digoxin were measured using an immunoassay technique. ...

Digoxin: use pattern in Estonia and bioavailability of the local market leader.

Science.gov (United States)

Pähkla, R; Irs, A; Oselin, K; Rootslane, L

1999-10-01

In comparison with neighbouring Scandinavian countries, the use of digoxin in Estonia is high. The present study was carried out to determine the use pattern of digoxin in Estonia and bioavailability of the local market leader preparation in comparison with Lanoxin. Drug use data were evaluated from the annual reports of wholesale companies. For the bioequivalence study, a single-blind cross-over randomised two-way single-dose comparative bioavailability study was performed using 14 healthy volunteers. Digoxin concentrations in serum samples and urine were measured by chemiluminescent competitive immunoassay. The use of digoxin in Estonia has increased by 35% during the period 1994-97. The steady market leader was the local generic drug. No statistically significant differences were found in any pharmacokinetic parameter between the generic preparation and Lanoxin. All parameters showed considerable variability. The total amount of drug excreted was the parameter with lowest inter- individual variation. The present study indicates that the generic digoxin preparation studied is bioequivalent to Lanoxin. The increasing use of digoxin in Estonia is not caused by low bioavailability of the local market leader but by therapeutic traditions.

Studies on digoxin derivatives in different biological media by radioimmunoassay

International Nuclear Information System (INIS)

Barmasch, Martha; Perez, L.N.; Altschuler, Noe.

1978-05-01

The fundamental aim of this study was to develop a methodology to be applied to pharmacological studies, directed to demonstrate the passage of digitalic compounds through the blood-brain barrier. This study was a comparative one between β methyl digoxin (βMD) and digitoxin (Dt). A methodology of radioimmunoassay was developed for different biological media: serum (S), plasma (P) and cerebro spinal fluid (CSF). In addition, the immunochemical behaviour (affinity, displacement, etc.) of βMD was studied when reacted with digoxin (D) and digoxin-antisera, supplied by the commercial kits utilized in these studies. (author) [es

Isolation of a urinary digitalis-like factor indistinguishable from digoxin

Energy Technology Data Exchange (ETDEWEB)

Goto, A.; Ishiguro, T.; Yamada, K.; Ishii, M.; Yoshioka, M.; Eguchi, C.; Shimora, M.; Sugimoto, T. (Univ. of Tokyo (Japan))

1990-12-31

A digitalis-like factor has been purified to apparent homogeneity from human urine based on the inhibitory effect on ({sup 3}H) ouabain binding to intact human erythrocytes. The purification scheme involved large scale adsorption followed by preparative, semipreparative and analytical high-performance liquid chromatography. The purified material showed a prominent digoxin-like immunoreactivity. The behaviour of the isolated substance was identical to that of authentic digoxin in three high-performance liquid chromatography and three thin-layer chromatography systems. Moreover, fast atom bombardment mass spectrum and proton nuclear magnetic resonance spectrum suggested that the purified material may be indistinguishable from digoxin.

Digoxin affects potassium homeostasis during exercise in patients with heart failure.

Science.gov (United States)

Schmidt, T A; Bundgaard, H; Olesen, H L; Secher, N H; Kjeldsen, K

1995-04-01

The aim was to evaluate whether digitalisation of heart failure patients affects extrarenal potassium handling during and following exercise, and to assess digoxin receptor occupancy in human skeletal muscle in vivo. In a paired study of before versus after digitalisation, 10 patients with congestive heart failure underwent identical exercise sessions consisting of three bouts of increasing work rates, 41-93 W, on a cycle ergometer. The final bouts were followed by exercise to exhaustion. The femoral vessels and brachial artery were catheterised. Arterial blood pressure, heart rate, leg blood flow, cardiac output, plasma potassium, haemoglobin, pH, and skeletal muscle receptor occupancy with digoxin in biopsies were determined. Occupancy of skeletal muscle Na/K-ATPase with digoxin was 9% (P digitalisation femoral venous plasma potassium increased by 0.2-0.3 mmol.litre-1 (P digitalisation the femoral venoarterial difference in plasma potassium increased by 50-100% (P digitalisation on plasma potassium were not the outcome of changes in haemodynamics, because cardiac output and leg blood flow increased by up to 13% and 19% (P < 0.05), nor was it the outcome of changes in haemoconcentration or pH. Extrarenal potassium handling is altered as a result of digoxin treatment. This is likely to reflect a reduced capacity of skeletal muscle Na/K-ATPase for active potassium uptake because of inhibition by digoxin, adding to the reduction of skeletal muscle Na/K-ATPase concentration induced by heart failure per se. In heart failure patients, improved haemodynamics induced by digoxin may, however, increase the capacity for physical conditioning. Thus the impairment of extrarenal potassium homeostasis by heart failure and digoxin treatment may be counterbalanced by training.

Electrophysiologic similarities of overdose between digoxin and bufadienolides found in a Chinese aphrodisiac

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Maxwell Bressman

2017-02-01

Full Text Available Classically derived from toad venom, bufadienolides are a group of cardioactive steroids with properties similar to digoxin. Some traditional Chinese medications, including several aphrodisiacs, contain bufadienolides. Owing to their physiologic similarities to digoxin, bufadienolides have been shown to produce a toxic profile similar to that of digoxin and there have been multiple case reports of the use of these aphrodisiacs resulting in death. This report will describe a case that illustrates the electrophysiologic similarities between bufadienolide toxicity and digoxin toxicity as well as the treatment of bufadienolide toxicity.

Digoxin Is Associated With Increased Shock Events and Electrical Storms in Patients With Implantable Cardioverter Defibrillators.

Science.gov (United States)

Mina, George S; Acharya, Madan; Shepherd, Taylor; Gobrial, George; Tekeste, Michael; Watti, Hussam; Bhandari, Ruchi; Saini, Aditya; Reddy, Pratap; Dominic, Paari

2018-03-01

Recently, digoxin use has been found to associate with higher mortality. Yet, potential mechanisms by which digoxin use increases mortality remain unclear. Increased arrhythmogenicity from digoxin use is one possibility. Thus, we aimed to evaluate the relation between digoxin and shock events in patients with implantable cardioverter defibrillators (ICDs). We performed a retrospective chart review of all patients with ICDs and at least 1 device interrogation at our institution between January 1, 2012, and January 1, 2015. We aimed to cover 1 year of interrogation period. Patients with heart failure, atrial fibrillation, or both were included in the analysis. Patients were divided into 2 groups based on digoxin use, defined as use of digoxin for any period of time during ICD interrogation period. Incidence of ICD shock events and electrical storms and hospitalizations were compared between the 2 groups. The study included 202 patients. Of those, 55 patients were on digoxin and 147 were not on digoxin. Patients on digoxin were more likely to receive ICD shocks (odds ratio [OR] = 2.5, 95% confidence interval [95% CI] = 1.01-6.18, P = .04) and have increased risk of electrical storms ( P = .02). Moreover, total hospitalizations were higher in digoxin users ( P = .02). Multivariate logistic regression analysis also showed that digoxin use was an independent predictor of shock events (OR = 4.07, 95% CI = 1.43-11.58, P = .009). Digoxin is associated with increased shock events and electrical storms in patients with ICDs; however, large randomized controlled studies are needed to confirm our findings.

Bigeminy: A result of digoxin and St John’s wort interaction

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Anđelić Slađana

2003-01-01

Full Text Available A case of an by digoxin under unusual circumstances is reported. An 80-year-old man, previously on long-term digoxin treatment, started consuming St John’s wort herbal tea (2 000 ml/daily because of frequent episodes of depression. After the cessation of consuming herbal tea containing Hypericum perforatum, digoxin poisoning developed in our patient. Electrocardiography revealed nodal bradicardia 36/min and bigeminy. Manifested symptoms were the consequence of interaction between digoxin and Hypericum perforatum which were consumed simultaneously, and the cessation of consuming St John’s wort herbal tea afterwards. Therapy was the same as in the standard digitalis poisoning. Consumers of St John’s wort combined with medical products are advised not to discontinue tea consumption on their own, without consulting their physician.

Cyclodextrine Screening for the Chiral Separation of Amlodipine Enantiomers by Capillary Electrophoresis

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Gabriel Hancu

2015-03-01

Full Text Available Purpose: Amlodipine is a long acting, dihydropyridine type calcium channel blocker frequently used in the treatment of hypertension and coronary insufficiency. The calcium channel blocking activity resides primarily in the S-amlodipine enantiomer, while R-amlodipine is a potent inhibitor of smooth muscle cell migration. Methods: In this study capillary electrophoresis was applied for the enantiomeric separation of amlodipine using different native and derivatized; neutral and charged cyclodextrines as chiral selectors. The effects of pH and composition of the background electrolyte, concentration and type of chiral selector, capillary temperature, running voltage and injection parameters have been investigated. Results: Stereoselective interactions were observed when using α-CD, β-CD, HP-β-CD, RAMEB, CM-β-CD and SBE-β-CD. Optimized separation conditions consisted on a 50 mM phosphate buffer, pH – 3.0, 20 mM RAMEB as chiral selector, + 25 kV applied voltage, 15°C temperature and UV detection at 238 nm. Using the optimized electrophoretic conditions we succeeded the chiral separation of amlodipine enantiomers in approximately 6 minute, the order of migration being R-amlodipine followed by S-amlodipine. The method was successfully applied for the determination of amlodipine enantiomers from commercially available pharmaceuticals. The linearity range, limits of detection and quantification, precision and accuracy were determined and the results obtained confirmed that the method was suitable for this purpose. Conclusion: It can be concluded that the proposed capillary electrophoresis methods can be useful for routine pharmaceutical applications with benefits of its effectivity, simplicity, short analysis time and low consumption of analytes, solvents and chiral selectors.

Prospective direct comparison of antihypertensive effect and safety between high-dose amlodipine or indapamide in hypertensive patients uncontrolled by standard doses of angiotensin receptor blockers and amlodipine.

Science.gov (United States)

Okamura, Keisuke; Shirai, Kazuyuki; Totake, Nao; Okuda, Tetsu; Urata, Hidenori

2018-01-01

When hypertension is uncontrolled by routine treatment with an angiotensin II receptor blocker (ARB) and the calcium channel blocker amlodipine (5 mg), the dose of amlodipine can be increased or a diuretic can be added. We investigated the more effective option in a prospective multicenter open-label study. Hypertensive patients were recruited if the target blood pressure (BP) in The Japanese Society of Hypertension 2009 guideline could not be achieved with standard-dose ARB therapy and amlodipine (5 mg). Patients were divided into three groups. Group-1 was switched to a combination of irbesartan (100 mg) and amlodipine (10 mg). Group-2A was changed to a combination of irbesartan (100 mg), amlodipine (5 mg), and indapamide, while Group-2B received a standard-dose ARB and amlodipine (5 mg) plus indapamide. Patients were assigned by their attending physicians and were followed for 6 months. The primary endpoint was the antihypertensive effect of each regimen. Group-1 contained 85 patients, Group-2A had 49 patients, and Group-2B had 4 patients. We only analyzed Group-1 and Group-2A due to the small size of Group-2B. In both groups, systolic BP and diastolic BP were significantly decreased up to 6 months (all p < 0.001). Reduction of systolic BP was greater in Group-1 than Group-2A after 1 month and 6 months (both p < 0.05). Uric acid was increased in Group-2A after 3 months, but not at 6 months. Although both regimens were effective for reducing BP, increasing amlodipine to 10 mg daily controlled hypertension without elevation of serum uric acid.

Carvedilol or propranolol in portal hypertension?

DEFF Research Database (Denmark)

Hobolth, Lise; Møller, Søren; Grønbæk, Henning

2012-01-01

Abstract Objectives. Carvedilol is a non-selective ß-blocker with intrinsic anti-a(1)-adrenergic activity, potentially more effective than propranolol in reducing hepatic venous pressure gradient (HVPG). We compared the long-term effect of carvedilol and propranolol on HVPG and assessed whether t...

The influence of intravenous canrenoate on the determination of digoxin in serum by radio- and enzyme-immunoassay

International Nuclear Information System (INIS)

Rietbrock, N.; Lichey, J.; Borner, K.; Freie Univ. Berlin

1979-01-01

Ten patients were kept on a constant maintenance dose of digoxin. During a baseline period of 6 days, blood samples were taken daily for analysis of digoxin in serum. On the 6th day the maintenance dose of digoxin was withheld and a single intravenous dose of 200mg potassium-canrenoate (AldactoneR) was administered to all patients. Digoxin in serum was determined by a classical radioimmunoassay with 125 I-digoxin and solid phase technique (RIA-NEN) and partly by a heterogenous enzyme-immunoassay (EnzymunR-Digoxin, Boehringer, Mannheim). Results of the radioimmunoassay indicated a rise of apparent serum digoxin levels with an average maximum of 201% of the mean baseline value 30 min after injection of canrenoate and a gradual return to the baseline value within 6 to 10 hours. Contrary to the radioimmunoassay there was no interference when using the enzyme-immunoassay in a subgroup of identical serum samples: serum digoxin levels remained constant throughout the test. Interference of determinations of digoxin in serum by spironolactone and its metabolites appear to be related to two factors: 1. The mode of administration and the amount of interfering drug, 2. the specifity of the digoxin antibody used in the kit. (orig.) [de

Comparison of vasodilator drug prazosin with digoxin in aortic regurgitation.

Science.gov (United States)

Hockings, B E; Cope, G D; Clarke, G M; Taylor, R R

1980-01-01

Intravenous administration of the vasodilator sodium nitroprusside has beneficial haemodynamic effects in subjects with severe aortic regurgitation while acute digitalisation can produce unwanted effects associated with an increase in systemic vascular resistance. This study compares the haemodynamic effects of the vasodilator prazosin and digoxin in eight patients with isolated severe aortic regurgitation. Prazosin 5 mg orally resulted in a 12 +/- 3 (SE) per cent increase in cardiac index (thermodilution), maintained over four to six hours, while digoxin 0.75 mg intravenously did not change the cardiac index. Prazosin reduced mean arterial pressure by 9 +/- 3 mmHg and systemic vascular resistance by 18 +/- 4 per cent while digoxin resulted in a 6 +/- 2 per cent increase in the latter. Mean pulmonary capillary wedge pressure fell 3 mmHg with prazosin. In this group of patients with severe aortic regurgitation but without severe cardiac failure, the changes with either drug, studied in doses conventionally used, were small but those with prazosin were directionally more desirable than those resulting from digoxin. PMID:7378215

Studies on cerebral protection of digoxin against hypoxic-ischemic brain damage in neonatal rats.

Science.gov (United States)

Peng, Kaiwei; Tan, Danfeng; He, Miao; Guo, Dandan; Huang, Juan; Wang, Xia; Liu, Chentao; Zheng, Xiangrong

2016-08-17

Hypoxic-ischemic brain damage (HIBD) is a major cause of neonatal acute deaths and chronic nervous system damage. Our present study was designed to investigate the possible neuroprotective effect of digoxin-induced pharmacological preconditioning after hypoxia-ischemia and underlying mechanisms. Neonatal rats were assigned randomly to control, HIBD, or HIBD+digoxin groups. Pharmacological preconditioning was induced by administration of digoxin 72 h before inducing HIBD by carotid occlusion+hypoxia. Behavioral assays, and neuropathological and apoptotic assessments were performed to examine the effects; the expression of Na/K ATPase was also assessed. Rats in the HIBD group showed deficiencies on the T-maze, radial water maze, and postural reflex tests, whereas the HIBD+digoxin group showed significant improvements on all behavioral tests. The rats treated with digoxin showed recovery of pathological conditions, increased number of neural cells and proliferative cells, and decreased number of apoptotic cells. Meanwhile, an increased expression level of Na/K ATPase was observed after digoxin preconditioning treatment. The preconditioning treatment of digoxin contributed toward an improved functional recovery and exerted a marked neuroprotective effect including promotion of cell proliferation and reduction of apoptosis after HIBD, and the neuroprotective action was likely associated with increased expression of Na/K ATPase.

Propranolol as an adjunct therapy for hyperthyroid tremor.

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Henderson, J M; Portmann, L; Van Melle, G; Haller, E; Ghika, J A

1997-01-01

We evaluated the use of propranolol as an adjunct to carbimazole in the treatment of hyperthyroid tremor and tachycardia in a double-blind, cross-over and placebo-controlled study. Seven patients were given carbimazole plus either placebo or propranolol (40 mg) for 1 month and then switched to the alternative adjunct treatment for a further month. All patients showed significant improvements (p tremor amplitude after 1 or 2 months from baseline. One month after the baseline, the mean improvements of heart rate were 23% for the carbimazole + placebo group and 38% for carbimazole + propranolol group. Tremor also improved during the 1st month of the study by 31% in the carbimazole + placebo group versus 59% in the carbimazole + propranolol group. Whereas further improvements were observed in both variables in those receiving propranolol as the second adjunct treatment, this was not the case in those who received placebo during the same period. These findings confirm that the beta-blocker propranolol is a useful adjunct in the early treatment of both the tremor and tachycardia of hyperthyroidism.

Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr1a P-glycoprotein

NARCIS (Netherlands)

Mayer, U; Wagenaar, E; Beijnen, J.H; Smit, J.W; Meijer, D.K F; van Asperen, J.; Borst, P; Schinkel, A.H

1 We have used mice with a disrupted mdrla P-glycoprotein gene (mdrIa (-/-) mice) to study the role of P-glycoprotein in the pharmacokinetics of digoxin, a model P-glycoprotein substrate. 2 [K-3]-digoxin at a dose of 0.2 mg kg(-1) was administered as a single i.v. or oral bolus injection. We

Use of digoxin and risk of death or readmission for heart failure and sinus rhythm

DEFF Research Database (Denmark)

Madelaire, Christian; Schou, Morten; Nelveg-Kristensen, Karl Emil

2016-01-01

BACKGROUND/OBJECTIVES: Digoxin is widely used as symptomatic treatment in heart failure (HF), but the role in contemporary treatment of HF with sinus rhythm (SR) is debatable. We investigated the risk of death and hospital readmission, according to digoxin use, in a nationwide cohort of digoxin...... to primary outcomes of all-cause mortality and HF readmission. RESULTS: The study population comprised 5327 digoxin users and 10,654 matched non-users with a median age of 77. During follow-up 10,643 (66.6%) patients died and 7584 (47.5%) patients were readmitted due to HF. Use of digoxin was associated...... with increased risk of death (hazard ratio (HR): 1.19, 95%-CI: 1.15-1.24) and increased risk of HF readmission (HR: 1.19, 95%-CI: 1.13-1.25). Cumulative incidences of readmission, considering death as a competing risk was 50% for digoxin users and 47% for non-users. The associations applied regardless...

EFFECTS OF AMLODIPINE, FOSINOPRIL AND METOPROLOL ON HEMODYNAMICS IN HYPERTENSIVE PATIENTS

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A. L. Hohlov

2007-01-01

Full Text Available Aim. To assess an efficacy of antihypertensive therapy with calcium antagonist, angiotensin converting enzyme inhibitor and β-blocker in patients with arterial hypertension (AH taking into account influence on central and peripheral hemodynamics.Material and methods. 60 patients with AH of I-II stage, 1-2 grade were studied. They were split in 3 groups. Patients of the first group received amlodipine (Tenox, 5-10 mg/d, the second group – fosinopril (Monopril, 10-20 mg/d and the third group – metoprolol (Metocard, 50-200 mg/d.Diuretics were added when necessary. Ambulatory blood pressure (BP monitoring, echocardiography, ultrasound investigation of brachiocephalic and main cerebral arteries, test on reactive hyperemia and nitroglycerine were conducted before and after 6 months of therapy.Results. Amlodipine, fosinopril and metoprolol had similar antihypertensive effect. Amlodipine was more effective in comparison with fosinopril and metoprolol in reduction of left ventricular (LV myocardial mass and improving of LV diastolic function. Amlodipine and fosinopril had positive effect on vascular remodeling. Metoprolol reduced in BP morning elevation and heart rate, but had no effect on systolic BP variability.Conclusion. Amlodipine, fosinopril and metoprolol have similar antihypertensive effect but different influence on the heart, arteries, BP variability and hemodinamics.

Phototransformation of amlodipine: degradation kinetics and identification of its photoproducts.

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Anna Jakimska

Full Text Available Nowadays, monitoring focuses on the primary compounds and does not include degradation products formed during various biological and chemical processes. Transformation products may have the same effects to human health and the environment or sometimes they can be more toxic than the parent compound. Unfortunately, knowledge about the formation of degradation products is still limited, however, can be very important for the environmental risk assessment. Firstly, the photodegradation kinetic of amlodipine was investigated in two experimental conditions: during the exposure to solar radiation and during the exposure to the light emitted by the xenon lamp. In all cases degradation of amlodipine followed a pseudo-first-order kinetics. In the next step, identification of transformation products of amlodipine formed during the exposure to xenon lamp irradiation was performed using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS. As a result sixteen photoproducts were identified, their structures were elucidated and ultimately the transformation pathway was proposed. Fifteen compounds (out of 16 photoproducts were newly identified and reported here for the first time; some of those compounds were formed from the first photoproduct, amlodipine pyridine derivative. Several analytes were formed only in acidic or basic conditions. Furthermore, the occurrence of amlodipine and its identified degradation products was investigated in environmental waters. Only one out of 16 compounds was found in wastewater effluent. The possibility of the sorption of examined analytes to sewage sludge particles was discussed based on QSAR.

Cardioprotective effect of amlodipine in oxidative stress induced by experimental myocardial infarction in rats

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Sudhira Begum

2007-12-01

Full Text Available The present study investigated whether the administration of amlodipine ameliorates oxidative stress induced by experimental myocardial infarction in rats. Adrenaline was administered and myocardial damage was evaluated biochemically [significantly increased serum aspertate aminotransferase (AST, lactate dehydrogenase (LDH and malondialdehyde (MDA levels of myocardial tissue] and histologically (morphological changes of myocardium. Amlodipine was administered as pretreatment for 14 days in adrenaline treated rats. Statistically significant amelioration in all the biochemical parameters supported by significantly improved myocardial morphology was observed in amlodipine pretreatment. It was concluded that amlodipine afforded cardioprotection by reducing oxidative stress induced in experimental myocardial infarction of catecholamine assault.

Hypothalamic digoxin, hemispheric chemical dominance and sarcoidosis.

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Ravi Kumar, A; Kurup, Parameswara Achutha

2004-06-01

The isoprenoid pathway produces three key metabolites: endogenous digoxin (membrane sodium-potassium ATPase inhibitor, immunomodulator and regulator of neurotransmitter/amino acid transport), dolichol (regulates N-glycosylation of proteins) and ubiquinone (free radical scavenger). The role of the isoprenoid pathway in the pathogenesis of sarcoidosis in relation to hemispheric dominance was studied. The isoprenoid pathway-related cascade was assessed in patients with systemic sarcoidosis with pulmonary involvement. The pathway was also assessed in patients with right hemispheric, left hemispheric and bihemispheric dominance for comparison to find out the role of hemispheric dominance in the pathogenesis of sarcoidosis. In patients with sarcoidosis there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in the cholesterol:phospholipid ratio and a reduction in the glycoconjugate level of red blood cell (RBC) membrane in this group of patients. The same biochemical patterns were obtained in individuals with right hemispheric dominance. In individuals with left hemispheric dominance the patterns were reversed. Endogenous digoxin, by activating the calcineurin signal transduction pathway of T cells, can contribute to immune activation in sarcoidosis. An altered glycoconjugate metabolism can lead to the generation of endogenous self-glycoprotein antigens in the lung as well as other tissues. Increased free radical generation can also lead to immune activation. The role of a dysfunctional isoprenoid pathway and endogenous digoxin in the pathogenesis of sarcoidosis in relation to right hemispheric chemical dominance is discussed. All the patients with sarcoidosis were right-handed/left hemispheric dominant according to the dichotic listening test, but their biochemical patterns

Comparative effect of fixed dose combination of Amlodipine + Bisoprolol versus Amlodipine and Bisoprolol alone on blood pressure in stage-2 essential hypertensive patients.

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Shirure PA,Tadvi NA, Bajait CS, Baig MS, Gade PR

2012-09-01

Full Text Available Background: Employment of low dose combinations of two antihypertensives, with different mode of action has gained acceptance worldwide for the treatment of mild to moderate hypertension. However, most studies in hypertensive disease have focused on monotherapy. The combination therapy in the treatment of hypertension is largely extrapolated from these monotherapy studies. Objectives: To study and compare the effect of amlodipine, bisoprolol and fixed dose combination of amlodipine + bisoprolol on blood pressure in stage-2 essential hypertensive patients. Methods: The present study was carried out in Department of Pharmacology in collaboration with Department of Medicine at Government Medical College and Hospital, Aurangabad. Results and Conclusion : Amlodipine + bisoprolol in fixed dose combination have showed significant blood pressure control in patients of stage-2 essential hypertension and the antihypertensive effect was greater than individual monotherapy study groups.

Comparison of digoxin concentration in plastic serum tubes with clot activator and heparinized plasma tubes.

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Dukić, Lora; Simundić, Ana-Maria; Malogorski, Davorin

2014-01-01

Sample type recommended by the manufacturer for the digoxin Abbott assay is either serum collected in glass tubes or plasma (sodium heparin, lithium heparin, citrate, EDTA or oxalate as anticoagulant) collected in plastic tubes. In our hospital samples are collected in plastic tubes. Our hypothesis was that the serum sample collected in plastic serum tube can be used interchangeably with plasma sample for measurement of digoxin concentration. Our aim was verification of plastic serum tubes for determination of digoxin concentration. Concentration of digoxin was determined simultaneously in 26 venous blood plasma (plastic Vacuette, LH Lithium heparin) and serum (plastic Vacuette, Z Serum Clot activator; both Greiner Bio-One GmbH, Kremsmünster, Austria) samples, on Abbott AxSYM analyzer using the original Abbott Digoxin III assay (Abbott, Wiesbaden, Germany). Tube comparability was assessed using the Passing Bablok regression and Bland-Altman plot. Serum and plasma digoxin concentrations are comparable. Passing Bablok intercept (0.08 [95% CI = -0.10 to 0.20]) and slope (0.99 [95% CI = 0.92 to 1.11]) showed there is no constant or proportional error. Blood samples drawn in plastic serum tubes and plastic plasma tubes can be interchangeably used for determination of digoxin concentration.

Effects of amlodipine on bone metabolism in male albino Wistar rats

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Iveta Gradošová

2011-01-01

Full Text Available Amlodipine (dihydropyridine-type calcium channel blocker is a widely used agent for the treatment of hypertension in human and veterinary medicine but detailed information about its effects on bone metabolism are missing. Therefore, the aim of our study was to investigate the effect of amlodipine on bone metabolism in male albino Wistar rats. Amlodipine (0.3 mg/100 g body weight; gavage was administered to 8 rats for 8 weeks. Control group (n = 8 received aqua pro inj. (0.2 ml/100 g body weight; gavage. Bone marker concentrations of carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I and aminoterminal propeptide of procollagen type I in serum, and of bone alkaline phosphatase (BALP in both serum and bone homogenate were measured by enzyme immunoassay. We investigated the expression of bone morphogenetic protein 2 (BMP-2 in proximal tibia using Western blotting, and bone mineral density was measured by Dual-energy X-ray Absorptiometry in lumbar and caudal vertebrae and in femoral areas. Mechanical properties of the femurs were measured by three-point bending of the shaft and compression testing of the femoral neck. After 8 weeks of amlodipine administration there was a significant decrease in serum concentrations of BALP (p = 0.0009 and CTX-I (p = 0.003, and the content of BALP in bone homogenate (p = 0.026 compared to the control. In addition, Western blot analysis indicated increased BMP-2 protein concentration after amlodipine administration. Our findings suggest that amlodipine has a retarding influence on bone metabolism in rats by decreasing bone turnover, which probably in consequence increases expression of BMP-2.

Radioimmunoassay of serum digoxin levels in digitalis intoxication

International Nuclear Information System (INIS)

Arendt, G.

1981-01-01

For 101 hospitalized patients where clinical symptoms of a glucosidine intoxication as a consequence of oral digoxin treatment were noted, serum digoxin levels were determined using a RIA kit of the Boehringer company (I-125 tracer, solid phase tube separation technique) on a fasted stomach prior to oral drug administration. An ECG was performed simultaneously and in addition kidney function parameters and electrolyte levels were determined. An anamnesis and clinical examination of the patients were also conducted. Interferences in the RIA method and gastro-intestinal illness resulting in changes in resorption behaviour were excluded. The group of patients showed collectively an average serum digoxin level of 2.9 +- 0.9 ng/ml with a range from 1.8 to 6.8 ng/ml, which was statistically significantly higher than the average value for 101 patients receiving long-term oral medication but without symptoms of glycosidine intoxication. According to the manufacture's specifications for the RIA kit, values > 2.0 ng/ml are considered as toxic, with values between 1.6 and 2.0 ng/mg falling into a ''grey zone''. A correlation was found between toxic serum values with changes in ECG pattern and subjective clinical symptoms of intoxication. A limitation of kidney function was responsible for the high serum glycoside levels in 62% of the patients. It was shown that the differing response of patients towards digitalis medication, above all in the case of long-term therapy, warrants an RIA determination of serum glycoside values in order to adjust the digoxin dose to individual requirements. (orig./MG) [de

Pharmacokinetic and bioequivalence study of a telmisartan/S-amlodipine fixed-dose combination (CKD-828) formulation and coadministered telmisartan and S-amlodipine in healthy subjects.

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Kang, Woo Youl; Seong, Sook Jin; Ohk, Boram; Gwon, Mi-Ri; Kim, Bo Kyung; La, Sookie; Kim, Hyun-Ju; Cho, Seungil; Yoon, Young-Ran; Yang, Dong Heon; Lee, Hae Won

2018-01-01

A new fixed-dose combination (FDC) formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828) has been developed to increase convenience (as only one tablet is required per day) and improve treatment compliance. The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography-tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period. Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (C max ) and the area under the plasma concentration-time curve from time 0 to the last measurement (AUC 0-t ) values of telmisartan were 522.29 ng/mL and 2,475.16 ng·h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng·h/mL for the individual agents concomitantly administered, respectively. The mean C max and AUC 0-t values of S-amlodipine were 2.71 ng/mL and 130.69 ng·h/mL for the FDC, and 2.74 ng/mL and 129.81 ng·h/mL for the individual agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the telmisartan C max and AUC 0-t (FDC of telmisartan and S-amlodipine/concomitant administration) were 0.8509 (0.7353-0.9846) and 0.9431 (0.8698-1.0226), respectively. The GMR and 90% CI for the S-amlodipine C max and AUC 0-t (FDC/concomitant administration) were 0.9829 (0.9143-1.0567) and 0.9632 (0.8798-1.0546), respectively. As the intrasubject variability of the C max for telmisartan administered individually was 42.94%, all 90% CIs of the GMRs fell within the predetermined acceptance range. Both treatments were well tolerated in this study. CKD-828 FDC tablets were shown to

Intravenous application of an anticalin dramatically lowers plasma digoxin levels and reduces its toxic effects in rats

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Eyer, Florian, E-mail: Florian.Eyer@mac.com [Department of Toxicology, Klinikum rechts der Isar, Munich (Germany); Steimer, Werner [Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Munich (Germany); Nitzsche, Thomas [Munich Center for Integrated Protein Science (CIPS-M), Freising-Weihenstephan (Germany); Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan (Germany); Jung, Nicole; Neuberger, Heidi [Department of Toxicology, Klinikum rechts der Isar, Munich (Germany); Müller, Christine [Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Munich (Germany); Schlapschy, Martin [Munich Center for Integrated Protein Science (CIPS-M), Freising-Weihenstephan (Germany); Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan (Germany); Zilker, Thomas [Department of Toxicology, Klinikum rechts der Isar, Munich (Germany); Skerra, Arne [Munich Center for Integrated Protein Science (CIPS-M), Freising-Weihenstephan (Germany); Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan (Germany)

2012-09-15

Lipocalins tailored with high affinity for prescribed ligands, so-called anticalins, constitute promising candidates as antidotes. Here, we present an animal study to investigate both pharmacokinetic and clinical effects of an anticalin specific for the digitalis compound digoxin. Intravenous digoxin (2.5–50 μg/kg/min) was administered to rats until first changes in the ECG occurred (dose finding study) or a priori for 30 min (kinetic study). The anticalin DigA16(H86N), dubbed DigiCal, was administered intravenously at absolute doses of 1, 5, 10 and 20 mg, while the control group received isotonic saline. Hemodynamic changes, several ECG parameters and digoxin concentration in plasma were monitored at given time intervals. After DigiCal administration free digoxin concentration in plasma ultrafiltrate declined dramatically within 1 min to the presumably non-toxic range. There was also a significant and DigiCal dose-dependent effect on longer survival, less ECG alterations, arrhythmia, and improved hemodynamics. Infusion of a lower digoxin dose (2.5 μg/kg/min) resulted in a more sustained reduction of free digoxin in plasma after DigiCal administration compared to a higher digoxin dose (25 μg/kg/min), whereas ECG and hemodynamic parameters did not markedly differ, reflecting the known relative insensitivity of rats towards digoxin toxicity. Notably, we observed a re-increase of free digoxin in plasma some time after bolus administration of DigiCal, which was presumably due to toxin redistribution from tissue in combination with the relatively fast renal clearance of the rather small protein antidote. We conclude that anticalins with appropriately engineered drug-binding activities and, possibly, prolonged plasma half-life offer prospects for next-generation antidotal therapy. -- Highlights: ► We provide an advanced model of digoxin toxicity in rats. ► We report on binding of digoxin to a novel designed anticalin. ► We report on pharmacokinetics of digoxin

A simplified radioimmunoassay for digoxin determination using a 125-I-labelled solid-phase kit

International Nuclear Information System (INIS)

Doering, W.; Bluemel, E.

1978-01-01

Our experience with a commercially available kit (Radioimmunoassay DIGOXIN, Boehringer, Mannheim) using ( 125 J)-labelled digoxin and antibody-coated tubes is reported. This simplified method requires only two pipetting steps per sample and results can be obtained in 70 min. The intra- and interassay coefficient of variation ranged between 7% and 8%. The specific digoxin antibody antibody gave no clinical relevant cross-reactions with spironolactone or prednisone ( [de

Successful management of airway hemangioma with propranolol.

Science.gov (United States)

Mendiratta, Vibhu; Varghese, Bincy; Chander, Ram; Parakh, Ankit; Solanki, Ravi S

2013-06-01

Airway hemangiomas can be difficult to manage and cause anxiety in both the parents and the treating physician. Propranolol, a nonselective beta-blocker, has recently been used for treating proliferating infantile hemangiomas. We report successful management of a proliferating, large, mixed infantile hemangioma with subglottic extension in an Indian infant using oral propranolol in a dose of 2mg/kg/day without any side effects. Induction of early involution and freedom from the side effects of steroid therapy seem encouraging for using propranolol as a first line treatment modality in the management of troublesome hemangiomas. © 2013 The International Society of Dermatology.

A Rare Case Report of Amlodipine-Induced Gingival Enlargement and Review of Its Pathogenesis

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Sanjeev Joshi

2013-01-01

Full Text Available Gingival enlargement is a common clinical feature of gingival and periodontal diseases. It is an unwanted side effect of certain systemic drugs given for nondental treatment. It is being reported with three main groups of drugs like calcium channel blockers (CCBs, immunosuppressants, and anticonvulsants. Among calcium channel blockers, nifedipine causes gingival hyperplasia in about 10% of patients, whereas the incidence of amlodipine-, a third generation calcium channel blocker, induced gingival hyperplasia is very limited. There are very few reports of amlodipine-induced gingival enlargement at a dose of 5 mg. We report a case of amlodipine-induced gingival enlargement in a 45-year-old hypertensive patient taking amlodipine at a dose of 5 mg.

Propranolol attenuates hemorrhage and accelerates wound healing in severely burned adults.

Science.gov (United States)

Ali, Arham; Herndon, David N; Mamachen, Ashish; Hasan, Samir; Andersen, Clark R; Grogans, Ro-Jon; Brewer, Jordan L; Lee, Jong O; Heffernan, Jamie; Suman, Oscar E; Finnerty, Celeste C

2015-05-04

Propranolol, a nonselective β-blocker, exerts an indirect effect on the vasculature by leaving α-adrenergic receptors unopposed, resulting in peripheral vasoconstriction. We have previously shown that propranolol diminishes peripheral blood following burn injury by increasing vascular resistance. The purpose of this study was to investigate whether wound healing and perioperative hemodynamics are affected by propranolol administration in severely burned adults. Sixty-nine adult patients with burns covering ≥ 30% of the total body surface area (TBSA) were enrolled in this IRB-approved study. Patients received standard burn care with (n = 35) or without (control, n = 34) propranolol. Propranolol was administered within 48 hours of burns and given throughout hospital discharge to decrease heart rate by approximately 20% from admission levels. Wound healing was determined by comparing the time between grafting procedures. Blood loss was determined by comparing pre- and postoperative hematocrit while factoring in operative graft area. Data were collected between first admission and first discharge. Demographics, burn size, and mortality were comparable in the control and propranolol groups. Patients in the propranolol group received an average propranolol dose of 3.3 ± 3.0 mg/kg/day. Daily average heart rate over the first 30 days was significantly lower in the propranolol group (P operative intervention is optimal.

Studies on cerebral protection of digoxin against ischemia/reperfusion injury in mice.

Science.gov (United States)

Kaur, Shaminder; Rehni, Ashish K; Singh, Nirmal; Jaggi, Amteshwar S

2009-04-01

The present study was designed to investigate the possible neuroprotective effect of digoxin induced pharmacological preconditioning (PP) and its probable mechanism. Bilateral carotid artery occlusion (BCAO) of 17 min followed by reperfusion for 24 h was employed to produce ischemia and reperfusion (I/R) induced cerebral injury in male swiss albino mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using elevated plus maze test. Degree of motor incoordination was evaluated using inclined beam walking test, rota rod test and lateral push test. Digoxin (0.08 mg/kg, i.p.) was administered 24 h before surgery in a separate group of animals to induce PP. BCAO followed by reperfusion, produced significant rise in cerebral infarct size along with impairment of memory and motor coordination. Digoxin treatment produced a significant decrease in cerebral infarct size and reversal of I/R induced impairment of memory and motor incoordination. Digoxin induced neuroprotective effect was abolished significantly by verapamil (15 mg/kg, i.p.), a L-type calcium channel blocker, ruthenium red (3 mg/kg, s.c.), an intracellular ryanodine receptor blocker and 3,4-dichlorobenzamil (Na(+)/Ca(2+) exchanger inhibitor). These findings indicate that digoxin preconditioning exerts a marked neuroprotective effect on the ischemic brain, which is possibly linked to digitalis induced increase in intracellular calcium levels eventually leading to the activation of calcium sensitive signal transduction cascades.

Interference factors in digoxin analysis, especially in the serum of pregnant women, by RIA

International Nuclear Information System (INIS)

Tratz, A.

1981-01-01

The causes of false digoxin concentrations measured in pregnant women by RIA were gone into; 103 sera of healthy women in their last trimester of pregnancy were analyzed by 4 different RIA methods. In 6 cases, falsepositive digoxin levels above 1.0 ng/ml were found; 4 of the measured digoxin levels were above 2.0 ng/ml, i.e. a clinically toxic concentration. No pseudodigoxin was detected post partum; however, the author was only able to make control measurements of 2 of the 3 positive sera between the 6th and 12th week post partum. The causes of this phenomenon remain unclear. It cannot be excluded that these pregnant women may have a still unknown hormone metabolite, resulting from a possible enzymatic defect, which cross-reacts with the digoxin antiserum and thus causes false-positive results. In those rare cases where pregnant women receive digitalis treatment, digoxin serum measurements by RIA must be analyzed very critically due to the possibility of false-positive results. (orig.) [de

Hypothalamic digoxin, hemispheric chemical dominance, and inflammatory bowel disease.

Science.gov (United States)

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-09-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. It was considered pertinent to assess the pathway in inflammatory bowel disease (ulcerative colitis and regional ileitis). Since endogenous digoxin can regulate neurotransmitter transport, the pathway and the related cascade were also assessed in individuals with differing hemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. All the patients with inflammatory bowel disease were right-handed/left hemispheric dominant by the dichotic listening test. The following parameters were measured in patients with inflammatory bowel disease and in individuals with differing hemispheric dominance: (1) plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; (2) tryptophan/tyrosine catabolic patterns; (3) free-radical metabolism; (4) glycoconjugate metabolism; and (5) membrane composition and RBC membrane Na+-K+ ATPase activity. Statistical analysis was done by ANOVA. In patients with inflammatory bowel disease there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these groups of patients. Inflammatory bowel disease is associated with an upregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This can contribute to immune activation, defective glycoprotein bowel antigen presentation, and autoimmunity and a schizophreniform psychosis important in its pathogenesis. The biochemical patterns obtained in inflammatory bowel disease is similar to those obtained in left-handed/right hemispheric dominant individuals by the dichotic listening test. But all the patients with peptic ulcer disease were right

Postmarketing comparison of labetalol and propranolol in hypertensive patients.

Science.gov (United States)

Due, D L; Giguere, G C; Plachetka, J R

1986-01-01

A survey was conducted to compare the safety and effectiveness of labetalol and propranolol under routine conditions of clinical use. Patients received either labetalol (n = 805) or propranolol (n = 135) twice daily, according to package insert instructions, for six weeks. Every two weeks the patients were evaluated and weight, heart rate, blood pressure, dose, and adverse symptoms were recorded. Both treatment groups experienced a significant decline in blood pressure at six weeks; blood pressure decreased by 24/15 mmHg in the labetalol patients and by 20/14 mmHg in the propranolol patients. Heart rate decreased significantly in both groups, but the drop in the propranolol group was greater than in the labetalol group. Significantly more propranolol-treated patients reported fatigue (15.2% versus 6.3%), impotence (9.0% versus 3.2%), bad dreams (2.3% versus 0.3%), and cold extremities (2.3% versus 0%). Dizziness was reported more frequently by the labetalol group (9.1% versus 3.8%). Overall, both drugs were safe and effective in treating hypertension, but complaints of beta-blocker-associated side effects were more frequent with propranolol.

Amlodipine Ameliorates Ischemia-Induced Neovascularization in Diabetic Rats through Endothelial Progenitor Cell Mobilization

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Jiayin Sun

2016-01-01

Full Text Available Objectives. We investigated whether amlodipine could improve angiogenic responses in a diabetic rat model of acute myocardial infarction (AMI through improving bone marrow endothelial progenitor cell (EPC mobilization, in the same way as angiotensin converting enzyme inhibitors. Methods. After induction of AMI by coronary artery ligation, diabetic rats were randomly assigned to receive perindopril (2 mgkg−1 day−1, amlodipine (2.5 mgkg−1 day−1, or vehicle by gavage (n=20 per group. Circulating EPC counts before ligation and on days 1, 3, 5, 7, 14, and 28 after AMI were measured in each group. Microvessel density, cardiac function, and cardiac remodeling were assessed 4 weeks after treatment. The signaling pathway related to EPC mobilization was also measured. Results. Circulating EPC count in amlodipine- and perindopril-treated rats peaked at day 7, to an obvious higher level than the control group peak which was reached earlier (at day 5. Rats treated with amlodipine showed improved postischemia neovascularization and cardiac function, together with reduced cardiac remodeling, decreased interstitial fibrosis, and cardiomyocyte apoptosis. Amlodipine treatment also increased cardiac SDF-1/CXCR4 expression and gave rise to activation of VEGF/Akt/eNOS signaling in bone marrow. Conclusions. Amlodipine promotes neovascularization by improving EPC mobilization from bone marrow in diabetic rats after AMI, and activation of VEGF/Akt/eNOS signaling may in part contribute to this.

INAPPROPRIATE USE OF DIGOXIN IN MEDICAL PRACTICE

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Debasish

2015-08-01

Full Text Available Digoxin, the old golden molecule is one of the commonly prescribed drugs prescribed by general medical practitioners when a patient presents with dyspnea. Inspite of being arrythmogenic and having narrow therapeutic window, physicians do not even hesitate to use even where it could be catastrophic. Most are unaware of the classical indicatio ns where as others use it in myth that it is life saving and miraculous although numerous studies clearly delineates that it does not improve cardiac mortality although delay hospitalization. Our study was a miniature one to improve the cautiousness before digoxin use in medical practice and delineate its irrational use among patients with cardiovascular disease. We studied 4562 patients who were consulted in AIIMS Cardiology and Medicine OPD between October 2014 to June 2015 having digoxin among their ther apeutic armamentarium and delineated their irrational use even in toxic conditions. Rational use was only evident in 2007 (44%cases where as it was advocated wrongly in 2555(56% of cases, most sufferers being rheumatic heart disease (51.27% population, hypertensive heart disease(17.88%, coronary artery disease(5.44%, COPD(12.88% and CKD(0.9% patients being in decreasing order. In RHD scenario mitral stenosis patients suffered most (56% followed by aortic stenosis patients (25% compared to regurgita nt lesions which are better tolerated

A linear graph for digoxin radioimmunoassay

International Nuclear Information System (INIS)

Smith, S.E.; Richter, A.

1975-01-01

The determination of drug or hormone concentrations by radio-immunoassay involves interpolation of values for radioisotope counts within standard curves, a technique which requires some dexterity in curve drawing and which results in some inaccuracy in practice. Most of the procedures designed to overcome these difficulties are complex and time-consuming. In radioimmunoassays involving saturation of the antibody-binding sites a special case exists in that the bound radioactivity is directly proportional to the specific activity of the ligand in the system. Thus a graph of the ratio of radioactivity bound in the absence to that in the presence of added non-radioactive ligand is linear against the concentration of added ligand (Hales,C.N., and Randle, P.J., 1963, Biochem. J., vol. 88, 137). A description is given of a simple and convenient modification of their method, and its application to the routine clinical determination of digoxin using a commercial kit (Lanoxitest β digoxin radioimmunoassay kit, Wellcome Reagents Ltd.). Specially constructed graph paper, which yields linearity with standard solutions, was designed so that it could be used directly without data transmission. The specific activity function appears as the upper arithmetical horizontal scale; corresponding values of the concentration of non-radioactive ligand in the solution added were individually calculated and appear on the lower scale opposite the appropriate values of the upper scale. The linearity of the graphs obtained confirmed that binding of digoxin was approximately constant through the range of clinical concentrations tested (0.5 to 8ng/ml), although binding declined slightly at higher concentrations. (U.K.)

Quantitative model for the blood pressure‐lowering interaction of valsartan and amlodipine

Science.gov (United States)

Heo, Young‐A; Holford, Nick; Kim, Yukyung; Son, Mijeong

2016-01-01

Aims The objective of this study was to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model to quantitatively describe the antihypertensive effect of combined therapy with amlodipine and valsartan. Methods PK modelling was used with data collected from 48 healthy volunteers receiving a single dose of combined formulation of 10 mg amlodipine and 160 mg valsartan. Systolic (SBP) and diastolic blood pressure (DBP) were recorded during combined administration. SBP and DBP data for each drug alone were gathered from the literature. PKPD models of each drug and for combined administration were built with NONMEM 7.3. Results A two‐compartment model with zero order absorption best described the PK data of both drugs. Amlodipine and valsartan monotherapy effects on SBP and DBP were best described by an I max model with an effect compartment delay. Combined therapy was described using a proportional interaction term as follows: (D1 + D2) +ALPHA×(D1 × D2). D1 and D2 are the predicted drug effects of amlodipine and valsartan monotherapy respectively. ALPHA is the interaction term for combined therapy. Quantitative estimates of ALPHA were −0.171 (95% CI: −0.218, −0.143) for SBP and −0.0312 (95% CI: −0.07739, −0.00283) for DBP. These infra‐additive interaction terms for both SBP and DBP were consistent with literature results for combined administration of drugs in these classes. Conclusion PKPD models for SBP and DBP successfully described the time course of the antihypertensive effects of amlodipine and valsartan. An infra‐additive interaction between amlodipine and valsartan when used in combined administration was confirmed and quantified. PMID:27504853

THE ROLE OF S-AMLODIPINE IN ARTERIAL HYPERTENSION THERAPY WITH COMBINATION OF CALCIUM CHANNEL BLOCKERS AND BETA-BLOCKERS

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M. A. Maksimova

2013-01-01

Full Text Available Aim. To study efficacy and safety of calcium channel blocker, S-amlodipine, in combination with β-blocker, atenolol, in patients with arterial hypertension (HT 1-2 degree com- pared to fixed combination of racemic amlodipine and atenolol.Material and methods. Patients (n=31, 7 men and 24 women with HT 1–2 degree were included into the study. The patients were randomized into two groups by the com- binations sequence. Treatment with each combination lasted 4 weeks. Office blood pressure (BP was assessed at baseline and at the end of the treatment periods, possible side effects were registered.Results. All patients completed the study. Both combination of S-amlodipine+atenolol and fixed combination of racemic amlodipine+atenolol reduced systolic (in average, -15.9 and -12.7 mm Hg, respectively and diastolic (in average, -7.3 and -5.3 mmHg, respectively BP significantly. Heart rate also decreased during therapy (in average, -3 and -4 bt/min, respectively. The differences between combinations BP and heart rate effects were not significant. 8 and 16 adverse events were registered during S-amlodipine+atenolol and racemic amlodipine+atenolol therapies, respectively Conclusion. Combination of S-amlodipine+atenolol, as well as combination of racemic amlodipine+atenolol are effective in the treatment of patients with HT 1-2 degree, however combination with S-amlodipine has less number of adverse events.

In-vitro displacement interaction of atenolol and amlodipine on binding with bovine serum albumin when co-administered

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Md. Ashraful Alam, Md. Abdul Awal, Mahbub Mostofa, Md. Kamrul Islam and Nusrat Subhan

2007-06-01

Full Text Available The binding of atenolol (selective β1-blocker and amlodipine (calcium channel blocker to bovine serum albumin (BSA was studied by equilibrium dialysis method in order to have an insight into the binding chemistry of these two to BSA. Free atenolol concentration was increased due to addition of amlodipine which reduced the binding of the compounds to BSA. However, the free fraction was increased to a level as it was expected from direct competitive displacement while the free atenolol concentration was increased according to increasing the amlodipine concentration when only the BSA was present. The result obtained when the binding site was blocked by sufficient amount of amlodipine was that the increment of free concentration of atenolol was prominent. When no amlodipine was added the free concentration of atenolol was only 28% whereas this release was 93 % to 98.01% when amlodipine was added with increasing concentration.

Comparison of propranolol and metoprolol in the management of hyperthyroidism.

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Murchison, L E; How, J; Bewsher, P D

1979-01-01

1 Propranolol and metoprolol were both effective in controlling the symptoms and signs of hyperthyroidism. 2 Propranolol caused a highly significant increase in serum reverse T3 concentrations with lesser changes in other serum thyroid hormone levels, whereas metoprolol did not have this effect. 3 Steady-state plasma propranolol and metoprolol levels showed marked inter-individual variation. Metoprolol concentrations showed relatively little intra-individual variability, and could be related to the clinical efficacy of the drug, whereas no such relationship was demonstrated for propranolol. PMID:391258

Oral versus topical propranolol for management of superficial ...

African Journals Online (AJOL)

was treated with oral propranolol and group B (n = 24) was treated with propranolol .... months during treatment, or if any undesirable drawbacks .... dosage and the serum concentration of the drug in this route [29]. However, McMahon et al.

A randomized, controlled trial of oral propranolol in infantile hemangioma.

Science.gov (United States)

Léauté-Labrèze, Christine; Hoeger, Peter; Mazereeuw-Hautier, Juliette; Guibaud, Laurent; Baselga, Eulalia; Posiunas, Gintas; Phillips, Roderic J; Caceres, Hector; Lopez Gutierrez, Juan Carlos; Ballona, Rosalia; Friedlander, Sheila Fallon; Powell, Julie; Perek, Danuta; Metz, Brandie; Barbarot, Sebastien; Maruani, Annabel; Szalai, Zsuzsanna Zsofia; Krol, Alfons; Boccara, Olivia; Foelster-Holst, Regina; Febrer Bosch, Maria Isabel; Su, John; Buckova, Hana; Torrelo, Antonio; Cambazard, Frederic; Grantzow, Rainer; Wargon, Orli; Wyrzykowski, Dariusz; Roessler, Jochen; Bernabeu-Wittel, Jose; Valencia, Adriana M; Przewratil, Przemyslaw; Glick, Sharon; Pope, Elena; Birchall, Nicholas; Benjamin, Latanya; Mancini, Anthony J; Vabres, Pierre; Souteyrand, Pierre; Frieden, Ilona J; Berul, Charles I; Mehta, Cyrus R; Prey, Sorilla; Boralevi, Franck; Morgan, Caroline C; Heritier, Stephane; Delarue, Alain; Voisard, Jean-Jacques

2015-02-19

Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited. We performed a multicenter, randomized, double-blind, adaptive, phase 2-3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy. Infants were randomly assigned to receive placebo or one of four propranolol regimens (1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months). A preplanned interim analysis was conducted to identify the regimen to study for the final efficacy analysis. The primary end point was success (complete or nearly complete resolution of the target hemangioma) or failure of trial treatment at week 24, as assessed by independent, centralized, blinded evaluations of standardized photographs. Of 460 infants who underwent randomization, 456 received treatment. On the basis of an interim analysis of the first 188 patients who completed 24 weeks of trial treatment, the regimen of 3 mg of propranolol per kilogram per day for 6 months was selected for the final efficacy analysis. The frequency of successful treatment was higher with this regimen than with placebo (60% vs. 4%, P<0.001). A total of 88% of patients who received the selected propranolol regimen showed improvement by week 5, versus 5% of patients who received placebo. A total of 10% of patients in whom treatment with propranolol was successful required systemic retreatment during follow-up. Known adverse events associated with propranolol (hypoglycemia, hypotension, bradycardia, and bronchospasm) occurred infrequently, with no significant difference in frequency between the placebo group and the groups receiving propranolol. This trial showed that propranolol was effective at a dose of 3 mg per kilogram per day for 6 months in the treatment of infantile hemangioma. (Funded by

Iodine-125--digoxin radioimmunoassay: comparison of commercial kits

International Nuclear Information System (INIS)

Battaglia, D.J.; Cianci, M.L.

1976-01-01

Iodine-125-digoxin radioimmunoassay kits available from Abbott Diagnostics (AD), Dade Division (D), Schwarz/Mann (SM), and Clinical Assays (CA) were evaluated with respect to assay quality. The kit accuracies did not differ significantly at 2.0 ng/ml and the interassay coefficients of variation ranged from 9 percent (AD) to 21.4 percent (CA). The accuracy for all kits above 4 ng/ml is questionable, and since serum-dilution values correlated well with undiluted serum values, the dilution method of dose quantitation is preferable for levels above 4 ng/ml. Although all the kits were adequate for evaluating digoxin at the 2 ng/ml level, the Abbott kit seems to be of slightly better quality

Original Research Monotherapy with amlodipine or ...

African Journals Online (AJOL)

hypertension is the most common cardiovascular disease ... on the electrolyte profile of Nigerians with mild to moderate hypertension. Methods ... sphygmomanometer. ... Figure 1: Systolic blood pressure measurements following treatment with amlodipine and ..... above, the age of the subjects may be a contributing factor;.

Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation.

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Alexander Zhyvoloup

2017-07-01

Full Text Available HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation.

Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation.

Science.gov (United States)

Zhyvoloup, Alexander; Melamed, Anat; Anderson, Ian; Planas, Delphine; Lee, Chen-Hsuin; Kriston-Vizi, Janos; Ketteler, Robin; Merritt, Andy; Routy, Jean-Pierre; Ancuta, Petronela; Bangham, Charles R M; Fassati, Ariberto

2017-07-01

HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation.

Antihypertensive treatment with telmisartan in a cat with amlodipine-induced gingival hyperplasia

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Lien Desmet

2017-12-01

Full Text Available Case summary Systemic arterial hypertension is commonly reported in middle-aged-to-older cats. Amlodipine is recommended as the initial antihypertensive drug in cats. In this case report, gingival hyperplasia secondary to the use of amlodipine in a cat is described. Benazepril as a monotherapy was unsuccessful in reducing blood pressure in this cat. After replacement of benazepril by telmisartan, gingival hyperplasia disappeared and blood pressure was well controlled. Relevance and novel information This case report describes the first reported case of reversible gingival hyperplasia as a result of the treatment with amlodipine. It also contains the first published data on the effect of telmisartan in a hypertensive cat.

Is digoxin an independent risk factor for long-term mortality after acute myocardial infarction?

DEFF Research Database (Denmark)

Køber, L; Torp-Pedersen, C; Gadsbøll, N

1994-01-01

age, LVEF, diabetes mellitus, heart failure, atrial fibrillation or flutter, ventricular fibrillation, gender, dose of furosemide at discharge and calcium antagonists and digoxin treatment as covariates, digoxin was independently associated with an increased risk of death (relative risk 1.8 (95...

An optical sensor for the determination of digoxin in serum samples based on a molecularly imprinted polymer membrane

International Nuclear Information System (INIS)

Paniagua Gonzalez, Gema; Fernandez Hernando, Pilar; Durand Alegria, J. S.

2009-01-01

This paper reports the synthesis and testing of a molecularly imprinted polymer membrane for digoxin analysis. Digoxin-specific bulk polymer was obtained by the UV initiated co-polymerisation of methacrylic acid and ethylene glycol dimethacrylate in acetonitrile as porogen. After extracting the template analyte, the ground polymer particles were mixed with plasticizer polyvinyl chloride to form a MIP membrane. A reference polymer membrane was prepared from the same mixture of monomers but with no template. The resultant membrane morphologies were examined by scanning electron microscopy. The imprinted membrane was tested as the recognition element in a digoxin-sensitive fluorescence sensor; sensor response was measured using standard solutions of digoxin at concentrations of up to 4 x 10 -3 mg L -1 . The detection limit was 3.17 x 10 -5 mg L -1 . Within- and between-day relative standard deviations RSD (n = 5) were in the range 4.5-5.5% and 5.5-6.5% respectively for 0 and 1 x 10 -3 mg L -1 digoxin concentrations. A selectivity study showed that compounds of similar structure to digoxin did not significantly interfere with detection for interferent concentrations at 10, 30 and 100 times higher than the digoxin concentration. This simply manufactured MIP membrane showed good recognition characteristics, a high affinity for digoxin, and provided satisfactory results in analyses of this analyte in human serum.

Noncardiogenic Pulmonary Edema after Amlodipine Overdose without Refractory Hypotension and Bradycardia

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M. Hedaiaty

2015-01-01

Full Text Available Amlodipine overdose can be life-threatening when manifesting as noncardiogenic pulmonary edema. Treatment remains challenging. We describe a case of noncardiogenic pulmonary edema without refractory hypotension and bradycardia after ingestion of 500 milligram amlodipine with suicidal intent. Mechanical ventilation, dexamethasone, atrovent HFA (ipratropium, pulmicort inhalation, and antibiotic therapy were used for the management. Length of hospital stay was 11 days. The patient was discharged with full recovery.

VERIFICATION HPLC METHOD OF QUANTITATIVE DETERMINATION OF AMLODIPINE IN TABLETS

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Khanin V. A

2014-10-01

Full Text Available Introduction. Amlodipine ((±-2-[(2-aminoetoksimethyl]-4-(2-chlorophenyl-1,4-dihydro-6-methyl-3,5-pyridine dicarboxylic acid 3-ethyl 5-methyl ester as besylate and small tally belongs to the group of selective long-acting calcium channel blockers, dihydropyridine derivatives. In clinical practice, as antianginal and antihypertensive agent for the treatment of cardiovascular diseases. It is produced in powder form, substance and finished dosage forms (tablets of 2.5, 5 and 10 mg. The scientific literature describes methods of quantitative determination of the drug by spectrophotometry – by his own light absorption and by reaction product with aloksan, chromatography techniques, kinetic-spectrophotometric method in substances and preparations and methods chromatomass spectrometry and stripping voltammetry. For the quantitative determination of amlodipine besylate British Pharmacopoeia and European Pharmacopoeia recommend the use of liquid chromatography method. In connection with the establishment of the second edition of SPhU and when it is comprised of articles on the finished product, we set out to analyze the characteristics of the validation of chromatographic quantitative determination of amlodipine besylate tablets and to verify the analytical procedure. Material & methods. In conducting research using substance amlodipine besylate series number AB0401013. Analysis subject pill “Amlodipine” series number 20113 manufacturer of “Pharmaceutical company “Zdorovye”. Analytical equipment used is: 2695 chromatograph with diode array detector 2996 firms Waters Corp. USA using column Nova-Pak C18 300 x 3,9 mm with a particle size of 4 μm, weight ER-182 company AND Japan, measuring vessel class A. Preparation of the test solution. To accurately sample powder tablets equivalent to 50 mg amlodipine, add 30 ml of methanol, shake for 30 minutes, dilute the solution to 50.0 ml with methanol and filtered. 5 ml of methanol solution adjusted to

Oral Propranolol: A New Treatment for Infants with Retinopathy of Prematurity?

Science.gov (United States)

Bührer, Christoph; Bassler, Dirk

2015-01-01

Oral propranolol has improved the treatment of infantile hemangiomas, and a pediatric oral solution of propranolol has recently been licensed in the USA and Europe. In very preterm infants, infantile hemangiomas are associated with the occurrence of retinopathy of prematurity (ROP), and both diseases share a peculiar time course, featuring a lag phase after birth followed by rapid growth and then gradual regression. To identify clinical studies evaluating the use of oral propranolol in preterm infants with ROP. Two small bicentric, pilot, randomized controlled trials found a nonsignificant reduction of ROP requiring intervention by laser treatment or bevacizumab injection of similar magnitude. Together, 6 of 35 (17%) infants who had been receiving oral propranolol underwent ROP intervention, as opposed to 14 of 36 (39%) controls (relative risk 0.42, 95% CI: 0.15-1.16). Randomized controlled trials are ongoing that investigate early preventive oral propranolol starting at 1 week of age and propranolol eye drops in preterm infants with stage 2 ROP. Further, large interventional studies are required to determine the clinical benefit-risk ratio of oral propranolol to prevent vision-threatening ROP in very preterm infants. © 2015 S. Karger AG, Basel.

Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients.

Science.gov (United States)

Jamerson, Kenneth; Weber, Michael A; Bakris, George L; Dahlöf, Björn; Pitt, Bertram; Shi, Victor; Hester, Allen; Gupte, Jitendra; Gatlin, Marjorie; Velazquez, Eric J

2008-12-04

The optimal combination drug therapy for hypertension is not established, although current U.S. guidelines recommend inclusion of a diuretic. We hypothesized that treatment with the combination of an angiotensin-converting-enzyme (ACE) inhibitor and a dihydropyridine calcium-channel blocker would be more effective in reducing the rate of cardiovascular events than treatment with an ACE inhibitor plus a thiazide diuretic. In a randomized, double-blind trial, we assigned 11,506 patients with hypertension who were at high risk for cardiovascular events to receive treatment with either benazepril plus amlodipine or benazepril plus hydrochlorothiazide. The primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization. The baseline characteristics of the two groups were similar. The trial was terminated early after a mean follow-up of 36 months, when the boundary of the prespecified stopping rule was exceeded. Mean blood pressures after dose adjustment were 131.6/73.3 mm Hg in the benazepril-amlodipine group and 132.5/74.4 mm Hg in the benazepril-hydrochlorothiazide group. There were 552 primary-outcome events in the benazepril-amlodipine group (9.6%) and 679 in the benazepril-hydrochlorothiazide group (11.8%), representing an absolute risk reduction with benazepril-amlodipine therapy of 2.2% and a relative risk reduction of 19.6% (hazard ratio, 0.80, 95% confidence interval [CI], 0.72 to 0.90; Pbenazepril-amlodipine combination was superior to the benazepril-hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events. (ClinicalTrials.gov number, NCT00170950.) 2008 Massachusetts Medical Society

Amlodipine-induced gingival hyperplasia in chronic renal

African Journals Online (AJOL)

Administrator

Keywords: Amlodipine, gingival hyperplasia, chronic renal failure. African Health ... for the treatment of hypertension and angina. Pharmacokinetic ... patient appealed to the dentist at first. ... Am Heart J. 1989 Nov; 118(5 Pt 2):. 1100-1103. 2.

Propranolol in treatment of huge and complicated infantile hemangiomas in egyptian children.

Science.gov (United States)

Hassan, Basheir A; Shreef, Khalid S

2014-01-01

Background. Infantile hemangiomas (IHs) are the most common benign tumours of infancy. Propranolol has recently been reported to be a highly effective treatment for IHs. This study aimed to evaluate the efficacy and side effects of propranolol for treatment of complicated cases of IHs. Patients and Methods. This prospective clinical study included 30 children with huge or complicated IHs; their ages ranged from 2 months to 1 year. They were treated by oral propranolol. Treatment outcomes were clinically evaluated. Results. Superficial cutaneous hemangiomas began to respond to propranolol therapy within one to two weeks after the onset of treatment. The mean treatment period that was needed for the occurrence of complete resolution was 9.4 months. Treatment with propranolol was well tolerated and had few side effects. No rebound growth of the tumors was noted when propranolol dosing stopped except in one case. Conclusion. Propranolol is a promising treatment for IHs without obvious side effects. However, further studies with longer follow-up periods are needed.

Comparison of propranolol and practolol in the management of hyperthyroidism.

Science.gov (United States)

Murchison, L E; Bewsher, P D; Chesters, M I; Ferrier, W R

1976-04-01

Twenty-one hyperthyroid patients participated in an 8-week double-blind crossover trial of propranolol and practolol, and the effecte of these drugs on the clinical and metabolic features of the disease were studied. Propranolol was marginally more effective than practolol, as measured by the hyperthyroid diagnostic index and anxiety scale. Propranolol produced a significant reduction in the serum concentration ratio of tri-iodothyronine to thyroxine, compatible with partial inhibition of peripheral deiodination of thyroxine. Adverse reactions occurred more frequently with propranolol than with practolol. In veiw of the efficacy of practoloo, further trials in hyperthyroid patients of newer beta1-adrenoceptor antagonists, preferably without partial agonist activity, are indicated.

Pharmacokinetic and bioequivalence study of a telmisartan/S-amlodipine fixed-dose combination (CKD-828 formulation and coadministered telmisartan and S-amlodipine in healthy subjects

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Kang WY

2018-03-01

Full Text Available Woo Youl Kang,1,2,* Sook Jin Seong,1,* Boram Ohk,1,2 Mi-Ri Gwon,1,3 Bo Kyung Kim,1,2 Sookie La,4 Hyun-Ju Kim,3 Seungil Cho,1 Young-Ran Yoon,1,2 Dong Heon Yang,5 Hae Won Lee1 1Clinical Trial Center, Kyungpook National University Hospital, Daegu, Republic of Korea; 2Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent, Kyungpook National University Graduate School, Daegu, Republic of Korea; 3Department of Molecular Medicine, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea; 4Analytical Research Division, Biocore Co Ltd, Seoul, Republic of Korea; 5Division of Cardiology, Department of Internal Medicine, Kyungpook National University School of Medicine & Hospital, Daegu, Republic of Korea *These authors contributed equally to this work Purpose: A new fixed-dose combination (FDC formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828 has been developed to increase convenience (as only one tablet is required per day and improve treatment compliance.Methods: The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography–tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period.Results: Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (Cmax and the area under the plasma concentration–time curve from time 0 to the last measurement (AUC0–t values of telmisartan were 522.29 ng/mL and 2,475.16 ng⋅h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng⋅h/mL for the individual agents

The effect of captopriland amlodipine on C-reactive protein concentrations in type 2 diabetic hypertensive patients

International Nuclear Information System (INIS)

Mahmood, I.H.

2008-01-01

To compare the effects of the ACE inhibitor captopril with the calcium channel blocker amlodipine on serum CRP concentrations in hypertensive type 2 diabetic patients. This is a case control study conducted in Al-Wafa Diabetic Center in Mosul. Serum CRP concentrations were measured in two groups of hypertensive type 2 diabetic patients before and after drug administration (group 1 on captopril therapy, group two on amlodipine therapy). A significant reduction of serum CRP level was demonstrated after treatment with captopril but not with amlodipine. Mean CRP concentration of the control group was statistically lower than those of captopril and amlodipine groups. The present study showed that hypertensive type 2 diabetic patients are associated with increased level of CRP and therapy with captopril but not amlodipine significantly reduced CRP, suggesting a possible anti-inflammatory action of captopril in addition to its BP lowering effects thus captopril may be regarded as the drug of choice in the treatment of BP in diabetic hypertensive patients. (author)

An optical sensor for the determination of digoxin in serum samples based on a molecularly imprinted polymer membrane

Energy Technology Data Exchange (ETDEWEB)

Paniagua Gonzalez, Gema [Departamento de Ciencias Analiticas, Facultad de Ciencias, Universidad Nacional de Educacion a Distancia (UNED), 28040 Madrid (Spain); Fernandez Hernando, Pilar, E-mail: pfhernando@ccia.uned.es [Departamento de Ciencias Analiticas, Facultad de Ciencias, Universidad Nacional de Educacion a Distancia (UNED), 28040 Madrid (Spain); Durand Alegria, J. S. [Departamento de Ciencias Analiticas, Facultad de Ciencias, Universidad Nacional de Educacion a Distancia (UNED), 28040 Madrid (Spain)

2009-04-13

This paper reports the synthesis and testing of a molecularly imprinted polymer membrane for digoxin analysis. Digoxin-specific bulk polymer was obtained by the UV initiated co-polymerisation of methacrylic acid and ethylene glycol dimethacrylate in acetonitrile as porogen. After extracting the template analyte, the ground polymer particles were mixed with plasticizer polyvinyl chloride to form a MIP membrane. A reference polymer membrane was prepared from the same mixture of monomers but with no template. The resultant membrane morphologies were examined by scanning electron microscopy. The imprinted membrane was tested as the recognition element in a digoxin-sensitive fluorescence sensor; sensor response was measured using standard solutions of digoxin at concentrations of up to 4 x 10{sup -3} mg L{sup -1}. The detection limit was 3.17 x 10{sup -5} mg L{sup -1}. Within- and between-day relative standard deviations RSD (n = 5) were in the range 4.5-5.5% and 5.5-6.5% respectively for 0 and 1 x 10{sup -3} mg L{sup -1} digoxin concentrations. A selectivity study showed that compounds of similar structure to digoxin did not significantly interfere with detection for interferent concentrations at 10, 30 and 100 times higher than the digoxin concentration. This simply manufactured MIP membrane showed good recognition characteristics, a high affinity for digoxin, and provided satisfactory results in analyses of this analyte in human serum.

Systemic propranolol acts centrally to reduce conditioned fear in rats without impairing extinction.

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Rodriguez-Romaguera, Jose; Sotres-Bayon, Francisco; Mueller, Devin; Quirk, Gregory J

2009-05-15

Previous work has implicated noradrenergic beta-receptors in the consolidation and reconsolidation of conditioned fear. Less is known, however, about their role in fear expression and extinction. The beta-receptor blocker propranolol has been used clinically to reduce anxiety. With an auditory fear conditioning task in rats, we assessed the effects of systemic propranolol on the expression and extinction of two measures of conditioned fear: freezing and suppression of bar-pressing. One day after receiving auditory fear conditioning, rats were injected with saline, propranolol, or peripheral beta-receptor blocker sotalol (both 10 mg/kg, IP). Twenty minutes after injection, rats were given either 6 or 12 extinction trials and were tested for extinction retention the following day. The effect of propranolol on the firing rate of neurons in prelimbic (PL) prefrontal cortex was also assessed. Propranolol reduced freezing by more than 50%, an effect that was evident from the first extinction trial. Suppression was also significantly reduced. Despite this, propranolol had no effect on the acquisition or retention of extinction. Unlike propranolol, sotalol did not affect fear expression, although both drugs significantly reduced heart rate. This suggests that propranolol acts centrally to reduce fear. Consistent with this, propranolol reduced the firing rate of PL neurons. Propranolol reduced the expression of conditioned fear, without interfering with extinction learning. Reduced fear with intact extinction suggests a possible use for propranolol in reducing anxiety during extinction-based exposure therapies, without interfering with long-term clinical response.

Amlodipine decreases fibrosis and cardiac hypertrophy in spontaneously hypertensive rats: persistent effects after withdrawal.

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Sevilla, María A; Voces, Felipe; Carrón, Rosalía; Guerrero, Estela I; Ardanaz, Noelia; San Román, Luis; Arévalo, Miguel A; Montero, María J

2004-07-02

Our objective was to examine the effect of chronic treatment with amlodipine on blood pressure, left ventricular hypertrophy, and fibrosis in spontaneously hypertensive rats and the persistence of such an effect after drug withdrawal. We investigated the effects of treatment with 2, 8 and 20 mg/kg/day of amlodipine given orally for six months and at three months after drug withdrawal. Systolic blood pressure was measured using the tail-cuff method. At the end of the study period, the heart was excised, the left ventricle was isolated, and the left ventricle weight/body weight ratio was calculated as a left ventricular hypertrophy index. Fibrosis, expressed as collagen volume fraction, was evaluated using an automated image-analysis system on sections stained with Sirius red. Age-matched untreated Wistar-Kyoto and SHR were used as normotensive and hypertensive controls, respectively. Systolic blood pressure was reduced in the treated SHR in a dose-dependent way and after amlodipine withdrawal it increased progressively, without reaching the values of the hypertensive controls. Cardiac hypertrophy was reduced by 8 and 20 mg/kg/day amlodipine, but when treatment was withdrawn only the group treated with 8 mg/kg/day maintained significant differences versus the hypertensive controls. All three doses of amlodipine reduced cardiac fibrosis and this regression persisted with the two highest doses after three months without treatment. We concluded that antihypertensive treatment with amlodipine is accompanied by a reduction in left ventricular hypertrophy and regression in collagen deposition. Treatment was more effective in preventing fibrosis than in preventing ventricular hypertrophy after drug withdrawal. Copyright 2004 Elsevier Inc.

Unmasking the Role of Uptake Transporters for Digoxin Uptake Across the Barriers of the Central Nervous System in Rat

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Kunal S Taskar

2017-03-01

Full Text Available The role of uptake transporter (organic anion–transporting polypeptide [Oatp] in the disposition of a P-glycoprotein (P-gp substrate (digoxin at the barriers of central nervous system, namely, the blood-brain barrier (BBB, blood-spinal cord barrier (BSCB, and brain-cerebrospinal fluid barrier (BCSFB, was studied using rat as a preclinical species. In vivo chemical inhibition of P-gp and Oatp was achieved using elacridar and rifampicin, respectively. Our findings show that (1 digoxin had a low brain-to-plasma concentration ratio (B/P (0.07 in rat; (2 in the presence of elacridar, the B/P of digoxin increased by about 12-fold; (3 rifampicin administration alone did not change the digoxin B/P significantly when compared with digoxin B/P alone; (4 rifampicin administration along with elacridar resulted only in 6-fold increase in the B/P of digoxin; (5 similar fold changes and trends were seen with the spinal cord-to-plasma concentration ratio of digoxin, indicating the similarity between BBB and the BSCB; and (6 unlike BBB and BSCB, the presence of rifampicin further increased the cerebrospinal fluid-to-plasma concentration ratio (CSF/P for digoxin, suggesting a differential orientation of the uptake transporters at the BCSFB (CSF to blood compared with the BBB (blood to brain. The observations for digoxin uptake, at least at the BBB and the BSCB, advocate the importance of uptake transporters (Oatps. However, the activity of such uptake transporters became evident only after inhibition of the efflux transporter (P-gp.

Investigation of forced and total degradation products of amlodipine besylate by liquid chromatography and liquid chromatography-mass spectrometry

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Stoiljković Zora Ž.

2014-01-01

Full Text Available An isocratic, reversed-phase liquid chromatographic method was applied for the investigation of the degradation products of amlodipine besylate under the stressed conditions in solution. Amlodipine besylate stock solutions were subjected to acid and alkali hydrolysis, chemical oxidation and photodegradation as well as to the electrochemical degradation by cyclic voltammetry in 0.05 mol/L NaHCO3 on gold electrode. The total degradation of amlodipine besylate was achieved in 5 mol/L NaOH at 80°C for 6 h and the compound with molecular formula C15H16NOCl was identified as a main degradation product. Under acidic (5 mol/L HCl at 80°C for 6 h stress conditions 75.2% of amlodipine besylate degradation was recorded. Oxidative degradation in the solution of 3% H2O2-methanol 80:20 at 80°C for 6 h showed that amlodipine besylate degraded to 80.1%. After 14 days of expose in photostability chamber amlodipine besylate solution showed degradation of 32.2%. In electrochemical degradation after 9 hours of cyclization the beginning of amlodipine oxidation was shifted for 200 mV to more negative potentials, with the degradation of 66.5%. Mass spectrometry analysis confirmed the presence of dehydro amlodipine derivate with molecular formula C20H23N2O5Cl in oxidative and acidic conditions while in electrochemical degradation was detected in traces. [Projekat Ministarsva nauke Republike Srbije, br. 172013

Concentration of (+/-)-propranolol in isolated, perfused lungs of rat.

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Dollery, C T; Junod, A F

1976-01-01

1 The metabolism and the accumulation of (+/-)-propranolol have been studied in isolated lungs of the rat, perfused with an artificial medium. 2 Little or no metabolism took place during the perfusion periods (up to 10 minutes). 3 Accumulation was observed with high tissue/medium ratios for substrate concentrations of 0.2 muM to 1 mM; there was evidence for saturability, but no real plateau could be seen. The presence of two binding sites with different affinities was established. 4 Cold greatly inhibited the accumulation process at low substrate concentrations, but had no effect at 1 mM propranolol. 5 Inhibition of accumulation was measured in the presence of imipramine, desmethylimipramine, nortryptiline, chlorpromazine and of Na+-free medium. Cocaine, 5-hydroxytryptamine and noradrenaline had no effect. Lidocaine enhanced the accumulation process. Release of previously bound propranolol was accelerated in the presence of propranolol and imipramine, unaffected by a Na+-free medium and decreased by cold and by lidocaine. 6 Experiments on lung tissue slices yielded qualitatively similar results to those obtained with perfused lungs. Ouabain and KCN had no or little effect on propranolol accumulation. PMID:1276542

LC-MS/MS Estimation of Propranolol level in Exhaled Breath Condensate

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Samin Hamidi 1, Maryam Amini 2, Maryam Khoubnasabjafari 3, Vahid Jouyban-Gharamaleki 4,5, Hossein Sate 6, Abolghasem Jouyban 5,7 *

2017-12-01

Full Text Available Background: Exhaled breath condensate (EBC could be used as a non-invasive and alternative specimen to urine and blood for monitoring propranolol levels. A simple, sensitive and selective liquid chromatography–tandem mass spectrometry (LC–MS/MS method is employed for the determination of propranolol in EBC samples. Methods: Samples directly injected to a C18 analytical column and isocratically separated using a mobile phase composed of methanol + acetic acid (99:1 v/v. Detection was performed by positive electrospray ionization in multiple reaction monitoring and selected ion recording modes. Results: The chromatographic separation was obtained within 6.0 min and was linear over the concentration range of 5.6–224.0 ng/mL (R2 = 0.999. The accuracy and precision of the method were within 15% according to FDA guideline. The found concentrations of propranolol in EBC of two patients receiving 80 mg/day were 30 and 40 ng/mL. Conclusion: Developed method was applied to determine propranolol levels in three patients receiving propranolol in their medication. The obtained propranolol levels in EBC could be used to develop simpler, cheaper and more feasible analytical methods to be used in routine analysis of propranolol in biomedical analytical laboratories.

Propranolol reduces the anxiety associated with day case surgery.

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Mealy, K; Ngeh, N; Gillen, P; Fitzpatrick, G; Keane, F B; Tanner, A

1996-01-01

To find out if propranolol, a non-cardioselective beta-blocker, can reduce the anxiety associated with day case surgery. Prospective randomized double blind trial. University hospital, Ireland. An unselected group of 53 patients undergoing day case surgery. Subjects randomised to receive either propranolol (10 mg) or placebo on the morning of operation. Blood pressure; pulse, anxiety, pain score and patient satisfaction. Mean (SD) Hospital Anxiety and Depression score was significantly lower in the propranolol group than in the control group (2.5 (0.7) compared with 4.6 (0.7), p anxiety.

Propranolol in Treatment of Huge and Complicated Infantile Hemangiomas in Egyptian Children

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Basheir A. Hassan

2014-01-01

Full Text Available Background. Infantile hemangiomas (IHs are the most common benign tumours of infancy. Propranolol has recently been reported to be a highly effective treatment for IHs. This study aimed to evaluate the efficacy and side effects of propranolol for treatment of complicated cases of IHs. Patients and Methods. This prospective clinical study included 30 children with huge or complicated IHs; their ages ranged from 2 months to 1 year. They were treated by oral propranolol. Treatment outcomes were clinically evaluated. Results. Superficial cutaneous hemangiomas began to respond to propranolol therapy within one to two weeks after the onset of treatment. The mean treatment period that was needed for the occurrence of complete resolution was 9.4 months. Treatment with propranolol was well tolerated and had few side effects. No rebound growth of the tumors was noted when propranolol dosing stopped except in one case. Conclusion. Propranolol is a promising treatment for IHs without obvious side effects. However, further studies with longer follow-up periods are needed.

Selection of Suitable Microorganism for Biocatalytic Oxidation Reaction of Racemic Propranolol

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Rahime SONGÜR

2017-12-01

Full Text Available Propranolol is one of the β-blockers which are pharmaceutically important, especially used for treatment of cardiovasculer disease. In this study, the production of enantiomerically pure propranolol was aimed via biocatalytic deracemization including tandem oxidation-reduction reactions of racemic propranolol. Within this content, firstly suitable microorganism for the oxidation of racemic propranolol was investigated. Alcohol dehydrogenase (ADH enzyme for oxidation of propranolol and NADH oxidase enzyme for cofactor regeneration were necessary for the oxidation reactions. For this reason, ADH and NADH oxidase enzymes activities of different microorganisms were measured to select the microorganism for using as enzyme source. These microorganisms are Lactobacillus kefir NRRL B-1839, Rhodotorula glutunis DSM 70398, Rhizopus oryzae CBS 111718, Rhizopus arhizus. The highest ADH and NADH oxidase activities were obtained for L. kefir.

Control of lithium tremor with propranolol.

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Lapierre, Y D

1976-04-03

Lithium tremor is an irregular, nonrhythmic tremor of the distal extremities, variable in both intensity and frequency. It is clinically differentiated from essential tremor and tremors due to anxiety and neuroleptics. The pathophysiologic mechanisms are hypothesized to be of perpheral origin. Five patients were successfully treated with propranolol. In general, the dosage of propranolol must be individually adjusted and is usually from 30 to 40 mg daily in divided doses. This blocker of beta-adrenergic receptors remains effective with long-term administration and increases in dosage are not required.

Amlodipine and Atorvastatin Improved Hypertensive Cardiac Remodeling through Regulation of MMPs/TIMPs in SHR Rats

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Jingchao Lu

2016-06-01

Full Text Available Background: MMPs/TIMPs system is well known to play important roles in pressure overload-induced cardiac remodeling, and Amlodipine and Atorvastatin have been showed to exert favourable protective effects on cardiovascular disease, however, it is not clear whether Amlodipine and Atorvastatin can improve hypertensive cardiac remodeling and whether the MMPs/TIMPs system is involved. The present study aims to answer these questions. Methods: 36 weeks old male spontaneous hypertension (SHR rats were randomly divided into four groups: 1. SHR control group, 2. Amlodipine alone (10 mg/kg/d group, 3. Atorvastatin alone (10 mg/kg/d group, 4.Combination of Amlodipine and Atorvastatin (10 mg/kg/d for each group. Same gender, weight and age of Wistar-Kyoto (WKY rats with normal blood pressure were used as normal control. Drugs were administered by oral gavage over 12 weeks. The blood pressure and left ventricle mass index were measured. Enzyme activity of MMP-2 and MMP-9 was assessed with Gelatin zymography. MMP-2, MMP-9, TIMP-1 and TIMP-2 mRNA and protein expression was studied by RT-PCR and Western blot. Single factor ANOVA and LSD-t test were used in statistical analysis. Results: Treatment with Amlodipine alone or combination with atorvastatin significantly decreased blood pressure, left ventricle mass index in SHR rats (P Conclusion: Amlodipine and Atorvastatin could improve ventricular remodeling in SHR rats through intervention with the imbalance of MMP-2/TIMP-2 and MMP-9/TIMP-1 system.

Comparative effects of amlodipine and benazepril on left atrial pressure in dogs with experimentally-induced mitral valve regurgitation.

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Suzuki, Shuji; Fukushima, Ryuji; Ishikawa, Taisuke; Yamamoto, Yuta; Hamabe, Lina; Kim, Soomin; Yoshiyuki, Rieko; Machida, Noboru; Tanaka, Ryou

2012-09-18

One of the purposes of treatment for dogs with mitral regurgitation (MR) is lowering left atrial pressure (LAP). There has been few study of the amlodipine in dogs with MR and amlodipine's effect on LAP has not been fully evaluated in a quantitative manner because of difficulties in directly measuring LAP. The objective of our study was to compare the short-term effects of amlodipine (0.2 mg/kg PO q12h) vs benazepril (0.5 mg/kg PO q12h), on LAP and echocardiographic parameters in five beagle dogs with experimentally-induced MR. LAP of eight dogs that has own control were measured using radiotelemetry system at baseline and again on days 1, 2, 3, 4, 5, 6, 7 of the drug administration. Mean LAP decreased significantly after amlodipine (11.20 ± 4.19 mmHg vs 14.61 ± 3.81 mmHg at baseline, p benazepril treatment (13.19 ± 3.47 mmHg, p > .05). LAP was lower after 7 days of amlodipine treatment than after 7 days of benazepril treatment. Significant reduction was seen for the first time 4 days after the administration amlodipine. The rate of the maximal area of the regurgitant jet signals to the left atrium area (ARJ/LAA) of the amlodipine treatment was significantly lower (p benazepril treatment. Although this study did not focus on adverse effects, amlodipine may be an effective drug for helping the patients with acute onset of severe MR, such as rupture of chordae tendinae or end stage patients were the LAP is likely to be elevated. Additional studies in clinical patients with degenerative mitral valve disease and acute chordal rupture are warranted because the blood-pressure lowering effects of amlodipine can decrease renal perfusion and this can further activate the RAAS.

Labetalol compared with propranolol in the treatment of black hypertensive patients.

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Saunders, E; Curry, C; Hinds, J; Kong, B W; Medakovic, M; Poland, M; Roper, K

1987-09-01

A double-blind parallel group study was conducted to examine the effects of oral labetalol, in doses from 100 to 800 mg BID, and propranolol, 40 to 320 mg, in patients with mild to moderate hypertension. The doses of labetalol (n = 74) and propranolol (n = 79) were titrated weekly to achieve a sitting diastolic blood pressure (DBP) of less than 90 mmHg or at least a 10-mmHg decrease from placebo baseline on two consecutive visits. A 2-month fixed-dose maintenance phase followed in which a diuretic could be added if the sitting DBP was greater than or equal to 100 mmHg on maximum doses of either drug. BP and heart rate were measured 8-12 hours after a dose in the sitting and standing positions. Labetalol was significantly more effective at the end of monotherapy than propranolol was in lowering both the sitting (p less than .05) and standing (p less than .04) DBP. The reduction in the systolic, although more pronounced for those on labetalol, was not significantly different; 53% of patients had a "good" response to labetalol compared with 30% of the propranolol group. Propranolol significantly (p less than 0.01) lowered heart rate compared with labetalol. Nine patients in the labetalol group and 10 in the propranolol group required a diuretic. The decrease in BP after the addition of a diuretic was comparable. Changes in plasma lipids were not significant, but HDL increased 9% with labetalol and decreased 2% with propranolol. Triglycerides increased 25% with labetalol and 31% with propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

One and three doses of propranolol a day in hypertension.

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van den Brink, G; Boer, P; van Asten, P; Dorhout Mees, E J; Geyskes, G G

1980-01-01

In 26 patients with essential hypertension who were on continuous chlorthalidone therapy, 1 and 3 daily doses of propranolol were compared in a crossover study. Plasma propranolol levels and heart rates had larger daily fluctuations on single-dose therapy than on 3 times daily; plasma renin activity was more constant. There was no significant difference in blood pressures. Once-daily propranolol dosage was well tolerated and possibly gave less rise to the troublesome side effect of vivid dreaming.

The role of propranolol as a radiosensitizer in gastric cancer treatment

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Liao XH

2018-03-01

Full Text Available Xinhua Liao, Prakash Chaudhary, Guanglin Qiu, Xiangming Che, Lin Fan General Surgery Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China Purpose: The National Comprehensive Cancer Network guidelines indicate that radiotherapy in gastric cancer shows limited effectiveness at reducing the growth of gastric cancer. Therefore, enhancing the sensitivity and effect of radiotherapy with propranolol, a β-adrenoceptor antagonist, could reduce tumor growth. The role of propranolol as a radiosensitizer has not been adequately studied; therefore, the purpose of the present study is to evaluate the effect of propranolol as a radiosensitizer against gastric cancer in vivo. Methods: Sixty-four male nude mice bearing tumor xenografts were randomly divided into four groups. Cell culture was performed using the human gastric adenocarcinoma cell line SGC-7901. Mice with tumor xenografts were treated with propranolol, isoproterenol, and radiation. The data for tumor weight and volume were obtained for statistical analyses. Furthermore, the expression levels of COX-2, NF-κB, VEGF, and EGFR were examined using immunohistochemical techniques and Western blotting.Results: The growth in the volume and weight of the tumor was lower in mouse models treated with propranolol and radiation therapy compared to the other groups. Decreased expression of NF-κB was also observed in treatment groups where both propranolol and radiation were used, leading to the reduction of COX-2, EGFR, and VEGF expression compared to that in the other groups.Conclusion: The present study indicated that propranolol potentiates the antitumor effects of radiotherapy in gastric cancer by inhibiting NF-κB expression and its downstream genes: VEGF, EGFR, and COX-2. Keywords: propranolol, radiosensitizer, gastric cancer, radiation therapy 

Design and stability study of an oral solution of amlodipine besylate for pediatric patients.

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van der Vossen, A C; van der Velde, I; Smeets, O S N M; Postma, D J; Vermes, A; Koch, B C P; Vulto, A G; Hanff, L M

2016-09-20

Amlodipine is an antihypertensive agent recommended for the management of hypertension in children and adolescents. The commercially available tablets of 5 and 10mg do not provide the necessary flexibility in dosing needed for treating children. Our goal was to develop a pediatric oral solution of amlodipine, using a robust manufacturing process suitable for ex-tempora and larger scale production. The parameters API and preservative content, related substances, appearance and pH were studied under four different storage conditions. Samples were analyzed up to 12months. Microbiological quality was studied in an 18-week in-use test based on a two-times daily dosing schedule. The stability of the formulation was influenced by storage conditions and composition. A formulation containing amlodipine besylate, sucrose syrup and methyl paraben remained physically stable for 12months at 4°C with no loss of amlodipine content. Related substances increased during the study but remained below 0.5%. In-use stability was proven up to 18weeks. Storage under refrigerated conditions was necessary to prevent precipitation and to obtain an acceptable shelf-life. In conclusion, we have developed and validated an amlodipine oral solution, suitable for the pediatric population. This liquid formulation is preferred over manipulated commercial dosage forms or non-standardized extemporaneously compounded formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of digoxin and. beta. -methyldigoxin on the heart rate of decompensated patients with atrial fibrillation

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Andersson, K E; Johansson, B W; Ledermann, H; von Schenck, H; Thorell, J I [Lund Univ. (Sweden). Clinical Pharmacological Lab.; Allmaenna Sjukhuset, Malmoe (Sweden). Heat Lab.; Allmaenna Sjukhuset, Malmoe (Sweden). Dept. of Clinical Chemistry)

1977-02-01

Eighteen patients with atrial fibrillation were given digoxin 0.13 mg twice daily for 3 weeks and ..beta..-methyldigoxin 0.10 mg twice daily for another 3 weeks. At the end of each 3 week period an exercise test was performed and the effects on the heart rate of the two drugs were compared. No difference in heart rate was obtained at rest, wheareas the heart rate after 6 min of exercise was higher during treatment with digoxin (131 beats/min) than when the patients were taking ..beta..-methyldigoxin (124 beats/min). There were no significant differences between digoxin and ..beta..-methyldigoxin in their effects on the ECT (R-R intervals, T-wave, Q-T duration). The plasma concentrations of the two glycosides were determined by radioimmunoassay and by /sup 86/Rb-uptake inhibition assay. Comparable plasma concentration values (1.0 ng/ml for digoxin, 1.1 ng/ml for ..beta..-methyldigoxin, mean values) were obtained by radioimmunoassay, but the /sup 86/Rb-technique gave significantly higher values (mean 1.5 ng/ml) for ..beta..-methyldigoxin. It is concluded that ..beta..-methyldigoxin is equal to digoxin for producing slowing of the heart rate in patients with atrial fibrillation.

Obtain and characterization of chitosan / propranolol microparticles by spray drying; Obtencao e caracterizacao de microparticulas de quitosana / propranolol por spray drying

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Nascimento, Ednaldo G. do; Silva Junior, Arnobio A. da, E-mail: ednaldogn@yahoo.com.br [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil); Santos, Katia S.C.R. dos [Universidade Federal do Amazonas (UFAM), Manaus, AM (brazil)

2015-07-01

The study investigated the application of chitosan microparticles as carriers into hard gelatin capsule containing propranolol, evaluating the variability of the molecular weight and the chitosan particles by spray drying. The formulations were characterized by average weight, dosing unit dose uniformity and dissolution profile according to the pharmacopoeia. While the microparticles were characterized by Fourier transformed infrared spectroscopy, scanning electron microscopy and X-ray diffraction. The results showed that chitosan microparticles obtained without the drug and then physically mixed with propranolol promoted a modified release 85% of the drug after 5 hours. While, chitosan microparticles sprayed with propranolol released only 55% at 5 hours is presented both as a modified release system. Samples of dried chitosan showed up amorphous and homogeneous and spherical morphology. (author)

Comparison of efficacy and tolerability of different brands of amlodipine in patients with mild to moderate hypertension

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Molouk Hadjibabaie

2015-10-01

Full Text Available Background: The efficacy of amlodipine, a calcium channel blocker, in treating systemic hypertension is well established but the most efficacious brand of this drug is still uncertain. The cost of different brands of amlodipine is tremendously different which may affect decision-making in hypertension treatment. The purpose of this study was to compare the efficacy and safety of different brands of amlodipine (Amlodipine, Amlopress, and Norvasc in the treatment of hypertension in adult patients.Methods: This was a double-blind, randomized, three-sequence crossover study. Ambulatory patients with hypertension who had the inclusion criteria were enrolled. Patients were randomized and entered into three groups to receive either brand of amlodipine in a crossover method. After every four weeks of treatment completed, the other brand of drug was prescribed. The total period of the study was 12 weeks for all three drugs including four weeks for each brand.Results: A total of 20 patients entered to the study, 15 completed the 12-week treatment schedule. The absolute reductions in seated and supine systolic blood pressure (SBP and diastolic blood pressure (DBP were similar with all three brands during the 4 weeks of treatment. Headache, malaise and weakness were the most common reported adverse effects (AE with all three drugs. Generic amlodipine had the most AE as compared with other brands. These AE were mild and did not require withdrawal of the drug. Conclusion: There is no statistical difference in lowering blood pressure by three different brands of amlodipine thus everyone which has the lowest price can be the first choice.

Solid phase tube radioimmunoassay for digoxin detection

International Nuclear Information System (INIS)

Stellner, K.; Glatz, C.; Linke, R.

1975-01-01

A solid phase radioimmunoassay with 125 I is described for cardiac patients. The test for the digoxin determination and the poisoning due to cardiac glycosides can be measured very accurately and carried out easily. In addition, the test determination can be automatically performed in connection with other tests. (GSE/LH) [de

Functional Vascular Study in Hypertensive Subjects with Type 2 Diabetes Using Losartan or Amlodipine

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Cesar Romaro Pozzobon

2014-07-01

Full Text Available Background: Antihypertensive drugs are used to control blood pressure (BP and reduce macro- and microvascular complications in hypertensive patients with diabetes. Objectives: The present study aimed to compare the functional vascular changes in hypertensive patients with type 2 diabetes mellitus after 6 weeks of treatment with amlodipine or losartan. Methods: Patients with a previous diagnosis of hypertension and type 2 diabetes mellitus were randomly divided into 2 groups and evaluated after 6 weeks of treatment with amlodipine (5 mg/day or losartan (100 mg/day. Patient evaluation included BP measurement, ambulatory BP monitoring, and assessment of vascular parameters using applanation tonometry, pulse wave velocity (PWV, and flow-mediated dilation (FMD of the brachial artery. Results: A total of 42 patients were evaluated (21 in each group, with a predominance of women (71% in both groups. The mean age of the patients in both groups was similar (amlodipine group: 54.9 ± 4.5 years; losartan group: 54.0 ± 6.9 years, with no significant difference in the mean BP [amlodipine group: 145 ± 14 mmHg (systolic and 84 ± 8 mmHg (diastolic; losartan group: 153 ± 19 mmHg (systolic and 90 ± 9 mmHg (diastolic]. The augmentation index (30% ± 9% and 36% ± 8%, p = 0.025 and augmentation pressure (16 ± 6 mmHg and 20 ± 8 mmHg, p = 0.045 were lower in the amlodipine group when compared with the losartan group. PWV and FMD were similar in both groups. Conclusions: Hypertensive patients with type 2 diabetes mellitus treated with amlodipine exhibited an improved pattern of pulse wave reflection in comparison with those treated with losartan. However, the use of losartan may be associated with independent vascular reactivity to the pressor effect.

Beneficial effects of combined benazepril-amlodipine on cardiac nitric oxide, cGMP, and TNF-alpha production after cardiac ischemia.

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Siragy, Helmy M; Xue, Chun; Webb, Randy L

2006-05-01

The aim of this study was to determine if myocardial inflammation is increased after myocardial ischemia and whether angiotensin-converting enzyme inhibitors, calcium channel blockers, or diuretics decrease mediators of inflammation in rats with induced myocardial ischemia. Changes in cardiac interstitial fluid (CIF) levels of nitric oxide metabolites (NOX), cyclic guanosine 3',5'-monophosphate (cGMP), angiotensin II (Ang II), and tumor necrosis factor-alpha (TNF-alpha) were monitored with/without oral administration of benazepril, amlodipine, combined benazepril-amlodipine, or hydrochlorothiazide. Using a microdialysis technique, levels of several mediators of inflammation were measured after sham operation or 30-minute occlusion of the left anterior descending coronary artery. Compared with sham animals, levels of CIF NOX and cGMP were decreased in animals with ischemia (P Benazepril or amlodipine significantly increased NOX levels (P benazepril significantly increased cGMP (P benazepril-amlodipine further increased CIF NOX and cGMP (P benazepril alone, or combined benazepril-amlodipine significantly reduced TNF-alpha (P benazepril-amlodipine may be beneficial for managing cardiac ischemia.

An HPLC method for the determination of digoxin in dissolution samples

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Milenković Miroslav Ž.

2010-01-01

Full Text Available An HPLC method for digoxin quantification in dissolution samples obtained as per the official British Pharmacopeia (BP method is presented in this paper. The chromatography was performed at 20 °C on a Symmetry C18; 3.5 ìm, 75 x 4.6 mm column with water - acetonitrile (72 : 28, v/v, as the mobile phase and UV detection at 220 nm. The method was found to be selective, linear, accurate and precise in the specified ranges. The LOD and LOQ were 0.015 μg mL-1 and 0.050 μg mL-1, respectively. Robustness testing was conducted to evaluate the impact of minor changes in the chromatographic parameters (i.e., acetonitrile fraction, flow rate of the mobile phase, column temperature and column length on the characteristics of the digoxin peak. A. full factorial design (24 was used to investigate the influence of the four variables The presented HPLC method was applied in quality and stability testing of Digoxin tablets 0.25 mg.

Successful Treatment of Mild Pediatric Kasabach-Merritt Phenomenon with Propranolol Monotherapy

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Worawut Choeyprasert

2014-01-01

Full Text Available Kasabach-Merritt phenomenon (KMP is relatively rare in childhood and adolescents with high mortality rate because of its hemorrhagic complications and unresponsiveness to treatments such as corticosteroids, vincristine, intravascular embolization, and/or surgery. Propranolol, a β-adrenergic receptor blocker, has a promising efficacy against vascular tumors such as infantile hemangiomas. But limited and variable data has been reported regarding the role of propranolol in treatment of KMP. We herein reported the successful treatment of mild pediatric KMP with propranolol monotherapy in a case of a five-week-old child with kaposiform hemangioendothelioma with successful treatment of both clinical and hematologic responses. After eight months of follow-up, patient still had stable cutaneous lesion while receiving propranolol monotherapy. Regular hematologic monitoring was done in order to detect any late relapse of the disease. Six months after discontinuation of propranolol, patient has still remained free of hematologic relapse, and primary cutaneous lesion has become a pale pink, 1 cm sized skin lesion.

Comparative effects of amlodipine and benazepril on Left Atrial Pressure in Dogs with experimentally-induced Mitral Valve Regurgitation

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Suzuki Shuji

2012-09-01

Full Text Available Abstract Background One of the purposes of treatment for dogs with mitral regurgitation (MR is lowering left atrial pressure (LAP. There has been few study of the amlodipine in dogs with MR and amlodipine’s effect on LAP has not been fully evaluated in a quantitative manner because of difficulties in directly measuring LAP. The objective of our study was to compare the short-term effects of amlodipine (0.2 mg/kg PO q12h vs benazepril (0.5 mg/kg PO q12h, on LAP and echocardiographic parameters in five beagle dogs with experimentally-induced MR. LAP of eight dogs that has own control were measured using radiotelemetry system at baseline and again on days 1, 2, 3, 4, 5, 6, 7 of the drug administration. Results Mean LAP decreased significantly after amlodipine (11.20 ± 4.19 mmHg vs 14.61 ± 3.81 mmHg at baseline, p  .05. LAP was lower after 7 days of amlodipine treatment than after 7 days of benazepril treatment. Significant reduction was seen for the first time 4 days after the administration amlodipine. The rate of the maximal area of the regurgitant jet signals to the left atrium area (ARJ/LAA of the amlodipine treatment was significantly lower (p  Conclusions LAP was significantly decreased after amlodipine treatment in dogs with surgically-induced MR but not after benazepril treatment. Although this study did not focus on adverse effects, amlodipine may be an effective drug for helping the patients with acute onset of severe MR, such as rupture of chordae tendinae or end stage patients were the LAP is likely to be elevated. Additional studies in clinical patients with degenerative mitral valve disease and acute chordal rupture are warranted because the blood-pressure lowering effects of amlodipine can decrease renal perfusion and this can further activate the RAAS.

Digoxin Use and Lower 30-day All-cause Readmission for Medicare Beneficiaries Hospitalized for Heart Failure

NARCIS (Netherlands)

Ahmed, Ali; Bourge, Robert C.; Fonarow, Gregg C.; Patel, Kanan; Morgan, Charity J.; Fleg, Jerome L.; Aban, Inmaculada B.; Love, Thomas E.; Yancy, Clyde W.; Deedwania, Prakash; van Veldhuisen, Dirk J.; Filippatos, Gerasimos S.; Anker, Stefan D.; Allman, Richard M.

BACKGROUND: Heart failure is the leading cause for hospital readmission, the reduction of which is a priority under the Affordable Care Act. Digoxin reduces 30-day all-cause hospital admission in chronic systolic heart failure. Whether digoxin is effective in reducing readmission after

Blood pressure effects of high-dose amlodipine-benazepril combination in Black and White hypertensive patients not controlled on monotherapy.

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Chrysant, Steven G

2012-06-01

Black hypertensive patients are more resistant to angiotensin-converting enzyme (ACE) inhibitor monotherapy than White patients. This resistance can be overcome with the combination of ACE inhibitors with diuretics or calcium-channel blockers (CCBs). The objective of this clinical investigation was to evaluate the antihypertensive effectiveness of monotherapy with the ACE inhibitor benazepril or the CCB amlodipine and their combination in Black and White hypertensive patients in two separate studies. This was a post hoc analysis of data from two separate studies, pooled because of their similarities, to increase the sample size. Outpatient Black and White hypertensive patients were selected for these studies. In study H2303, 201 patients of both sexes and races, whose mean seated diastolic blood pressure (MSDBP) was ≥95 mmHg after 4 weeks of single-blind treatment with benazepril 40 mg/day, were randomized into two groups. Group 1 received benazepril 40 mg/day and group 2 received amlodipine/benazepril 5/40 mg/day, which was uptitrated to amlodipine/benazepril 10/40 mg/day at week 4 of the study. In study H2304, 812 similar patients, whose MSDBP was ≥95 mmHg after 4 weeks of single-blind treatment with amlodipine 10 mg/day, were randomized into three groups. Group 1 received amlodipine/benazepril 10/20 mg/day, uptitrated to amlodipine/benazepril 10/40 mg/day after 2 weeks. Group 2 received amlodipine/benazepril 10/20 mg/day. Group 3 received amlodipine 10 mg/day. All three groups were followed up for 6 additional weeks. This report presents the results of post hoc analysis of pooled data from two separate but similar studies. Combination therapy resulted in greater lowering of MSDBP and mean seated systolic blood pressure (MSSBP) than monotherapy with either benazepril or amlodipine (p benazepril 10/20 mg/day resulted in greater blood pressure (BP) reductions in White patients than in Black patients (p benazepril 10/40�

Less adrenergic response to mental task during verapamil compared to amlodipine treatment in hypertensive subjects

NARCIS (Netherlands)

Sevre, K; Lefrandt, JD; Eide, [No Value; Smit, AJ; Rostrup, M

2001-01-01

We compared the effects of amlodipine and verapamil slow release on autonomic responses to a 5-min mental arithmetic test (MST) in patients with mild to moderate hypertension. Twenty subjects received 8 weeks of verapamil slow release 240 mg or amlodipine 10 mg in a double-blind crossover design,

The effects of digoxin and β-methyldigoxin on the heart rate of decompensated patients with atrial fibrillation

International Nuclear Information System (INIS)

Andersson, K.E.; Johansson, B.W.; Ledermann, H.; Schenck, H. von; Thorell, J.I.; Allmaenna Sjukhuset, Malmoe; Allmaenna Sjukhuset, Malmoe

1977-01-01

Eighteen patients with atrial fibrillation were given digoxin 0.13 mg twice daily for 3 weeks and β-methyldigoxin 0.10 mg twice daily for another 3 weeks. At the end of each 3 week period an exercise test was performed and the effects on the heart rate of the two drugs were compared. No difference in heart rate was obtained at rest, wheareas the heart rate after 6 min of exercise was higher during treatment with digoxin (131 beats/min) than when the patients were taking β-methyldigoxin (124 beats/min). There were no significant differences between digoxin and β-methyldigoxin in their effects on the ECT (R-R intervals, T-wave, Q-T duration). The plasma concentrations of the two glycosides were determined by radioimmunoassay and by 86 Rb-uptake inhibition assay. Comparable plasma concentration values (1.0 ng/ml for digoxin, 1.1 ng/ml for β-methyldigoxin, mean values) were obtained by radioimmunoassay, but the 86 Rb-technique gave significantly higher values (mean 1.5 ng/ml) for β-methyldigoxin. It is concluded that β-methyldigoxin is equal to digoxin for producing slowing of the heart rate in patients with atrial fibrillation. (orig.) [de

[Simultaneous determination of amlodipine, benazepril and benazeprilat in human plasma by LC-HESI/MS/MS method].

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Pan, Hua-Ling; Lin, Li-Shan; Ding, Jue-Fang; Chen, Xiao-Yan; Zhong, Da-Fang

2014-01-01

The study aims to develop a rapid, sensitive and specified method of liquid chromatography with heated electrospray ionization tandem mass spectrometry (LC-HESI/MS/MS) for simultaneous determination of amlodipine, benazepril and benazeprilat in human plasma using amlodipine-d4 and ubenimex as internal standards (ISs). Selected reaction monitoring (SRM) with heated electrospray ionization (HESI) was used in the positive mode for mass spectrometric detection. Analytes and ISs were extracted from plasma by simple protein precipitation. The reconstituted samples were chromatographed on a C18 (100 mm x 4.6 mm, 5 microm) column with mixture of methanol-acetonitrile-5 mmol.L- ammonium acetate-formic acid (30 : 30 : 40 : 0.1) as mobile phase at a flow rate of 0.6 mL.min-1. The standard curves were demonstrated to be linear in the range of 0.02 to 6.00 ng.mL-1 for amlodipine, 0.2 to 1,500 ng.mL-1 for benazepril and benazeprilat with r2>0.99 for each analyte. The lower limit of quantitation was identifiable and reproducible at 0.02, 0.2 and 0.2 ng mL-1 for amlodipine, benazepril and benazeprilat, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limit across all concentrations. The plasma samples were stable after four freeze-thaw cycles and being stored for 93 days at -20 degrees C. The method was applied to a pharmacokinetic study of a fixed-dose combination of amlodipine and benazepril on Chinese healthy volunteers.

Transport inhibition of digoxin using several common P-gp expressing cell lines is not necessarily reporting only on inhibitor binding to P-gp.

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Annie Albin Lumen

Full Text Available We have reported that the P-gp substrate digoxin required basolateral and apical uptake transport in excess of that allowed by digoxin passive permeability (as measured in the presence of GF120918 to achieve the observed efflux kinetics across MDCK-MDR1-NKI (The Netherlands Cancer Institute confluent cell monolayers. That is, GF120918 inhibitable uptake transport was kinetically required. Therefore, IC50 measurements using digoxin as a probe substrate in this cell line could be due to inhibition of P-gp, of digoxin uptake transport, or both. This kinetic analysis is now extended to include three additional cell lines: MDCK-MDR1-NIH (National Institute of Health, Caco-2 and CPT-B2 (Caco-2 cells with BCRP knockdown. These cells similarly exhibit GF120918 inhibitable uptake transport of digoxin. We demonstrate that inhibition of digoxin transport across these cell lines by GF120918, cyclosporine, ketoconazole and verapamil is greater than can be explained by inhibition of P-gp alone. We examined three hypotheses for this non-P-gp inhibition. The inhibitors can: (1 bind to a basolateral digoxin uptake transporter, thereby inhibiting digoxin's cellular uptake; (2 partition into the basolateral membrane and directly reduce membrane permeability; (3 aggregate with digoxin in the donor chamber, thereby reducing the free concentration of digoxin, with concomitant reduction in digoxin uptake. Data and simulations show that hypothesis 1 was found to be uniformly acceptable. Hypothesis 2 was found to be uniformly unlikely. Hypothesis 3 was unlikely for GF120918 and cyclosporine, but further studies are needed to completely adjudicate whether hetero-dimerization contributes to the non-P-gp inhibition for ketoconazole and verapamil. We also find that P-gp substrates with relatively low passive permeability such as digoxin, loperamide and vinblastine kinetically require basolateral uptake transport over that allowed by +GF120918 passive permeability, while

Continuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth

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Guo XN

2017-09-01

Full Text Available Xiaonan Guo,1,* Xiaoshuang Zhu,1,* Dakan Liu,1 Yubin Gong,1 Jing Sun,2 Changxian Dong1 1Department of Hemangioma and Vascular Malformation, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: To reduce the adverse effects and high frequency of administration of propranolol to treat infantile hemangioma, we first utilized propranolol-loaded liposomes-in-microsphere (PLIM as a novel topical release system to realize sustained release of propranolol.Methods: PLIM was developed from encapsulating propranolol-loaded liposomes (PLs in microspheres made of poly(lactic-co-glycolic acid-b-poly(ethylene glycol-b-poly(lactic-co-glycolic acid copolymers (PLGA-PEG-PLGA. The release profile of propranolol from PLIM was evaluated, and its biological activity was investigated in vitro using proliferation assays on hemangioma stem cells (HemSCs. Tumor inhibition was studied in nude mice bearing human subcutaneous infantile hemangioma.Results: The microspheres were of desired particle size (~77.8 µm and drug encapsulation efficiency (~23.9% and achieved sustained drug release for 40 days. PLIM exerted efficient inhibition of the proliferation of HemSCs and significantly reduced the expression of two angiogenesis factors (vascular endothelial growth factor-A [VEGF-A] and basic fibroblast growth factor [bFGF] in HemSCs. Notably, the therapeutic effect of PLIM in hemangioma was superior to that of propranolol and PL in vivo, as reflected by significantly reduced hemangioma volume, weight, and microvessel density. The mean hemangioma weight of the PLIM-treated group was significantly lower than that of other groups (saline =0.28 g, propranolol =0.21 g, PL =0.13 g, PLIM =0.03 g; PLIM vs saline: P<0.001, PLIM vs propranolol: P<0.001, PLIM vs PL: P<0.001. The mean microvessel density of

Pharmacokinetic interaction of telmisartan with s-amlodipine: an open-label, two-period crossover study in healthy Korean male volunteers.

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Noh, Yook-Hwan; Lim, Hyeong-Seok; Kim, Mi Jo; Kim, Yo Han; Choi, Hee Youn; Sung, Hye Ryoung; Jin, Seok-Joon; Lim, Jonglae; Bae, Kyun-Seop

2012-07-01

Telmisartan belongs to a class of orally active angiotensin II receptor blockers (ARBs), and S-amlodipine is an enantiomer of amlodipine. Amlodipine is a racemic mixture and the calcium channel blocking (CCB) effect is confined to S-amlodipine, whereas R-amlodipine has a 1000-fold lower activity and no racemization occurs in vivo in human plasma. Combination therapy of ARBs with CCBs provides advantages for blood pressure control and vascular protection over monotherapy. To investigate the effects of coadministration of telmisartan and S-amlodipine on the steady-state pharmacokinetic properties of each drug as a drug-drug interaction study required before developing the fixed-dose combination agent. This study comprised 2 separate parts, A and B; each was a multiple-dose, open-label, 2-sequence, 2-period, crossover study in healthy male Korean volunteers. In part A, volunteers were administered 80 mg of telmisartan, either alone or with 5 mg of S-amlodipine. In part B, volunteers were administered 5 mg of S-amlodipine, either alone or with 80 mg of telmisartan. Blood samples were taken on days 9 and 37, following the final dose of each treatment, and at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours after administration in part A, and were taken at 0 (predose), 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, and 24 hours after administration in part B. Plasma concentrations were determined using LC-MS/MS. The pharmacokinetic properties of each drug after coadministration of telmisartan and S-amlodipine were compared with those of each drug administered alone. Tolerability was assessed using measurements of vital signs, clinical chemistry tests, and interviews. Fifty-six volunteers were enrolled (32 in part A and 24 in part B), and all completed except 4 volunteers (3 withdrawn in part A and 1 withdrawn in part B). The geometric mean ratios (GMRs) (90% CI) for the C(max,ss) and AUC(τ,ss) of telmisartan (with or without S-amlodipine) were 1.039 (0

Increased activity of digoxin-like substance in low-renin hypertension in acromegaly

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Soszynski, P.; Slowinska-Srzednicka, J.; Zgliczynski, S. (Medical Center for Postgraduate Education, Warsaw (Poland))

1990-01-01

Arterial hypertension is common in acromegaly, but the pathogenesis of this complication remains unknown. To determine the role of an endogenous Na,K pump inhibitor/digoxin-like substance (DLS) in the pathogenesis of hypertension in acromegaly 76 subjects: 28 with acromegaly, 20 with essential hypertension and 28 healthy controls were studied. Serum DLS was measured with the use of radioimmunoassay and bioassay by the inhibition of digoxin-sensitive erythrocyte 86-Rb uptake. In acromegaly, the activity of DLS was significantly increased and plasma renin activity decreased in the hypertensive group, as compared with that of the normotensive group and controls. Moreover, DLS was elevated in the low-renin group of essential hypertension, as compared with that of the normal/high-renin group or controls. The activity of DLS correlated positively with mean arterial pressure and negatively with plasma renin activity, but not with growth hormone levels. In conclusion, an endogenous sodium pump inhibitor/digoxin-like substance may play a role in the pathogenesis of low-renin hypertension in acromegaly.

Increased activity of digoxin-like substance in low-renin hypertension in acromegaly

International Nuclear Information System (INIS)

Soszynski, P.; Slowinska-Srzednicka, J.; Zgliczynski, S.

1990-01-01

Arterial hypertension is common in acromegaly, but the pathogenesis of this complication remains unknown. To determine the role of an endogenous Na,K pump inhibitor/digoxin-like substance (DLS) in the pathogenesis of hypertension in acromegaly 76 subjects: 28 with acromegaly, 20 with essential hypertension and 28 healthy controls were studied. Serum DLS was measured with the use of radioimmunoassay and bioassay by the inhibition of digoxin-sensitive erythrocyte 86-Rb uptake. In acromegaly, the activity of DLS was significantly increased and plasma renin activity decreased in the hypertensive group, as compared with that of the normotensive group and controls. Moreover, DLS was elevated in the low-renin group of essential hypertension, as compared with that of the normal/high-renin group or controls. The activity of DLS correlated positively with mean arterial pressure and negatively with plasma renin activity, but not with growth hormone levels. In conclusion, an endogenous sodium pump inhibitor/digoxin-like substance may play a role in the pathogenesis of low-renin hypertension in acromegaly

Effects of haemolysis, urea and bilirubin on the precision of digoxin and insulin radioimmunoassays

Energy Technology Data Exchange (ETDEWEB)

Dwenger, A.; Trautschold, I.

1982-01-01

The influence of haemolysis, uraemia and hyperbilirubinaemia on the radioimmunoassay for both digoxin and insulin has been investigated for five separation techniques (dextran/charcoal; coated tube; polyethyleneglycol 4000; sodium sulphite; double antibody). Recoveries, and intra- and interassay precision were calculated. It was demonstrated that even in serum samples with a rather high degree of haemolysis (haemoglobin up to 50 g/l) digoxin can be measured by using each of the five separation techniques without any significant interference. Visible haemolysis (haemoglobin above 200 mg/l) leads either to disturbance or to a complete failure of insulin radioimmunoassays with all separation techniques. This effect can be largely neutralized, and precision improved, by using N-ethyl-maleimide. With the exception of the coated tube separation technique the intraassay precision has a CV of < 10%, and the interassay CV is between 10 and 20%. Elevated urea concentrations interfered in the digoxin radioimmuno-assay only when the coated tube technique was used. The insulin radioimmunoassay, however was affected by high urea when either the double antibody or the coated tube technique was used. Here the intraassay precision also has a coefficient of variation < 10%, the interassay CV lying between 10 and 20%. Bilirubin influenced the digoxin test when the sodium sulphite separation was used, and it affected the insulin determinations with polyethyleneglycol 4000 and sodium sulphite. The intra- and interassay precision were however also around 10% and between 10 and 20% respectively. Compared with the interassay precision of 15% CV for digoxin and 13% for insulin for a pool-serum from blood donors, the decrease of interassay precision caused by haemolysis, uraemia and hyperbilirubin-aemia was insignificant.

Zero crossing and ratio spectra derivative spectrophotometry for the dissolution tests of amlodipine and perindopril in their fixed dose formulations

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Maczka Paulina

2014-06-01

Full Text Available Dissolution tests of amlodipine and perindopril from their fixed dose formulations were performed in 900 mL of phosphate buffer of pH 5.5 at 37°C using the paddle apparatus. Then, two simple and rapid derivative spectrophotometric methods were used for the quantitative measurements of amlodipine and perindopril. The first method was zero crossing first derivative spectrophotometry in which measuring of amplitudes at 253 nm for amlodipine and 229 nm for perindopril were used. The second method was ratio derivative spectrophotometry in which spectra of amlodipine over the linearity range were divided by one selected standard spectrum of perindopril and then amplitudes at 242 nm were measured. Similarly, spectra of perindopril were divided by one selected standard spectrum of amlodipine and then amplitudes at 298 nm were measured. Both of the methods were validated to meet official requirements and were demonstrated to be selective, precise and accurate. Since there is no official monograph for these drugs in binary formulations, the dissolution tests and quantification procedure presented here can be used as a quality control test for amlodipine and perindopril in respective dosage forms.

Evaluation of Propranolol Effect on Experimental Acute and Chronic Toxoplasmosis Using Quantitative PCR

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Montazeri, Mahbobeh; Ebrahimzadeh, Mohammad Ali; Ahmadpour, Ehsan; Sharif, Mehdi; Sarvi, Shahabeddin

2016-01-01

Current therapies against toxoplasmosis are limited, and drugs have significant side effects and low efficacies. We evaluated the potential anti-Toxoplasma activity of propranolol at a dose of 2 or 3 mg/kg of body weight/day in vivo in the acute and chronic phases. Propranolol as a cell membrane-stabilizing agent is a suitable drug for inhibiting the entrance of Toxoplasma gondii tachyzoites into cells. The acute-phase assay was performed using propranolol, pyrimethamine, and propranolol plus pyrimethamine before (pretreatment) and after (posttreatment) intraperitoneal challenge with 1 × 103 tachyzoites of the virulent T. gondii strain RH in BALB/c mice. Also, in the chronic phase, treatment was performed 12 h before intraperitoneal challenge with 1 × 106 tachyzoites of the virulent strain RH of T. gondii in rats. One week (in the acute phase) and 2 months (in the chronic phase) after postinfection, tissues were isolated and DNA was extracted. Subsequently, parasite load was calculated using quantitative PCR (qPCR). In the acute phase, in both groups, significant anti-Toxoplasma activity was observed using propranolol (P toxoplasmosis. Also, propranolol combined with pyrimethamine reduced the parasite load as well as significantly increased survival of mice in the pretreatment group. In the chronic phase, anti-Toxoplasma activity and decreased parasite load in tissues were observed with propranolol. In conclusion, the presented results demonstrate that propranolol, as an orally available drug, is effective at low doses against acute and latent murine toxoplasmosis, and the efficiency of the drug is increased when it is used in combination therapy with pyrimethamine. PMID:27645234

A critical appraisal of a further three new commercial digoxin radioimmunoassay kits with reference to cross-reacting substances

International Nuclear Information System (INIS)

Wood, W.G.; Wachter, C.

1979-01-01

A further 3 digoxin radioimmunoassay (RIA) kits have been evaluated for performance and cross-reaction with digitoxin, spironolactone, canrenone and furosemide (Lasix-Hoechst). Effects of serum protein concentrations have also been tested. The kits tested were from the following manufacturers: A) Diagnostic Products Corporation Digoxin RIA Kit. B) Byk-Mallinckrodt SPAC Digoxin Kit. C) Boehringer-Mannheim Digoxin RIA Kit. All kits used a 125 I-labelled tracer. Kit A used a conventional liquid phase system using double-antibody separation for bound and free drug. Kits B and C used a solid-phase antibody coated tube method. All kits showed a lower cross-reaction to digitoxin than quoted by the manufacturer. Cross-reaction to spironolactone (Aldactone - Boehringer-Mannheim) was less than 1.50 nmol/l at a serum concentration of 125 mg/l Aldactone in all 3 kits. The cross-reaction to canrenone was somewhat higher, 5.2 nmol/l 'digoxin' being measured in one kit at a serum canrenone concentration of 125 mg/l. There was no cross-reaction with furosemide in any kit, even at a serum concentration of 5 g/l. The coated-tube assays were affected by serum albumin and globulin concentration changes, one kit showing a difference of over 50% binding in the range 1-20% albumin. The double-antibody kit did not show dependence on the concentration of these proteins. All kits measured digoxin with good reproducibility in the range 0.40-10.0 nmol/l. (orig.) [de

Hypothalamic digoxin, hemispheric chemical dominance, and chronic bronchitis emphysema.

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Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-09-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin (membrane sodium-potassium ATPase inhibitor, immunomodulator, and regulator of neurotransmitter/amino acid transport), dolichol (regulates N-glycosylation of proteins), and ubiquinone (free radical scavenger). This was assessed in patients with chronic bronchitis emphysema. The pathway was also assessed in patients with right hemispheric, left hemispheric, and bihemispheric dominance to find the role of hemispheric dominance in the pathogenesis of chronic bronchitis emphysema. All the 15 patients with chronic bronchitis emphysema were right-handed/left hemispheric dominant by the dichotic listening test. In patients with chronic bronchitis emphysema there was elevated digoxin synthesis, increased dolichol, and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate levels of RBC membrane in patients with chronic bronchitis emphysema. The same biochemical patterns were obtained in individuals with right hemispheric dominance. Endogenous digoxin by activating the calcineurin signal transduction pathway of T-cell can contribute to immune activation in chronic bronchitis emphysema. Increased free radical generation can also lead to immune activation. Endogenous synthesis of nicotine can contribute to the pathogenesis of the disease. Altered glycoconjugate metabolism and membranogenesis can lead to defective lysosomal stability contributing to the disease process by increased release of lysosomal proteases. The role of an endogenous digoxin and hemispheric dominance in the pathogenesis of chronic bronchitis emphysema and in the regulation of lung structure/function is discussed. The biochemical patterns obtained in chronic bronchitis emphysema is similar to those obtained in left

Evidence for Enhanced Intestinal Absorption of Digoxin by P ...

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Purpose: To investigate the influence of macrolides as P-glycoprotein inhibitors on the level of intestinal ... The effective permeability of the drug was calculated after analyzing the ... associated with oral formulation factors such ... high performance liquid chromatography ..... pharmacokinetics of intravenous digoxin in.

Lectins Labelled with Digoxin as a Novel Tool to Study Glycoconjugates

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Jerka Dumić

2002-01-01

Full Text Available In recent years it has become clear that carbohydrate portions of glycoconjugates are performing numerous vital physiological functions in higher organisms. However, since glycobiology is a relatively new science, and carbohydrate structures are highly complex, the continuous development of novel analytical techniques is necessary to support the process of understanding the intricate nature of glycoconjugate structure and function. The introduction of digoxin as a novel tag for labelling of lectins that are being used to analyse glycoconjugates in immunoassay-like techniques is described. Lectins labelled with digoxin have significant advantages over biotin- or digoxigenin-labelled lectins and will hopefully prove to be a useful addition to the repertoire of glycobiological tools.

Propranolol in Treatment of Huge and Complicated Infantile Hemangiomas in Egyptian Children

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Hassan, Basheir A.; Shreef, Khalid S.

2014-01-01

Background. Infantile hemangiomas (IHs) are the most common benign tumours of infancy. Propranolol has recently been reported to be a highly effective treatment for IHs. This study aimed to evaluate the efficacy and side effects of propranolol for treatment of complicated cases of IHs. Patients and Methods. This prospective clinical study included 30 children with huge or complicated IHs; their ages ranged from 2 months to 1 year. They were treated by oral propranolol. Treatment outcomes were...

A clinical trial of the beta blocker propranolol in premature ejaculation.

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Cooper, A J; Magnus, R V

1984-01-01

Twelve male patients, with a primary complaint of premature ejaculation in a setting of chronic anxiety with prominent somatic manifestations, participated in a double-blind trial: propranolol against placebo. The study consisted of 5 X 4 week phases: run-in, propranolol or placebo--120 mg/day allocated randomly, wash-out; placebo or propranolol and run-out, in a balanced design. Anxiety was rated initially, and every 2 weeks, throughout the trial using the Hamilton Rating Scale. Sitting blood pressure and pulse were also noted. The time to coital ejaculation (every 3 days) was recorded using a stopwatch, and subjects were also required to rate "overall coital satisfaction" and "quality of erection". Neither prematurity nor other signs/symptoms of anxiety improved on the preparations, which were statistically equivalent. Moderate beta-blockade was achieved with propranolol as evidenced by a median reduction in pulse rate of 5 beats/min.

Hypothalamic digoxin, hemispheric chemical dominance, and interstitial lung disease.

Science.gov (United States)

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-10-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. This was assessed in patients with idiopathic pulmonary fibrosis and in individuals of differing hemispheric dominance to find out the role of hemispheric dominance in the pathogenesis of idiopathic pulmonary fibrosis. All 15 cases of interstitial lung disease were right-handed/left hemispheric dominant by the dichotic listening test. The isoprenoidal metabolites--digoxin, dolichol, and ubiquinone, RBC membrane Na(+)-K+ ATPase activity, serum magnesium, tyrosine/tryptophan catabolic patterns, free radical metabolism, glycoconjugate metabolism, and RBC membrane composition--were assessed in idiopathic pulmonary fibrosis as well as in individuals with differing hemispheric dominance. In patients with idiopathic pulmonary fibrosis there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in patients with idiopathic pulmonary fibrosis. Isoprenoid pathway dysfunction con tributes to the pathogenesis of idiopathic pulmonary fibrosis. The biochemical patterns obtained in interstitial lung disease are similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. However, all the patients with interstitial lung disease were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Interstitial lung disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

Performance of radioimmunoassays for digoxin as evaluated by a group experiment

International Nuclear Information System (INIS)

Dwenger, A.; Friedel, R.; Trautschold, I.

1977-01-01

In order to gather informations on the performance of routinely employed test system for the radioimmunological determination of digoxin in serum a group experiment was set up in which 36 laboratories in the Federal Republic of Germany took part. They were asked to determine the digoxin content in 25 specimens including a recovery curve, sera with pathologic composition and known concentrations of digoxin, sera from a pharmacokinetic study and commercial control sera. This identity of the specimens was withheld from the participants. As far as accuracy and precision are concerned the results reported for a total of 54 assays were better than those obtained in group experiments on radioimmunological determination of hormones. Recovery ranged from 90% to 110% in 57%, from 80% to 120% in 85% of the assays. Reproducibility in the series expressed as coefficient of variation was better than 5% in 54%, better than 10% in 85% of the assays. Considerable differences were found for the cross-reactivities of antibodies with digitoxin and metabolites of spironolactone. Dysproteinemia seems to be an unsolved problem whereas moderate hemolysis and hyperlipemia did not lead to severe errors. Improvements, especially with respect to inter-laboratory variances can be expected mainly from a further standardization of standard preparations. (orig.) [de

Studying structurally-mechanical characteristics suppositories with amlodipine

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Fadi Al Zedan

2013-02-01

Full Text Available Rheological behaviour suppositories with amlodipine on lypofiles to a basis are studied and character of temperature effect on their structurally-mechanical properties is positioned. It is revealed that the temperature of carrying out of technological operations of homogenization and overflow suppositories 50-55ºС is optimum, providing necessary fluidity suppositories masses at hypodispersion in it reacting and aids.

Effects of carvedilol and propranolol on circulatory regulation and oxygenation in cirrhosis

DEFF Research Database (Denmark)

Hobolth, Lise; Bendtsen, Flemming; Hansen, Erik F

2014-01-01

=16) or propranolol (n=13). Cardiac, systemic and splanchnic parameters along with oxygen saturation and plasma renin were measured at inclusion and after 3 months. RESULTS: Arterial blood pressure, heart rate, and cardiac output decreased equally, central circulation time and systemic vascular...... oxygen gradient remained constant in both groups. Hepatic venous pressure gradient decreased equally in the carvedilol and propranolol groups (-17% and -20%, non significant). CONCLUSIONS: Systemic haemodynamics and pulmonary effects of carvedilol and propranolol are modest and this study could...

Hypothalamic digoxin and hemispheric chemical dominance: relation to speech and language dysfunction.

Science.gov (United States)

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-06-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. Since endogenous digoxin can regulate neurotransmitter transport and dolichols can modulate glycoconjugate synthesis important in synaptic connectivity, the pathway was assessed in patients with dyslexia, delayed recovery from global aphasia consequent to a dominant hemispheric thrombotic infarct, and developmental delay of speech milestone. The pathway was also studied in right hemispheric, left hemispheric, and bihemispheric dominance to find out the role of hemispheric dominance in the pathogenesis of speech disorders. The plasma/serum--activity of HMG CoA reductase, magnesium, digoxin, dolichol, ubiquinone--and tryptophan/tyrosine catabolic patterns, as well as RBC (Na+)-K+ ATPase activity, were measured in the above mentioned groups. The glycoconjugate metabolism and membrane composition was also studied. The study showed that in dyslexia, developmental delay of speech milestone, and delayed recovery from global aphasia there was an upregulated isoprenoidal pathway with increased digoxin and dolichol levels. The membrane (Na+)-K+ ATPase activity, serum magnesium and ubiquinone levels were low. The tryptophan catabolites were increased and the tyrosine catabolites including dopamine decreased in the serum contributing to a speech dysfunction. There was an increase in carbohydrate residues of glycoproteins, glycosaminoglycans, and glycolipids levels as well as an increased activity of GAG degrading enzymes and glyco hydrolases in the serum. The cholesterol:phospholipid ratio of RBC membrane increased and membrane glycoconjugates showed a decrease. All of these could contribute to altered synaptic inactivity in these disorders. The patterns correlated with those obtained in right hemispheric chemical dominance. Right hemispheric chemical dominance may play a role in the genesis of these disorders. Hemispheric chemical dominance has no correlation with handedness

Efficacy and safety of olmesartan medoxomil and hydrochlorothiazide compared with benazepril and amlodipine besylate.

Science.gov (United States)

Kereiakes, Dean J; Neutel, Joel M; Punzi, Henry A; Xu, Jianbo; Lipka, Leslie J; Dubiel, Robert

2007-01-01

Most patients with stage 2 hypertension require two or more antihypertensive agents in order to achieve the BP goals recommended in current treatment guidelines. Accordingly, combinations of two drugs with different mechanisms of antihypertensive action are widely used. The aim of this randomized, double-blind, multicenter 12-week study was to compare the efficacy, safety, and tolerability of a combination of olmesartan medoxomil/hydrochlorothiazide (HCTZ) with that of benazepril plus amlodipine besylate in patients with stage 2 hypertension. Patients were eligible for randomization following a 3- to 4-week placebo run-in period if they had either (i) mean seated DBP>or=90 mm Hg butor=160 mm Hg but or=100 mm Hg butor=95 mm Hg and145 mm Hg andbenazepril (10 mg/day for 2 weeks; then 20 mg/day for 2 weeks; then benazepril 20 mg/day plus amlodipine besylate 5 mg/day for 4 weeks; then benazepril 20 mg/day plus amlodipine besylate 10 mg/day for 4 weeks). The primary endpoint was change from baseline in mean SBP at the end of week 12 (end of study). Secondary endpoints included DBP after completion of monotherapy and combination therapy at the end of weeks 4 and 12, SBP at the end of week 4, and percentage of patients attaining BP goals ofbenazepril plus amlodipine besylate (least square [LS] mean change: -32.5 vs -26.5 mm Hg, p=0.024; LS mean treatment difference -6.0 mm Hg; 95% CI -11.1, -0.8 mm Hg). The LS mean change for reduction in DBP approached statistical significance with olmesartan medoxomil/HCTZ compared with the benazepril-based regimen (p=0.056) at week 12 (end of study). BP reductions showed statistically significant differences between treatment groups favoring olmesartan medoxomil/HCTZ in both SBP and DBP at week 8. The percentage of patients achieving goal rates at the end of the study for olmesartan medoxomil/HCTZ and benazepril plus amlodipine besylate, respectively, were 66.3% versus 44.7% (p=0.006) forbenazepril plus amlodipine besylate 20/5 and 20

Propranolol for extensive hemangiomas of infancy: two case reports Hemangiomas extensos da infância tratados com propranolol: relato de dois caso

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Luíza Helena dos Santos Cavaleiro

2011-06-01

Full Text Available Hemangiomas are the most common benign tumors of childhood. They show rapid growth, followed by a regression phase that culminates in the partial or total disappearance of the lesion. Therapeutic options should be evaluated for extensive cases. Systemic glucocorticoids are the therapy of choice; however, there are reports that propranolol offers better and faster results. We report two cases of large volume infantile hemangioma associated with functional limitation and aesthetic disfigurement, treated successfully with propranolol, a drug that comes as a therapeutic option providing satisfactory and maintained results, with few side effects.Hemangiomas são os tumores benignos mais frequentes da infância, apresentando como história natural crescimento rápido, seguido de uma fase de regressão que culmina com o desaparecimento parcial ou total da lesão. Opções terapêuticas devem ser avaliadas para casos extensos. Os glicocorticoides sistêmicos são a terapia de escolha; contudo, há relatos de que o propranolol oferece resultados melhores e mais rápidos. Este trabalho descreve dois casos de hemangioma infantil de grande volume associados à limitação funcional e desfiguração estética com significativa resposta ao propranolol, droga esta que surge como uma proposta terapêutica oferecendo resultados satisfatórios e mantidos, com poucos efeitos colaterais.

Therapeutic drug monitoring of digoxin in cardiac heart failure outpatients: comparisons of two analytical methods

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Isabel Cristina Medeiros Barros

2014-01-01

Full Text Available Objective: To compare two analytical techniques used in the determination of plasma digoxin (LC-MS/MS and immunoassay and to verify which one better answer the need of the clinical monitoring routine of patients with cardiac heart failure. Method: The clinical findings in 15 cardiac heart failure (CHF outpatients of the Cardiac Heart Service of the Goias Federal University Clinical Hospital were investigated. Blood samples of the patients were collected and analysed by Immunoassay and by Liquid Chromatography coupled to Mass Spectrometry (LC-MS/MS. Results: The results of the statistic test (Student p = 0,05 showed a significant difference between the analytical methods: immunoassay concentrations were higher than the concentrations determined by LCMS/ MS. The explanation may be because immunoassay method measures digoxin plus other metabolites and endogenous substances, while the LC-MS/MS method measures only the digoxin molecule. None of the patients, showed relevant clinical data suggestive of digitalis intoxication, even several drugs with potential interaction were associated with treatment. Conclusion: It was concluded, therefore, that LC-MS/MS me thod is safer, more selective and specific than immunoassay, being an option for therapeutic drug monitoring of digoxin, since the reference values would be obtain for digoxinemia by LC-MS/MS.

Obtain and characterization of chitosan / propranolol microparticles by spray drying

International Nuclear Information System (INIS)

Nascimento, Ednaldo G. do; Silva Junior, Arnobio A. da; Santos, Katia S.C.R. dos

2015-01-01

The study investigated the application of chitosan microparticles as carriers into hard gelatin capsule containing propranolol, evaluating the variability of the molecular weight and the chitosan particles by spray drying. The formulations were characterized by average weight, dosing unit dose uniformity and dissolution profile according to the pharmacopoeia. While the microparticles were characterized by Fourier transformed infrared spectroscopy, scanning electron microscopy and X-ray diffraction. The results showed that chitosan microparticles obtained without the drug and then physically mixed with propranolol promoted a modified release 85% of the drug after 5 hours. While, chitosan microparticles sprayed with propranolol released only 55% at 5 hours is presented both as a modified release system. Samples of dried chitosan showed up amorphous and homogeneous and spherical morphology. (author)

Digoxinforgiftning hos et spædbarn grundet forveksling af flasker med magistrelt fremstillet medicin

DEFF Research Database (Denmark)

Hansen, Louise Lindholdt; Herskind, Anne Maria

2014-01-01

-fragment and atropine. After three days of hospitalization she was discharged well-being. We suspect that the explanation for this intoxication is due to confusion of bottles of magistral preparations of medicine, as they were very identical. Therefore we call for increased attention in children receiving this type......We hereby describe a case report of a 9-month-old girl, who was accidentally intoxicated with digoxin since her parents by mistake gave her digoxin instead of propranolol. At admission sinusbradycardia and a first-degree atrioventricular block was found and she was treated with antidigitalis Fab...

Cyproheptadine versus propranolol in the prevention of migraine headaches in children

International Nuclear Information System (INIS)

Asadi, B.; Khorvash, F.

2012-01-01

Objective: There are conflicting results on the efficacy of propranolol and cyproheptadine in the prevention of migraine headaches in children. Therefore, in this study, we evaluated the efficacy of propranolol versus cyproheptadine in the prevention of migraine headaches. Methodology: This was a randomized, double-blind trial. Sixty children aged 8-15 yrs with migraine headaches were randomized to be treated with either propranolol (40-80 mg per day) or cyproheptadine (8-12 mg per day) for 4 weeks. The patients were requested to record the Severity and duration of their headaches during a 2-week period before starting the intervention. The patients were followed at 2-week intervals for a period of 1 month after starting treatment. The headache diary was analyzed for each patient and was compared with baseline using SPSS software and statistical tests including the student's t-test. Results: Out of 60 patients at baseline, nine patients in the cyproheptadine group and six patients in the propranolol group did not appear at the appropriate time for follow-up visits and therefore were excluded from the study. The mean age in the cyproheptadine group was 11.9+-2.23 years and in the propranolol group was 0.7 +- 2.33 years. Based on the diaries, the results Showed that propranolol and cyproheptadine decreased headaches by 54.61% and 70.53% (p < 0.05), respectively, at the end of four weeks of treatment. Conclusion: Overall, the results of our study suggest that cyproheptadine is a good choice for prevention of migraine headache in pediatric group although more prolonged study with higher number of the patient is recommended. (author)

Phase II trial of second-line erlotinib and digoxin for nonsmall cell lung cancer (NSCLC

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Fadi Kayali

2011-02-01

Full Text Available Fadi Kayali, Muhamad A Janjua, Damian A Laber, Donald Miller, Goetz H KloeckerUniversity of Louisville, James Graham Brown Cancer Center, Louisville, KY, USABackground: In vitro digoxin sensitizes cancer cells to the induction of apoptosis by chemotherapy. Inhibition of the Na/K-ATPase enzyme by ouabain disturbs the intracellular ion composition of cancer cells, altering cellular homeostasis. This suggests that inhibition of the Na/K pump results in cellular sensitization of malignant but not benign cells to the induction of apoptosis. Epidemiologic studies have also shown beneficial effects of digitalis in breast cancer incidence. At ASCO (American Society of Clinical Oncology 2007 our group presented a Phase II study showing encouraging results by adding digoxin to biochemotherapy for melanoma. Erlotinib is one of the standard second-line treatments for nonsmall cell lung cancer (NSCLC, with a response rate (RR of 10%. This study's hypothesis was that adding digoxin to erlotinib will improve the RR and time to progression (TTP in NSCLC.Methods: Patients with progressive disease (PD after chemotherapy were enrolled if they had an ECOG (Eastern Cooperative Oncology Group score from 0 to 2 and good organ function. Daily erlotinib 150 mg and digoxin 0.25 mg were taken by mouth. The digoxin dose was adjusted to keep levels between 1 and 2 ng/mL. Computed tomography scans were done every 6 weeks. Treatment continued until PD or significant toxicity occurred.Results: Patient accrual lasted from March 2006 until August 2008 and was stopped early at the time of interim analysis. Twenty-eight patients were enrolled, and 24 who completed at least 6 weeks of therapy are presented here. All patients had unresectable NSCLC stage III/IV at diagnosis. Median age was 61 (34–78, 14 were female, 17 had prior radiation (not involving the target lesions, 23 had one prior chemotherapy, and one subject had two. Only one patient was a never-smoker. Histologies were

Influence of the cardiac glycoside digoxin on cardiac troponin I, acid-base and electrolyte balance, and haematobiochemical profiles in healthy donkeys (Equus asinus).

Science.gov (United States)

Tharwat, Mohamed; Al-Sobayil, Fahd

2014-03-12

The effect of digoxin administration on the serum concentration of the cardiac troponin I (cTnI) has not been reported to date in equidae. This study was therefore designed to evaluate the effect of digoxin on cardiac cell damage in donkeys (Equus asinus) as assessed by cTnI, acid-base and electrolyte balance and haematobiochemical profiles. Ten clinically healthy donkeys were given an IV infusion of digoxin at a dose of 14 μg/kg. Blood samples were collected from the donkeys up through 72 h post-injection. Three of the donkeys exhibited increased heart and respiratory rates post-injection. In the other seven animals, the heart and respiratory rates were lower 4 h post-injection. The serum digoxin concentration increased significantly at many time points after injection. The serum concentration of cTnI did not differ significantly between pre- and post-injection. An increase in blood pH was noted at 3 h after digoxin injection. There were also increases in PO2 and in oxygen saturation. Decreases in PCO2 at 2 to 48 h post-injection as well as a decrease in blood lactate at 4 h post-injection were observed. The serum concentration of glucose remained significantly elevated at all-time points after digoxin injection. It is concluded that administration of digoxin to healthy donkeys (14 μg/kg) did not result in elevations of serum cTnI concentration, signs of digoxin intoxication, ECG abnormalities and did not increase serum concentrations of blood urea nitrogen and creatinine.

The Use of Digoxin in Patients With Worsening Chronic Heart Failure Reconsidering an Old Drug to Reduce Hospital Admissions

NARCIS (Netherlands)

Ambrosy, Andrew P.; Butler, Javed; Ahmed, Ali; Vaduganathan, Muthiah; van Veldhuisen, Dirk J.; Colucci, Wilson S.; Gheorghiade, Mihai

2014-01-01

Digoxin is the oldest cardiac drug still in contemporary use, yet its role in the management of patients with heart failure (HF) remains controversial. A purified cardiac glycoside derived from the foxglove plant, digoxin increases ejection fraction, augments cardiac output, and reduces pulmonary

Dose-response relationships of propranolol in Chinese subjects with different CYP2D6 genotypes.

Science.gov (United States)

Huang, Chin-Wei; Lai, Ming-Liang; Lin, Min-Shung; Lee, Hwei-Ling; Huang, Jin-Ding

2003-01-01

For clinical treatment, a smaller dosage of propranolol is often used among Chinese people. Propranolol is metabolized by polymorphic CYP2D6. We postulate that the lower propranolol dosage in Chinese is due to a slower CYP2D6 metabolism. A majority of the Chinese population has the nucleotide T188 in the CYP2D6 gene (CYP2D6*10) instead of C188 (CYP2D6*1), which most white subjects have. Chinese subjects of different CYP2D6*1/CYP2D6*10 genotypes have been shown to have different propranolol pharmacokinetic characteristics. In this study, we compared the beta-blockade effects of propranolol in Chinese subjects of the two different CYP2D6 genotypes. Based on the nucleotide 188 genotypes, two groups of 10 healthy subjects each were selected. Each subject was given a 10-, 20-, or 40-mg rac-propranolol tablet three times a day for 3 days in 3 different phases. Heart rate and blood pressure were measured in both supine and upright positions. The heart rate was also determined during treadmill exercise test. Plasma concentration of S-propranolol at 2 hrs after the last-dose administration was measured. Despite therebeing higher S-propranolol plasma concentration in CYP2D6*10 subjects than in CYP2D6*1 subjects at 10- and 20-mg dosage, the dose-response relationship was not significantly different in these subjects. Our results do not support the hypothesis that CYP2D6*1/CYP2D6*10 polymorphism may affect the beta-blockade effect of propranolol in Chinese subjects.

Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis

NARCIS (Netherlands)

S.A. Steenen (Serge A.); A.J. van Wijk (Arjen); G.J.M.G. Van Der Heijden (Geert J.M.G.); R. van Westrhenen (Roos); J. de Lange (Jan); A. de Jongh (Ad)

2016-01-01

textabstractThe effects of propranolol in the treatment of anxiety disorders have not been systematically evaluated previously. The aim was to conduct a systematic review and meta-analysis of randomised controlled trials, addressing the efficacy of oral propranolol versus placebo or other medication

Changes in the pharmacokinetics of digoxin in polyuria in streptozotocin-induced diabetic mice and lithium carbonate-treated mice.

Science.gov (United States)

Ikarashi, Nobutomo; Kagami, Mai; Kobayashi, Yasushi; Ishii, Makoto; Toda, Takahiro; Ochiai, Wataru; Sugiyama, Kiyoshi

2011-06-01

In humans, digoxin is mainly eliminated through the kidneys unchanged, and renal clearance represents approximately 70% of the total clearance. In this study, we used the mouse models to examine digoxin pharmacokinetics in polyuria induced by diabetes mellitus and lithium carbonate (Li(2)CO(3)) administration, including mechanistic evaluation of the contribution of glomerular filtration, tubular secretion, and tubular reabsorption. After digoxin administration to streptozotocin (STZ)-induced diabetic mice, digoxin CL/F increased to approximately 2.2 times that in normal mice. After treatment with Li(2)CO(3) (0.2%) for 10 days, the CL/F increased approximately 1.1 times for normal mice and 1.6 times for STZ mice. Creatinine clearance (CLcr) and the renal mRNA expression levels of mdr1a did not differ significantly between the normal, STZ, and Li(2)CO(3)-treated mice. The urine volume of STZ mice was approximately 26 mL/day, 22 times that of normal mice. The urine volume of Li(2)CO(3)-treated mice increased approximately 7.3 times for normal mice and 2.3 times for STZ mice. These results suggest that the therapeutic effect of digoxin may be significantly reduced in the presence of polyuria either induced by diabetes mellitus or manifested as an adverse effect of Li(2)CO(3) in diabetic patients, along with increased urine volume.

Propranolol medication among coronary patients: relationship to type A behavior and cardiovascular response.

Science.gov (United States)

Krantz, D S; Durel, L A; Davia, J E; Shaffer, R T; Arabian, J M; Dembroski, T M; MacDougall, J M

1982-09-01

The present correlational study compared behavioral and psychophysiological characteristics of coronary patients who were either medicated or not medicated with the beta-adrenergic blocking drug propranolol. Eighty-eight patients were given a structured Type A interview (SI) and a history quiz while heart rate and blood pressure were monitored. Data were analyzed controlling for age, sex, extent of coronary artery disease, and history of angina. Results indicated that patients taking propranolol (n = 65) were significantly lower in intensity of Type A behavior than patients not taking propranolol (n = 23). No effects were obtained for patients medicated or not medicated with diuretics, nitrates, or other CNS active drugs. Propranolol patients also showed lesser heart rate and rate-pressure product responses to the interview, but did not differ in blood pressure responses. Components of Type A which were lower in propranolol patients included speech stylistics (loud/explosive, rapid/accelerated, potential for hostility). Content of responses to the SI and scores on the Jenkins Activity Survey did not differ between the groups. An explanation for these results is offered in terms of the effects of propranolol on peripheral sympathetic responses, and evidence for a physiological substrate for Type A behavior. A conceptualization of the Type A pattern in terms of cognitive and physiological components is advanced, and implications for clinical intervention are discussed.

The use of propranolol in the treatment of anxiety disorders.

Science.gov (United States)

Fonte, R J; Stevenson, J M

1985-01-01

The authors review the available literature on the use of propranolol in the treatment of anxiety disorders. First studied in 1966, propranolol has been shown to be most effective in the control of certain somatic symptoms associated with anxiety. Despite these studies, however, it is still not certain where this beta-adrenergic blocker fits into the overall treatment of anxiety disorders. Reasons for this uncertainty and other related problems are discussed.

The early and late effects of digoxin treatment on the sodium transport, sodium content and Na+K+- ATPase or erythrocytes.

Science.gov (United States)

Cumberbatch, M; Zareian, K; Davidson, C; Morgan, D B; Swaminathan, R

1981-01-01

1 Erythrocyte sodium content, sodium transport (ouabain sensitive sodium flux Eos, and ouabain sensitive efflux rate constant ERCos) sodium, potassium activated ouabain sensitive adenosine triphosphatase (Na+K+ATPase) and plasma digoxin were measured in patients during acute digitalisation and in patients who were on long-term digoxin treatment. 2 In the six patients who were studied during digitalisation, the ERCos and Na+K+ATPase activity decreased and erythrocyte sodium content increased during days 2-4 treatment, but there was no change in Eos. 3 In 39 patients on long term digoxin therapy (2-119 months) the erythrocyte sodium content was normal, but the erythrocyte Na+K+ATPase activity was higher than the control group. When the results from these 39 patients were divided according to the duration of treatment it was found that the erythrocyte sodium content was higher in patients treated for 2-4 months than in patients treated for longer periods and the erythrocyte Na+K+ATPase activity increased with duration of treatment. In eight patients (duration of treatment greater than 29 months) in whom ERCos and Eos were measured, ERCos and Eos were higher than the control group. 4 The results suggest that the effects of digoxin on erythrocytes which occur during acute digoxin treatment do not persist in the long term. 5 The possible explanation for the higher ERCos, Eos and Na+K+ATPase activity in patients treated with digoxin for more than 2 months is discussed. PMID:6268133

Atenolol vs. propranolol in essential tremor. A controlled, quantitative study.

Science.gov (United States)

Larsen, T A; Teräväinen, H; Calne, D B

1982-11-01

The beta-1 selective, hydrophilic adrenoceptor blocking drug atenolol (100 mg daily) was compared to the non-selective, lipid-soluble beta-blocker propranolol (240 mg daily), and to placebo, in a double-blind cross-over study in 24 patients with essential tremor. Atenolol and propranolol caused a similar decrease in heart rate. Both beta-blockers also suppressed the tremor intensity; there was no significant difference between them, but both were significantly better than placebo. These drugs did not affect tremor frequency. Twelve of the patients preferred propranolol subjectively, one preferred atenolol and none preferred placebo. No marked side-effects were observed. It was concluded that atenolol and other cardio-selective blockers offer an alternative for patients unable to tolerate the non-selective drugs. The site of action and receptor sub-type involved have still to be determined.

The pathogenesis of propranolol-withdrawal syndrome in essential hypertension.

Science.gov (United States)

Kristensen, B O; Steiness, E; Weeke, J

1979-12-01

1. In hypertension, the beta-adrenoreceptor-blocker-withdrawal syndrome comprises tachycardia, sweating, tremor and general malaise, symptoms resembling thyrotoxicosis. 2. The effect of abrupt cessation of propranolol on serum concentrations of thyroxine (T4) and triiodothyronine (T3) was therefore investigated in five patients with uncomplicated essential hypertension, treated with propranolol in doses from 160 to 480 mg/day. 3. Four of the five patients developed one or more of the above-mentioned symptoms within 2-6 days after withdrawal of propranolol. 4. A mean relative increase in serum free T3 of 51% (range 22-74%) was found in these four patients on the day of onset of symptoms. 5. The increase in free T3 in the five patients correlated positively with total serum propranolol on the last day the drug was given (r = 0.91, 2P = 0.03). 6. As an increase in T3 was found only in patients suffering the withdrawal syndrome, and was maximal the day the symptoms appeared, despite a variation in time of onset from 2 to 6 days, it is suggested that the beta-adrenoreceptor-blocker-withdrawal syndrome, at least partially, is caused by rebound increased production of T3, induced by the well-known inhibition of the monodeiodination of T4 to T3 during beta-adrenoreceptor blockade. 7. This assumption may explain the clinical symptoms and the reported transient increased beta-adrenoreceptor sensitivity with unchanged serum concentrations of catecholamines.

Propranolol transport across the inner blood-retinal barrier: potential involvement of a novel organic cation transporter.

Science.gov (United States)

Kubo, Yoshiyuki; Shimizu, Yoshimi; Kusagawa, Yusuke; Akanuma, Shin-Ichi; Hosoya, Ken-Ichi

2013-09-01

The influx transport of propranolol across the inner blood-retinal barrier (BRB) was investigated. In the in vivo analysis of carotid artery single-injection method, [(3) H]propranolol uptake by the retina was greater than that of an internal reference compound, and was reduced by several organic cations. In the in vitro uptake study, TR-iBRB2 cells, an in vitro model of the inner BRB, showed a time-, concentration-, pH- and temperature-dependent [(3) H]propranolol uptake, suggesting the involvement of a carrier-mediated transport process in the influx of propranolol across the inner BRB. In the inhibition study, various organic cations, including drugs and candidates for the treatment of the retinal diseases, inhibited the [(3) H]propranolol uptake by TR-iBRB2 cells with no significant effects by the substrates and inhibitors of well-characterized organic cation transporters, suggesting that the influx transport of propranolol is performed by a novel transporter at the inner BRB. An analysis of the relationship between the inhibitory effect and the lipophilicity of inhibitors suggests a lipophilicity-dependent inhibitory effect of amines on the [(3) H]propranolol uptake by TR-iBRB2 cells. These results showed that influx transport of propranolol across the inner BRB is performed by a carrier-mediated transport process, suggesting the involvement of a novel organic cation transporter. Copyright © 2013 Wiley Periodicals, Inc.

Determination of digoxin by enzyme immunoassay and radioimmunoassay

International Nuclear Information System (INIS)

Mueller, H.; Braeuer, H.; Foerster, G.; Reinhardt, M.

1978-01-01

The results of parallel determinations of digoxin in the sera of non selected patients (n=104) by enzyme immunoassay (EMIT.EIA) and radioimmunoassay (J-125 labeled RIA) were compared with each other. The determinations revealed considerably different concentrations; the values determined by EIA were statistical lower (for EIA 1,09+'0,99ng/ml, for RIA 1,34+'1,01ng/ml, p [de

Synergistic anticonvulsant effects of pregabalin and amlodipine on acute seizure model of epilepsy in mice.

Science.gov (United States)

Qureshi, Itefaq Hussain; Riaz, Azra; Khan, Rafeeq Alam; Siddiqui, Afaq Ahmed

2017-08-01

Status epilepticus is a life threatening neurological medical emergency. It may cause serious damage to the brain and even death in many cases if not treated properly. There is limited choice of drugs for the short term and long term management of status epilepticus and the dugs recommended for status epilepticus possess various side effects. The present study was designed to investigate synergistic anticonvulsant effects of pregabalin with amlodipine on acute seizure model of epilepsy in mice. Pentylenetetrazole was used to induce acute seizures which mimic status epilepticus. Pregabalin and amlodipine were used in combination to evaluate synergistic anti-seizure effects on acute seizure model of epilepsy in mice. Diazepam and valproate were used as reference dugs. The acute anti-convulsive activity of pregabalin with amlodipine was evaluated in vivo by the chemical induced seizures and their anti-seizure effects were compared with pentylenetetrazole, reference drugs and to their individual effects. The anti-seizure effects of tested drugs were recorded in seconds on seizure characteristics such as latency of onset of threshold seizures, rearing and fallings and Hind limbs tonic extensions. The seizure protection and mortality to the animals exhibited by the drugs were recorded in percentage. Combination regimen of pregabalin with amlodipine exhibited dose dependent significant synergistic anticonvulsant effects on acute seizures which were superior to their individual effects and equivalent to reference drugs.

Targeting Hypertension with Valsartan: Lessons Learned from the Valsartan/HCTZ Versus Amlodipine in Stage II Hypertensive Patients (VAST Trial

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Luis M Ruilope

2006-03-01

Full Text Available Many patients with hypertension, especially those at increased risk because of additional cardiovascular risk factors, require treatment with more than one antihypertensive agent to achieve target blood pressure (BP goals. Many different classes of antihypertensive agents are available: a renin-angiotensin-aldosterone system (RAAS blocker and a diuretic are widely used in combination.Here we report the results of the recently completed Valsartan/HCTZ versus Amlodipine in STage II hypertensive patients (VAST trial. In this 24-week study, patients with moderate hypertension and at least one other cardiovascular risk factor were treated with a combination of valsartan 160 mg and hydrochlorothiazide (HCTZ 12.5 or 25 mg once daily (o.d., or with amlodipine monotherapy (10 mg o.d.. Overall, valsartan plus HCTZ 25 mg reduced systolic BP significantly more than amlodipine monotherapy, and with fewer adverse events. In addition, combination therapy resulted in a trend towards more favourable outcomes with respect to pro-thrombotic and proinflammatory markers than amlodipine alone.

Targeting Hypertension with Valsartan: Lessons Learned from the Valsartan/HCTZ Versus Amlodipine in Stage II Hypertensive Patients (VAST Trial

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Luis M Ruilope

2006-03-01

Full Text Available Many patients with hypertension, especially those at increased risk because of additional cardiovascular risk factors, require treatment with more than one antihypertensive agent to achieve target blood pressure (BP goals. Many different classes of antihypertensive agents are available: a renin-angiotensin-aldosterone system (RAAS blocker and a diuretic are widely used in combination. Here we report the results of the recently completed Valsartan/HCTZ versus Amlodipine in STage II hypertensive patients (VAST trial. In this 24-week study, patients with moderate hypertension and at least one other cardiovascular risk factor were treated with a combination of valsartan 160 mg and hydrochlorothiazide (HCTZ 12.5 or 25 mg once daily (o.d., or with amlodipine monotherapy (10 mg o.d.. Overall, valsartan plus HCTZ 25 mg reduced systolic BP significantly more than amlodipine monotherapy, and with fewer adverse events. In addition, combination therapy resulted in a trend towards more favourable outcomes with respect to pro-thrombotic and pro-inflammatory markers than amlodipine alone.

Digoxin Downregulates NDRG1 and VEGF through the Inhibition of HIF-1α under Hypoxic Conditions in Human Lung Adenocarcinoma A549 Cells

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Dong Wei

2013-04-01

Full Text Available Digoxin, an inhibitor of Na+/K+ ATPase, has been used in the treatment of heart-related diseases (such as congestive heart failure and atrial arrhythmia for decades. Recently, it was reported that digoxin is also an effective HIF-1α inhibitor. We investigated whether digoxin could suppress tumor cell growth through HIF-1α in non-small cell lung cancer cells (A549 cells under hypoxic conditions. An MTT assay was used to measure cell viability. RT-PCR and western blotting were performed to analyze the mRNA and protein expression of VEGF, NDRG1, and HIF-1α. HIF-1α nuclear translocation was then determined by EMSA. Digoxin was found to inhibit the proliferation of A549 cells under hypoxic conditions. Our results showed that hypoxia led to the upregulation of VEGF, NDRG1, and HIF-1α both at the mRNA and protein levels. We also found that the hypoxia-induced overexpression of VEGF, NDRG1, and HIF-1α was suppressed by digoxin in a concentration-dependent manner. As expected, our EMSA results demonstrated that under hypoxic conditions HIF-1α nuclear translocation was also markedly reduced by digoxin in a concentration-dependent manner. Our results suggest that digoxin downregulated hypoxia-induced overexpression of VEGF and NDRG1 at the transcriptional level probably through the inhibition of HIF-1α synthesis in A549 cells.

Clinical Utility of Amlodipine/Valsartan Fixed-Dose Combination in the Management of Hypertension in Chinese Patients

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Wenbo He, MD

2017-02-01

Full Text Available Amlodipine/valsartan (Aml/Val single-pill combination (SPC therapy has been widely used and studied in clinical practice in recent years. This article reviews the Chinese and English literature on the clinical use of Aml/Val SPC therapy in Chinese hypertensive patients. According to five studies concerning the efficacy and safety of this treatment, Aml/Val SPC therapy was more efficacious than monotherapy with valsartan, amlodipine, or the nifedipine gastrointestinal therapeutic system. This treatment showed greater blood pressure-lowering effects, a higher blood pressure control rate, and a higher response rate. Aml/Val SPC treatment was well tolerated, with adverse event rates similar to those of monotherapy with valsartan or amlodipine and significantly rarer adverse events compared with the nifedipine gastrointestinal therapeutic system. Aml/Val SPC is a highly efficacious and well-tolerated antihypertensive treatment in Chinese hypertensive patients.

[Blood pressure lowering efficacy of telmisartan and amlodipine taking on the morning or at bedtime: ABPM results].

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Peng, Gui-cheng; Wang, Yi-fang; Xiao, Yong; Chen, Jian-fu; Yang, Yu; Ye, Yu-liang; Sai, Shuang-qiao; Huang, Jin-xiang

2013-06-01

To observe the blood lowering effect of telmisartan and amlodipine taking on the morning or at bedtime in hypertensive patients. A total of 108 individuals with hypertension (grade 2 or above) were randomized to receive telmisartan and amlodipine in one of the following four therapeutic schemes: Group A (26 cases): both medications taken on the morning; Group B (28 cases): both medication taken at bedtime; Group C (27 cases): telmisartan on the morning and amlodipine at bedtime; or Group D (27 cases): amlodipine on the morning and telmisartan at bedtime. ABPM was performed before and after 8 weeks treatment. BP was significantly reduced in 4 groups and the value of 24 hours SBP/DBP decline for each group after treatment was 29.94/16.32, 31.37/18.35, 29.49/17.30 and 25.80/15.51 mm Hg (1 mm Hg = 0.133 kPa) respectively (P 0.05). The night-time BP decline and the distributive difference of dipper, non-dipper, extreme dipper and reverse dipper pattern were similar among groups at both baseline and after various treatment regimens (all P > 0.05) . Morning blood pressure surge (MBPS) after treatment in group B declined more significantly than other groups (P < 0.05). Telmisartan/amlodipine administered either on the morning or at bedtime can effectively reduce blood pressure. The efficacy of BP lowering is independent of the drug taking time. There is a trend both in better BP lowering and less BP variability when two medications are administered at bedtime.

Changing characteristics of the TDx digoxin II assay in detecting bufadienolides in a traditional Chinese medicine: for better or worse?

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Panesar, Nirmal S; Chan, Kam W; Law, Lap K

2005-10-01

In 1992, apparent digoxin concentrations determined by the Abbott TDx II assay 5 hours after the ingestion of 10 pills of traditional Chinese medicine containing toad secretions (chan su) by 7 volunteers, yielded results that were equimolar to bufalin measured by 2 in-house bufalin radioimmunoassays (RIAs). Recently, a 17-year-old Chinese female unintentionally took 100 (instead of 10) of these pills for a sore throat but suffered no ill effects. The blood bufalin concentration at 3 hours by 1 of the 2 RIAs was 10.93 nmol/L, which was commensurate with the dose. However, the apparent digoxin measured by a TDx II assay produced in 2004 was only 3.08 nmol/L, which probably reflects the change in the specificity of the polyclonal digoxin antisera used in the assay over the years. In 1989, the TDx assay was commended for its ability to detect poisoning from plant and animal cardenolides, a property that seems to be waning and, thus, bad news for those wishing to use the assay to detect alternative cardenolides. But, on the other hand, it possibly eliminates the "specter" of digoxin-like immunoreactive substance (DLIS) that has afflicted some digoxin assays, which can only be good news.

4-Aminopyridine (fampridine) effectively treats amlodipine poisoning: A case report

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Wilffert, B.; Boskma, R.J.; Van Der Voort, P.H.J.; Uges, D.R.A.; Van Roon, E.N.; Brouwers, J.R.B.J.

2007-01-01

A case of a serious poisoning with the calcium entry blocker amlodipine is described, which was treated effectively with 4-aminopyridine. Calcium is suggested as general treatment of poisoning with calcium entry blockers in many guidelines. The use of intravenous 4-aminopyridine is theoretically

4-Aminopyridine (fampridine) effectively treats amlodipine poisoning : a case report

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Wilffert, B.; Boskma, R. J.; van der Voort, P. H. J.; Uges, D. R. A.; van Roon, E. N.; Brouwers, J. R. B. J.

2007-01-01

A case of a serious poisoning with the calcium entry blocker amlodipine is described, which was treated effectively with 4-aminopyridine. Calcium is suggested as general treatment of poisoning with calcium entry blockers in many guidelines. The use of intravenous 4-aminopyridine is theoretically

Neuroanatomical heterogeneity of essential tremor according to propranolol response.

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Seok Jong Chung

Full Text Available BACKGROUND: Recent studies have suggested that essential tremor (ET is a more complex and heterogeneous clinical entity than initially thought. In the present study, we assessed the pattern of cortical thickness and diffusion tensor white matter (WM changes in patients with ET according to the response to propranolol to explore the pathogenesis underlying the clinical heterogeneity of ET. METHODS: A total of 32 patients with drug naive ET were recruited prospectively from the Movement Disorders outpatient clinic. The patients were divided into a propranolol-responder group (n = 18 and a non-responder group (n = 14. We analyzed the pattern of cortical thickness and diffusion tensor WM changes between these two groups and performed correlation analysis between imaging and clinical parameters. RESULTS: There were no significant differences in demographic characteristics, general cognition, or results of detailed neuropsychological tests between the groups. The non-responder group showed more severe cortical atrophy in the left orbitofrontal cortex and right temporal cortex relative to responders. However, the responders exhibited significantly lower fractional anisotropy values in the bilateral frontal, corpus callosal, and right parietotemporal WM compared with the non-responder group. There were no significant clusters where the cortical thickness or WM alterations were significantly correlated with initial tremor severity or disease duration. CONCLUSIONS: The present data suggest that patients with ET have heterogeneous cortical thinning and WM alteration with respect to responsiveness to propranolol, suggesting that propranolol responsiveness may be a predictive factor to determine ET subtypes in terms of neuroanatomical heterogeneity.

Digoxin derivatives with selectivity for the α2β3 isoform of Na,K-ATPase potently reduce intraocular pressure.

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Katz, Adriana; Tal, Daniel M; Heller, Dan; Habeck, Michael; Ben Zeev, Efrat; Rabah, Bilal; Bar Kana, Yaniv; Marcovich, Arie L; Karlish, Steven J D

2015-11-03

The ciliary epithelium in the eye consists of pigmented epithelial cells that express the α1β1 isoform of Na,K-ATPase and nonpigmented epithelial cells that express mainly the α2β3 isoform. In principle, a Na,K-ATPase inhibitor with selectivity for α2β3 that penetrates the cornea could effectively reduce intraocular pressure, with minimal systemic or local toxicity. We have recently synthesized perhydro-1,4-oxazepine derivatives of digoxin by NaIO4 oxidation of the third digitoxose and reductive amination with various R-NH2 substituents and identified derivatives with significant selectivity for human α2β1 over α1β1 (up to 7.5-fold). When applied topically, the most α2-selective derivatives effectively prevented or reversed pharmacologically raised intraocular pressure in rabbits. A recent structure of Na,K-ATPase, with bound digoxin, shows the third digitoxose approaching one residue in the β1 subunit, Gln84, suggesting a role for β in digoxin binding. Gln84 in β1 is replaced by Val88 in β3. Assuming that alkyl substituents might interact with β3Val88, we synthesized perhydro-1,4-oxazepine derivatives of digoxin with diverse alkyl substituents. The methylcyclopropyl and cyclobutyl derivatives are strongly selective for α2β3 over α1β1 (22-33-fold respectively), as determined either with purified human isoform proteins or intact bovine nonpigmented epithelium cells. When applied topically on rabbit eyes, these derivatives potently reduce both pharmacologically raised and basal intraocular pressure. The cyclobutyl derivative is more efficient than Latanoprost, the most widely used glaucoma drug. Thus, the conclusion is that α2β3-selective digoxin derivatives effectively penetrate the cornea and inhibit the Na,K-ATPase, hence reducing aqueous humor production. The new digoxin derivatives may have potential for glaucoma drug therapy.

Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery

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M.J.C. Carmona

2005-05-01

Full Text Available The pharmacokinetics of propranolol may be altered by hypothermic cardiopulmonary bypass (CPB, resulting in unpredictable postoperative hemodynamic responses to usual doses. The objective of the present study was to investigate the pharmacokinetics of propranolol in patients undergoing coronary artery bypass grafting (CABG by CPB under moderate hypothermia. We evaluated 11 patients, 4 women and 7 men (mean age 57 ± 8 years, mean weight 75.4 ± 11.9 kg and mean body surface area 1.83 ± 0.19 m², receiving propranolol before surgery (80-240 mg a day and postoperatively (10 mg a day. Plasma propranolol levels were measured before and after CPB by high-performance liquid chromatography. Pharmacokinetic Solutions 2.0 software was used to estimate the pharmacokinetic parameters after administration of the drug pre- and postoperatively. There was an increase of biological half-life from 4.5 (95% CI = 3.9-6.9 to 10.6 h (95% CI = 8.2-14.7; P < 0.01 and an increase in volume of distribution from 4.9 (95% CI = 3.2-14.3 to 8.3 l/kg (95% CI = 6.5-32.1; P < 0.05, while total clearance remained unchanged 9.2 (95% CI = 7.7-24.6 vs 10.7 ml min-1 kg-1 (95% CI = 7.7-26.6; NS after surgery. In conclusion, increases in drug distribution could be explained in part by hemodilution during CPB. On the other hand, the increase of biological half-life can be attributed to changes in hepatic metabolism induced by CPB under moderate hypothermia. These alterations in the pharmacokinetics of propranolol after CABG with hypothermic CPB might induce a greater myocardial depression in response to propranolol than would be expected with an equivalent dose during the postoperative period.

Potentiation of Morphine-Induced Antinociception by Propranolol: The Involvement of Dopamine and GABA Systems

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Elham A. Afify

2017-11-01

Full Text Available Tolerance to the analgesic effect of morphine is a major clinical problem which can be managed by co-administration of another drug. This study investigated the ability of propranolol to potentiate the antinociceptive action of morphine and the possible mechanisms underlying this effect. Antinociception was assessed in three nociceptive tests (thermal, hot plate, (visceral, acetic acid, and (inflammatory, formalin test in mice and quantified by measuring the percent maximum possible effect, the percent inhibition of acetic acid-evoked writhing response, and the area under the curve values of number of flinches for treated mice, respectively. The study revealed that propranolol (0.25–20 mg/Kg, IP administration did not produce analgesia in mice. However, 10 mg/Kg propranolol, enhanced the antinociceptive effect of sub-analgesic doses of morphine (0.2, 1, and 2 mg/Kg, IP in the three nociceptive tests. It also shifted the dose response curve of morphine to the left. The combined effect of propranolol and morphine was attenuated by haloperidol (D2 receptor antagonist, 1.5 mg/Kg, IP, and bicuculline (GABAA receptor antagonist, 2 mg/Kg, IP. Repeated daily administration of propranolol (10 mg/Kg, IP did not alter the nociceptive responses in the three pain tests, but it significantly potentiated morphine-induced antinociception in the hot plate, acetic acid-evoked writhing, and in the second phase of formalin tests. Together, the data suggest that a cross-talk exists between the opioidergic and adrenergic systems and implicate dopamine and GABA systems in this synergistic effect of morphine-propranolol combination. Propranolol may serve as an adjuvant therapy to potentiate the effect of opioid analgesics.

Atorvastatin calcium plus amlodipine for the treatment of hypertension.

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Delgado-Montero, Antonia; Zamorano, Jose L

2012-12-01

Hypertension (HTN) and dyslipemia (DYL) are two of the major modifiable cardiovascular (CV) risk factors, determinants in the development of cerebrovascular and coronary heart disease (CHD). Many patients have both risk factors which increase their total CV risk compared with patients with only one risk factor. Treatment guideline recommendations are poorly implemented in real practice, in part due to numerous and complicated drug regimes which hamper patient´s adherence. In this article the authors describe the first combined fixed-dose pill of an antihypertensive and a lipid-lowering agent, the single-pill combination of amlodipine besylate and atorvastatin calcium (SPAA). They summarize the pharmacokinetic and pharmacodynamic properties of both compounds and the main randomized clinical studies, as well as real-world observational studies, made with the new combined formulation. The use of the single-pill amlodipine and atorvastatin is an adequate option for the clinician to treat hypertensive patients with DYL or high CV risk burden, with proven efficacy, tolerability, cost-effectiveness, and the advantage of improving patient treatment compliance.

Propranolol modulates the collateral vascular responsiveness to vasopressin via a G(α)-mediated pathway in portal hypertensive rats.

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Lee, Jing-Yi; Huo, Teh-Ia; Huang, Hui-Chun; Lee, Fa-Yauh; Lin, Han-Chieh; Chuang, Chiao-Lin; Chang, Ching-Chih; Wang, Sun-Sang; Lee, Shou-Dong

2011-12-01

Gastro-oesophageal variceal haemorrhage is one of the most dreadful complications of portal hypertension and can be controlled with vasoconstrictors. Nevertheless, sympathetic tone abnormality and vascular hyporesponsiveness in portal hypertension may impede the haemostatic effects of vasoconstrictors. Propranolol, a β-blocker binding the G-protein-coupled adrenoceptor, is a portal hypotensive agent. However, whether propranolol influences the collateral vasoresponse is unknown. Portal hypertension was induced by PVL (portal vein ligation) in Sprague-Dawley rats. In an acute study with an in situ perfusion model, the collateral responsiveness to AVP (arginine vasopressin) was evaluated with vehicle, propranolol (10 μmol/l), propranolol plus suramin (100 μmol/l, a G(α) inhibitor) or suramin pre-incubation. G(α) mRNA expression in the splenorenal shunt, the most prominent intra-abdominal collateral vessel, was measured. In the chronic study, rats received DW (distilled water) or propranolol (10 mg x kg(-1) of body weight x day(-1)) for 9 days. Then the concentration-response relationship of AVP and G(α) mRNA expression were assessed. Propranolol pre-incubation elevated the perfusion pressure changes of collaterals in response to AVP, which was inhibited by suramin. The splenorenal shunt G(αq) and G(α11) mRNA expression were enhanced by propranolol. The group treated with propranolol plus suramin had a down-regulation of G(α11) as compared with the propranolol group. Chronic propranolol treatment reduced mean arterial pressure, PP (portal pressure) and the perfusion pressure changes of collaterals to AVP. G(αs) expression was up-regulated. In conclusion, propranolol pre-incubation enhanced the portal-systemic collateral AVP responsiveness in portal hypertensive rats, which was related to G(αq) and G(α11) up-regulation. In contrast, the attenuated AVP responsiveness by chronic propranolol treatment was related to G(αs) up-regulation. The G(α) signalling

Effect of amlodipine, lisinopril and allopurinol on acetaminophen-induced hepatotoxicity in rats

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Nesreen E.M. Mohammed

2016-11-01

Conclusion: Amlodipine, lisinopril or allopurinol can protect against acetaminophen-induced hepatotoxicity, showing mechanistic roles of calcium channels, angiotensin converting enzyme and xanthine oxidase enzyme in the pathogenesis of hepatotoxicity induced by acetaminophen.

Amlodipine and valsartan as components of a rational and effective fixed-dose combination

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Bernard Waeber

2009-03-01

Full Text Available Bernard Waeber1, Luis M Ruilope21Division of Clinical Pathophysiology, University Hospital, Faculty of Biology and Medicine, University of Lausanne, Switzerland; 2Hypertension Unit, Hospital 12 de Octubre, Madrid, SpainAbstract: Pharmacological treatment of hypertension is effective in preventing cardiovascular and renal complications. Calcium antagonists and blockers of the renin-angiotensin system are widely used today to initiate antihypertensive therapy but, when given as monotherapy, do not suffice in most patients to normalize blood pressure. Combining the two types of agents considerably increases the antihypertensive efficacy, but not at the expense of a deterioration of tolerability. This is exemplified by the experience accumulated with the recently developed fixed dose combination containing the AT1-receptor blocker valsartan (160 mg and the dihydropyridine amlodipine (5 or 10 mg. In a randomized trial, an 8-week treatment normalized blood pressure (<140/90 mmHg within 8 weeks in a large fraction of hypertensive patients (78.4% and 85.2% using the 5/160 [n = 371] and 10/160 mg [n = 377] dosage, respectively. Like all AT1-receptor blockers valsartan has a placebo-like tolerability. Valsartan prevents to a large extent the occurrence amlodipine-induced peripheral edema. Both amlodipine and valsartan have beneficial effects on cardiovascular morbidity and mortality, as well as protective effects on renal function. The co-administration of these two agents is therefore very attractive, as it enables a rapid and sustained blood pressure control in hypertensive patients. The availability of a fixed-dose combination based on amlodipine and valsartan is expected therefore to facilitate the management of hypertension, to improve long-term adherence with antihypertensive therapy and, ultimately, to have a positive impact on cardiovascular and renal outcomes.Keywords: antihypertensive therapy, fixed-dose combination, calcium antagonists

Beneficial effect of low dose Amlodipine vs Nifedipine on serum cholesterol profile of rabbits receiving standard diet.

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Bavane DS, Rajesh CS, Gurudatta Moharir, Bharatha Ambadasu

2013-01-01

Full Text Available To investigate the effect of low dose amlodipine v/s nifedipine on serum cholesterol profile of rabbits receiving standard diet. Methods: Fourty Newzealand rabbits were selected for the study. Their cholesterol profile was estimated at the beginning of the study. Rabbits were grouped into 4 groups receiving standard diet (control group, standard diet + vehicle propylene glycol, standard diet + nifedipine dissolved in propylene glycol and standard diet + amlodipine dissolved in propylene glycol. Along with standard diet they were treated with respective drugs for ten weeks. At the end of ten weeks serum cholesterol profile was estimated. Results: The cholesterol profile was estimated at the beginning and at the end of ten weeks. Total cholesterol in the amlodipine group decreased from 97±4.06 mg/dl to 90±4.2 mg/dl and HDL-Cholesterol increased from 32.01±4.40 mg/dl to 37±4.60 mg/dl after 10 week treatment but these changes were not significant. LDL cholesterol decreased significantly in rabbits with low dose of amlodipine from 55.42±3.32 mg/dl to 32.40±3.22 mg/dl and. In the nifedipine group there was a slight increase in total cholesterol from 102.49±5.16 mg/dl to 106±5.39 mg/dl, HDL cholesterol from 34.10±2.80 to 35.16±2.82 mg/dl and LDL cholesterol also increased from 56.20±2.20 mg/dl to 59.00±2.20 mg/dl after 10 week treatment. Conclusion: The study shows amlodipine produces favorable alterations in serum cholesterol profile

Successful use of digoxin-specific immune Fab in the treatment of severe Nerium oleander toxicosis in a dog.

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Pao-Franco, Amaris; Hammond, Tara N; Weatherton, Linda K; DeClementi, Camille; Forney, Scott D

2017-09-01

To describe a case in which digoxin-specific immune Fab was used successfully in a dog with severe oleander toxicosis secondary to ingesting plant material. A 6-year-old intact female Rhodesian Ridgeback mixed breed dog was presented for severe oleander toxicosis and was refractory to all antiarrhythmic therapies and supportive care. Digoxin-specific immune Fab was successful in treating this dog. The dog recovered but suffered ischemic injuries, the long-term effects of which are unknown. This report describes the successful use of digoxin-specific immune Fab in the treatment of oleander toxicosis in a dog, which has not previously been published in veterinary literature. Oleander poisoning can be associated with permanent cardiac arrhythmias due to the ischemic damage. © Veterinary Emergency and Critical Care Society 2017.

The significance of amlodipine on autonomic nervous system adjustment (ANSA method: A new approach in the treatment of hypertension

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Milovanović Branislav

2009-01-01

Full Text Available Introduction. Cardiovascular autonomic modulation is altered in patients with essential hypertension. Objective To evaluate acute and long-term effects of amlodipine on cardiovascular autonomic function and haemodynamic status in patients with mild essential hypertension. Methods. Ninety patients (43 male, mean age 52.12 ±10.7 years with mild hypertension were tested before, 30 minutes after the first 5 mg oral dose of amlodipine and three weeks after monotherapy with amlodipine. A comprehensive study protocol was done including finger blood pressure variability (BPV and heart rate variability (HRV beat-to-beat analysis with impedance cardiography, ECG with software short-term HRV and nonlinear analysis, 24-hour Holter ECG monitoring with QT and HRV analysis, 24-hour blood pressure (BP monitoring with systolic and diastolic BPV analysis, cardiovascular autonomic reflex tests, cold pressure test, mental stress test. The patients were also divided into sympathetic and parasympathetic groups, depending on predominance in short time spectral analysis of sympathovagal balance according to low frequency and high frequency values. Results. We confirmed a significant systolic and diastolic BP reduction, and a reduction of pulse pressure during day, night and early morning hours. The reduction of supraventricular and ventricular ectopic beats during the night was also achieved with therapy, but without statistical significance. The increment of sympathetic activity in early phase of amlodipine therapy was without statistical significance and persistence of sympathetic predominance after a few weeks of therapy detected based on the results of short-term spectral HRV analysis. All time domain parameters of long-term HRV analysis were decreased and low frequency amongst spectral parameters. Amlodipne reduced baroreflex sensitivity after three weeks of therapy, but increased it immediately after the administration of the first dose. Conclusion. The results

Simultaneous determination of telmisartan and amlodipine in dog plasma by LC-MS-MS.

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Wang, Baolian; Sheng, Li; Li, Yan

2015-01-01

A simple, rapid and sensitive method was established for the simultaneous determination of telmisartan and amlodipine in dog plasma by a HPLC-MS-MS analysis. The plasma sample preparation was a simple deproteinization by the addition of three volumes of methanol/acetonitrile mixture followed by centrifugation. The analytes and internal standard diphenhydramine were separated on a Zorbax SB-C18 column with a mobile phase of acetonitrile : water (45 : 55, v/v) at a flow rate of 0.2 mL/min with an operating temperature of 25°C. Detection was carried out by electrospray ionization in positive-ion multiple reaction monitoring mode. The calibration plots in dog plasma were linear over the ranges of 0.5-2,000 ng/mL for telmisartan and 0.5-500 ng/mL for amlodipine. The lower limit of quantification was 0.5 ng/mL for two analytes. The intra- and interday precisions (RSD%) were within 9.0%. The average recoveries of analytes were >85.0%. The method was successfully applied to the pharmacokinetic study of the two compounds after oral administration of telmisartan-amlodipine combination preparation to dogs. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Is Time an Important Problem in Management of Hypertension and Hypercholesterolemia by Using an Amlodipine-Atorvastatin Single Pill Combination?

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Zeng, Rui; Wang, Mian; Zhang, Li

2016-07-26

BACKGROUND Is the timing of dosing for amlodipine and atorvastatin important with regard to therapeutic efficacy? To answer this question, we designed an outpatient, practice-based, case-control study lasting 8 weeks. MATERIAL AND METHODS Two hundred patients were divided into 2 groups: in Group I, patients were provided with a single pill containing amlodipine/atorvastatin (5/20 mg) to be taken each night at 10 pm, and in Group II, patients were taking amlodipine (5 mg) and atorvastatin (20 mg) each morning at 7 am. RESULTS Our results indicated no obvious difference in blood pressure control between the 2 groups. Taking amlodipine at night not only lowered blood pressure, but it also provided better control during the peak blood pressure in the morning. Hypercholesterolemia control in the 2 groups was also not significantly different, taking atorvastatin in the morning was as effective as dosing at night in patients with hypercholesterolemia. While the carotid IMT, hs-CRP, and LVMI were significantly lower after treatment, no differences were found between the 2 groups. Although no obvious difference was found in adverse drug reactions between the 2 groups, compliance was much better in the single-pill group than in patients taking the 2 medications separately. CONCLUSIONS In conclusion, single-pill amlodipine-atorvastatin taken at night can lower blood pressure and reduce the morning peak blood pressure levels the next day. Additionally, this dosing method could improve patient adherence to the therapy.

Hypothalamic digoxin and hemispheric chemical dominance--relation to the pathogenesis of senile osteoporosis, degenerative osteoarthritis, and spondylosis.

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Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-03-01

The isoprenoid pathway produces three key metabolites: i) digoxin (a membrane sodium-potassium ATPase inhibitor which can regulate intracellular calcium/magnesium ratios), ii) dolichol (which regulates N-glycosylation of proteins), and iii) ubiquinone (a free radical scavenger), all of which are important in bone and joint metabolism. The pathway was assessed in senile osteoporosis, spondylosis, and osteoarthritis. Digoxin could possibly play a role in the genesis of cerebral dominance because it can regulate multiple neurotransmitter systems. The pathway was also assessed in individuals of differing hemispheric dominance for comparison and to find out the role of cerebral dominance in the pathogenesis of these diseases. The plasma/serum-activity of HMG CoA reductase, magnesium, digoxin, dolichol, ubiquinone, and tryptophan/tyrosine catabolic patterns, as well as RBC Na(+)-K+ ATPase activity, were measured in the above mentioned groups. The glycoconjugate metabolism, free radical metabolism, and membrane composition were also studied. The pathway was upregulated with increased digoxin synthesis in patients with spondylosis and osteoarthritis. In this group of patients, the glycoconjugate levels and dolichol levels were increased and lysosomal stability reduced. The ubiquinone levels were low and free radicals increased in spondylosis and osteoarthritis. On the other hand, in senile osteoporosis, the isoprenoid pathway was downregulated and digoxin synthesis reduced. The glycoconjugate and dolichol levels were low and lysosomal stability increased. The ubiquinone levels were increased and free radical production increased in senile osteoporosis. The significance of these changes in the pathogenesis of osteoarthritis, spondylosis, and osteoporosis is discussed. The hyperdigoxinemic state is seen in osteoarthritis and spondylosis and in right hemispheric dominance. The hypodigoxinemic state is seen in left hemispheric dominance and senile osteoporosis. Hemispheric

Effects of intravenous propranolol on heat pain sensitivity in healthy men.

Science.gov (United States)

Schweinhardt, P; Abulhasan, Y B; Koeva, V; Balderi, T; Kim, D J; Alhujairi, M; Carli, F

2013-05-01

Clinical studies have shown opioid-sparing effects of β-adrenergic antagonists perioperatively and β-blockers are being investigated for chronic musculoskeletal pain. However, the direct analgesic effects of β-blockers have rarely been examined in healthy humans. In a randomized, counter-balanced, double-blind, within-subject crossover design, we tested the effect of the lipophilic β-blocker propranolol (0.035 mg/kg body weight i.v.) on heat pain sensitivity in 39 healthy males, compared with placebo. To test for peripheral versus central effects, the peripherally acting β-blocker sotalol was also examined. Experimental stimuli were brief superficial noxious heat stimuli applied to the volar forearm. Non-painful cold stimuli were included to test for specificity. Sedation, mood and anxiety were assessed to investigate potential mechanisms underlying any analgesic effect. β-blocker effects on blood pressure were incorporated into the analysis because of a known inverse relationship between pain sensitivity and systolic blood pressure. Propranolol significantly decreased perceived intensity of heat pain stimuli but only in participants with small propranolol-induced blood pressure decreases. Even in this group, the effect was small (4%). Propranolol did not influence perceived intensity of non-noxious stimuli and had no effect on sedation, anxiety or mood. Sotalol did not influence heat pain sensitivity. Propranolol decreased pain sensitivity but its analgesic effects were small and counteracted by blood pressure decreases. The analgesic effects were not mediated by peripheral β-receptor blockade, sedation, mood or anxiety. The small effect indicates that the utility of β-blockers for clinical pain must be related to factors that do not play a significant role for experimental pain. © 2012 European Federation of International Association for the Study of Pain Chapters.

Efficacy and duration of benazepril plus amlodipine or hydrochlorothiazide on 24-hour ambulatory systolic blood pressure control.

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Jamerson, Kenneth A; Devereux, Richard; Bakris, George L; Dahlöf, Björn; Pitt, Bertram; Velazquez, Eric J; Weir, Matthew; Kelly, Roxzana Y; Hua, Tsushung A; Hester, Allen; Weber, Michael A

2011-02-01

The combination of benazepril plus amlodipine was shown to be more effective than benazepril plus hydrochlorothiazide in reducing cardiovascular events in the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial. There was a small difference in clinic systolic blood pressure between the treatment arms favoring benazepril plus amlodipine. Ambulatory blood pressure monitoring provides a more rigorous estimate of blood pressure effects. A subset of 573 subjects underwent ambulatory blood pressure monitoring during year 2. Readings were obtained every 20 minutes during a 24-hour period. Between-treatment differences (benazepril plus amlodipine versus benazepril plus hydrochlorothiazide) in mean values were analyzed using ANOVA. Treatment comparisons with respect to categorical variables were made using Pearson's χ². At year 2, the treatment groups did not differ significantly in 24-hour mean daytime or nighttime blood pressures (values of 123.9, 125.9, and 118.1 mm Hg for benazepril plus amlodipine group versus 122.3, 124.1, and 116.9 for the benazepril plus hydrochlorothiazide group), with mean between-group differences of 1.6, 1.8, and 1.2 mm Hg, respectively. Blood pressure control rates (24-hour mean systolic blood pressure <130 mm Hg on ambulatory blood pressure monitoring) were greater than 80% in both groups. Nighttime systolic blood pressure provided additional risk prediction after adjusting for the effects of drugs. The 24-hour blood pressure control was similar in both treatment arms, supporting the interpretation that the difference in cardiovascular outcomes favoring a renin angiotensin system blocker combined with amlodipine rather than hydrochlorothiazide shown in the ACCOMPLISH trial was not caused by differences in blood pressure, but instead intrinsic properties (metabolic or hemodynamic) of the combination therapies.

Effects of Propranolol on the Left Ventricular Volume of Normal Subjects During CT Coronary Angiography

International Nuclear Information System (INIS)

Mo, Yuan Heng; Jaw, Fu Shan; Wang, Yung Cheng; Jeng, Chin Ming; Peng, Shinn Forng

2011-01-01

The purpose of this study is to determine the effects of propranolol on the left ventricular (LV) volume during CT coronary angiography. The LV volume of 252 normal Chinese subjects (126 subjects with propranolol medication and 126 age- and gender-matched Chinese subjects without medication) was estimated using 64 slices multi-detector CT (MDCT). The heart rate difference was analyzed by the logistic linear regression model with variables that included gender, age, body height, body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP) and the dosage of propranolol. The following global LV functional parameters were calculated: the real-end diastolic volume (EDV), the real-end systolic volume (ESV) and the real-ejection fraction (EF). The female subjects had a greater decrease of heart rate after taking propranolol. The difference of heart rate was negatively correlated with the dosage of propranolol. The real-EDV, the real-ESV and the real-EF ranged from 48.1 to 109 mL/m2, 6.1 to 57.1 mL/m2 and 41% to 88%, respectively. There was no significant difference in the SBP and DBP between the groups without and with propranolol medication (123 ± 17 and 80 ± 10 mmHg; 120 ± 14 and 80 ± 11 mmHg, respectively). The real-EDV showed no significant difference between these two groups, but the real-ESV and real-EF showed significant differences between these two groups (69.4 ± 9.3 and 70.6 ± 8.9 mL/m2; 23.5 ± 5.7 and 25.6 ± 3.7 mL/m2, 66.5 ± 5.1% and 63.5 ± 4.6%, respectively). The difference of heart rate is significantly influenced by gender and the dosage of propranolol. Propranolol will also increase the ESV, which contributes to a decreased EF, while the SBP, DBP and EDV are not statistically changed.

Influence of preoperative propranolol on cardiac index during the anhepatic phase of liver transplantation

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Emerson Seiberlich

2015-06-01

Full Text Available INTRODUCTION: Liver transplantation is the best therapeutic option for end-stage liver disease. Non-selective beta-blocker medications such as propranolol act directly on the cardiovascular system and are often used in the prevention of gastrointestinal bleeding resulting from HP. The effects of propranolol on cardiovascular system of cirrhotic patients during liver transplantation are not known. OBJECTIVE: Evaluate the influence of propranolol used preoperatively on cardiac index during the anhepatic phase of liver transplantation. METHOD: 101 adult patients (73 male [72.2%] who underwent cadaveric donor orthotopic liver transplantation by piggyback technique with preservation of the retrohepatic inferior vena cava performed at Hospital das Clinicas, Federal University of Minas Gerais were evaluated. There was no difference in severity between groups by the MELD system, p = 0.70. The preoperative use of propranolol and the cardiac index outcome were compared during the anhepatic phase of liver transplantation in 5 groups (I: increased cardiac index, II: cardiac index reduction lower than 16%, III: cardiac index reduction equal to or greater than 16% and less than 31%, IV: cardiac index reduction equal to or greater than 31% and less than 46%, V: cardiac index reduction equal to or greater than 46%. RESULTS: Patients in group I (46.4% who received propranolol preoperatively were statistically similar to groups II (60%, III (72.7%, IV (50% and V (30.8%, p = 0.57. CONCLUSION: The use of propranolol before transplantation as prophylaxis for gastrointestinal bleeding may be considered safe, as it was not associated with worsening of cardiac index in anhepatic phase of liver transplantation.

21-Benzylidene Digoxin: A Proapoptotic Cardenolide of Cancer Cells That Up-Regulates Na,K-ATPase and Epithelial Tight Junctions

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Rocha, Sayonarah C.; Pessoa, Marco T. C.; Neves, Luiza D. R.; Alves, Silmara L. G.; Silva, Luciana M.; Santos, Herica L.; Oliveira, Soraya M. F.; Taranto, Alex G.; Comar, Moacyr; Gomes, Isabella V.; Santos, Fabio V.; Paixão, Natasha; Quintas, Luis E. M.; Noël, François; Pereira, Antonio F.; Tessis, Ana C. S. C.; Gomes, Natalia L. S.; Moreira, Otacilio C.; Rincon-Heredia, Ruth; Varotti, Fernando P.; Blanco, Gustavo; Villar, Jose A. F. P.; Contreras, Rubén G.; Barbosa, Leandro A.

2014-01-01

Cardiotonic steroids are used to treat heart failure and arrhythmia and have promising anticancer effects. The prototypic cardiotonic steroid ouabain may also be a hormone that modulates epithelial cell adhesion. Cardiotonic steroids consist of a steroid nucleus and a lactone ring, and their biological effects depend on the binding to their receptor, Na,K-ATPase, through which, they inhibit Na+ and K+ ion transport and activate of several intracellular signaling pathways. In this study, we added a styrene group to the lactone ring of the cardiotonic steroid digoxin, to obtain 21-benzylidene digoxin (21-BD), and investigated the effects of this synthetic cardiotonic steroid in different cell models. Molecular modeling indicates that 21-BD binds to its target Na,K-ATPase with low affinity, adopting a different pharmacophoric conformation when bound to its receptor than digoxin. Accordingly, 21-DB, at relatively high µM amounts inhibits the activity of Na,K-ATPase α1, but not α2 and α3 isoforms. In addition, 21-BD targets other proteins outside the Na,K-ATPase, inhibiting the multidrug exporter Pdr5p. When used on whole cells at low µM concentrations, 21-BD produces several effects, including: 1) up-regulation of Na,K-ATPase expression and activity in HeLa and RKO cancer cells, which is not found for digoxin, 2) cell specific changes in cell viability, reducing it in HeLa and RKO cancer cells, but increasing it in normal epithelial MDCK cells, which is different from the response to digoxin, and 3) changes in cell-cell interaction, altering the molecular composition of tight junctions and elevating transepithelial electrical resistance of MDCK monolayers, an effect previously found for ouabain. These results indicate that modification of the lactone ring of digoxin provides new properties to the compound, and shows that the structural change introduced could be used for the design of cardiotonic steroid with novel functions. PMID:25290152

Reduction of cerebral injury in stroke-prone spontaneously hypertensive rats by amlodipine

NARCIS (Netherlands)

Blezer, E.L.A.; Nicolaij, K.; Goldschmeding, R.C.; Koomans, H.A.; Joles, Jaap

2002-01-01

Dihydropyridine Ca2+ channel antagonists, initiated together with high salt intake, prevent the development of hypertension and subsequent cerebral damage in stroke-prone spontaneously hypertensive rats (SHRSP). We hypothesized that the dihydropyridine Ca2+ channel antagonist amlodipine

Zumbido pulsátil: tratamento com clonazepan e propranolol Pulsatile tinnitus: treatment with clonazepam and propranolol

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Sergio Albertino

2005-02-01

Full Text Available O zumbido pulsátil sincrônico com os batimentos cardíacos é pouco freqüente, sendo de etiologia tanto vascular arterial (malformações, fístulas artério-venosas ou venosa (anormalidades do bulbo jugular, tumor glômico jugular ou timpânico. A identificação precoce da etiologia é essencial para que a terapêutica adequada possa ser instituída. A angioressonância possibilita a identificação de alterações vasculares com maior precisão. Relatamos um caso onde, após o diagnóstico de uma alteração vascular arterial, foi instituído o tratamento com propranolol e clonazepam, com melhora da sintomatologia.Pulsatile tinnitus synchronous with heartbeat is rare and normally has vascular origin: arterial (malformation, arterial anatomical variation or venous (aberrant jugular bulb, glomus tumors, tympanic glomus tumor. Early etiology identification is essential for appropriate treatment to be established. Magnetic angioresonance makes the vascular identification possible and precise. We report a case of arterial anatomical variation in which the treatment was propranolol and clonazepam, showing tinnitus improvement.

Long-term effects of oral propranolol on splanchnic and systemic haemodynamics in patients with cirrhosis and oesophageal varices

DEFF Research Database (Denmark)

Bendtsen, F; Henriksen, Jens Henrik Sahl; Sørensen, T I

1991-01-01

1 year of treatment with propranolol, whereas a decrease in azygos blood flow was observed only in the propranolol group. The beneficial effect of propranolol on the risk of bleeding from oesophageal varices may, therefore, mostly be due to a selective decrease in collateral blood flow and thereby...

Plasma digoxin concentrations and urinary excretion during a 'simpler' regimen of infant digitalization.

Science.gov (United States)

Savage, M O; Hibble, A G; Pickering, D

1975-01-01

We have measured the plasma concentrations in sick neonates and infants being administered digoxin by a safer regimen. In the presence of normal renal function the plasma concentrations appear to be satisfactory. PMID:1103751

Therapeutic drug monitoring of amlodipine and the Z-FHL/HHL ratio ...

African Journals Online (AJOL)

Globally, high blood pressure (BP) is the leading single risk factor for ... concentrations and clinical effect or toxicity and those with a narrow therapeutic ..... The pharmacokinetics of amlodipine in healthy volunteers after. 120 ... revealed by high-performance liquid chromatography-tandem mass spectrometry (HP LC-MS/MS).

Three-compartmental analysis of effects of D-propranolol on thyroid hormone kinetics

International Nuclear Information System (INIS)

Van Der Heijden, J.T.M.; Krenning, E.P.; Van Toor, H.; Hennemann, G.; Docter, R.

1988-01-01

Tracer thyroxine (T 4 ), 3,3',5-triiodothyronine (T 3 ), and 3,3',5'-triiodothyronine (rT 3 ) kinetic studies were performed in normal T 4 substituted subjects before and during oral D-propranolol treatment to determine whether changes in thyroid hormone metabolism in a propranolol-induced low-T 3 syndrome result from inhibition of 5'-deiodination or inhibition of transport of iodothyronines into tissues. Data were analyzed according to a three-compartmental model of distribution and metabolism. No changes were observed in size of the three T 4 compartments or in fractional and mass transfer rates of T 4 from plasma to the rapidly (REP) and slowly (SEP) equilibrating pools. Serum T 3 , free T 3 , T 3 plasma pool, T 3 mass transfer rate to REP and SEP, and the T 3 pool masses were all significantly decreased during propranolol to a similar extent as the T 3 plasma production rate (PR). It is concluded that the D-propranolol-induced changes in thyroid hormone metabolism, resulting in a low-T 3 syndrome, are due to inhibition of thyroid hormone deiodination. This is in contrast to the low-T 3 syndrome during caloric deprivation, which results from inhibition of transport of iodothyronines into the liver

Role of triple fixed combination valsartan, amlodipine and hydrochlorothiazide in controlling blood pressure

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Monica Doménech

2010-04-01

Full Text Available Monica Doménech, Antonio CocaHypertension Unit, Department of Internal Medicine, Institute of Internal Medicine and Dermatology, Hospital Clinic (IDIBAPS, University of Barcelona, SpainAbstract: Hypertension is one of the main risk factors for the development of cardiovascular diseases and the search for new therapeutic strategies aimed at optimizing its control remains an ongoing research and clinical challenge. In recent years, there has been a marked increase in the use of combinations of antihypertensive drugs with complementary mechanisms of action, with the aims of reducing blood pressure levels more rapidly and vigorously than strategies employing monotherapy and improving treatment compliance and adhesion. Therefore, as recommended by the 2009 reappraisal of the European Society of Hypertension/European Society of Cardiology Guidelines, the use of a triple combination that combines a calcium channel blocker, an angiotensin II receptor blocker and a thiazide diuretic seems a reasonable and efficacious combination for the management of hypertensive patients with moderate, high or very high risk. This article reviews the clinical trials carried out with the fixed combination of amlodipine/valsartan/hydrochlorothiazide at the doses recommended for each drug in monotherapy. The data show that this combination achieved greater reductions in mean sitting diastolic and systolic blood pressure than amlodipine, valsartan or hydrochlorothiazide in monotherapy, with favorable pharmacodynamic and pharmacokinetic profiles. The triple combination at high single doses should be used with caution in elderly patients and those with renal or liver failure. Although the tolerability and safety of the triple combination are good, the mostfrequently reported adverse effects were peripheral edema, headache and dizziness. Analytical alterations were consistent with the already-known biochemical effects of amlodipine, valsartan or hydrochlorothiazide in

A novel method for radioimmunoassay and its application to the assay of digoxin

International Nuclear Information System (INIS)

Lader, S.R.

1977-01-01

A novel radioimmunoassay method has been developed for digoxin which eliminates the need for centrifugation while retaining a short incubation time at ambient temperature. The apparatus used consists of a plastic reaction chamber containing a pad of absorbent material impregnated with solid phase antibody. A mixture of tracer and standard (or tracer and sample) is pipetted onto the antibody-containing pad and at the end of the thirty minute incubation period radioactivity remaining unbound to antibody is drawn through the pad into an absorbent filter by capillary attraction. The specificity, sensitivity, precision and accuracy of the method are described. Clinical evaluation of the method has been carried out in two laboratories in the United Kingdom and four in the United States of America. The consistency of performance of the new digoxin method as judged by precision and accuracy were quite striking compared with the wide variation in performance of routine in-house methods. Thus, results for between assay reproducibility show that C.V.'s for the novel method ranged from 9.6% to 15.5% while those for the routine assays ranged from 7% to 27,8%. The recovery of digoxin added to serum varied from 85% to 117% for the new method and from 88% to 164% with in-house methods. In a total of 640 clinical samples the results compared well with those obtained with established in-house procedures. (orig.) [de

Effects of hypertension and ovariectomy on rat hepatocytes. Are amlodipine and lacidipine protective? (A stereological and histological study).

Science.gov (United States)

Dursun, Hakan; Albayrak, Fatih; Uyanik, Abdullah; Keleş, Nuri Osman; Beyzagül, Polat; Bayram, Ednan; Halici, Zekai; Altunkaynak, Zuhal Berrin; Süleyman, Halis; Okçu, Nihat; Ünal, Bünyamin

2010-12-01

Calcium channel blockers are increasingly used for the treatment of hypertension. Menopause and hypertension are both important risk factors for liver damage and several other circulatory abnormalities. The aim of this study was to determine the effects of amlodipine and lacidipine in an ovariectomy-induced postmenopausal period model and a deoxycorticosterone acetate-salt-induced hypertensive model in rats. In this study, animals were divided into six groups as follows: control (Group 1), hypertension (Group 2), ovariectomy (Group 3), ovariectomy and hypertension (Group 4), ovariectomy, hypertension and amlodipine-treated (Group 5), and ovariectomy, hypertension and lacidipine-treated (Group 6). At the end of the experiment, the livers were removed and tissue samples were histologically and stereologically examined. The numerical densities of the hepatocytes according to group were 0.000422, 0.00329, 0.000272, 0.00259, 0.00374 and 0.000346 μm3, respectively. Significant differences were found between values of all groups (phypertension in Groups 5 and 6. Our experimental results show that both hypertension and the postmenopausal period have negative effects on the number of hepatocytes and histological structure of the liver. Both amlodipine and lacidipine appear to ameliorate the hypertension and/or postmenopausal period-related decrease in hepatocyte number. We thus suggest that lacidipine and particularly amlodipine have important protective and recovering effects on the liver.

[Successful treatment of fetal supraventricular tachycardia with a combination of digoxin and amiodarone].

Science.gov (United States)

Hajdú, J; Szabó, I; Német, J

1996-10-06

The supraventricular tachycardia is a life threatening state in the intrauterine life. It can cause non-immune hydrops fetalis, intrauterine death or complications during the delivery. The unexplained tachycardia can cause fetal distress and premature delivery. Usually the digoxin is the first drug of choice for transplacental cardioversion. If digitalisation does not achieve cardioversion, the second line antiarrhythmic drugs should be instituted. Amiodarone has been suggested as a therapeutic alternative after failure of digoxin-verapamil combination. We give a drug in standard therapeutic doses for four-five days and after it we determine whether it is effective or not. We should determine the newer therapy or termination of pregnancy. The transplacental administration of amiodarone may be dangerous because of fetal cretinism. Our case is the first in Hungary-in our best knowledge- and we suggest the amiodarone for transplacental therapy.

Hypothalamic digoxin, hemispheric chemical dominance, and oncogenesis: evidence from multiple myeloma.

Science.gov (United States)

Kurup, Ravi Kumar; Kurup, Paramesware Achutha

2003-12-01

This study assessed the changes in the isoprenoid pathway and its metabolites digoxin, dolichol, and ubiquinone in multiple myeloma. The isoprenoid pathway and digoxin status were also studied for comparison in individuals of differing hemispheric dominance to find out the rote of cerebral dominance in the genesis of multiple myeloma and neoplasms. The following parameters were assessed: isoprenoid pathway metabolites, tyrosine and tryptophan catabolites, glycoconjugate metabolism, RBC membrane composition, and free radical metabolism--in multiple myeloma, as well as in individuals of differing hemispheric dominance. There was elevation in plasma HMG CoA reductase activity, serum digoxin, and dolichol, and a reduction in RBC membrane Na(+)-K+ ATPase activity, serum ubiquinone, and magnesium levels. Serum tryptophan, serotonin, nicotine, strychnine, and quinolinic acid were elevated, while tyrosine, dopamine, noradrenaline, and morphine were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions, the activity of GAG degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins, and serum glycolipids were elevated. The RBC membrane glycosaminoglycans, hexose, and fucose residues of glycoproteins, cholesterol, and phospholipids were reduced. The activity of all free-radical scavenging enzymes, concentration of glutathione, iron binding capacity, and ceruloplasmin decreased significantly, while the concentration of lipid peroxidation products and nitric oxide increased. Hyperdigoxinemia-related altered intracellular Ca++/Mg++ ratios mediated oncogene activation, dolichol-induced altered glycoconjugate metabolism, and ubiquinone deficiency-related mitochondrial dysfunction can contribute to the pathogenesis of multiple myeloma. The biochemical patterns obtained in multiple myeloma are similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. But all the patients with

Hypothalamic digoxin and hemispheric chemical dominance: relation to alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration.

Science.gov (United States)

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-08-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin (modulate tryptophan/tyrosine transport), dolichol (important in N -glycosylation of proteins), and ubiquinone (free radical scavenger). It was considered pertinent to assess the pathway in alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration. Since endogenous digoxin can regulate neurotransmitter transport, the pathway was also assessed in individuals with differing hemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. In the patient group there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites as reduced endogenous morphine synthesis from tyrosine. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these groups of patients. The same patterns were obtained in individuals with right hemispheric chemical dominance. Alcoholic cirrhosis, alcoholic addiction, and acquired hepatocerebral degeneration are associated with an upregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This can contribute to NMDA excitotoxicity and altered connective tissue/lipid metabolism important in its pathogenesis. Endogenous morphine deficiency plays a role in alcoholic addiction. Alcoholic cirrhosis, addiction, and acquired hepato -cerebral degeneration occur in right hemispheric chemically dominant individuals. Ninety percent of the patients with alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration were right-handed and left hemispheric dominant by the dichotic listening test. However, their biochemical patterns were similar to those obtained in right hemispheric chemical dominance. Hemispheric chemical dominance is a different entity and has no correlation

Metoprolol and propranolol in essential tremor: a double-blind, controlled study.

Science.gov (United States)

Calzetti, S; Findley, L J; Gresty, M A; Perucca, E; Richens, A

1981-01-01

Single oral doses of propranolol (120 mg), metoprolol (150 mg) and placebo were given in a randomised, double-blind fashion to 23 patients with essential tremor. Both beta blockers were significantly more effective than placebo in reducing the magnitude of tremor. The decrease in tremor produced by metoprolol (47, sem 9%, n = 23) was not significantly different from that observed propranolol (55, sem 5%, n = 23). Tachycardia on standing was antagonised by both drugs to a similar extent. These findings suggest that metoprolol may represent a valuable alternative to propranolol in the treatment of essential tremor. The data is consistent with the hypothesis that the tremorolytic effect of beta blockers in these patients may be unrelated to peripheral beta-2 adreno-receptor blockade, being possibly mediated by other central or peripheral modes of action of these drugs. However, it cannot be excluded that at the dose used, metoprolol had lost its relative cardio-selectivity and that the reduction in tremor was mediated by competitive antagonism at beta-2 receptor sites in skeletal muscle. PMID:7031187

Partition coefficient n-octanol/water of propranolol and atenolol at different temperatures: Experimental and theoretical studies

International Nuclear Information System (INIS)

Mohsen-Nia, M.; Ebrahimabadi, A.H.; Niknahad, B.

2012-01-01

Highlights: ► n-Octanol/water partition coefficients of propranolol and atenolol were measured. ► The effect of temperature on the partition coefficient was studied. ► The equilibrium data were correlated using the NRTL and UNIQUAC activity models. ► The binary interaction parameters of the activity models were reported. ► It is concluded that propranolol is more hydrophobic than the atenolol at 298.15 K. - Abstract: The n-octanol/water partition coefficients of propranolol and atenolol were experimentally determined by ultraviolet (UV) spectroscopy at T = (298.15, 310.15 and 314.15) K. All measurements were made at the maximum wavelength corresponding to maximum absorption. The results showed that the n-octanol/water partition coefficients of propranolol and atenolol increase with the increase of temperature. The experimental data of this work were also used to examine the phase equilibrium correlating capability of some liquid-phase models. The equilibrium experimental data were correlated using the NRTL and UNIQUAC activity coefficient models and the binary interaction parameters were reported. The average root-mea n-square deviations (RMSD) between the experimental and calculated mass fractions of the (n-octanol + propranolol + water) and (n-octanol + atenolol + water) systems were determined. From the partition coefficients obtained, it is concluded that propranolol (log P ow = 3.12 ± 0.14) is more hydrophobic than the atenolol (log P ow = 0.16 ± 0.01) at T = 298.15 K.

Effects of haemolysis, urea and bilirubin on the precision of digoxin and insulin radioimmunoassays

International Nuclear Information System (INIS)

Dwenger, A.; Trautschold, I.

1982-01-01

The influence of haemolysis, uraemia and hyperbilirubinaemia on the radioimmunoassay for both digoxin and insulin has been investigated for five separation techniques (dextran/charcoal; coated tube; polyethyleneglycol 4000; sodium sulphite; double antibody). Recoveries, and intra- and interassay precision were calculated. It was demonstrated that even in serum samples with a rather high degree of haemolysis (haemoglobin up to 50 g/l) digoxin can be measured by using each of the five separation techniques without any significant interference. Visible haemolysis (haemoglobin above 200 mg/l) leads either to disturbance or to a complete failure of insulin radioimmunoassays with all separation techniques. This effect can be largely neutralized, and precision improved, by using N-ethyl-maleimide. With the exception of the coated tube separation technique the intraassay precision has a CV of [de

Comparative pharmacokinetics of a fixed-dose combination vs concomitant administration of telmisartan and S-amlodipine in healthy adult volunteers

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Oh M

2017-12-01

Full Text Available Minkyung Oh,1,2,* Sung-Eun Park,3,* Jong-Lyul Ghim,1–3 Young-Kyung Choi,1 Eon-Jeong Shim,1–3 Jae-Gook Shin,1–3 Eun-Young Kim1–3 1Department of Pharmacology, 2PharmacoGenomics Research Center, Inje University College of Medicine, Busan, 3Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Republic of Korea *These authors contributed equally to this work Objective: This study compared the pharmacokinetic (PK and safety profiles of a fixed-dose combination (FDC formulation of telmisartan and S-amlodipine with those of concomitant administration of the two drugs.Materials and methods: This was an open-label, randomized, crossover study in healthy male Koreans. All subjects were administered an FDC tablet containing 40 mg telmisartan and 5 mg S-amlodipine and were also coadministered the same dose of both drugs given separately. The crossover study design included a 14-day washout period between the two treatments. Blood samples were collected up to 168 h following drug administration. The plasma concentrations of telmisartan and S-amlodipine were determined by liquid chromatography tandem mass spectrometry. PK parameters and plasma concentration–time curves were compared. Safety was assessed by measuring vital signs, clinical laboratory tests, physical examinations, and patient interviews.Results: The geometric mean ratios and 90% CIs for the maximum plasma concentration (Cmax and area under the curve from time zero to the last sampling time (AUCt were 0.8782 (0.8167–0.9444 and 0.9662 (0.9210–1.0136 for telmisartan and 1.0069 (0.9723–1.0427 and 1.0324 (0.9969–1.0690 for S-amlodipine, respectively. A total of 36 adverse events (AEs were reported by 23 subjects, but no statistical differences were observed between the two treatments. The most frequently reported AE was a mild-to-moderate headache that was generally self-limiting.Conclusion: For both telmisartan and S-amlodipine, the Cmax and AUCt 90% CIs

Amlodipine and the Successful Management of Post-Electroconvulsive Therapy Agitation.

Science.gov (United States)

Shahriari, Ali; Khooshideh, Maryam; Sheikh, Mahdi

2016-01-01

Electroconvulsive therapy (ECT) is a highly effective nonpharmacologic treatment for the management of depression and some other psychiatric disorders. Post-ECT agitation occurs in up to 12% of ECT treatments and is characterized by motor restlessness, irritability, disorientation, and panic-like behaviors. The severity of post-ECT agitation ranges from mild and self-limited to serious and severe forms requiring prompt medical intervention to protect the patient and the medical staff. In severe agitation medical management may be necessary which consists of using sedative agents, either benzodiazepines or propofol. The side-effects of these sedative agents, especially in the elderly population, necessitate finding ways that could help the prevention of the occurrence of agitation after ECT treatments. We report a 68-year-old female with major depression who was referred for ECT. She experienced severe post-ECT agitation requiring medical intervention after all ECT treatments. Administering of oral amlodipine (5 mg) one hour before ECT treatment successfully prevented the occurrence of post-ECT agitation in this patient. We briefly discuss the possible underlying mechanisms and pathophysiology of amlodipine in the prevention of post-ECT agitation.

Amlodipine and the Successful Management of Post-Electroconvulsive Therapy Agitation

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Ali Shahriari

2016-01-01

Full Text Available Electroconvulsive therapy (ECT is a highly effective nonpharmacologic treatment for the management of depression and some other psychiatric disorders. Post-ECT agitation occurs in up to 12% of ECT treatments and is characterized by motor restlessness, irritability, disorientation, and panic-like behaviors. The severity of post-ECT agitation ranges from mild and self-limited to serious and severe forms requiring prompt medical intervention to protect the patient and the medical staff. In severe agitation medical management may be necessary which consists of using sedative agents, either benzodiazepines or propofol. The side-effects of these sedative agents, especially in the elderly population, necessitate finding ways that could help the prevention of the occurrence of agitation after ECT treatments. We report a 68-year-old female with major depression who was referred for ECT. She experienced severe post-ECT agitation requiring medical intervention after all ECT treatments. Administering of oral amlodipine (5 mg one hour before ECT treatment successfully prevented the occurrence of post-ECT agitation in this patient. We briefly discuss the possible underlying mechanisms and pathophysiology of amlodipine in the prevention of post-ECT agitation.

Lack of effect of long-term amlodipine on insulin sensitivity and plasma insulin in obese patients with essential hypertension

DEFF Research Database (Denmark)

de Courten, Maximilian; Ferrari, P; Schneider, M

1993-01-01

Method of Bergman, fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure in 20 obese, non-diabetic patients with essential hypertension before and after 6 weeks of placebo and again after 6 months of amlodipine. Ten patients......To evaluate the effects of long-term treatment antihypertensive with the dihydropyridine calcium antagonist amlodipine on insulin sensitivity, plasma insulin, and lipoprotein metabolism in obese hypertensive patients. We measured the insulin sensitivity index (SI), determined by the Minimal Model...... [mean body mass index (BMI) 30.2 kg.m-2] had been on prior treatment with a thiazide diuretic in low dosage and/or a beta-adrenoceptor blocker (group A), and 10 matched patients [BMI 31.8 kg.m-2] had been previously untreated (group B). Amlodipine was started in a dose of 5 mg and was increased to 10 mg...

Comparative pharmacokinetics of a fixed-dose combination vs concomitant administration of telmisartan and S-amlodipine in healthy adult volunteers.

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Oh, Minkyung; Park, Sung-Eun; Ghim, Jong-Lyul; Choi, Young-Kyung; Shim, Eon-Jeong; Shin, Jae-Gook; Kim, Eun-Young

2017-01-01

This study compared the pharmacokinetic (PK) and safety profiles of a fixed-dose combination (FDC) formulation of telmisartan and S-amlodipine with those of concomitant administration of the two drugs. This was an open-label, randomized, crossover study in healthy male Koreans. All subjects were administered an FDC tablet containing 40 mg telmisartan and 5 mg S-amlodipine and were also coadministered the same dose of both drugs given separately. The crossover study design included a 14-day washout period between the two treatments. Blood samples were collected up to 168 h following drug administration. The plasma concentrations of telmisartan and S-amlodipine were determined by liquid chromatography tandem mass spectrometry. PK parameters and plasma concentration-time curves were compared. Safety was assessed by measuring vital signs, clinical laboratory tests, physical examinations, and patient interviews. The geometric mean ratios and 90% CIs for the maximum plasma concentration (C max ) and area under the curve from time zero to the last sampling time (AUC t ) were 0.8782 (0.8167-0.9444) and 0.9662 (0.9210-1.0136) for telmisartan and 1.0069 (0.9723-1.0427) and 1.0324 (0.9969-1.0690) for S-amlodipine, respectively. A total of 36 adverse events (AEs) were reported by 23 subjects, but no statistical differences were observed between the two treatments. The most frequently reported AE was a mild-to-moderate headache that was generally self-limiting. For both telmisartan and S-amlodipine, the C max and AUC t 90% CIs were between ln (0.8) and ln (1.25). These results suggest that the FDC formulation is pharmacokinetically bioequivalent and has a similar safety profile to the coadministration of these drugs.

Treatment with triple combination of atorvastatin, perindopril, and amlodipine in patients with stable coronary artery disease: A subgroup analysis from the PAPA-CAD study.

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Dézsi, Csaba András

2018-01-01

Background In patients with stable coronary artery disease, aspirin, a statin, and an angiotensin-converting enzyme inhibitor are recommended as first-line agents for secondary prevention. Subgroup analyses of the previously published Hungarian Perindopril plus Amlodipine in PAtients with Coronary Artery Disease (PAPA-CAD) non-interventional trial demonstrated that the addition of the metabolically beneficial, fixed combination of perindopril + amlodipine to atorvastatin further improves the patient's lipid profile. Methods The PAPA-CAD study, a 6-month open-label, prospective, multicenter, observational/non-interventional survey evaluated data accumulated from patients with hypertensive patients with stable coronary artery disease. The herein-reported subgroup analysis was conducted using the findings from those 1130 patients, who were taking atorvastatin in addition to the fixed combination of perindopril + amlodipine at the time of all four study visits (i.e., at baseline and 1, 3, and 6 months later). Results In the subgroup of patients taking atorvastatin as an add-on agent, 82.5% reached the target blood pressure of 140/90 mmHg compared with 78.8% of those not taking a statin. The addition of atorvastatin to the fixed combination of perindopril + amlodipine resulted in further significant improvements of key metabolic parameters. Conclusion This subgroup analysis confirmed that favorable synergism exists among perindopril, amlodipine, and atorvastatin.

EFFECTS OF AMLODIPIN AND METOPROLOL ON AUTONOMIC SYSTEM IN EMOTIONAL AND COLD TESTS IN HYPERTENSIVE PATIENTS WITH DIFFERENT PSYCHOLOGICAL PROFILE

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M. P. Rubanova

2006-01-01

Full Text Available Aim. To asses effects of amlodipin and metoprolol on autonomic system in emotional and cold tests in hypertensive patients with different psychological profile (PP Material and methods. 61 patients with arterial hypertension of II grade were observed. Therapy with amlodipin or metoprolol was prescribed and allowed to reach target blood pressure (BP level in all the patients. Patients were divided into 2 groups: 1-st one – patients with normal PP, 2-nd group – patients with subclinical depression. Patients were examined before and 30 days after therapy. Examination included ambulatory BP monitoring, assessment of autonomic status by variational intervalometry and spectral analysis of heart rate variability (HRV in cold and emotional tests. Depression and anxiety levels were determined with Bek’s and HADS scales.  Results. Treatment with amlodipin  and metoprolol can result in improvement, worsening or unchanging of PP.  In hypertensive patients with subclinical depression improving their PP resulted in autonomic reaction change: sympathetic activity increases and reaction on stress becomes more adequate. If subclinical depression occurred in hypertensive patients because of amlodipin and metoprolol therapy, sympathetic system stress-reaction decreased and parasympathetic influence increased. Conclusion. The study results show necessity of psychometric examination of hypertensive patients in order to reveal subclinical depression and anxiety.  

Determinants of Propranolol's Selective Effect on Loss Aversion.

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Sokol-Hessner, Peter; Lackovic, Sandra F; Tobe, Russell H; Camerer, Colin F; Leventhal, Bennett L; Phelps, Elizabeth A

2015-07-01

Research on emotion and decision making has suggested that arousal mediates risky decisions, but several distinct and often confounded processes drive such choices. We used econometric modeling to separate and quantify the unique contributions of loss aversion, risk attitudes, and choice consistency to risky decision making. We administered the beta-blocker propranolol in a double-blind, placebo-controlled within-subjects study, targeting the neurohormonal basis of physiological arousal. Matching our intervention's pharmacological specificity with a quantitative model delineating decision-making components allowed us to identify the causal relationships between arousal and decision making that do and do not exist. Propranolol selectively reduced loss aversion in a baseline- and dose-dependent manner (i.e., as a function of initial loss aversion and body mass index), and did not affect risk attitudes or choice consistency. These findings provide evidence for a specific, modulatory, and causal relationship between precise components of emotion and risky decision making. © The Author(s) 2015.

The Brain and Propranolol Pharmacokinetics in the Elderly

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Andy R. Eugene

2015-09-01

Full Text Available Propranolol, a non-selective β-blocker, has been found to have a tremendous array of indications. Recent evidence has suggested that propranolol may be effective in patients suffering from post-traumatic stress disorder by suppressing activity in the amygdala and thereby inhibiting emotional memory formation. Dosage requirements have been well established in the pediatric and adult population, however, there has been no definitive geriatric dose recommended in the package inserts made available to the public. The aim of this paper is to use pharmacokinetic simulations in order to establish a pharmacokinetic profile dosage equivalent for the elderly as has been found in young patients. After completing the Monte-Carlo simulations for the elderly and young patients, a single 10mg dose in the elderly has shown comparable pharmacokinetic profiles as found in young patients administered a 40mg single dose.

The efficacy and safety of fixed-dose combination of amlodipine/benazepril in Chinese essential hypertensive patients not adequately controlled with benazepril monotherapy: a multicenter, randomized, double-blind, double-dummy, parallel-group clinical trial.

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Yan, Pingping; Fan, Weihu

2014-01-01

This double-blind, double-dummy clinical trial evaluated the efficacy and safety of two strengths of fixed-dose combination of amlodipine/benazepril in Chinese hypertensive patients not adequately controlled with benazepril. Of 442 patients who received treatment with benazepril 10 mg for 4 weeks, 341 patients failed to achieve to diastolic blood pressure (DBP) benazepril 2.5/10 mg, or amlodipine/benazepril 5/10 mg, or benazepril 10 mg for 8 weeks. BP reductions with amodipinel/benazepril 2.5/10 mg (15.2/11.8 mmHg) or amlodipine/benazepril 5/10 mg (15.4/12.4 mmHg) were significantly greater than that with benazepril 10 mg (9.88/9.46 mmHg) at study end (p benazepril). BP control rate was 83.8% with amlodipine/benazepril 2.5/10 mg, 80.2% with amlodipine/benazepril 5/10 mg, 64.9% with benazepril 10 mg at study end (p benazepril). Three groups were generally well tolerated. Our study indicated that amlodipine/benazepril fixed-dose combination offered significant additional BP reductions and BP control rate compared with the continuation of benazepril monotherapy. No significant differences were observed in both BP reductions and BP control rate between amlodipine/benazepril 2.5/10 mg and amlodipine/benazepril 5/10 mg.

Consolidation and reconsolidation are impaired by oral propranolol administered before but not after memory (re)activation in humans.

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Thomas, Émilie; Saumier, Daniel; Pitman, Roger K; Tremblay, Jacques; Brunet, Alain

2017-07-01

Propranolol administered immediately after learning or after recall has been found to impair memory consolidation or reconsolidation (respectively) in animals, but less reliably so in humans. Since reconsolidation impairment has been proposed as a treatment for mental disorders that have at their core an emotional memory, it is desirable to understand how to reliably reduce the strength of pathogenic memories in humans. We postulated that since humans (unlike experimental animals) typically receive propranolol orally, this introduces a delay before this drug can exert its memory impairment effects, which may render it less effective. As a means to test this, in two double-blind placebo-controlled experiments, we examined the capacity of propranolol to impair consolidation and reconsolidation as a function of timing of ingestion in healthy subjects. In Experiment 1, (n=36), propranolol administered immediately after learning or recall failed to impair the consolidation or reconsolidation of the memory of a standardized slideshow with an accompanying emotional story. In Experiment 2 (n=50), propranolol given 60-75min before learning or recall successfully impaired memory consolidation and reconsolidation. These results suggest that it is possible to achieve reliable memory impairment in humans if propranolol is given before learning or before recall, but not after. Copyright © 2016 Elsevier Inc. All rights reserved.

Selectivity analyses of γ-benzylidene digoxin derivatives to different Na,K-ATPase α isoforms: a molecular docking approach.

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Pessôa, Marco T C; Alves, Silmara L G; Taranto, Alex G; Villar, José A F P; Blanco, Gustavo; Barbosa, Leandro A

2018-12-01

Digoxin and other cardiotonic steroids (CTS) exert their effect by inhibiting Na,K-ATPase (NKA) activity. CTS bind to the various NKA isoforms that are expressed in different cell types, which gives CTS their narrow therapeutic index. We have synthesised a series of digoxin derivatives (γ-Benzylidene digoxin derivatives) with substitutions in the lactone ring (including non-oxygen and ether groups), to obtain CTS with better NKA isoform specificity. Some of these derivatives show some NKA isoform selective effects, with BD-3, BD-8, and BD-13 increasing NKA α2 activity, BD-5 inhibiting NKA α1 and NKA α3, BD-10 reducing NKA α1, but stimulating NKA α2 and α3; and BD-14, BD-15, and BD-16 enhancing NKA α3 activity. A molecular-docking approach favoured NKA isoform specific interactions for the compounds that supported their observed activity. These results show that BD compounds are a new type of CTS with the capacity to target NKA activity in an isoform-specific manner.

In vitro transdermal delivery of propranolol hydrochloride through rat skin from various niosomal formulations

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Eskandar Moghimipour

2013-09-01

Full Text Available   Objective(s: The purpose of the present study was to prepare and to evaluate a novel niosome as transdermal drug delivery system for propranolol hydrochloride and to compare the in vitro efficiency of niosome by either thin film hydration or hand shaking method.   Materials and Methods: Niosomes were prepared by Thin Film Hydration (TFH or Hand Shaking (HS method. Propranolol niosomes were prepared using different surfactants (span20, 80 ratios and a constant cholesterol concentration. In vitro characterization of niosomes included microscopical observation, size distribution, laser light scattering evaluation, stability of propranolol niosomes and permeability of formulations in phosphate buffer (pH=7 through rat abdominal skin. Results: The percentage of entrapment efficiency (%EE increased with increase in surfactant concentration in all formulations. Among them, F3 formulation (containing span80:cholesterol ratio of 3:1 showed the highest entrapment efficiency (86.74±2.01%, Jss (6.33μg/cm2.h and permeability coefficient ( . By increasing the percentage of entrapment efficiency (resulting in increase in surfactant concentration, the drug released time is not prolonged. Among all the formulations, F4 needed more time for maximum drug release. Among these formulations, F4 was also found to have the maximum vesicle size as compared to other formulations. It was observed that niosomal suspension prepared from span 80 was more stable than span 20. Conclusion: This study demonstrates that niosomal formulations may offer a promise transdermal delivery of propranolol which improves drug efficiency and can be used for controlled delivery of propranolol

Propranolol Effects on Decompression Sickness in a Simulated DISSUB Rescue in Swine.

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Forbes, Angela S; Regis, David P; Hall, Aaron A; Mahon, Richard T; Cronin, William A

2017-04-01

Disabled submarine (DISSUB) survivors may face elevated CO2 levels and inert gas saturation, putting them at risk for CO2 toxicity and decompression sickness (DCS). Propranolol was shown to reduce CO2 production in an experimental DISSUB model in humans but its effects on DCS in a DISSUB rescue scenario are unknown. A 100% oxygen prebreathe (OPB) reduces DCS incidence and severity and is incorporated into some DISSUB rescue protocols. We used a swine model of DISSUB rescue to study the effect of propranolol on DCS incidence and mortality with and without an OPB. In Experiment 1, male Yorkshire Swine (70 kg) were pressurized to 2.8 ATA for 22 h. Propranolol 1.0 mg · kg-1 (IV) was administered at 21.25 h. At 22 h, the animal was rapidly decompressed and observed for DCS type, onset time, and mortality. Experimental animals (N = 21; 69 ± 4.1 kg), PROP1.0, were compared to PROP1.0-OPB45 (N = 8; 69 ± 2.8 kg) with the same dive profile, except for a 45 min OPB prior to decompression. In Experiment 2, the same methodology was used with the following changes: swine pressurized to 2.8 ATA for 28 h; experimental group (N = 25; 67 ± 3.3 kg), PROP0.5 bis, propranolol 0.5 mg · kg-1 bis (twice) (IV) was administered at 22 h and 26 h. Control animals (N = 25; 67 ± 3.9 kg) received normal saline. OPB reduced mortality in PROP1.0-OBP45 compared to PROP1.0 (0% vs. 71%). PROP0.5 bis had increased mortality compared to CONTROL (60-% vs. 4%). Administration of beta blockers prior to saturation decompression appears to increase DCS and worsen mortality in a swine model; however, their effects in bounce diving remain unknown.Forbes AS, Regis DP, HallAA, Mahon RT, Cronin WA. Propranolol effects on decompression sickness in a simulated DISSUB rescue in swine. Aerosp Med Hum Perform. 2017; 88(4):385-391.

Digoxin-like immunoreactivity, endogeneous cardiac glycoside-like factors (s) and natriuretic hormone

International Nuclear Information System (INIS)

Clerico, A.

1987-01-01

Endogenous factors crossreacting with antidigoxin antibodies (digoxin-like immunoreactive substances=DLIS) have been found in several tissues and body fluids of animals and humans, using commercially avaiable digoxin RIA or EIA methods. Detectable DLIS concentration were found in blood and urine extracts of adults (normal healthy controls, hypertensive patients and salt loaded healthy subjects), while higher levels were generally observed in plasma samples of pregnant women, newborns and patients with renal insufficiency. The chemical characteristics of this endogenous factor are, at present, unknown, although it has been suggested that DLIS could be a substance with low molecular weight. Experimental studies and theoretical consideration suggest that DLIS, in addition to reacting with antibodies, might also bind to the specific cellular receptor of the cardiac glycosides and thus inhibit the membrane Na + /K + ATPase (sodium pump). Therefore, it has been suggested that DLSI is an endogeneous modulator of the membrane sodium-potassium pump and it could play a role in the regulation of fluid and electrolytes muscular tone of myocardial and also in pathogenesis of hypertension

The therapeutic efficacy of propranolol in children with recurrent primary epistaxis

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Bjelakovic, Bojko; Bojanovic, Mila; Lukic, Stevo; Saranac, Ljiljana; Vukomanovic, Vladislav; Prijic, Sergej; Zivkovic, Nikola; Randjelovic, Dusica

2013-01-01

We hypothesized that some characteristics of beta-blockers, including negative inotropic, peripheral vasoconstrictor, and antiangiogenic effects, might be potentially useful in treating children with epistaxis. From June 2010 to March 2012, a total of seven children with recurrent primary epistaxis resistant to conventional management were observed at our institution. An overall effectiveness of propranolol was noted in all seven children when given a dose of 1.5–2 mg/kg/day (divided into three doses) as a second line therapy for terminating epistaxis. Based on our first experience, we believe that propranolol could be a favorable treatment option for patients with primary epistaxis. PMID:23467483

Usefulness and safety of propranolol injection into vein for acquisition of coronary multidetector-row computed tomography

International Nuclear Information System (INIS)

Sekine, Takako; Kodama, Takahide; Kondo, Takeshi

2010-01-01

A low heart rate (HR), associated with a prolonged slow filling phase (SF), is necessary to obtain a high quality coronary CT at a low radiation dose with conventional 64 multidetector-row computed tomography (MDCT). The purpose of our study was to confirm the safety of injecting propranolol (2-10 mg) into the vein for lowering heart rate in patients requiring MDCT and to document the effect of the drug on HR, PQ and SF. Of 1290 consecutive patients who were initially considered for enrollment in the coronary MDCT study, 40 patients with atrial fibrillations, 3 with atrial flutters, and 13 with artificial pacemakers were excluded. Of the remaining 1234 patients (M/F=714/520), 331 had already taken an oral beta-blocker before the CT examination, and were included in the study. In patients with no contraindications, propranolol was aggressively injected (2-10 mg) into the vein to reduce the HR. In patients not taking an oral beta blocker, 2 mg propranolol reduced the HR by -10±5 bpm and 10 mg, by -20±7 bpm. However, in patients taking an oral beta-blocker, the decrease in HR by propranolol was minimal (2 mg, -6±4 bpm; 10 mg, -10±6 bpm). Propranolol significantly prolonged the PQ interval (from 169±27 to 179±29 ms, P<0.0001), and SF (from 125±69 to 264±79 ms, P<0.0001). Adverse effects of propranolol injection were observed in only 3 [2 mild hypotension and 1 paroxysmal atrial fibrillation (recovered to sinus rhythm by DC counter shock)] of 3212 patients. All 3 patients became stable after 1 or 2 hours of rest and could return home. Propranolol injection was a relatively safe and useful method to reduce HR and prolong SF, necessary for obtaining high quality coronary MDCT with a low radiation dose. (author)

Atenolol Versus Propranolol for Treatment of Infantile Hemangiomas During the Proliferative Phase: A Retrospective Noninferiority Study.

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Bayart, Cheryl B; Tamburro, Joan E; Vidimos, Allison T; Wang, Lu; Golden, Alex B

2017-07-01

The nonselective beta-blocker propranolol is the current criterion standard for treatment of infantile hemangiomas (IHs) and the first therapy that the U.S. Food and Drug Administration has approved for the condition, but concern about adverse effects, such as bronchospasm, hypoglycemia, and sleep disturbances, has sparked interest in the use of alternative agents such as the selective β1 antagonist atenolol. Our aim was to compare the efficacy and adverse effect profiles of atenolol with those of propranolol in the treatment of IHs in a retrospective noninferiority trial. Twenty-seven children with IHs treated with atenolol according to the Cleveland Clinic foundation's standardized clinical assessment and management plan (SCAMP) met inclusion criteria and were compared with a matched group of 53 children with IHs treated with propranolol. Three reviewers assessed response to therapy using a modified version of the previously validated Hemangioma Activity Score (HAS). The mean change in HAS was -2.94 ± 1.20 for patients treated with atenolol and -2.96 ± 1.42 for those treated with propranolol. There was no statistically significant difference in pre- and posttreatment modified HAS scores between the two groups (p = 0.60). There was no significant difference in the overall rate of adverse effects (p = 0.10), although 11% of patients treated with propranolol experienced reactive airway symptoms, whereas this was not seen in any of the patients treated with atenolol. Our study supports previous findings that atenolol is at least as effective as propranolol for treatment of IHs and poses less risk of bronchospasm. Our SCAMP proposes guidelines for dosing and monitoring parameters. © 2017 Wiley Periodicals, Inc.

The effect of left frontal transcranial direct-current stimulation on propranolol-induced fear memory acquisition and consolidation deficits.

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Nasehi, Mohammad; Khani-Abyaneh, Mozhgan; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

2017-07-28

Accumulating evidence supports the efficacy of transcranial direct current stimulation (tDCS) in modulating numerous cognitive functions. Despite the fact that tDCS has been used for the enhancement of memory and cognition, very few animal studies have addressed its impact on the modulation of fear memory. This study was designed to determine whether pre/post-training frontal tDCS application would alter fear memory acquisition and/or consolidation deficits induced by propranolol in NMRI mice. Results indicated that administration of β1-adrenoceptor blocker propranolol (0.1mg/kg) impaired fear memory retrieval. Pre/post-training application of anodal tDCS when propranolol was administered prior to training reversed contextual memory retrieval whereas only the anodal application prior to training could induce the same result in the auditory test. Meanwhile, anodal stimulation had no effect on fear memories by itself. Moreover, regardless of when cathode was applied and propranolol administered, their combination restored contextual memory retrieval, while only cathodal stimulation prior to training facilitated the contextual memory retrieval. Also, auditory memory retrieval was restored when cathodal stimulation and propranolol occurred prior to training but it was abolished when stimulation occurred after training and propranolol was administered prior to training. Collectively, our findings show that tDCS applied on the left frontal cortex of mice affects fear memory performance. This alteration seems to be task-dependent and varies depending on the nature and timing of the stimulation. In certain conditions, tDCS reverses the effect of propranolol. These results provide initial evidence to support the timely use of tDCS for the modulation of fear-related memories. Copyright © 2017 Elsevier B.V. All rights reserved.

Hypothalamic digoxin, hemispheric chemical dominance, and mesenteric artery occlusion.

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Kurup, Ravi Kumar; Kurup, Paramesware Achutha

2003-12-01

The role of the isoprenoid pathway in vascular thrombosis, especially mesenteric artery occlusion and its relation to hemispheric dominance, was assessed in this study. The following parameters were measured in patients with mesenteric artery occlusion and individuals with right hemispheric, left hemispheric, and bihemispheric dominance: (1) plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; (2) tryptophan/tyrosine catabolic patterns; (3) free radical metabolism; (4) glycoconjugate metabolism; and (5) membrane composition. In patients with mesenteric artery occlusion there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, low ubiquinone, and elevated free radical levels. The RBC membrane Na(+)-K+ ATPase activity and serum magnesium were decreased. There was also an increase in tryptophan catabolites and reduction in tyrosine catabolites in the serum. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these patients. The biochemical patterns obtained in mesenteric artery occlusion is similar to those obtained in left-handed/right hemispheric dominant individuals by the dichotic listening test. But all the patients with mesenteric artery occlusion were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Mesenteric artery occlusion occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function. Hemispheric chemical dominance may thus control the risk for developing vascular thrombosis in individuals.

Evaluation of palatability of 10 commercial amlodipine orally disintegrating tablets by gustatory sensation testing, OD-mate as a new disintegration apparatus and the artificial taste sensor.

Science.gov (United States)

Uchida, Takahiro; Yoshida, Miyako; Hazekawa, Mai; Haraguchi, Tamami; Furuno, Hiroyuki; Teraoka, Makoto; Ikezaki, Hidekazu

2013-09-01

The purpose of this study was to evaluate and compare the palatability of 10 formulations (the original manufacturer's formulation and nine generics) of amlodipine orally disintegrating tablets (ODTs) by means of human gustatory sensation testing, disintegration/dissolution testing and the evaluation of bitterness intensity using a taste sensor. Initially, the palatability, dissolution and bitterness intensity of the ODTs were evaluated in gustatory sensation tests. Second, the disintegration times of the ODTs were measured using the OD-mate, a newly developed apparatus for measuring the disintegration of ODTs, and lastly, the bitterness intensities were evaluated using an artificial taste sensor. Using factor analysis, the factors most affecting the palatability of amlodipine ODTs were found to be disintegration and taste. There was high correlation between the disintegration times of the 10 amlodipine ODTs estimated in human gustatory testing and those found using the OD-mate. The bitterness intensities of amlodipine ODTs 10, 20 and 30 s after starting the conventional brief dissolution test and the values determined by the taste sensor were highly correlated with the bitterness intensities determined in gustatory sensation testing. The OD-mate and the taste sensor may be useful for predicting the disintegration and bitterness intensity of amlodipine ODTs in the mouth. © 2013 Royal Pharmaceutical Society.

Benazepril combined with either amlodipine or hydrochlorothiazide is more effective than monotherapy for blood pressure control and prevention of end-organ injury in hypertensive Dahl rats.

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Zhou, Ming-Sheng; Jaimes, Edgar A; Raij, Leopoldo

2006-07-01

We studied the effect of hydrochlorothiazide (HCTZ), the angiotensin-converting enzyme inhibitor benazepril, the calcium channel blocker amlodipine, or a combination of benazepril/amlodipine or benazepril/HCTZ on systolic blood pressure (BP) and end-organ injury (left ventricular hypertrophy, proteinuria, and endothelium-dependent relaxation to acetylcholine) in hypertensive Dahl salt-sensitive rats fed either a normal-salt (0.5% NaCl) or high-salt (4% NaCl) diet for 6 weeks. Rats fed a high-salt diet developed hypertension and significant end-organ injury. Monotherapy with HCTZ (75 mg/L in drinking water) or amlodipine (10 mg/kg/day by gavage) reduced systolic BP and proteinuria; benazepril (40 mg/kg/day by gavage) decreased proteinuria without significantly lowering systolic BP. In rats receiving a high-salt diet, only HCTZ reduced left ventricular hypertrophy, whereas endothelium-dependent relaxation was improved by amlodipine and benazepril but not by HCTZ. Combining benazepril with either amlodipine or HCTZ dramatically reduced systolic BP and end-organ injury. These data clearly support clinical studies suggesting that combination therapy is more effective than monotherapy for systolic BP control and prevention of end-organ injury. Complementary mechanisms of action of agents from different antihypertensive classes appear to facilitate the greater benefit on BP and end-organ injury.

Corticosterone and propranolol's role on taste recognition memory.

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Ruetti, E; Justel, N; Mustaca, A; Boccia, M

2014-12-01

Taste recognition is a robust procedure to study learning and memory processes, as well as the different stages involved in them, i.e. encoding, storage and recall. Considerable evidence indicates that adrenal hormones and the noradrenergic system play an important role in aversive and appetitive memory formation in rats and humans. The present experiments were designed to characterize the effects of immediate post training corticosterone (Experiment 1) and propranolol administration (Experiment 2 and 3) on taste recognition memory. Administration of a high dose of corticosterone (5mg/kg, sc) impairs consolidation of taste memory, but the low and moderate doses (1 and 3mg/kg, sc) didn't affect it. On the other hand, immediate post-training administration of propranolol (1 and 2mg/kg, ip) impaired taste recognition memory. These effects were time-dependent since no effects were seen when drug administration was delayed 3h after training. These findings support the importance of stress hormones and noradrenergic system on the modulation of taste memory consolidation. Copyright © 2014. Published by Elsevier Inc.

Analysis of Digoxin and Metildigoxin in Whole Blood Using Solid-Phase Extraction and Liquid Chromatography Tandem Mass Spectrometry

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Paula Melo

2012-01-01

Full Text Available A simple and rapid UPLC/MS/MS method has been developed and validated for the analysis of digoxin and metildigoxin in whole blood. Samples were prepared by SPE extraction with Oasis HLB columns. Separation was achieved with an ACQUITY UPLC HSS T3 column (2.1×100; 1.8 μm, at 35°C. The mobile phase consisted of acetonitrile (70% and ammonium formate 5 mM (30%. Total run time was 1.5 min operating at isocratic mode with a flow rate of 0.3 mL/min. Mass spectrometry detection was performed by positive mode electrospray, on the ammonium adducts with two transitions for each analyte and one for the IS (d3-digoxin. The method proved to be specific and linear over the range (0.3–10 ng/mL. This technique also showed high sensitivity with a 0.09 ng/mL LOD and a 0.28 ng/mL LOQ, for both substances. Percentage recovery ranged from 83 to 100% for digoxin and from 62 to 94% for metildigoxin. The intra- and interday precision CV were ≤10%.

Determination of the Effects of Digoxin on the Right Ventricular Function in Patients Undergoing Pneumonectomy

Directory of Open Access Journals (Sweden)

Alireza Sharifian Attar

2014-02-01

Full Text Available Introduction: Pneumonectomy is the standard treatment of lung cancer, even though patients should undergo several evaluations before surgery; deterioration of cardiopulmonary function after pulmonary resection is inevitable. We have evaluated the effects of digoxin on the improvement of right ventricular function and prevention of probable complications after lung resection surgery. Materials and Methods: All patients who were candidate for pneumonectomy or extensive lobectomy in Ghaem hospital from 2010 to 2012 were enrolled into this study and were divided into two groups randomly. The first group (group D received digoxin during surgery and in the second group (group C normal saline was administered as placebo. Echocardiographic evaluation of the patients was accomplished the day before and the day after surgery. Results: Among 20 patients in each group, male to female ratio was almost 2:1 and mean age was 63.8 (ranged 46-83 years. The most common cause of pneumonectomy was lung cancer. Comparison of the preoperative demographic variables, blood biochemistry, pulmonary function tests, echocardiographic and blood gas indexes showed no statistically significant differences between two groups. ,But postoperative evaluations showed a significant improvement in left ventricular ejection fraction in group D. Right ventricular systolic and diastolic diameters and pulmonary artery pressure were decreased significantly  as well. Conclusion: According to our results, we suggest a single dose of digoxin during lung resection surgery to improve cardiac performance after pneumonectomy.

Reversal of propranolol blockade of adrenergic receptors and related toxicity with drugs that increase cyclic AMP.

Science.gov (United States)

Whitehurst, V E; Vick, J A; Alleva, F R; Zhang, J; Joseph, X; Balazs, T

1999-09-01

An overdose of propranolol, a widely used nonselective beta-adrenergic receptor blocking agent, can result in hypotension and bradycardia leading to irreversible shock and death. In addition, the blockade of adrenergic receptors can lead to alterations in neurotransmitter receptors resulting in the interruption of the activity of other second messengers and the ultimate cellular responses. In the present experiment, three agents, aminophylline, amrinone, and forskolin were tested in an attempt to reverse the potential lethal effects of a propranolol overdose in dogs. Twenty-two anesthetized beagle dogs were given a 10-min infusion of propranolol at a dose of 1 mg/kg/min. Six of the dogs, treated only with intravenous saline, served as controls. Within 15-30 min all six control dogs exhibited profound hypotension and severe bradycardia that led to cardiogenic shock and death. Seven dogs were treated with intravenous aminophylline 20 mg/kg 5 min after the end of the propranolol infusion. Within 10-15 min heart rate and systemic arterial blood pressure returned to near control levels, and all seven dogs survived. Intravenous amrinone (2-3 mg/kg) given to five dogs, and forskolin (1-2 mg/kg) given to four dogs, also increased heart rate and systemic arterial blood pressure but the recovery of these parameters was appreciably slower than that seen with aminophylline. All of these animals also survived with no apparent adverse effects. Histopathologic evaluation of the hearts of the dogs treated with aminophylline showed less damage (vacuolization, inflammation, hemorrhage) than the hearts from animals given propranolol alone. Results of this study showed that these three drugs, all of which increase cyclic AMP, are capable of reversing the otherwise lethal effects of a propranolol overdose in dogs.

the effect of ascorbic acid and propranolol on normal sleep

African Journals Online (AJOL)

sleep promoting effects in the wistar rats in doses of propranolol. Conclusion: It is possible ... motor activities as swimming, flying, walking, running, rearing and hopping etc. ..... The Homotypical Cortex - The ssociation Areas. Physiological and ...

Scottish immunoassay support service quality control scheme for thyroxine, triiodothyronine, and digoxin assays: analysis of first 18 months' experience

International Nuclear Information System (INIS)

Ratcliffe, W.A.; Logue, F.C.; Ratcliffe, J.G.

1978-01-01

Initial experience of the Scottish Immunoassay Support Service Quality Control scheme for thyroxin(T4), triiodothyronine (T3), and digoxin is analysed. For T4, radioimmunoassay (RIA) methods gave values close to the all-method mean. Competitive protein binding (CPB) kits gave values significantly higher (by 12%) in one and lower (by 10%) in another, probably due to the extraction of interfering substances such as non-esterified fatty acids or thyroid hormone binding proteins. The range of between-batch precision of individual laboratories was 10.8-47.5% (mean 17.8%) over the clinically relevant range. It was particularly poor at levels below the lower limit of the normal range. For T3 RIA, kit methods gave significantly higher values than independent methods although recovery of exogenous T3 was approximately quantitative with both. Cross reaction of T4 in T3 assays was insignificant. The range of between-batch precision for individual laboratories was 11.4-35.5% (mean 21.9%), and was poorest at levels of 1 nmol/l or less. For digoxin RIA, Lanoxitest γ gave significantly higher values than other methods, and over-recovered exogenous digoxin. The range of between-batch precision was 13.8-35.2% (mean 21.6%), and was poorest at levels of 1 nmol/l or less. The distribution of liquid human serum specimens at ambient temperature was satisfactory for quality control of T4, T3, and digoxin RIA but not for T4 by the Thyopac 4 method. Ox serum was unsuitable for certain T4 RIA methods. (author)

Influence of propranolol on uptake of radioiodinated heptadecanoic acid and thallium-201 in the dog heart

International Nuclear Information System (INIS)

Wall, E.E. van der; Eenige, M.J. van; Scholtalbers, S.; Visser, F.C.; Roos, J.P.; Westera, G.; Hollander, W. de

1983-01-01

In an experimental study, the influence of propranolol on myocardial uptake of radioiodinated heptadecanoic acid ( 131 I-HDA) and thallium-201 ( 201 Tl) in the dog heart was assessed. Uptake of 131 I-HDA and 201 Tl was evaluated in ten control dogs and in ten dogs 20 min after IV administration of propranolol (0.15 mg/kg). In both groups, four healthy dogs were studied and six dogs were studied after coronary artery occlusion. It was shown that both total uptake of 131 I-HDA and 201 Tl did not alter significantly, regardless of significant changes in hemodynamic parameters and total arterial plasma FFA levels. However, distribution of both 131 I-HDA and 201 Tl was markedly affected by propranolol, since the endocardial to epicardial ratio showed significantly higher values in the ischemic myocardial regions. The results of our study indicate that propranolol (1) preserves myocardial perfusion in the normal and acutely ischemic dog heart, and (2) gives a more favorable distribution in the ischemic myocardial region towards the subendocardial layers. (orig.)

A comparative study of propranolol versus silver nitrate cautery in the treatment of recurrent primary epistaxis in children

Science.gov (United States)

Ahmed, Ahmed E; Abo El-Magd, Essam A; Hasan, Gamal M; El-Asheer, Osama M

2015-01-01

Background Epistaxis is a common medical problem in pediatric population. Although in most cases it is mild and self-limiting, a proportion of childhood epistaxis is massive, recurrent, or resistant to conventional management. Objective To compare effectiveness of propranolol as a treatment option for childhood epistaxis versus conventional silver nitrate cautery. Study design and methodology This is a prospective interventional comparative study that was carried out during a period of 1 year (January 1, 2013 to December 31, 2013) at Qena University Hospital and Assiut University Children’s Hospital. One hundred children aged 6–12 years who presented with epistaxis to Qena University Hospital and Assiut University Children’s Hospital during the study period and fulfilling the inclusion criteria were included in the study. They were randomly assigned into one of two interventional groups, where 50 children were treated with oral propranolol (propranolol treatment group) and another 50 children were treated with conventional silver nitrate cautery (cauterization treatment group) for their epistaxis. Propranolol was given at a dose of 1.5–2 mg/kg/day (divided into three doses). Patients were followed for 6 months after their discharge for recurrence of epistaxis. Results Both groups of patients showed minimal recurrent epistaxis with rates of 14% for propranolol treated group and 12% for cauterization group, with no statistically significant difference between both groups. Local pain was found to be more in patients treated with silver nitrate cauterization. Conclusion Treatment of primary epistaxis with propranolol or silver nitrate cautery showed equal rates of recurrence, and local nasal pain was slightly more among silver nitrate cauterization treated group. Propranolol could be a favorable treatment option for patients with primary epistaxis. Further studies that include multiple centers and larger number of patients are recommended for more clarification

Disparate effects of eplerenone, amlodipine and telmisartan on podocyte injury in aldosterone-infused rats

NARCIS (Netherlands)

Liang, Wei; Chen, Cheng; Shi, Jing; Ren, Zhilong; Hu, Fengqi; van Goor, Harry; Singhal, Pravin C.; Ding, Guohua

Background. Several studies in patients with primary aldosteronism (PA) have suggested that aldosterone (ALD) is directly contributing to albuminuria. However, there are limited data pertaining to the direct role of ALD in (EPL), telmisartan (TEL) and amlodipine (AML) on ALD-induced renal structural

Effects of propranolol and clonidine on brain edema, blood-brain barrier permeability, and endothelial glycocalyx disruption after fluid percussion brain injury in the rat

DEFF Research Database (Denmark)

Genét, Gustav Folmer; Bentzer, Peter; Hansen, Morten Bagge

2018-01-01

clonidine would decrease brain edema, blood-brain barrier permeability, and glycocalyx disruption at 24 hours after trauma. METHODS: We subjected 53 adult male Sprague-Dawley rats to lateral fluid percussion brain injury and randomized infusion with propranolol (n = 16), propranolol + clonidine (n = 16......), vehicle (n = 16), or sham (n = 5) for 24 hours. Primary outcome was brain water content at 24 hours. Secondary outcomes were blood-brain barrier permeability and plasma levels of syndecan-1 (glycocalyx disruption), cell damage (histone-complexed DNA fragments), epinephrine, norepinephrine, and animal.......555). We found no effect of propranolol and propranolol/clonidine on blood-brain barrier permeability and animal motor scores. Unexpectedly, propranolol and propranolol/clonidine caused an increase in epinephrine and syndecan-1 levels. CONCLUSION: This study does not provide any support for unselective...

Ecotoxicological evaluation of propranolol hydrochloride and losartan potassium to Lemna minor L. (1753) individually and in binary mixtures.

Science.gov (United States)

Godoy, Aline A; Kummrow, Fábio; Pamplin, Paulo Augusto Z

2015-07-01

Antihypertensive pharmaceuticals, including the beta-blockers, are one of the most detected therapeutic classes in the environment. The ecotoxicity of propranolol hydrochloride and losartan potassium was evaluated, both individually and combined in a binary mixture, by using the Lemna minor growth inhibition test. The endpoints evaluated in the single-pharmaceutical tests were frond number, total frond area and fresh weight. For the evaluation of the mixture toxicity, the selected endpoint was frond number. Water quality criteria values (WQC) were derived for the protection of freshwater and saltwater pelagic communities regarding the effects induced by propranolol and losartan using ecotoxicological data from the literature, including our data. The risks associated with both pharmaceutical effects on non-target organisms were quantified through the measured environmental concentration (MEC)/predicted-no-effect concentration (PNEC) ratios. For propranolol, the total frond area was the most sensitive endpoint (EC50 = 77.3 mg L(-1)), while for losartan there was no statistically significant difference between the endpoints. Losartan is only slightly more toxic than propranolol. Both concentration addition and independent action models overestimated the mixture toxicity of the pharmaceuticals at all the effect concentration levels evaluated. The joint action of both pharmaceuticals showed an antagonistic interaction to L. minor. Derived WQC assumed lower values for propranolol than for losartan. The MEC/PNEC ratios showed that propranolol may pose a risk for the most sensitive aquatic species, while acceptable risks posed by losartan were estimated for most of aquatic matrices. To the authors knowledge these are the first data about losartan toxicity for L. minor.

Effect of propranolol in head tremor: quantitative study following single-dose and sustained drug administration.

Science.gov (United States)

Calzetti, S; Sasso, E; Negrotti, A; Baratti, M; Fava, R

1992-12-01

The effect of the beta-adrenoceptor antagonist propranolol has been investigated in nine patients suffering from isolated (six patients) or prominent (three patients) essential tremor of the head. In a double-blind, placebo-controlled study the tremorolytic efficacy of propranolol has been assessed by a quantitative accelerometric method after a single oral dose (120 mg) and following 2 weeks of sustained treatment with two different dosage regimens of the drug (120 and 240 mg daily). As compared with placebo, a significant reduction in tremor magnitude was found following a single oral dose but not on sustained administration of the beta-blocker at either dosage. The results suggest that the efficacy of sustained propranolol on isolated or prominent essential head tremor is less predictable and satisfactory than expected on the basis of the single-dose response, as compared with hand tremor.

Prevalent digoxin use and subsequent risk of death or hospitalization in ambulatory heart failure patients with a reduced ejection fraction-Findings from the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) randomized controlled trial.

Science.gov (United States)

Ambrosy, Andrew P; Bhatt, Ankeet S; Stebbins, Amanda L; Wruck, Lisa M; Fudim, Marat; Greene, Stephen J; Kraus, William E; O'Connor, Christopher M; Piña, Ileana L; Whellan, David J; Mentz, Robert J

2018-05-01

Despite more than 200 years of clinical experience and a pivotal trial, recently published research has called into question the safety and efficacy of digoxin therapy in heart failure (HF). HF-ACTION (ClinicalTrials.gov Number: NCT00047437) enrolled 2331 outpatients with HF and an EF ≤35% between April 2003 and February 2007 and randomized them to aerobic exercise training versus usual care. Patients were grouped according to prevalent digoxin status at baseline. The association between digoxin therapy and outcomes was assessed using Cox proportional hazard and inverse-probability weighted (IPW) regression models adjusted for demographics, medical history, medications, laboratory values, quality of life, and exercise parameters. The prevalence of digoxin therapy decreased from 52% during the first 6 months of enrollment to 35% at the end of the HF-ACTION trial (P <0.0001). Study participants were 59± 13 years of age, 72% were male, and approximately half had an ischemic etiology of HF. Patients receiving digoxin at baseline tended to be younger and were more likely to report New York Heart Association functional class III/IV symptoms (rather than class II) compared to those not receiving digoxin. Patients taking digoxin had worse baseline exercise capacity as measured by peak VO 2 and 6-min walk test and greater impairments in health status as reflected by the Kansas City Cardiomyopathy Questionnaire. The association between digoxin and the risk of death or hospitalization differed depending on whether Cox proportional hazard (Hazard Ratio 1.03, 95% Confidence Interval 0.92-1.16; P = .62) or IPW regression models (HR 1.08, 95% CI 1.00-1.17; P = .057) were used to adjust for potential confounders. Although digoxin use was associated with high-risk clinical features, the association between digoxin therapy and outcomes was dependent on the statistical methods used for multivariable adjustment. Clinical equipoise exists and additional prospective research is

Impact of Statin Therapy on the Blood Pressure-Lowering Efficacy of a Single-Pill Perindopril/Amlodipine Combination in Hypertensive Patients with Hypercholesterolemia.

Science.gov (United States)

Sirenko, Yuriy; Radchenko, Ganna

2017-03-01

Several lines of research indicate that statins can lower blood pressure (BP) independently of their lipid-lowering effects when used as monotherapy and in combination with antihypertensive agents. This short-term, open-label study examined whether statin therapy had a synergistic effect on the BP-lowering efficacy of perindopril/amlodipine in a subgroup of patients in the PERSPECTIVA study with concomitant hypertension and hypercholesterolemia, with or without statin at baseline. The PERSPECTIVA study recruited 732 adults with untreated or uncontrolled hypertension. This subgroup analysis of PERSPECTIVA included 587 patients with concomitant hypertension and hypercholesterolemia (mean age 56.7 years) of whom 226 were receiving a statin at baseline (statin [+] group) and 361 were not (statin [-] group). All patients received treatment with single-pill combination perindopril/amlodipine at a dose of 5/5, 10/5 or 10/10 mg/day. The study duration was 60 days with follow-up visits for BP monitoring at 7, 15, 30 and 60 days. At day 60, BP control (statin [+] vs statin [-] group: 73 vs 64% respectively (+14%, P statin [+] group, the single-pill perindopril/amlodipine combination significantly reduced BP in patients previously untreated (n = 18), or treated with monotherapy (n = 97), dual therapy (n = 93), or triple therapy (n = 18): -38.8/-20.0, -39.1/-20.1, -38.0/-19.4, -39.9/-18.3 mmHg respectively (P statin [+] group (0.9%) vs the statin [-] group (2.5%). BP control rates in patients with uncontrolled hypertension and concomitant hypercholesterolemia are significantly improved with a treatment regimen that combines perindopril/amlodipine with statin therapy, regardless of previous antihypertensive therapy. This subanalysis of the PERSPECTIVA study supports the synergistic BP-lowering effect of statins and perindopril/amlodipine.

A rapid liquid chromatography tandem mass spectrometry-based method for measuring propranolol on dried blood spots.

Science.gov (United States)

Della Bona, Maria Luisa; Malvagia, Sabrina; Villanelli, Fabio; Giocaliere, Elisa; Ombrone, Daniela; Funghini, Silvia; Filippi, Luca; Cavallaro, Giacomo; Bagnoli, Paola; Guerrini, Renzo; la Marca, Giancarlo

2013-05-05

Propranolol, a non-selective beta blocker drug, is used in young infants and newborns for treating several heart diseases; its pharmacokinetics has been extensively evaluated in adult patients using extrapolation to treat pediatric population. The purpose of the present study was to develop and validate a method to measure propranolol levels in dried blood spots. The analysis was performed by using liquid chromatography/tandem mass spectrometry operating in multiple reaction monitoring mode. The calibration curve in matrix was linear in the concentration range of 2.5-200 μg/L with correlation coefficient r=0.9996. Intra-day and inter-day precisions and biases were less than 8.0% (n=10) and 11.5% (n=10) respectively. The recoveries ranged from 94 to 100% and the matrix effect did not result in a severe signal suppression. Propranolol on dried blood spot showed a good stability at three different temperatures for one month. This paper describes a micromethod for measuring propranolol levels on dried blood spot, which determines a great advantage in neonates or young infants during pharmacokinetic studies because of less invasive sampling and small blood volume required. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparison of betaxolol, a new beta 1-adrenergic antagonist, to propranolol in the treatment of mild to moderate hypertension.

Science.gov (United States)

Davidov, M E; Glazer, N; Wollam, G; Zager, P G; Cangiano, J

1988-07-01

A double-blind, multicenter study compared the safety and efficacy of oral betaxolol 10 to 40 mg once daily (n = 68) with propranolol 40 to 160 mg twice daily (n = 73) in the treatment of mild to moderate essential hypertension. Both agents produced significant (P less than 0.01) and comparable reductions in mean supine systolic and diastolic blood pressures (7/11 mm Hg on betaxolol and 9/10 mm Hg on propranolol). Both betaxolol and propranolol significantly (P less than 0.01) reduced mean supine heart rate by 9 beats per minute. Patients achieved a more significant (P less than 0.01) reduction in blood pressure earlier (weeks 2 and 4 of the titration period) with betaxolol. By the end of treatment there was no significant difference in response between treatment groups. A higher incidence of central nervous system side effects (insomnia, bizarre dreams, depression, hallucinations, dizziness), however, was seen with propranolol than with betaxolol. Overall, the data show that in patients with mild to moderate essential hypertension, betaxolol 10 to 40 mg administered once daily is as effective as and better tolerated than propranolol 40 to 160 mg administered twice daily.

Amlodipine induced plasma cell granuloma of the gingiva: A novel case report.

Science.gov (United States)

Vishnudas, Bhandari; Sameer, Zope; Shriram, Bansode; Rekha, Kardile

2014-07-01

Drug-induced gingival overgrowth (DIGO) can be a serious concern for both patients and clinicians. DIGO is a well-documented side-effect of some pharmacologic agents, including, but not limited to, calcium channel blockers, phenytoin, and cyclosporine. Plasma cell granulomas (pseudotumors) are exceedingly rare, non-neoplastic, reactive tumor-like proliferation, primarily composed of plasma cells that manifest primarily in the lungs, but may occur in various anatomic locations. Intraoral plasma cell granulomas involving the lip, oral mucosa, tongue, and gingiva have been reported in the past. This is the first case report of amlodipine induced plasma cell granuloma of the gingiva in the medical literature presenting a 54 year-old female patient with hypertension, who received amlodipine (10 mg/day, single dose orally) for 2 years, sought medical attention because of developing maxillary anterior massive gingival overgrowth causing functional and esthetic problem, which was treated by excisional biopsy. Histologically, these lesions were composed of mature plasma cells, showing polyclonality for both lambda and kappa light chains and fibrovascular connective tissue stroma confirming a diagnosis of plasma cell granuloma. This case also highlights the need to biopsy for unusual lesions to rule out potential neoplasms.

Preparation and controlled release of mesoporous MCM-41/propranolol hydrochloride composite drug.

Science.gov (United States)

Zhai, Qing-Zhou

2013-01-01

This article used MCM-41 as a carrier for the assembly of propranolol hydrochloride by the impregnation method. By means of chemical analysis, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy and low-temperature N(2) adsorption-desorption at 77 K, the characterization was made for the prepared materials. The propranolol hydrochloride guest assembly capacity was 316.20 ± 0.31 mg/g (drug/MCM-41). Powder XRD test results indicated that during the process of incorporation, the frameworks of the MCM-41 were not destroyed and the crystalline degrees of the host-guest nanocomposite materials prepared still remained highly ordered. Characterization by SEM and TEM showed that the composite material presented spherical particle and the average particle size of composite material was 186 nm. FT-IR spectra showed that the MCM-41 framework existed well in the (MCM-41)-propranolol hydrochloride composite. Low-temperature nitrogen adsorption-desorption results at 77 K showed that the guest partially occupied the channels of the molecular sieves. Results of the release of the prepared composite drug in simulated body fluid indicated that the drug can release up to 32 h and its maximum released amount was 99.20 ± 0.11%. In the simulated gastric juice release pattern of drug, the maximum time for the drug release was discovered to be 6 h and the maximum cumulative released amount of propranolol hydrochloride was 45.13 ± 0.23%. The drug sustained-release time was 10 h in simulated intestinal fluid and the maximum cumulative released amount was 62.05 ± 0.13%. The prepared MCM-41 is a well-controlled drug delivery carrier.

Nanomagnet-based removal of lead and digoxin from living rats

Science.gov (United States)

Herrmann, Inge K.; Schlegel, Andrea; Graf, Rolf; Schumacher, Christoph M.; Senn, Nico; Hasler, Melanie; Gschwind, Sabrina; Hirt, Ann-Marie; Günther, Detlef; Clavien, Pierre-Alain; Stark, Wendelin J.; Beck-Schimmer, Beatrice

2013-08-01

In a number of clinical conditions such as intoxication, bacteraemia or autoimmune diseases the removal of the disease-causing factor from blood would be the most direct cure. However, physicochemical characteristics of the target compounds limit the applicability of classical filtration and diffusion-based processes. In this work, we present a first in vivo magnetic blood purification rodent animal model and demonstrate its ability to rapidly clear toxins from blood circulation using two model toxins with stable plasma levels (lead (Pb2+) and digoxin). Ultra-strong functionalized metal nanomagnets are employed to eliminate the toxin from whole blood in an extracorporeal circuit. In the present experimental demonstration over 40% of the toxin (i.e. lead or digoxin) was removed within the first 10 minutes and over 75% within 40 minutes. After capturing the target substance, a magnetic trap prevents the toxin-loaded nanoparticles from entering the blood circulation. Elemental analysis and magnetic hysteresis measurements confirm full particle recovery by simple magnetic separation (residual particle concentration below 1 μg mL-1 (detection limit)). We demonstrate that magnetic separation-based blood purification offers rapid blood cleaning from noxious agents, germs or other deleterious materials with relevance to a number of clinical conditions. Based on this new approach, current blood purification technologies can be extended to efficiently remove disease-causing factors, e.g. overdosed drugs, bacteria or cancer cells without being limited by filter cut-offs or column surface saturation.

Removal of toxicity the pharmaceutical propranolol and your mixture with fluoxetine hydrochloride in aqueous solution using radiation with electron beam; Remocao da toxicidade do farmaco propranolol e de sua mistura com cloridrato de fluoxetina em solucao aquosa empregando irradiacao com feixe de eletrons

Energy Technology Data Exchange (ETDEWEB)

Boiani, Nathalia Fonseca

2016-07-01

Environmental health has been damage due to incorrect disposal of products and by-products. Among emerging pollutants it is possible to account with several pharmaceuticals, causing those problems when disposed in the environment by effluents. Conventional processing techniques are insufficient in removal of the pharmaceuticals, for having resistant waste and low biodegradability. Thus the advanced oxidation processes have been studied as an alternative for the treatment of different types of effluents. The objective of this study was to apply the process of irradiation with electron beam in order to reduce the toxic effects of propranolol, and the mixture with fluoxetine hydrochloride in aqueous solution. Ecotoxicological tests conducted with propranolol, and the mixture with fluoxetine hydrochloride, for Daphnia similis microcrustacean, and the Vibrio fischeri bacterium. It was observed that D. similis was more sensitive to propranolol drug and to the mixture, when compared to bacterium V.fischeri. After being subjected to the treatment with ionizing radiation, all applied doses to the propranolol and the mixture, showed significant reduction of toxicity, for D. similis. Different were the results for V. fischeri, when only 5.0 kGy reduced toxicity to propranolol. The mixture of pharmaceuticals required 2.5 and 5.0 kGy for reducing toxicity. 5.0 kGy showed the best removal efficiency for toxicity: 79.94 % for D. similis and 15.64 % for V. fischeri, when exposed to propranolol. The mixture reduction efficacy were 81.59% and 26.93 % for D.similis and V.fischeri, respectively. (author)

Effects of propranolol in combination with radiation on apoptosis and survival of gastric cancer cells in vitro

International Nuclear Information System (INIS)

Liao, Xinhua; Che, Xiangming; Zhao, Wei; Zhang, Danjie; Long, Houlong; Chaudhary, Prakash; Li, Haijun

2010-01-01

The National Comprehensive Cancer Network (NCCN) guidelines recommend radiotherapy as a standard treatment for patients with a high risk of recurrence in gastric cancer. Because gastric cancer demonstrates limited sensitivity to radiotherapy, a radiosensitizer might therefore be useful to enhance the radiosensitivity of patients with advanced gastric carcinoma. In this study, we evaluated if propranolol, a β-adrenoceptor (β-AR) antagonist, could enhance radiosensitivity and explored its precise molecular mechanism in gastric cancer cells. Human gastric adenocarcinoma cell lines (SGC-7901 and BGC-823) were treated with or without propranolol and exposed to radiation. Cell viability and clonogenic survival assays were performed, and cell apoptosis was evaluated with flow cytometry. In addition, the expression of nuclear factor κB (NF-κB), vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX-2), and epidermal growth factor receptor (EGFR) were detected by western blot and real-time reverse transcription polymerase chain reaction (PCR). Propranolol combined with radiation decreased cell viability and clonogenic survivability. Furthermore, it also induced apoptosis in both cell lines tested, as determined by Annexin V staining. In addition, treatment with propranolol decreased the level of NF-κB and, subsequently, down-regulated VEGF, COX-2, and EGFR expression. Taken together, these results suggested that propranolol enhanced the sensitivity of gastric cancer cells to radiation through the inhibition of β-ARs and the downstream NF-κB-VEGF/EGFR/COX-2 pathway

PATHOGENESIS OF IMMUNE ALTERATIONS AND CORRECTIVE ROLE OF AMLODIPINE IN EXPERIMENTAL CHRONIC RENAL FAILURE

Directory of Open Access Journals (Sweden)

M. V. Osikov

2016-01-01

Full Text Available The purpose of this study was to assess some mechanisms of changes in immune state, and to evaluate a role of amlodipine, a known calcium channel blocker, as a potential corrective drug in experimental chronic renal failure (CRF. An animal CRF model was produced in rats by a two-stage operative resection of 5/6 of the renal tissue. Amlodipine is used per os at a daily dose of 0.25 mg/kg for 7 days. Flow cytofluorimetric approach was used to discern peripheral blood lymphocytes: CD3+ (mainly, T lymphocytes, CD45RA+ (mainly, B cells, as well as the following cell markers: Annexin 5-FITC+/7-AAD- (early apoptosis, Annexin 5-FITC+/7-AAD+ (late apoptosis and, in part, necrotic cells. Moreover, we have measured serum concentrations of urea, creatinine, phosphate, total calcium, parathyroid hormone (PTH, IL-1β, IL-4, interferon-γ, superoxide dismutase (SOD and catalase activities. Evaluation of Th1- and Th2-dependent immune response was carried out, respectively, by detection of delayed-type hypersensitivity, and scoring the antibody-forming cells in rat spleen induced by immunization with allogeneic erythrocytes. Primary, secondary and final products of lipid peroxidation were evaluated in lipid extracts from peripheral blood lymphocytes. Changes of immune state in CRF included depression of Th1 and Th2 dependent immune response, reduced number of lymphocytes bearing T and В cell markers, increased IL-1β concentrations in blood, along with decreased amounts of IFNγ and IL-4. Probable pathogenesis of the altered immune state may be associated with increased number of peripheral lymphocytes being at early and late stages of apoptosis/necrosis, elevated blood levels of IL-1β, total calcium, parathyroid hormone, reduced concentrations of IFNγ, and increased contents of primary, secondary and final peroxidation products in peripheral blood lymphocytes, being accompanied by inhibition of the SOD and catalase activity in blood plasma

The effect on serum enzymes of intramuscular injections of digoxin, bumetanide, pentazocine and isotonic sodium chloride

DEFF Research Database (Denmark)

Andersen, Klaus Ejner; Damsgaard, T

1976-01-01

Intramuscular injections of digoxin, bumetanide, pentazocine or isotonic sodium chloride have been given to 39 patients. We followed the serum concentrations of creatine kinase (CK), aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH) and LDH isoenzymes for 4 days. Ten patients receiving...

Effect of propranolol on survival in patients with decompensated cirrhosis

DEFF Research Database (Denmark)

Bang, Ulrich C; Benfield, Thomas; Hyldstrup, Lars

2016-01-01

BACKGROUND & AIMS: We assessed the impact of propranolol on death, risk of hepatorenal syndrome and peritonitis in patients with cirrhosis. METHODS: This study was a retrospective observational study and data were retrieved from Danish databases. We used our own criteria to stratify the patients...

Treatment of Aluminium Phosphide Poisoning with a Combination of Intravenous Glucagon, Digoxin and Antioxidant Agents

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Zohreh Oghabian

2016-08-01

Full Text Available Aluminium phosphide (AlP is used to protect stored grains from rodents. It produces phosphine gas (PH3, a mitochondrial poison thought to cause toxicity by blocking the cytochrome c oxidase enzyme and inhibiting oxidative phosphorylation, which results in cell death. AlP poisoning has a high mortality rate among humans due to the rapid onset of cardiogenic shock and metabolic acidosis, despite aggressive treatment. We report a 21-yearold male who was referred to the Afzalipour Hospital, Kerman, Iran, in 2015 after having intentionally ingested a 3 g AlP tablet. He was successfully treated with crystalloid fluids, vasopressors, sodium bicarbonate, digoxin, glucagon and antioxidant agents and was discharged from the hospital six days after admission in good clinical condition. For the treatment of AlP poisoning, the combination of glucagon and digoxin with antioxidant agents should be considered. However, evaluation of further cases is necessary to optimise treatment protocols.

A Psychophysiologic Study of Weakening Traumatic Combat Memories With Post-Reactivation Propranolol

National Research Council Canada - National Science Library

Pitman, Roger K

2008-01-01

The objective of this project is to test whether the beta-adrenergic blocker propranolol, given following combat memory reactivation, results in a significantly greater weakening of traumatic memories...

Effect of meal and propranolol on whole body and splanchnic oxygen consumption in patients with cirrhosis

DEFF Research Database (Denmark)

Krag, Aleksander; Simonsen, Lene; Henriksen, Jens H

2006-01-01

Our aim was to measure whole body energy expenditure after a mixed liquid meal, with and without simultaneous propranolol infusion, in patients with cirrhosis. We also wanted to investigate the effect of propranolol on substrate fluxes and oxygen uptake in the tissues drained by the hepatic vein ...... as splanchnic oxygen uptake. The splanchnic reduction in oxygen consumption can explain almost the entire reduction in whole body oxygen consumption....

Insulin versus Lipid Emulsion in a Rabbit Model of Severe Propranolol Toxicity: A Pilot Study

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Martyn Harvey

2011-01-01

Full Text Available Background and objective. Beta-blocker overdose may result in intractable cardiovascular collapse despite conventional antidotal treatments. High dose insulin/glucose (ING, and more recently intravenous lipid emulsion (ILE, have been proposed as potentially beneficial therapies in beta blocker intoxication. We compare efficacy of the novel antidotes ING, with ILE, in a rabbit model of combined enteric/intravenous propranolol toxicity. Methods. Sedated, mechanically ventilated and invasively monitored New Zealand White rabbits underwent mini-laparotomy and enterostomy formation with 40 mg/kg propranolol instilled into the proximal small bowel. At 30 minutes propranolol infusion was commenced at 4 mg/kg/hr and continued to a target mean arterial pressure (MAP of 50% baseline MAP. Animals were resuscitated with insulin at 3 U/kg plus 0.5 g/kg glucose (ING group, or 10 mL/kg 20% Intralipid (ILE group. Results. Rate pressure product (RPP; RPP = heart rate × mean arterial pressure was greatest in the ING group at 60 minutes (P<.05. A trend toward greater heart rate was observed in the ING group (P=.06. No difference was observed in survival between groups (4/5 ING versus 2/5 ILE; P=.524. Conclusions. High dose insulin resulted in greater rate pressure product compared with lipid emulsion in this rabbit model of severe enteric/intravenous propranolol toxicity.

[Absence of effect of propranolol on urinary excretion of 3-methylhistidine in hyperthyroidism].

Science.gov (United States)

Beylot, M; Riou, J P; Sautot, G; Mornex, R

Lean body mass and muscle protein breakdown were evaluated in euthyroid and hyperthyroid subjects by measuring the urinary excretion of creatinine and 3-methylhistidine. Since catecholamines probably have an inhibitory effect on muscle protein catabolism through a beta-receptor mechanism, the effects of propranolol on 3-methylhistidine excretion were also evaluated in hyperthyroid subjects. Hyperthyroid subjects had a lower lean body mass (34.9 +/- 6.3 kg versus 47.7 +/- 8.9 kg, p less than 0.001) and a greater 3-methylhistidine excretion (25.1 +/- 7.4 versus 19.0 +/- 4.8 mumol/mmol creatinine, p less than 0.05) than euthyroid subjects. Propranolol administered orally to hyperthyroid subjects decreased pulse rate (p less than 0.01) and plasma triiodothyronine concentrations (from 5.40 +/- 2.28 to 3.61 +/- 1.61 nmol/l, p less than 0.01), but did not modify urinary 3-methylhistidine excretion (24.8 +/- 8.7 versus 25.1 +/- 7.4 mumol/mmol creatinine). These results suggest that muscle wasting in hyperthyroidism is related to increased protein catabolism. This increased protein breakdown is not modified by short term administration of propranolol, a beta-blocking agent widely used in the management of hyperthyroidism.

A Psychophysiologic Study of Weakening Traumatic Combat Memories With Post-Reactivation Propranolol

National Research Council Canada - National Science Library

Pitman, Roger K

2008-01-01

...) propranolol, will show significantly smaller psychophysiologic responses during script-driven imagery testing a week later, indicative of weakening of the emotional memory, compared to those who receive (non-reactivation...

The influence of the flavonoid quercetin on the interaction of propranolol with human serum albumin: Experimental and theoretical approaches

Energy Technology Data Exchange (ETDEWEB)

Mohseni-Shahri, Fatemeh S., E-mail: fmohsenishahri@gmail.com [Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad (Iran, Islamic Republic of); Housaindokht, Mohammad R. [Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad (Iran, Islamic Republic of); Bozorgmehr, Mohammad R. [Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad (Iran, Islamic Republic of); Moosavi-Movahedi, Ali A. [Institute of Biochemistry and Biophysics, University of Tehran, Tehran (Iran, Islamic Republic of)

2014-10-15

The binding of propranolol (PROP) to human serum albumin (HSA) in the absence and presence of quercetin (QUER) in aqueous solution was investigated by multiple techniques. The presence of quercetin (QUER) increased binding constant of propranolol (PROP) with HSA. Fluorescence spectroscopy showed that quercetin (QUER) could quench the HSA fluorescence spectra. The results of synchronous fluorescence, resonance light scattering (RLS) and three-dimensional fluorescence spectra showed that propranolol (PROP) and quercetin (QUER) would alter the micro-environment around tryptophan (Trp) and tyrosine (Tyr) residues. According molecular dynamics (MD) simulation results suggested that these ligands can interact with the protein, with affecting the secondary structure of HSA and with a modification of its tertiary structure. Molecular docking studies showed that the affinity and binding site of each of the ligands to HSA altered in the presence of the other. All above results may have related consequence in rationalizing the interferences of ordinary food to cardiac dysrhythmias treatments. - Highlights: • The presence of quercetin increased binding constant of propranolol with HSA. • Quercetin quenched the fluorescence of HSA through a static quenching mechanism. • The binding of propranolol and quercetin with HSA induced partial unfolding. • The tertiary structure of HSA changed after ligand binding. • After the binding of quercetin, the helix content of HSA declined.

Application of receiver operating characteristic analysis to refine the prediction of potential digoxin drug interactionss

NARCIS (Netherlands)

Ellens, H.; Deng, S.; Coleman, J.; Bentz, J.; Taub, M.E.; Ragueneau-Majlessi, I.; Chung, S.P.; Herédi-Szabó, K.; Neuhoff, S.; Palm, J.; Balimane, P.; Zhang, L.; Jamei, M.; Hanna, I.; O'connor, M.; Bednarczyk, D.; Forsgard, M.; Chu, X.; Funk, C.; Guo, A.; Hillgren, K.M.; Li, L.; Pak, A.Y.; Perloff, E.S.; Rajaraman, G.; Salphati, L.; Taur, J.-S.; Weitz, D.; Wortelboer, H.M.; Xia, C.Q.; Xiao, G.; Yamagata, T.; Lee, C.A.

2013-01-01

In the 2012 Food and Drug Administration (FDA) draft guidance on drug-drug interactions (DDIs), a new molecular entity that inhibits Pglycoprotein (P-gp) may need a clinical DDI study with a P-gp substrate such as digoxin when themaximumconcentration of inhibitor at steady state divided by IC50

Value of digoxin in heart failure and sinus rhythm : New features of an old drug?

NARCIS (Netherlands)

vanVeldhuisen, DJ; deGraeff, PA; Remme, WJ

1996-01-01

Digoxin has been a controversial drug since its introduction >200 years ago. Although its efficacy in patients with heart failure and atrial fibrillation is clear, its value in patients with heart failure and sinus rhythm has often been questioned. In the 1980s, reports of some large-scale trials

Effect of Semaglutide on the Pharmacokinetics of Metformin, Warfarin, Atorvastatin and Digoxin in Healthy Subjects.

Science.gov (United States)

Hausner, Helene; Derving Karsbøl, Julie; Holst, Anders G; Jacobsen, Jacob B; Wagner, Frank-Dietrich; Golor, Georg; Anderson, Thomas W

2017-11-01

Semaglutide is a glucagon-like peptide-1 analogue in development for the once-weekly treatment of type 2 diabetes mellitus. Its effect on the rate and extent of absorption of concomitant oral medications (metformin, warfarin, atorvastatin and digoxin) was evaluated in healthy subjects. Subjects received metformin (500 mg twice daily for 3.5 days), warfarin (25 mg, single dose), atorvastatin (40 mg, single dose) or digoxin (0.5 mg, single dose) before and with subcutaneous semaglutide treatment at steady state (1.0 mg). Lack of drug-drug interaction was concluded if the 90% confidence intervals for the area under the plasma concentration-time curve ratio before and with semaglutide were within a pre-specified interval (0.80-1.25). Overall, metformin, warfarin, atorvastatin and digoxin pharmacokinetics were not affected to a clinically relevant degree with semaglutide co-administration. Estimated area under the plasma concentration-time curve ratios for all concomitant medications before and with semaglutide treatment were within the pre-specified interval. In addition, semaglutide did not affect maximum plasma concentration of concomitant medications to a relevant degree. Furthermore, no clinically relevant change in international normalised ratio response to warfarin was observed with semaglutide co-administration. Most adverse events with semaglutide treatment were mild or moderate. Adverse events with semaglutide and co-administered medication were comparable to those reported during treatment with semaglutide alone, and were mostly gastrointestinal related. No clinically significant pharmacokinetic or pharmacodynamic interactions were identified and no new safety issues observed with combined treatment with semaglutide. This suggests that no dose adjustments should be required when semaglutide is administered concomitantly with these medications.

EVALUATION OF PRIMARY PROPHYLAXIS WITH PROPRANOLOL AND ELASTIC BAND LIGATION IN VARICEAL BLEEDING IN CIRRHOTIC CHILDREN AND ADOLESCENTS

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Júlio Rocha PIMENTA

Full Text Available ABSTRACT Background The efficacy of nonselective β-blocker and endoscopic procedures, such as endoscopic variceal ligation, as primary prophylaxis of variceal hemorrhage in cirrhotic adults was demonstrated by numerous controlled trials, but in pediatric population, few are the number of studies. Objective The objective of this study is to evaluate the primary prophylaxis with β-blocker in cirrhotic children and adolescents with portal hypertension. Methods This is a cohort study encompassing 26 cirrhotic patients. β-blocker prophylaxis was performed with propranolol. When contraindicated the use of β-blocker, or if side effects presents, the patients were referred to endoscopic therapy with band ligation. Patients were evaluated by endoscopy, and those who had varicose veins of medium and large caliber or reddish spots, regardless of the caliber of varices, received primary prophylaxis. Results Of the 26 patients evaluated, 9 (34.6% had contraindications to the use of propranolol and were referred for endoscopic prophylaxis. Six (35.3% of the 17 patients who received β-blocker (propranolol, had bled after a median follow-up time of 1.9 years. β-blockage dosage varied from 1 mg/kg/day to 3.1 mg/kg/day and seven (41.2% patients had the propranolol suspended due to fail of the β-blockage or adverse effects, such as drowsiness, bronchospasm and hypotension. Patients who received endoscopic prophylaxis (elastic bandage had no bleeding during the follow-up period. Conclusion All of the patients that had upper gastroinstestinal bleeding in this study were under propranolol prophylaxis. The use of propranolol showed a high number of contraindications and side effects, requiring referral to endoscopic prophylaxis. The endoscopic prophylaxis was effective in reducing episodes of bleeding.

Propranolol's effects on the consolidation and reconsolidation of long-term emotional memory in healthy participants: a meta-analysis.

Science.gov (United States)

Lonergan, Michelle H; Olivera-Figueroa, Lening A; Pitman, Roger K; Brunet, Alain

2013-07-01

Considering the pivotal role of negative emotional experiences in the development and persistence of mental disorders, interfering with the consolidation/reconsolidation of such experiences would open the door to a novel treatment approach in psychiatry. We conducted a meta-analysis on the experimental evidence regarding the capacity of the ß-blocker propranolol to block the consolidation/reconsolidation of emotional memories in healthy adults. Selected studies consisted of randomized, double-blind experiments assessing long-term memory for emotional material in healthy adults and involved at least 1 propranolol and 1 placebo condition. We searched PsycInfo, PubMed, Web of Science, Cochrane Central, PILOTS, Google Scholar and clinicaltrials.org for eligible studies from the period 1995-2012. Ten consolidation (n = 259) and 8 reconsolidation (n = 308) experiments met the inclusion criteria. We calculated effect sizes (Hedges g) using a random effects model. Compared with placebo, propranolol given before memory consolidation reduced subsequent recall for negatively valenced stories, pictures and word lists (Hedges g = 0.44, 95% confidence interval [CI] 0.14-0.74). Propranolol before reconsolidation also reduced subsequent recall for negatively valenced emotional words and the expression of cue-elicited fear responses (Hedges g = 0.56, 95% CI 0.13-1.00). Limitations include the moderate number of studies examining the influence of propranolol on emotional memory consolidation and reconsolidation in healthy adults and the fact that most samples consisted entirely of young adults, which may limit the ecological validity of results. Propranolol shows promise in reducing subsequent memory for new or recalled emotional material in healthy adults. However, future studies will need to investigate whether more powerful idiosyncratic emotional memories can also be weakened and whether this weakening can bring about long-lasting symptomatic relief in clinical populations

Changes in cardiac glycoside receptor sites /sup 86/ rubidium uptake and intracellular sodium concentrations in the erythrocytes of patients receiving digoxin during the early phases of treatment of cardiac failure in regular rhythm and of atrial fibrillation

Energy Technology Data Exchange (ETDEWEB)

Ford, A R; Aronson, J K; Grahame-Smith, D G; Carver, J G [Medical Research Council, Oxford (UK)

1979-08-01

Measurements of the binding of 12-..cap alpha..-(/sup 3/H)-digoxin to the membranes of intact erythrocytes, erythrocytic /sup 86/Rb uptake and intraerythrocytic sodium concentrations have been made in the red cells of patients receiving digoxin in the short-term for atrial fibrillation or cardiac failure in regular rhythm. During the first few days of treatment (/sup 3/H)-digoxin binding and /sup 86/Rb uptake fall and intraerythrocytic sodium concentrations rise. Subsequently parallel fluctuations occur in (/sup 3/H)-digoxin binding and /sup 86/Rb uptake but not in intraerythrocytic sodium concentrations and the significance of the fluctuations is discussed. The values of all three measurements correlate significantly with the response of the heart in sinus rhythm as measured by QS/sub 2/I. Plasma digoxin concentrations do not correlate with QS/sub 2/I.

Comparative effectiveness of carvedilol and propranolol on glycemic control and insulin resistance associated with L-thyroxin-induced hyperthyroidism--an experimental study.

Science.gov (United States)

Bhatt, Parloop; Makwana, Dharmesh; Santani, Devdas; Goyal, Ramesh

2007-05-01

The present study was undertaken to investigate the effectiveness of adrenergic antagonists carvedilol and propranolol on L-thyroxin-induced cardiovascular and metabolic disturbances in rats. Treatment with L-thyroxin sodium (75 mg/kg body mass, s.c., every alternate day for 3 weeks), produced a significant increase in food and water intake, body temperature, heart rate, systolic blood pressure, along with an increase in serum T3, T4, and triglyceride levels. Besides a significant reduction in body mass, serum levels of TSH and cholesterol were also reduced following L-thyroxin treatment. Carvedilol (10 mg/kg body mass, orally) and propranolol (10 mg/kg body mass, i.p.) administered daily in the third week to 2 separate groups of L-thyroxin-treated animals reversed thyroxin-induced loss in body mass and rise in body temperature, blood pressure, and heart rate. Propranolol treatment increased TSH levels and decreased T3 and T4 levels in hyperthyroid animals, whereas carvedilol did not produce any effect on thyroid hormones. Carvedilol treatment reversed thyroxin induced hypertriglyceridemia, whereas propranolol treatment had no effect. Both carvedilol and propranolol prevented decrease in cholesterol levels induced by thyroxine. Compared with normal animals, L-thyroxin-treated animals showed a state of hyperglycemia, hyperinsulinaemia, impaired glucose tolerance, and insulin resistance, as inferred from elevated fasting serum glucose and insulin levels, higher area under the curve over 120 min for glucose, and decreased insulin sensitivity index (KITT). Propranolol and carvedilol treatment significantly decreased fasting serum glucose levels. Treatment with propranolol did not alter serum insulin levels, area-under-the-curve glucose, or KITT values. However, treatment with carvedilol significantly reduced area-under-the-curve glucose, decreased fasting serum insulin levels and significantly increased KITT values. In conclusion, carvedilol appears to produce

Using Propranolol to Block Memory Reconsolidation in Female Veterans with PTSD

Science.gov (United States)

2015-11-01

half-time support for an undergraduate student to process de- identified data and help with dissemination of recruitment materials. REPORTABLE...experience with Male Veterans and presents an important limitation to the consideration of propranolol as a PTSD treatment. Further, patient dropout

[Fixed drug combinations in hypertension: a budget impact analysis for the Spanish Health System on the marketing of a fixed combination of olmesartan/amlodipine].

Science.gov (United States)

Belén Ferro-Rey, M; Roca-Cusachs, Alex; Sicras-Mainar, Antoni; Alvarez-Martín, Carlos; de Salas-Cansado, Marina

2011-07-01

To carry out a budget impact analysis (BIA) of olmesartan/amlodipine (20/5, 40/5 and 40/10mg) marketed as a fixed combination (FC) in its approved indication for the National Health System (NHS). We developed a decision tree model in order to estimate usual hypertension treatment algorithm in Spanish clinical practice. The BIA has been developed from the perspective of the NHS for a period of 3 years (years 2010-2012). Spanish hypertensive population ≥ 35 years old. Introduction into the market of a fixed combination (FC) olmesartan/amlodipine in Spain. Expected costs to be assumed by the Spanish NHS (RRP-VAT) for hypertensive population able to be treated with the FC versus currently assumed costs by the NHS with free combination olmesartan and amlodipine. Estimated pharmaceutical costs in hypertensive population treated with olmesartan and amlodipine (2 pills) would be €25.2M (1(st) year), €26.4M (2011), €27.6M (2012), with a total 3-year period of €79.2M. According to patient tree model, the population able to be treated with FC would be 71,283 patients (2010), with a growth rate of 4.8% in the successive years, which supposes an annual cost of €21.2M (2010), €21.8M (2011) and €22.4M (2012), with a total 3-year period of €65.4M. The BIA shows savings of €13.8M in a total 3-year period. The BIA of FC olmesartan/amlodipine could generate net savings of €13.8M for the NHS in the period ranging from years 2010 to 2012. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Paradoxical physiological responses to propranolol in a Rett syndrome patient: a case report.

Science.gov (United States)

Santosh, P J; Bell, L; Lievesley, K; Singh, J; Fiori, F

2016-11-29

Rett Syndrome (RTT), caused by a loss-of-function in the epigenetic modulator: X-linked methyl-CpG binding protein 2 (MeCP2), is a pervasive neurological disorder characterized by compromised brain functions, anxiety, severe mental retardation, language and learning disabilities, repetitive stereotyped hand movements and developmental regression. An imbalance in the sympathetic and the parasympathetic nervous system (dysautonomia) and the resulting autonomic storms is a frequent occurrence in patients with RTT. The prototypical beta blocker propranolol has been used to manage sympathetic hyperactivity in patients with RTT. A 13 year old girl with RTT was referred to the Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD), South London and Maudsley NHS Foundation Trust. Her clinical picture included disordered breathing with concomitant hyperventilation and apnoea, epilepsy, scoliosis, no QT prolongation (QT/QTc [372/467 ms on automated electrocardiogram [ECG], but manually calculated to be 440 ms]), no cardiac abnormalities (PR interval: 104 ms, QRS duration: 78 ms), and generalised anxiety disorder (ICD-10-CM Diagnosis Code F41.1). She was also constipated and was fed via percutaneous endoscopic gastrostomy (PEG). To manage the dysautonomia, propranolol was given (5 mg and 10 mg) and in parallel her physiological parameters, including heart rate, skin temperature and skin transpiration, were monitored continuously for 24 h as she went about her activities of daily living. Whilst her skin temperature increased and skin transpiration decreased, unexpectedly there was a significant paradoxical increase in the patient's average heart rate following propranolol treatment. Here, we present a unique case of a paradoxical increase in heart rate response following propranolol treatment for managing dysautonomia in a child with RTT. Further studies are warranted to better understand the underlying dysautonomia in patients with RTT and

Removal of toxicity the pharmaceutical propranolol and your mixture with fluoxetine hydrochloride in aqueous solution using radiation with electron beam

International Nuclear Information System (INIS)

Boiani, Nathalia Fonseca

2016-01-01

Environmental health has been damage due to incorrect disposal of products and by-products. Among emerging pollutants it is possible to account with several pharmaceuticals, causing those problems when disposed in the environment by effluents. Conventional processing techniques are insufficient in removal of the pharmaceuticals, for having resistant waste and low biodegradability. Thus the advanced oxidation processes have been studied as an alternative for the treatment of different types of effluents. The objective of this study was to apply the process of irradiation with electron beam in order to reduce the toxic effects of propranolol, and the mixture with fluoxetine hydrochloride in aqueous solution. Ecotoxicological tests conducted with propranolol, and the mixture with fluoxetine hydrochloride, for Daphnia similis microcrustacean, and the Vibrio fischeri bacterium. It was observed that D. similis was more sensitive to propranolol drug and to the mixture, when compared to bacterium V.fischeri. After being subjected to the treatment with ionizing radiation, all applied doses to the propranolol and the mixture, showed significant reduction of toxicity, for D. similis. Different were the results for V. fischeri, when only 5.0 kGy reduced toxicity to propranolol. The mixture of pharmaceuticals required 2.5 and 5.0 kGy for reducing toxicity. 5.0 kGy showed the best removal efficiency for toxicity: 79.94 % for D. similis and 15.64 % for V. fischeri, when exposed to propranolol. The mixture reduction efficacy were 81.59% and 26.93 % for D.similis and V.fischeri, respectively. (author)

Effects of propranolol on conversational reciprocity in autism spectrum disorder: a pilot, double-blind, single-dose psychopharmacological challenge study.

Science.gov (United States)

Zamzow, Rachel M; Ferguson, Bradley J; Stichter, Janine P; Porges, Eric C; Ragsdale, Alexandra S; Lewis, Morgan L; Beversdorf, David Q

2016-04-01

Pharmacological intervention for autism spectrum disorder (ASD) is an important addition to treatment, yet currently available agents target co-morbid psychiatric concerns, such as aggression and irritability. Propranolol, a beta-adrenergic antagonist with anxiolytic effects, has been shown to improve verbal fluency and working memory in adults and adolescents with ASD in single-dose challenges. The present pilot study explores the acute effects of propranolol on a measure of conversational reciprocity in this population. We also examined whether autonomic activity and anxiety moderate or mediate response to the drug, given relationships between these variables and ASD, as well as the drug's effects. In a within-subject crossover design, 20 individuals with ASD received a single dose of propranolol or placebo during two sessions in a double-blinded, counterbalanced manner. After drug administration, participants performed a conversational reciprocity task by engaging in a short conversation with the researcher. Measurements of autonomic activity and anxiety were obtained before and after drug administration. Propranolol significantly improved performance on the conversational reciprocity task total [d = 0.40] and nonverbal communication domain scores when compared to the placebo condition. However, neither autonomic activity nor anxiety was significantly associated with drug response. Acute propranolol administration improved conversational reciprocity in ASD. Further exploration of these preliminary findings, as well as other potential treatment response predictors, with serial doses is warranted.

A study of the relationship between serum bile acids and propranolol pharmacokinetics and pharmacodynamics in patients with liver cirrhosis and in healthy controls.

Directory of Open Access Journals (Sweden)

Anne B Taegtmeyer

Full Text Available The main objectives of the study were to determine the exposure and bioavailability of oral propranolol and to investigate their associations with serum bile acid concentration in patients with liver cirrhosis and in healthy controls. A further objective was to study the pharmacodynamics of propranolol. An open-label crossover study was performed to determine the pharmacokinetics and pharmacodynamics of propranolol after oral (40 mg and intravenous (1 mg administration as well as the concentration of total and individual fasting serum bile acids in 15 patients with liver cirrhosis and 5 healthy controls. After intravenous propranolol, patients showed a 1.8-fold increase in the area under the plasma concentration-time curve (AUC0-∞, a 1.8-fold increase in volume of distribution and a 3-fold increase in the elimination half-life (mean ± SEM: 641±100 vs. 205±43 minutes compared to controls. After oral application, AUC0-∞ and elimination half-life of propranolol were increased 6- and 4-fold, respectively, and bioavailability 3-fold (83±8 vs. 27±9.2%. Maximal effects on blood pressure and heart rate occurred during the first 4 and first 2 hours, respectively, after intravenous and oral application in both patients and controls. Total serum bile acid concentrations were higher in patients than controls (42±11 vs. 2.7±0.3 µmol/L and were linearly correlated with the serum chenodeoxycholic acid concentration. There was a linear correlation between the SBA concentration and propranolol oral AUC0-∞ in subjects not receiving interacting drugs (r2 = 0.73, n = 18. The bioavailability of and exposure to oral propranolol are increased in patients with cirrhosis. Fasting serum bile acid concentration may be helpful in predicting the exposure to oral propranolol in these patients.

A Comparative Study of the Management of Stage 2 hypertension by Combined therapy with Losartan, Amlodipine and Hydrochlorothiazide

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Reza Jafarzadeh Esfehani

2012-09-01

Full Text Available Background: The most effective and accurate treatment of hypertensive patients reduces cardiovascular events and improves the quality of life. Objective: This study compared the efficacy and safety of combined (combination therapy with an angiotensin-receptor blocker (ARB a calcium-channel blocker (CCB (Losartan / Amloidipine 50/10mg vs maximal combination doses of ARB with hydrochlorothiazide (Losartan /HCTZ 100/25 mg and maximal combination doses of CCB with HCTZ (Amlodipine /HCTZ 10/25 mg in the management of stage 2 hypertension. Methods: This randomized clinical trial (RTC comprised 478 hypertensive patients with mean age 50.5±5.21 years, and took place between January 2010 and December 2011 in Vasei Hospital clinic in Sabzevar. Antihypertensive drugs were washed out after 5 days of discontinuation of drugs and the patients with mean blood pressure in sitting position ≥ 160 and <200 mmHg in systole and ≥ 100 and <110 mmHg in diastole were randomized into three groups: Losartan / Amlodipine 50/10 mg (n =164 , Losartan / HCTZ 100/25 mg (n =155 and Amlodipine / HCTZ 10/25 mg (n =159. The end point was reaching the blood pressure below 140/90 within 56 days of treatment in each group. Results: There was a significant difference in systolic blood pressure reductions between treatment groups (P<0.001 and also there was a significant difference between groups in reducing diastolic blood pressure (P<0.01. The highest systolic and diastolic blood pressure reduction respectively was found in Amlodipine/losartane and losartane/HTCZ group. The ANCOVA analysis revealed that only treatment regimen had a significant effect (P=0.01 and other factor including Age, Gender, Diabetes Mellitus, Smoking and High serum cholesterol didn’t have significant effect on blood pressure reduction. Conclusion: ARB/CCB combination therapy reduced blood pressure more effectively than the maximal doses of ARB or CCB with HCTZ in stage 2 hypertensive patients within

Studies on the comparability of the results from different methods for the radioimmunological determination of digoxin

International Nuclear Information System (INIS)

Dwenger, A.; Trautschold, I.

1978-01-01

Three iodine-125-digoxin radioimmunoassay kits (A Amersham Buchler; B Boehringer Mannheim; C Schwarz Mann/Becton Dickinson) were evaluated with respect to assay quality and comparability of the results. Intra- and interassay variances were calculated for the following types of samples: Three media (a pool serum; b artificial human serum; c buffer solution with albumin and globulin) containing pure digoxin, sera from a pharmacokinetic study, sera with different concentrations of proteins, a hemolytic serum and sera with digitoxin and metabolites of spironolactone. The intra-assay precision depended on the medium of the sample and was higher for samples with identical digoxin concentrations in an identical medium (e.g. CV for 2 μg/l in medium a for kit A: 4.3% for kit B: 7.0%; for kit C: 2.2%) than for samples with identical antigen concentrations in different media (CV for 2 μg/l in media a, b and c for kit A: 6.4%; for kit B: 9.1%; for kit C: 4.3%). The mean recovery in the range 0.5-4 μg/l depended on the kind of medium (a, b or c) and varied for kit A from 84.4% to 100.8%, for kit B from 112.0% to 119.6%, and for kit C from 98.0% to 104.5%. Decreasing serum protein concentrations to less than one half of the physiological concentration gave false negative results for kit A and fals positive results for kit C; for kit B this dependency was not be observed, but there was a decrease of reproducibility. (orig./AJ) [de

The combined propranolol/TSST paradigm--a new method for psychoneuroendocrinology.

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Julie Andrews

Full Text Available Upon perception of a stimulus as stressful, the human brain reacts with the activation of the hypothalamus-pituitary-adrenal (HPA axis and the sympathetic nervous system (SNS, to mobilize energy resources to better cope with the stressor. Since the perception of the stressor is the initial stimulus, a synchronicity between the subjective perception of stress and the physiological stress reactivity should be expected. However, according to a recent meta-analysis, these associations are weak and inconsistent. The goal of the current study was to investigate the interaction between the SNS, HPA and subjective stress perceptions, by introducing an experimental manipulation of this interaction. For this purpose, we combined the SNS inhibitor propranolol with the Trier Social Stress Test, and measured endocrinological and psychological responses to the stressor. Thirty healthy male participants were recruited and randomly assigned to either a propranolol (PROP; n = 15 or placebo (PLC; n = 15 group. All subjects were administered 80 mg of propranolol 60 minutes prior to exposure to psychosocial stress. Salivary cortisol and alpha amylase (sAA, heart rate, blood pressure and subjective stress responses were assessed throughout the study. We observed significantly reduced sAA levels and heart rate increases in the PROP group in response to stress, with no effects of the drug on systolic or diastolic blood pressure changes. In line with previous studies, a significant increase in cortisol was seen in response to the stress exposure. Importantly, the cortisol increase was significantly higher in the PROP group. A typical increase in subjective stress could be seen in both groups, with no significant group differences emerging. Complementing previous work, this study further demonstrates a significant interaction between the HPA and the SNS during acute stress. The HPA activity was found to be elevated in the presence of a suppressed SNS in

A model to study intestinal and hepatic metabolism of propranolol in the dog.

Science.gov (United States)

Mills, P C; Siebert, G A; Roberts, M S

2004-02-01

A model to investigate hepatic drug uptake and metabolism in the dog was developed for this study. Catheters were placed in the portal and hepatic veins during exploratory laparotomy to collect pre- and posthepatic blood samples at defined intervals. Drug concentrations in the portal vein were taken to reflect intestinal uptake and metabolism of an p.o. administered drug (propranolol), while differences in drug and metabolite concentrations between portal and hepatic veins reflected hepatic uptake and metabolism. A significant difference in propranolol concentration between hepatic and portal veins confirmed a high hepatic extraction of this therapeutic agent in the dog. This technically uncomplicated model may be used experimentally or clinically to determine hepatic function and metabolism of drugs that may be administered during anaesthesia and surgery.

Assessment of the effectiveness of topical propranolol 4% gel for infantile hemangiomas.

Science.gov (United States)

Mashiah, Jacob; Kutz, Ana; Rabia, Smail Hadj; Ilan, Efrat Bar; Goldberg, Ilan; Sprecher, Eli; Harel, Avikam

2017-02-01

Infantile hemangiomas (IHs) are the most common vascular tumors in children. Because of their benign character and natural involution, the vast majority of IHs do not require any treatment. In the past few years, topical beta blockers have been reported to be an effective treatment of superficial IHs. We sought to evaluate the clinical effectiveness and safety profile of topical propranolol 4% gel for the treatment of IHs. A retrospective study of all cases of IHs treated with topical propranolol 4% gel between 2013 and 2015 was performed. All patients were evaluated in a pediatric dermatology unit of a tertiary medical center. Epidemiologic, clinical, and treatment data, including effectiveness score and safety, were reviewed. The study included 63 patients with a total of 75 IHs. Of the total number of IHs, 43 (57.3%) showed a good response to treatment, 19 (25.3%) a partial response, and 13 (17.33%) poor or no response, thus 62 (82.6%) had good or partial response to treatment. Age at treatment initiation, treatment time, thickness of the superficial component, and size of the lesions were shown to predict response to therapy. Out of the entire examined group, only two patients reported minor local side effects manifested by irritation, redness, and scaling of the treated area. No systemic adverse effects were reported. This is an uncontrolled retrospective study. Propranolol 4% gel is a safe and efficient topical therapy for IH. © 2017 The International Society of Dermatology.

Synthesis of nano-sized stereoselective imprinted polymer by copolymerization of (S)-2-(acrylamido) propanoic acid and ethylene glycol dimethacrylate in the presence of racemic propranolol and copper ion

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Alizadeh, Taher, E-mail: talizadeh@ut.ac.ir [Department of Analytical Chemistry, Faculty of Chemistry, University College of Science, University of Tehran, P.O. Box 14155-6455, Tehran (Iran, Islamic Republic of); Bagherzadeh, Azam; Shamkhali, Amir Nasser [Department of Applied Chemistry, Faculty of Science, University of Mohaghegh Ardabili, Ardabil (Iran, Islamic Republic of)

2016-06-01

A new chiral functional monomer of (S)-2-(acrylamido) propanoic acid was obtained by reaction of (L)-alanine with acryloyl chloride. The resulting monomer was characterized by FT-IR and HNMR and then utilized for the preparation of chiral imprinted polymer (CIP). This was carried out by copolymerization of (L)-alanine-derived chiral monomer and ethylene glycol dimethacrylate, in the presence of racemic propranolol and copper nitrate, via precipitation polymerization technique, resulting in nano-sized networked polymer particles. The polymer obtained was characterized by scanning electron microscopy and FT-IR. The non-imprinted polymer was also synthesized and used as blank polymer. Density functional theory (DFT) was also employed to optimize the structures of two diasterometric ternary complexes, suspected to be created in the pre-polymerization step, by reaction of optically active isomers of propranolol, copper ion and (S)-2-(acrylamido) propanoic acid. Relative energies and other characteristics of the described complexes, calculated by the DFT, predicted the higher stability of (S)-propranolol involved complex, compared to (R)-propranolol participated complex. Practical batch extraction test which employed CIP as solid phase adsorbent, indicated that the CIP recognized selectively (S)-propranolol in the racemic mixture of propranolol; whereas, the non-imprinted polymer (NIP) showed no differentiation capability between two optically active isomers of propranolol. - Highlights: • A new chiral functional monomer of (S)-2-(acrylamido) propanoic acid was synthesized. • (S)-propranolol-selective imprinted polymer was synthesized using the chiral monomer. • Racemic propranolol mixed with Cu(II) was used as template in the imprinting. • Density functional theory was employed to clarify the imprinting mechanism. • (S)-propranolol-Cu(II) complex was shown to conduct the imprinting process.

Temporomandibular joint dislocation due to acute propranolol intoxication

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Abbas Aghabiklooei

2010-07-01

Full Text Available Abbas Aghabiklooei1, Homan Elahi2, Babak Mostafazadeh31Department of Medical Toxicology and Forensic Medicine, Iran University of Medical Sciences, Tehran, Iran; 2Firouzgar Hospital, Department of ENT, Tehran, Iran; 3Department of Medical Toxicology and Forensic Medicine, Shaheed Beheshty University of Medical Sciences, Tehran, IranAbstract: Temporomandibular joint (TMJ dislocation has not previously been reported as a complication of beta-blocker toxicity. We are reporting two cases of TMJ dislocation resulted from acute severe intoxication with pure propranolol (PPL for the first time. Bilateral TMJ dislocation happened in two patients who were admitted to intensive care unit with diagnosis of severe acute PPL toxicity. Clinical diagnosis of TMJ dislocation was obtained by physical examination. Successful reduction was performed for both patients without subsequent recurrence in two weeks following hospital discharge. Both of our subjects had no previous history of lower jaw dislocation. There was not any risk factor for dislocation such as convulsion during admission period, recent face trauma, or oral manipulation by the medical team. This study showed that TMJ dislocation may occur after severe acute PPL toxicity probably due to spastic contraction of the lateral pterygoid muscle. This is against previously mentioned hypothesis that stated masseteric muscles contraction as the main cause of a bilateral dislocated TMJ.Keywords: propranolol, toxicity, temporomandibular joint dislocation

Chronic effects assessment and plasma concentrations of the {beta}-blocker propranolol in fathead minnows (Pimephales promelas)

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Giltrow, Emma [Institute for the Environment, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom); Eccles, Paul D. [Institute for the Environment, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom); Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom); Winter, Matthew J.; McCormack, Paul J. [AstraZeneca Safety, Health and Environment, Brixham Environmental Laboratory, Freshwater Quarry, Brixham, Devon TQ5 8BA (United Kingdom); Rand-Weaver, Mariann [Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom); Hutchinson, Thomas H. [Natural Environmental Research Council, Plymouth Marine Laboratory, Prospect Place, The Hoe, Plymouth PL1 3DH (United Kingdom); Sumpter, John P., E-mail: john.sumpter@brunel.ac.uk [Institute for the Environment, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom)

2009-11-27

The presence of many human pharmaceuticals in the aquatic environment is now a worldwide concern, yet little is known of the chronic effects that these bioactive substances may be having on aquatic organisms. Propranolol, a non-specific beta adrenoreceptor blocker ({beta}-blocker), is used to treat high blood pressure and heart disease in humans. Propranolol has been found in surface waters worldwide at concentrations ranging from 12 to 590 ng/L. To test the potential for ecologically relevant effects in fish in receiving waters, short-term (21 days) adult reproduction studies were conducted, in which fathead minnows were exposed to nominal concentrations of propranolol hydrochloride [CAS number 318-98-9] ranging from 0.001 to 10 mg/L (measured concentrations typically from 78 to 130%). Exposure of fish to 3.4 mg/L (measured) over 3 days caused 100% mortality or severe toxicity requiring euthanasia. The most sensitive endpoints from the studies were a decrease in hatchability (with regard to the number of days to hatch) and a concentration-related increase in female gonadal somatic index (GSI), giving LOEC{sup hatchability} and LOEC{sup female} {sup GSI} values of 0.1 mg/L. Concentration-related decreases in weights of male fish were also observed, with LOEC{sup m}ale wet weight value of 1.0 mg/L, and the LOEC{sup r}eproduction value was 1.0 mg/L. Collectively, these data do not suggest that propranolol was acting as a reproductive toxin. Plasma concentrations of propranolol in male fish exposed to nominal concentrations of 0.1 and 1.0 mg/L were 0.34 and 15.00 mg/L, respectively, which constitutes 436 and 1546% of measured water concentrations. These compare with predicted concentrations of 0.07 and 0.84 mg/L, and thus to a degree support the use of partition coefficient models for predicting concentrations in plasma in fish. In addition, propranolol plasma concentrations in fish exposed to water concentrations of 0.1 and 1.0 mg/L were greater than the human

Chronic effects assessment and plasma concentrations of the β-blocker propranolol in fathead minnows (Pimephales promelas)

International Nuclear Information System (INIS)

Giltrow, Emma; Eccles, Paul D.; Winter, Matthew J.; McCormack, Paul J.; Rand-Weaver, Mariann; Hutchinson, Thomas H.; Sumpter, John P.

2009-01-01

The presence of many human pharmaceuticals in the aquatic environment is now a worldwide concern, yet little is known of the chronic effects that these bioactive substances may be having on aquatic organisms. Propranolol, a non-specific beta adrenoreceptor blocker (β-blocker), is used to treat high blood pressure and heart disease in humans. Propranolol has been found in surface waters worldwide at concentrations ranging from 12 to 590 ng/L. To test the potential for ecologically relevant effects in fish in receiving waters, short-term (21 days) adult reproduction studies were conducted, in which fathead minnows were exposed to nominal concentrations of propranolol hydrochloride [CAS number 318-98-9] ranging from 0.001 to 10 mg/L (measured concentrations typically from 78 to 130%). Exposure of fish to 3.4 mg/L (measured) over 3 days caused 100% mortality or severe toxicity requiring euthanasia. The most sensitive endpoints from the studies were a decrease in hatchability (with regard to the number of days to hatch) and a concentration-related increase in female gonadal somatic index (GSI), giving LOEC hatchability and LOEC female GSI values of 0.1 mg/L. Concentration-related decreases in weights of male fish were also observed, with LOEC m ale wet weight value of 1.0 mg/L, and the LOEC r eproduction value was 1.0 mg/L. Collectively, these data do not suggest that propranolol was acting as a reproductive toxin. Plasma concentrations of propranolol in male fish exposed to nominal concentrations of 0.1 and 1.0 mg/L were 0.34 and 15.00 mg/L, respectively, which constitutes 436 and 1546% of measured water concentrations. These compare with predicted concentrations of 0.07 and 0.84 mg/L, and thus to a degree support the use of partition coefficient models for predicting concentrations in plasma in fish. In addition, propranolol plasma concentrations in fish exposed to water concentrations of 0.1 and 1.0 mg/L were greater than the human therapeutic plasma concentration

A Psychophysiologic Study of Weakening Traumatic Combat Memories with Post-Reactivation Propranolol

Science.gov (United States)

2011-06-01

Research Protection Office, subjects gave written informed consent. Study medication Propranolol hydrochloride is a non-selective synthetic β1...confounding substances, including opiates, barbiturates, and methadone , at the time of the script-driven imagery procedure. When the analyses were repeated

Structures and characterization of digoxin- and bufalin-bound Na+,K+-ATPase compared with the ouabain-bound complex

DEFF Research Database (Denmark)

Laursen, Mette; Gregersen, Jonas Lindholt; Yatime, Laure

2015-01-01

. These functionalities have specific influence on the binding properties. We report crystal structures of the Na+,K+-ATPase in the E2P form in complex with bufalin (a nonglycosylated CTS with a six-membered lactone) and digoxin (a trisaccharide-conjugated CTS with a five-membered lactone) and compare......Cardiotonic steroids (CTSs) are specific and potent inhibitors of the Na+,K+-ATPase, with highest affinity to the phosphoenzyme (E2P) forms. CTSs are comprised of a steroid core, which can be glycosylated, and a varying number of substituents, including a five- or six-membered lactone...... in site II of the digoxin and ouabain complexes, whereas both sites are occupied by K+ in the E2P–bufalin complex. In all complexes, αM4 adopts a wound form, characteristic for the E2P state and favorable for high-affinity CTS binding. We conclude that the occupants of the cation-binding site and the type...

Can combining different risk interventions into a single formulation contribute to improved cardiovascular disease risk reduction? The single pill of amlodipine/atorvastatin

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FD Richard Hobbs

2007-11-01

Full Text Available FD Richard HobbsUniversity of Birmingham, Edgbaston, Birmingham B15 2TT, UK.Abstract: In order to prevent cardiovascular events, it is essential to effectively manage overall risk of cardiovascular disease. However, despite guideline recommendations to this effect, current management of the major, modifiable cardiovascular risk factors such as hypertension and dyslipidemia is disconnected and patient adherence to therapy is poor. This is particularly important for patients with multiple cardiovascular risk factors, who are often prescribed multiple medications. The JEWEL study program investigated the use of single-pill amlodipine/atorvastatin as a strategy to improve management of these patients. The JEWEL program consisted of two 16-week, international, openlabel, multicenter, titration-to-goal studies in patients with hypertension and dyslipidemia. The two studies differed based on country of enrollment and certain tertiary endpoints, but the overall designs were very similar. Patients were enrolled from 255 centers across Canada and 13 European countries. The study was designed to assess the efficacy, safety, and utility of amlodipine/atorvastatin single pill therapy in a real-world setting. Patients were initiated at a dose of amlodipine 5 mg/atorvastatin 10 mg, unless previously treated, and were uptitrated as necessary. The primary efficacy parameter was the percentage of patients, at different levels of cardiovascular risk, achieving country-specific guideline-recommended target levels for blood pressure and lipids. A secondary analysis of efficacy measured attainment of the same single goal for blood pressure across all study participants (JEWEL I and II and the same single goal for LDL-C across all study participants (JEWEL I and II. The program utilized a newly developed questionnaire to gain better understanding of participants’ beliefs and behaviors towards medical treatment of their multiple risk factors. Approximately 2850

Comparative efficacy of amlodipine and hydrochlorthiazide-amiloride in cases of mild essential hypertension in outdoor patients at Combined Military Hospital Multan

International Nuclear Information System (INIS)

Ullah, M.U.; Khan, M.B.; Tahir, M.; Alamgir, W.; Yousif, M.A.

2010-01-01

To compare antihypertensive effect of fixed dose combination Hydrochlorothiazide-Amiloride and Amlodipine in patients of mild essential hypertension. After fulfilling the inclusion criteria of mild essential hypertension, defined as per recommendations of Seventh Joint National Committee (JNC 7) for treatment of Hypertension as stage 1 hypertension, systolic blood pressure (SBP) amlodipine and hydrochlorthiazide-amiloride 140-159-mmHg and Diastolic blood pressure(DBP) greater or equal to 90-99-mmHg, 100 patients were randomized into two study groups using a table of random numbers. Group 1 received tab amlodipine (5 mg) and Group 2 received tab hydrocholrthiazide-amiloride (25 mg-2.5mg). Informed written consent was taken. The patients were followed on subsequent visits (6 in total) for five months and systolic and diastolic blood pressure was recorded carefully. All the data thus obtained were processed and analyzed using SPSS version 10.0. Mean and standard deviation (SD) were calculated for age, diastolic and systolic blood pressure. In group 1 the drop in mean SBP between first and last visit was 15.42 mm Hg. In group 2 the drop in mean SBP between first and last visit was 18.34 mm Hg. In group 1, the drop in mean DBP between first and last visit was 10.08 mm Hg. In group 2 the drop in mean DBP between first and last visit was 14.65 mmHg. Mean drop in SBP of both the groups were compared with each other and found to be significantly different (P=0.003). Similarly mean drop in DBP of both the groups were compared with each other and found to be significant statistically (P=0.001). Hydrochlorothiazide-Amiloride had significantly better antihypertensive effect than Amlodipine in patients of mild essential hypertension at the end of five months therapy. (author)

Comparative influence of propranolol and verapamil on glycemic control and histamine sensitivity associated with L-thyroxine-induced hyperthyroidism - an experimental study.

Science.gov (United States)

Bhatt, Parloop A; Makwana, Dharmesh

2008-02-01

The present investigation was undertaken to study the comparative effectiveness of beta-adrenergic antagonist propranolol and calcium channel blocker verapamil on L-thyroxine-induced alteration on glycemic control and histamine sensitivity on rats and guinea pigs, respectively. Injection of L-thyroxine sodium every alternate day for 3 weeks in guinea pigs (75 microg/kg, i.p.) and rats (75 mg/kg, s.c.) produced a condition similar to thyrotoxicosis. Verapamil and propranolol administered daily in the third week along with L-thyroxine to two separate groups of hyperthyroid animals reversed thyroxine-induced loss in body weight, reduction in serum TSH levels, and rise in body temperature. Effect on glucose metabolism and insulin sensitivity was studied on rats. Compared to normal rats, L-thyroxine-treated animals showed a state of hyperglycemia, hyperinsulinemia, impaired glucose tolerance, and insulin resistance. Propranolol (10 mg/kg, i.p.) treatment significantly decreased fasting serum glucose levels without affecting serum insulin levels, AUC glucose, and K(ITT) values. Treatment with verapamil (5 mg/kg, i.p.) significantly reduced fasting serum glucose and insulin levels, AUC glucose, and significantly increased K(ITT) values. Effect of propranolol (15 mg/kg, orally) and verapamil (20 mg/kg, orally) treatment on histamine sensitivity was studied on L-thyroxine-treated guinea pigs. Compared to normal guinea pigs, L-thyroxine-treated guinea pigs showed an increased sensitivity to histamine-induced asphyxia. Verapamil treatment reversed this increased histamine sensitivity while propranolol aggravated it. In conclusion, compared to propranolol, verapamil has advantageous effects on glucose metabolism, insulin and histamine sensitivity and could therefore be a valuable addition as an adjunctive therapy option currently available for thyrotoxicosis associated with diabetes and/or anaphylaxis.

Propranolol decreases retention of fear memory by modulating the stability of surface glutamate receptor GluA1 subunits in the lateral amygdala.

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Zhou, Jun; Luo, Yi; Zhang, Jie-Ting; Li, Ming-Xing; Wang, Can-Ming; Guan, Xin-Lei; Wu, Peng-Fei; Hu, Zhuang-Li; Jin, You; Ni, Lan; Wang, Fang; Chen, Jian-Guo

2015-11-01

Posttraumatic stress disorder (PTSD) is a mental disorder with enhanced retention of fear memory and has profound impact on quality of life for millions of people worldwide. The β-adrenoceptor antagonist propranolol has been used in preclinical and clinical studies for the treatment of PTSD, but the mechanisms underlying its potential efficacy on fear memory retention remain to be elucidated. We investigated the action of propranolol on the retention of conditioned fear memory, the surface expression of glutamate receptor GluA1 subunits of AMPA receptors and synaptic adaptation in the lateral amygdala (LA) of rats. Propranolol attenuated reactivation-induced strengthening of fear retention while reducing enhanced surface expression of GluA1 subunits and restoring the impaired long-term depression in LA. These effects of propranolol were mediated by antagonizing reactivation-induced enhancement of adrenergic signalling, which activates PKA and calcium/calmodulin-dependent protein kinase II and then regulates the trafficking of AMPA receptors via phosphorylation of GluA1 subunits at the C-terminus. Both i.p. injection and intra-amygdala infusion of propranolol attenuated reactivation-induced enhancement of fear retention. Reactivation strengthens fear retention by increasing the level of noradrenaline and promotes the surface expression of GluA1 subunits and the excitatory synaptic transmission in LA. These findings uncover one mechanism underlying the efficiency of propranolol on retention of fear memories and suggest that β-adrenoceptor antagonists, which act centrally, may be more suitable for the treatment of PTSD. © 2015 The British Pharmacological Society.

Development and validation of an rp-hplc method for simultaneous determination of Ramipril and Amlodipine in tablets

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Shi-Ying Dai

2013-12-01

Full Text Available An rp-hplc method for the simultaneous determination of Ramipril (RP and Amlodipine (AL in tablets was developed and validated by Chinese Pharmacopoeia 2010. The linearity of the proposed method was investigated in the range of 0.01–0.25 mg/mL (r2=0.9998 for RP and 0.014–0.36 mg/mL (r2=0.9997 for AL. The limits of detection (LOD were 0.06 μg/mL and 0.02 μg/mL for RP and AL, and the limits of quantitation (LOQ were 0.2 μg/mL and 0.07 μg/mL, respectively. Some major impurities and degradation products did not disturb the detection of RP and AL and the assay can thus be considered stability-indicating. Keywords: Ramipril, Amlodipine, RP-HPLC, Stability-indicating

Multi-generational effects of propranolol on Daphnia magna at different environmental concentrations

International Nuclear Information System (INIS)

Jeong, Tae-Yong; Kim, Hyun Young; Kim, Sang Don

2015-01-01

To evaluate the effects of propranolol on Daphnia magna (D. magna), we employed a multi-generational exposure period for eight generations and an environmentally relevant low concentration with 1.5 ng/L, 0.2 μg/L and 26 μg/L to reflect a realistic exposure scenario. Physiological endpoints were checked, including growth, number of neonates, heart rate, frequency of abdominal appendage movement and malformation rate of neonates. In the results, growth and abdominal appendage movement were affected by environmental concentration during several generations, and the responses showed consistent tendencies of response increase with concentration increase. Heart rate was the only endpoint affected throughout all exposure generations. Inhibitory and acceleratory effects on heart rate, growth and abdominal appendage movement suggest that it is necessary to cover sub-lethal endpoints of non-targeted organisms in eco-toxicity study because the physiological responses were detected at much lower concentrations than the results of traditional toxicity tests, including environmental concentration. - Highlights: • Multi-generational exposure was conducted to evaluate the effect of propranolol on Daphnia magna. • Heart rate was the only endpoint affected throughout all exposure generations. • Growth and abdominal appendage movement were affected at environmental concentrations. • Time series fluctuations in responses appeared with no tendencies throughout all generations. • It is necessary to cover sub-organismal endpoints and long-term exposure in ecotoxicity test. - Heart rate, growth and abdominal appendage movement of D. magna were affected by the multigenerational exposure of propranolol at environmental levels.

The effect of ascorbic acid and propranolol on normal sleep and ...

African Journals Online (AJOL)

This study was designed to investigate the possible effects of ascorbic acid on open field locomotor activity and normal sleep in healthy adult rats and evaluate how these correlate with those of propranolol. MethodS: Eighty healthy adult Wistar rats of both sexes were divided into two groups of 40 animals each group.

Effect of ethanol, cimetidine and propranolol on toluene metabolism in man

DEFF Research Database (Denmark)

Døssing, M; Bælum, Jesper; Hansen, S H

1984-01-01

In a climatic exposure chamber four healthy volunteers were exposed to 100ppm toluene, 100ppm toluene + ethanol, 100ppm toluene + cimetidine, and 100ppm toluene + propranolol for 7h each at random over four consecutive days. A control experiment and 3.5h of exposure to 200ppm toluene were also...

Separation of digoxin by luiquid-luiquid extraction from extracts of foxglove secondary glycosides

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Novković Vesna V.

2014-01-01

Full Text Available The present study deals with the extraction of digoxin (Dgx from chloroform and trichloroethylene extracts of the secondary glycosides of fermented foxglove (Digitalis lanata Ehrh. foliage by liquid-liquid extraction. The extraction degree (ED of Dgx achieved by maceration and percolation using 10% vol. aqueous ethanol solutions were higher than 95%. Using trichlorethylene and chloroform, the ED of Dgx of about 100% and 96%, respectively from the liquid ethanolic extracts (macerate or percolate were achieved by the four-cycle extraction. Fifteen separating funnels were employed for the liquid-liquid extraction. Three different four-component two-phase systems (ethanol:water - chloroform:ethyl acetate, ethanol:water - chloroform:trichloroethylene and ethanol:water - trichloroethylene:ethyl acetate were tested as an extracting solvent to get the final product having more than 98% of Dgx. The initial amount of the chloroform or trichloroethylene extract in the light phase was varied between 5 and 25 g/L, while the volume ratio of light and heavy phases was in the range of 1:1 to 1:2. The best Dgx yield of 98% was achieved with the system ethanol:water - chloroform:trichloroethylene 35:15:20:30 at the volume ratio of the phases of 1:1.1 and at the initial amount of the extract of 15 g/L. Purity of the separated digoxin was 99.8 %. [Projekat Ministarstva nauke Republike Srbije, br. TR-34012

Comparative digoxin determination in serum by means of a radioimmuno- and an enzyme immunoassay

International Nuclear Information System (INIS)

Reinhard, M.

1981-01-01

Two immunologic measuring methods for the quantitative digoxin determination in serum were compared. One method bases on the principle of radioisotope dilution, the second one on the principle of enzyme inhibition. The radioimmunoassay served as reference method. The limit of detection for RIA is 0.23 ng/ml, for EIA 0.40 ng/ml. For both methods the measuring range extends up to approx. 5.5 ng/ml. The degree of precision in series is 8.2% for RIA, 10.8% for EIA. Day-to-day precision is 4.4% for RIA, 15.2% for EIA. On comparison, the 59 serum samples of patients who received digoxin did not show any systematic difference. The results obtained can be transformed by means of the equations Csub(EIA) = 0.041 ng/ml + 0.936 Csub(RIA). In pathologic sera, however, there are significant differences disfavoring EIA, because due to high color concentrations or turbidities these sera do not permit any or any exact extinction measurements. The enzyme immunoassay should not be used with such sera. With regard to practicability the EIA corresponds more or less to RIA. The EIA can essentially be economized by using semi-microcuvettes and applying only the half of the recommended enzyme and antibody volume. (orig.) [de

AAS and spectrophotometric determination of propranolol HCl and metoprolol tartrate.

Science.gov (United States)

El-Ries, M A; Abou Attia, F M; Ibrahim, S A

2000-12-15

Two simple and accurate spectrophotometric methods are described for the determination of propranolol hydrochloride (I) and metoprolol tartrate (II). The methods are based on the reaction of each drug as a secondary amine: (a) with carbon disulphide, the formed complex extracted into iso-butyl methyl ketone (IBMK) after chelation with Cu(II) ions at pH 7.5, followed by measuring the absorbance at 435.4 nm or indirectly for the drug by flame atomic absorption spectrophotometry (AAS). The calibration graph is linear up to 40 and 60 microg ml(-1) with apparent molar absorptivities of 6.89 x 10(3) and 1.08 x 104 l mol(-1) cm(-1) and correlation coefficients of 0.9994 and 0.9995 for propranolol and metoprolol, respectively; (b) with pi-acceptors, tetracyanoethylene (TCNE), or chloranilic acid (CLA) to give highly coloured complex species. The coloured products are quantitated spectrophotometrically at 415 or 510 nm for the two drugs with TCNE and CLA, respectively, and obey Beer's Law with RSD less than 2.0. The methods were applied to the determination of these drugs in pharmaceutical preparation without interferences.

Multiway analysis methods applied to the fluorescence excitation-emission dataset for the simultaneous quantification of valsartan and amlodipine in tablets

Science.gov (United States)

Dinç, Erdal; Ertekin, Zehra Ceren; Büker, Eda

2017-09-01

In this study, excitation-emission matrix datasets, which have strong overlapping bands, were processed by using four different chemometric calibration algorithms consisting of parallel factor analysis, Tucker3, three-way partial least squares and unfolded partial least squares for the simultaneous quantitative estimation of valsartan and amlodipine besylate in tablets. In analyses, preliminary separation step was not used before the application of parallel factor analysis Tucker3, three-way partial least squares and unfolded partial least squares approaches for the analysis of the related drug substances in samples. Three-way excitation-emission matrix data array was obtained by concatenating excitation-emission matrices of the calibration set, validation set, and commercial tablet samples. The excitation-emission matrix data array was used to get parallel factor analysis, Tucker3, three-way partial least squares and unfolded partial least squares calibrations and to predict the amounts of valsartan and amlodipine besylate in samples. For all the methods, calibration and prediction of valsartan and amlodipine besylate were performed in the working concentration ranges of 0.25-4.50 μg/mL. The validity and the performance of all the proposed methods were checked by using the validation parameters. From the analysis results, it was concluded that the described two-way and three-way algorithmic methods were very useful for the simultaneous quantitative resolution and routine analysis of the related drug substances in marketed samples.

Losartan in combination with propranolol slows the aortic root dilatation in neonatal Marfan syndrome

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Lu-Hang Liu

2018-04-01

Full Text Available Neonatal Marfan syndrome, in contrast to classical Marfan syndrome, is characterized by rapidly progressive multi-valvular cardiac disease and death from congestive heart failure, typically within the first year of life. Due to the rarity of this condition, treatment for neonatal Marfan syndrome has not been well studied. In this report, a combination of losartan and propranolol reduced the aortic root dilatation rate after three months of losartan therapy. Genetic analysis in this patient revealed a mutation in exon 25 of the FBN1 gene, which typically results in a shorter life expectancy. However, the patient's heart failure was controlled by losartan, propranolol and other anti-congestive medications, which may have prolonged his survival. Key Words: FBN1, losartan, neonatal Marfan syndrome

Losartan in combination with propranolol slows the aortic root dilatation in neonatal Marfan syndrome.

Science.gov (United States)

Liu, Lu-Hang; Lin, Shan-Miao; Lin, Dar-Shong; Chen, Ming-Ren

2018-04-01

Neonatal Marfan syndrome, in contrast to classical Marfan syndrome, is characterized by rapidly progressive multi-valvular cardiac disease and death from congestive heart failure, typically within the first year of life. Due to the rarity of this condition, treatment for neonatal Marfan syndrome has not been well studied. In this report, a combination of losartan and propranolol reduced the aortic root dilatation rate after three months of losartan therapy. Genetic analysis in this patient revealed a mutation in exon 25 of the FBN1 gene, which typically results in a shorter life expectancy. However, the patient's heart failure was controlled by losartan, propranolol and other anti-congestive medications, which may have prolonged his survival. Copyright © 2017. Published by Elsevier B.V.

Dose response characterization of the association of serum digoxin concentration with mortality outcomes in the Digitalis Investigation Group trial

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Adams, Kirkwood F.; Butler, Javed; Patterson, J. Herbert; Stough, Wendy Gattis; Bauman, Jerry L.; van Veldhuisen, Dirk J.; Schwartz, Todd A.; Sabbah, Hani; Mackowiak, John I.; Ventura, Hector O.; Ghali, Jalal K.

AimsMany patients with heart failure and reduced EF remain at high risk for hospitalization despite evidence-based therapy. Digoxin may decrease hospitalization; however, uncertainty persists concerning its proper administration and effect on mortality. This study investigated whether using dose

Enantiomeric separation and quantitative determination of propranolol enantiomers in pharmaceutical preparations by chiral liquid chromatography Separação e determinação quantitativa dos enantiômeros do propranolol em preparações farmacêuticas por cromatografia quiral

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Anil K. Singh

2004-09-01

Full Text Available This paper describes validated direct liquid chromatographic chiral methods for enantiomeric separation and quantitative determination of clinically significant ²-blocking agent, propranolol. A liquid chromatographic method was validated and applied for enantiomeric determination of propranolol enantiomers in pharmaceutical formulations. Separation were obtained in polar organic mode on a ±-Burke 2® chiral stationary phase (250 x 4.6 mm, 5µm with mobile phase composed of dichloromethane:methanol (90:10 v/v, along with 12 mM of ammonium acetate, at a flow rate of 0.9 mL/min. Detection was made by ultraviolet absorption at 280 nm. In all cases the run time was less than 10 min. The correlation coefficient for linear regression curves of R-propranolol and S-propranolol were 0.9995 and 0.9998 respectively. The intra-day precision, expressed as RSD was less than 2%. The accuracy determined by average recovery of R-propranolol and S-propranolol from sample matrices were 97.3% and 100.1% in commercial sample and 99.5% and 100.4% in simulated samples, respectively. Excellent levels of limit of detection (mean value = 1.34 ng and limit of quantitation (mean value = 4.47 ng, along with rapid elution time of both enantiomers, makes the method useful for routine enantiomeric quality control applications.Neste trabalho é descrito um método validado empregando a cromatografia líquida de alta eficiência com fase estacionária quiral para a separação e determinação quantitativa dos enantiômeros do propranolol em formulações farmacêuticas. A separação foi obtida em meio orgânico polar empregando a coluna ±-Burke 2® como fase estacionária quiral (250 x 4,6 mm, 5 µm e fase móvel constituída por diclorometano: metanol (90:10 v/v juntamente com 12 mM de acetato de amônio e vazão de 0,9 mL/min. A detecção foi efetuada por absorção no ultravioleta a 280 nm. Em todos casos o tempo de corrida foi menor do que 10 min. O coeficiente de

A validated RP-HPLC method for simultaneous determination of propranolol and valsartan in bulk drug and gel formulation

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Imam, Syed Sarim; Ahad, Abdul; Aqil, Mohammed; Sultana, Yasmin; Ali, Asgar

2013-01-01

Objective: A simple, precise, and stability indicating high performance liquid chromatography (HPLC) method was developed and validated for the simultaneous determination of propranolol hydrochloride and valsartan in pharmaceutical dosage form. Materials and Methods: The method involves the use of easily available inexpensive laboratory reagents. The separation was achieved on Hypersil ODS C-18 column (250*4.6 mm, i.d., 5 μm particle size) with isocratic flow with UV detector. The mobile phase at a flow rate of 1.0 mL/min consisted of acetonitrile, methanol, and 0.01 M disodium hydrogen phosphate (pH 3.5) in the ratio of 50:35:15 v/v. Results: A linear response was observed over the concentration range 5-50 μg/mL of propranolol and the concentration range 4-32 μg/mL of valsartan. Limit of detection and limit of quantitation for propranolol were 0.27 μg/mL and 0.85 μg/mL, and for valsartan were 0.45 μg/mL and 1.39 μg/mL, respectively. The method was successfully validated in accordance to ICH guidelines acceptance criteria for linearity, accuracy, precision, specificity, robustness. Conclusion: The analysis concluded that the method was selective for simultaneous estimation of propranolol and valsartan can be potentially used for the estimation of these drugs in combined dosage form. PMID:23559826

Disinhibition by propranolol and chlordiazepoxide of nonrewarded lever-pressing in the rat is unaffected by dorsal noradrenergic bundle lesion.

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Salmon, P; Tsaltas, E; Gray, J A

1989-03-01

Ten male Sprague-Dawley rats received 6-hydroxydopamine-induced lesions of the dorsal noradrenergic bundle and 10 others underwent control operations. The lesion depleted levels of noradrenaline in the hippocampus to 2% of those in the controls. All rats were then trained for 16 sessions to lever-press in a Skinner box on a variable interval 18 sec schedule of food-reinforcement, then for 42 days on a successive discrimination between periods of variable interval (VI 18 sec) food-reinforcement and periods of extinction. This report describes the effects of chlordiazepoxide (CDP; 5 mg/kg) and propranolol (5 and 10 mg/kg) injected intraperitoneally in both groups on modified ABBA designs after this training. Both drugs increased the response rates in extinction periods. The effect of propranolol was similar at each dose and smaller than that of CDP. Although CDP and propranolol (5 mg/kg) increased variable interval response rates also, this could not account for the effect on extinction response rates. Responding did not differ between the lesioned and control animals and the effects of drugs were similar in each group. It is unlikely that CDP or propranolol release nonrewarded responding by disrupting transmission in the dorsal noradrenergic bundle.

Efficacy of carvedilol versus propranolol versus variceal band ligation for primary prevention of variceal bleeding.

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Abd ElRahim, Ayman Yosry; Fouad, Rabab; Khairy, Marwa; Elsharkawy, Aisha; Fathalah, Waleed; Khatamish, Haytham; Khorshid, Omayma; Moussa, Mona; Seyam, Moataz

2018-01-01

Band ligation and propranolol are the current therapies for primary prevention of variceal bleeding. Carvedilol is a rising nonselective beta-blocker used for reducing portal pressure with favorable outcome. The aim of this study to assess the efficacy of carvedilol, propranolol, and band ligation for primary prevention of variceal bleeding based on the effect of each regimen on progression of Child score and portal hypertensive gastropathy after 1 year. The study included 264 cirrhotic patients with medium/large-sized varices who were candidates for primary prophylaxis of variceal bleeding. Patients were randomly divided into three groups: group I: band ligation; group II: propranolol; group III: carvedilol. Group I showed higher success rate of 75 %, followed by group III with 70.2 % and group II with 65.2 %. Risk of bleeding was comparable between the three groups, with group II carrying the highest rate of complications (34.7 %) followed by group III (14.2 %) and finally group I (5.7 %). After 1 year of follow-up, Child score did not improve in any of the studied groups, while portal hypertensive gastropathy significantly increased in group I but decreased in groups II and III. Band ligation is the best treatment option for primary prevention of variceal bleeding with minimal complications. Carvedilol is a good pharmaceutical alternative medicine to propranolol with lesser side-effects. Progress of liver disease as represented by Child score is not affected by any of the primary variceal prophylactic regimens, although medical treatment reduces portal hypertensive gastropathy. Choice of treatment depends on patient will, compliance with treatment, and endoscopist competence.

Sequential Spectrophotometric Method for the Simultaneous Determination of Amlodipine, Valsartan, and Hydrochlorothiazide in Coformulated Tablets

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Hany W. Darwish

2013-01-01

Full Text Available A new, simple and specific spectrophotometric method was developed and validated in accordance with ICH guidelines for the simultaneous estimation of Amlodipine (AML, Valsartan (VAL, and Hydrochlorothiazide (HCT in their ternary mixture. In this method three techniques were used, namely, direct spectrophotometry, ratio subtraction, and isoabsorptive point. Amlodipine (AML was first determined by direct spectrophotometry and then ratio subtraction was applied to remove the AML spectrum from the mixture spectrum. Hydrochlorothiazide (HCT could then be determined directly without interference from Valsartan (VAL which could be determined using the isoabsorptive point theory. The calibration curve is linear over the concentration ranges of 4–32, 4–44 and 6–20 μg/mL for AML, VAL, and HCT, respectively. This method was tested by analyzing synthetic mixtures of the above drugs and was successfully applied to commercial pharmaceutical preparation of the drugs, where the standard deviation is <2 in the assay of raw materials and tablets. The method was validated according to the ICH guidelines and accuracy, precision, repeatability, and robustness were found to be within the acceptable limits.

Preparation and preclinical evaluation of 68Ga-DOTA-amlodipine for L-type calcium channel imaging

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Firuzyar, Tahereh; Jalilian, Amir Reza; Aboudzadeh, Mohammad Reza; Sadeghpour, Hossein; Shafiee-Ardestani, Mahdi; Khalaj, Ali

2016-01-01

Aim: In order to develop a possible tracer for L-type calcium channel imaging, we here report the development of a Ga-68 amlodipine derivative for possible PET imaging. Materials and Methods: Amlodipine DOTA conjugate was synthesized, characterized and went through calcium channel blockade, toxicity, apoptosis/necrosis tests. [68Ga] DOTA AMLO was prepared at optimized conditions followed by stability tests, partition coefficient determination and biodistribution studies using tissue counting and co incidence imaging up to 2 h. Results: [68Ga] DOTA AMLO was prepared at pH 4–5 in 7–10 min at 95°C in high radiochemical purity (>99%, radio thin layer chromatography; specific activity: 1.9–2.1 GBq/mmol) and was stable up to 4 h with a log P of −0.94. Calcium channel rich tissues including myocardium, and tissues with smooth muscle cells such as colon, intestine, and lungs demonstrated significant uptake. Co incidence images supported the biodistribution data up to 2 h. Conclusions: The complex can be a candidate for further positron emission tomography imaging for L type calcium channels. PMID:27833311

Extracorporeal life support and digoxin-specific Fab fragments for successful management of Taxus baccata intoxication with low output and ventricular arrhythmia.

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Farag, Mina; Badowski, Dominika; Koschny, Ronald; Skopp, Gisela; Brcic, Andreas; Szabo, Gabor B

2017-12-01

Yew plants are evergreen shrubs which are widely spread throughout the northern hemisphere. Taxane alkaloid derivatives, mainly taxine B, represent the main toxins of Taxus baccata and are highly cardiotoxic. Due to the lack of randomized clinical trials, case reports on accidental or suicidal yew intoxications build the only source of knowledge of clinical treatment options. We report the case of a suicidal yew ingestion admitted to our hospital under prolonged cardiopulmonary resuscitation due to pulseless electrical activity. Extra-corporeal life support (ECLS) was established to maintain adequate organ perfusion. Repeated administration of digoxin-specific Fab antibody fragments, which cross-react with taxine, was associated with an immediate conversion from asystole to broad-complex bradycardia and a gradual normalization of the electrocardiogram (ECG). This was paralleled by a recovery of the cardiac function and weaning from the ECLS. The taxine metabolite 3,5-dimethoxyphenol could be detected by mass spectrometry before but not after the first Fab-fragment treatment. In contrast, the total amount of taxine (including the neutralized, Fab fragment-bound fraction) was increased after each Fab fragment administration, suggesting an accumulation of neutralized, since antibody-bound taxine in the blood by anti-digoxin Fab fragments. In conclusion, the successful clinical course of this case suggests a benefit of an early anti-digoxin Fab-fragment administration for the treatment of yew intoxication. Copyright © 2017 Elsevier Inc. All rights reserved.

Combined Treatment with Amlodipine and Atorvastatin Calcium Reduces Circulating Levels of Intercellular Adhesion Molecule-1 and Tumor Necrosis Factor-α in Hypertensive Patients with Prediabetes.

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Huang, Zhouqing; Chen, Chen; Li, Sheng; Kong, Fanqi; Shan, Peiren; Huang, Weijian

2016-01-01

To assess the effect of amlodipine and atorvastatin on intercellular adhesion molecule (ICAM)-1 and tumor necrosis factor (TNF)-α expression, as endothelial function and inflammation indicators, respectively, in hypertensive patients with and without prediabetes. Forty-five consecutive patients with hypertension, diagnosed according to JNC7, were divided into two groups based on the presence (HD group, n = 23) or absence (H group, n = 22) of prediabetes, diagnosed according to 2010 ADA criteria, including impaired glucose tolerance (IGT) and fasting glucose tests. All patients simultaneously underwent 12-week treatment with daily single-pill amlodipine besylate/atorvastatin calcium combination (5/10 mg; Hisun-Pfizer Pharmaceuticals Co. Ltd). Serum isolated before and after treatment from overnight fasting blood samples was analyzed by ELISA. In the HD and H groups after vs. before 12-week amlodipine/atorvastatin treatment, there were significantly (all P atorvastatin improved endothelial function and inflammation, as reflected by lower circulating levels of ICAM-1 and TNF-α, more prominently in hypertensives with than without prediabetes. Starting statin treatment before overt diabetes in hypertensives might thus improve cardiovascular outcomes.

Controlled treatment of primary hypertension with propranolol and spironolactone. A crossover study with special reference to initial plasma renin activity.

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Karlberg, B E; Kågedal, B; Tegler, L; Tolagen, K; Bergman, B

1976-03-31

Twenty-seven patients with hypertension were randomly allocated to a 10 month crossover study. Treatment consisted of spironolactone (200 mg/day for 2 months), propranolol (320 mg/day for 2 months) and combined administration of both drugs at half the dosage. Between treatment periods placebo was given for 2 months. Fourteen patients were previously untreated. The average pretreatment blood pressure for the entire group was 188/114 +/- 16/7(mean +/- standard deviation) mm Hg supine and 188/118 +/- 20/9 mm Hg standing. Both spironolactone and propranolol reduced blood pressure significantly in both the supine and standing positions. Upright plasma renin activity was determined by radioimmunoassay of angiotensin I. The average initial level was 1.9 +/- 1.2 (range 0.4 to 5.0) ng/ml/hr. There was a close correlation between plasma renin activity and the effects of the drugs: With increasing renin level the response to propranolol was better whereas the opposite was true for spironolactone. The combination of spironolactone and propranolol decreased the blood pressure still further in the supine and standing positions, irrespective of initial plasma renin activity. All patients achieved a normal supine pressure. Blood pressure and plasma renin activity returned toward pretreatment values during placebo administration. It is concluded that pretreatment levels of plasma renin activity can predict the antihypertensive response to propranolol and spironolactone. The combination of the two drugs, which have different modes of action, will effectively reduce blood pressure in hypertension. The results support the concept that the renin-angiotensin-aldo-sterone system may be involved in primary hypertension.

Development and validation of different methods manipulating zero order and first order spectra for determination of the partially overlapped mixture benazepril and amlodipine: A comparative study

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Hemdan, A.

2016-07-01

Three simple, selective, and accurate spectrophotometric methods have been developed and then validated for the analysis of Benazepril (BENZ) and Amlodipine (AML) in bulk powder and pharmaceutical dosage form. The first method is the absorption factor (AF) for zero order and amplitude factor (P-F) for first order spectrum, where both BENZ and AML can be measured from their resolved zero order spectra at 238 nm or from their first order spectra at 253 nm. The second method is the constant multiplication coupled with constant subtraction (CM-CS) for zero order and successive derivative subtraction-constant multiplication (SDS-CM) for first order spectrum, where both BENZ and AML can be measured from their resolved zero order spectra at 240 nm and 238 nm, respectively, or from their first order spectra at 214 nm and 253 nm for Benazepril and Amlodipine respectively. The third method is the novel constant multiplication coupled with derivative zero crossing (CM-DZC) which is a stability indicating assay method for determination of Benazepril and Amlodipine in presence of the main degradation product of Benazepril which is Benazeprilate (BENZT). The three methods were validated as per the ICH guidelines and the standard curves were found to be linear in the range of 5-60 μg/mL for Benazepril and 5-30 for Amlodipine, with well accepted mean correlation coefficient for each analyte. The intra-day and inter-day precision and accuracy results were well within the acceptable limits.

[Comparison of benazepril monotherapy to amlodipine plus benazepril in the treatment of patients with mild and moderate hypertension: a multicentre, randomized, double-blind, parallel-controlled study].

Science.gov (United States)

Fan, Chao-mei; Yan, Li-rong; Tao, Yong-kang; Wang, Li; Li, Yu-qing; Gao, Ming-ming; Wang, Yan-ni; Li, Cheng-xiang; Wang, Xiao-wan; Lu, Xiao-lei; Pang, Hui-min; Li, Yi-shi

2011-01-01

To evaluate the efficacy and tolerability of the fixed combination of amlodipine 5 mg/benazepril 10 mg once-daily therapy, compared with benazepril, 10 mg, monotherapy in patients with mild and moderate hypertension, and to evaluate the 24 h antihypertensive efficacy and the duration of action by ambulatory blood pressure monitoring. In a multicenter, randomized, double-blind, parallel controlled trial, 356 cases of hypertensive patients after 2 weeks wash-out, and then given 4 weeks of benazepril 10 mg monotherapy, 220 patients with mean seated diastolic blood pressure (SeDBP) remained ≥ 90 mm Hg (1 mm Hg = 0.133 kPa) were randomly divided into benazepril 10 mg/amlodipine 5 mg (BZ10/AML5) fixed-dose combination therapy group (once a day, n = 113), and benazepril monotherapy group (daily 20 mg, n = 107). In the two groups the patients with SeDBP ≥ 90 mm Hg were doubled the dosage of the initial regimen at the end of 4-week treatment for additional 4 weeks, and the patients with SeDBP benazepril/amlodipine (10 mg/5 mg) and benazepril (20 mg) alone were 83.1%/76.0% and 85.8%/79.5%, respectively. Adverse events rates were 16.8% in the combination therapy group and 35.5% in the monotherapy group (P benazepril/amlodipine was superior to benazepril monotherapy and was well tolerated in patients with essential hypertension and allowing a satisfactory BP control for 24 hours.

Predictors of systolic BP benazepril plus amlodipine or hydrochlorothiazide) in the ACCOMPLISH Study.

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Kjeldsen, Sverre E; Jamerson, Kenneth A; Bakris, George L; Pitt, Bertram; Dahlöf, Björn; Velazquez, Eric J; Hua, Tsushung A; Kelly, Roxzana Y; Zappe, Dion; Hester, Allen; Tuomilehto, Jaakko; Ostergren, Jan; Ibsen, Hans; Weber, Michael

2012-04-01

The ACCOMPLISH Trial investigated intensive antihypertensive combination treatment with benazepril + amlodipine (B+A) or benazepril + hydrochlorothiazide (B+H) on cardiovascular outcomes in patients with systolic hypertension. We analyzed the baseline predictors of achieving a systolic blood pressure (SBP) Nordic region) and Caucasian ethnicity in both randomization arms. A higher diastolic BP and the use of lipid lowering agents indicated favorable effects in the B+H arm only. The predictors of uncontrolled SBP were: (i) higher baseline SBP values, (ii) higher number of previous antihypertensive medications in both arms, (iii) the previous use of insulin in the B+A arm, and (iv) pre-trial calcium channel blocker (CCB) use in the B+H arm. Additionally, pre-trial use of thiazides and electrocardiogram (ECG)-left ventricular hypertrophy (LVH) at baseline predicted higher, and smoking lower absolute SBP in the B+A arm and the use of thiazides and proteinuria a higher SBP in the B+H arm. Irrespective of treatment, patients in the USA and Caucasians achieved better SBP control, whereas higher baseline SBP and more previous antihypertensive medications indicated less control. Concomitant use of lipid lowering treatment indicated a better SBP control in the benazepril + hydrochlorothiazide arm. Lastly, insulin use and ECG-LVH in the benazepril + amlodipine arm and proteinuria in the benazepril + hydrochlorothiazide arm indicated poor control.

Efficacy of fix dose combination (atorvastatin and amlodipine) in treatment of uncontrolled hypertension and dyslipidemia

International Nuclear Information System (INIS)

Bashir, S.; Sherwani, M.U.K.; Batool, A.

2012-01-01

The fixed-dose combination containing the antihypertensive agent amlodipine and the statin, atorvastatin, is the first combination of its kind designed to treat two risk factors for cardiovascular disease (CVD), i.e., hypertension and dyslipidemia. in this study, blood pressure and lipid lowering effects of combination of amlodipine and atorvastatin were evaluated in uncontrolled hypertensive patients. Methods: Thirty patients both male and female in the age group 35-60 years attending the hypertensive clinic of PMRC FJMC suffering from uncontrolled hypertension were selected. baseline blood pressure was checked after half hour rest in sitting and standing position using mercury sphygmomanometer. Blood sample was collected from all patients after overnight fasting for assessment of serum cholesterol, triglycerides, LDL and HDL cholesterol levels. they were prescribed with fixed dose combination of 5 mg amlodipine and 10 mg atorvastatin. Patients were followed for their blood pressure measurement after every 4 weeks up to 12 weeks. At the end of 12 weeks their fasting blood sample was taken again for determination of serum cholesterol, triglyceride, IDL and HDL cholesterol levels. Results: Systolic blood pressure after 4, 8 and 12 weeks was significantly lower at all intervals from baseline. when systolic blood pressure after 8 and 12 weeks was compared with 4 weeks, the effect was again significant (p=0.024, p=0.002 respectively). There was no significant reduction seen in 8 versus 12 weeks (p=0.493). Diastolic blood pressure at 4, 8 and 12 weeks was significantly lower from baseline. Diastolic blood pressure after 4 and 8 weeks when compared with 8 and 12 weeks was not significantly low (p=0.99 and 0.91 respectively). Lipid profile of the patients was significantly reduced from baseline after twelve weeks of fixed dose combination of treatment (p<0.000). Conclusion: Combination therapy proved to be effective in controlling hypertension and dyslipidemia than single

Efficacy of fix dose combination (atorvastatin and amlodipine) in treatment of uncontrolled hypertension and dyslipidemia

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Bashir, S; Sherwani, M U.K.; Batool, A [Fatima Jinnah Medical College, Lahore (Pakistan)

2012-07-15

The fixed-dose combination containing the antihypertensive agent amlodipine and the statin, atorvastatin, is the first combination of its kind designed to treat two risk factors for cardiovascular disease (CVD), i.e., hypertension and dyslipidemia. in this study, blood pressure and lipid lowering effects of combination of amlodipine and atorvastatin were evaluated in uncontrolled hypertensive patients. Methods: Thirty patients both male and female in the age group 35-60 years attending the hypertensive clinic of PMRC FJMC suffering from uncontrolled hypertension were selected. baseline blood pressure was checked after half hour rest in sitting and standing position using mercury sphygmomanometer. Blood sample was collected from all patients after overnight fasting for assessment of serum cholesterol, triglycerides, LDL and HDL cholesterol levels. they were prescribed with fixed dose combination of 5 mg amlodipine and 10 mg atorvastatin. Patients were followed for their blood pressure measurement after every 4 weeks up to 12 weeks. At the end of 12 weeks their fasting blood sample was taken again for determination of serum cholesterol, triglyceride, IDL and HDL cholesterol levels. Results: Systolic blood pressure after 4, 8 and 12 weeks was significantly lower at all intervals from baseline. when systolic blood pressure after 8 and 12 weeks was compared with 4 weeks, the effect was again significant (p=0.024, p=0.002 respectively). There was no significant reduction seen in 8 versus 12 weeks (p=0.493). Diastolic blood pressure at 4, 8 and 12 weeks was significantly lower from baseline. Diastolic blood pressure after 4 and 8 weeks when compared with 8 and 12 weeks was not significantly low (p=0.99 and 0.91 respectively). Lipid profile of the patients was significantly reduced from baseline after twelve weeks of fixed dose combination of treatment (p<0.000). Conclusion: Combination therapy proved to be effective in controlling hypertension and dyslipidemia than single

[Pharmacogenetic approaches to predicting the efficiency and safety of amlodipine in patients with arterial hypertension].

Science.gov (United States)

Sychev, D A; Shih, N V; Kalle, E G; Ryzhikova, K A; Morozova, T E

2017-10-01

An open, non-comparative, prospective clinical study was conducted to evaluate the antihypertensive efficacy and tolerability of amlodipine, a calcium antagonist, in patients with arterial hypertension (AH) I-II stages, depending on the genotype for the polymorphic marker C3435T of the ABCB1 gene. The study included 100 patients with AH I-II stages, aged from 45 to 58 years. The initial dose of amlodipine was 5 mg, duration of treatment was 12 weeks. General clinical examination methods, office measurement and daily blood pressure monitoring, tolerance evaluation, and genotyping using the ABCB1 polymorphic marker C3435T by the PCR-RFLP method (polymerase chain reaction and restriction fragment length polymorphism) were used. The statistical analysis of results was carried out using the Mann-Whitney U test for quantitative variables, Kruskal-Wallis one-way analysis of variance (ANOVA) for three independent groups of quantitative data. Excellent antihypertensive efficacy with the CC genotype was found in 11.8% patients, with CT - 33.9%, with TT - 43.3%; good - 35.3%, 32.1%, and 33.3% respectively, satisfactory - 52.9%, 34,0% and 23.4% respectively. Six patients with the CT genotype and nine patients with the CC genotype required the increase in the dose to 10 mg. The number of patients with Adverse drug reactions (ADR) were found in 35.3% of patients with the CC genotype, 6.7% with the TT genotype and 11.3% with the CT genotype. The Kruskal-Wallis test revealed significant differences between CC and TT genotypes in the degree of decrease in SBP (p=0.02), antihypertensive efficacy parameter (p=0.02), an increase in dose requirements (p = 0.04) and the incidence of ADR(p=0.05). In AH patients (I-II stage) with the TT genotype of the C3435T gene polymorphism one can expect higher rates of antihypertensive efficacy of amlodipine in combination with a good safety profile and the lowest ADR percentage, while patients with the CC genotype more likely to develop ADR and

Cost Minimization Analysis of Antihypertensive Therapy with Captopril-Hydrochlorothiazide and Amlodipine-Hydrochlorothiazide in One of Hospitals in Bandung

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Andini Faramitha

2017-09-01

Full Text Available The successful therapy of stage 2 hypertension can be supported by the administration of antihypertensive. Existence of various antihypertensive alternative, making pharmacoeconomics study is needed in order to have an effective and efficient therapy. Purpose of this study is to find the antihypertensive group therapy which is more efficient in cost (cost minimization which used in the treatment of stage 2 hypertension in patients at one hospital in Bandung from 2011 until 2013. This study is an observational reserach with retrospective data collection. Data retrieval is done by taking the medical records of hospitalized patients who received therapy of stage 2 hypertension antihypertensive, captopril-hydrochlorothiazide or amlodipin-hydrochlorothiazide. Components that are collected include the cost of antihypertensive, supportive therapy costs, the cost of action, administrative expenses and cost of hospitalization. The result of the study cost minimization analysis showed that the total cost of treatment with the antihypertensive captopril-hydrochlorothiazide is lower compared to amlodipin- hydrochlorothiazide, with the difference amounting to Rp126,798.

Development and Validation of a Chromatography Method Using Tandem UV/Charged Aerosol Detector for Simultaneous Determination of Amlodipine Besylate and Olmesartan Medoxomil: Application to Drug-Excipient Compatibility Study

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Ariadne M. Brondi

2017-01-01

Full Text Available A study was carried out to investigate compatibility of amlodipine besylate and olmesartan medoxomil with a variety of pharmaceutical excipients. Both drugs are antihypertensive agents that can be administered alone, in monotherapy, or in pharmaceutical association. The studies were performed using binary and ternary mixtures, and samples were stored for 3 and 6 months at 40°C under 75% relative humidity and dry conditions. For this study, a method based on high-performance liquid chromatography (HPLC was developed and validated for the simultaneous determination of amlodipine besylate and olmesartan medoxomil in samples from pharmaceutical preformulation studies using diode array detector (DAD and charged aerosol detector (CAD. The runtime per sample was 10 min with retention time of 7.926 min and 4.408 min for amlodipine and olmesartan, respectively. The validation was performed according to ICH guidelines. The calibration curve presents linear dynamic range from 12 to 250 μg mL−1 for amlodipine and from 25 to 500 μg mL−1 for olmesartan with coefficient of determination (R2 ≥ 0.9908 while repeatability and reproducibility (expressed as relative standard deviation were lower than 1.0%. The excipients such as corn starch, croscarmellose sodium, magnesium stearate, polyvinyl alcohol, talc, polyvinylpyrrolidone, lactose monohydrate, and polyethylene glycol showed potential incompatibilities after accelerated stability testing.

A randomized, controlled study evaluating effects of amlodipine addition to chelators to reduce iron loading in patients with thalassemia major.

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Eghbali, Aziz; Kazemi, Hamideh; Taherahmadi, Hassan; Ghandi, Yazdan; Rafiei, Mohammad; Bagheri, Bahador

2017-12-01

Cardiomyopathy due to iron overload can be fatal in patients with thalassemia major. Calcium channel blockers seem to be effective to reduce iron loading. Our goal was to study effects of amlodipine addition to chelators on iron loading in patients with thalassemia major. This randomized, controlled, and single-center trial was performed on 56 patients with thalassemia major. Patients were randomized 1:1 to combined group (iron chelator plus amlodipine) or control group (iron chelator) for 1 year. Iron content was measured by magnetic resonance imaging; heart T2*, and liver T2*. Serum ferritin was also measured. After 12 months of treatment, myocardial T2* values had significant improvement in combined group (21.9 ± 8.0 ms to 24.5 ± 7.6 ms; P < .05); Difference between two groups was significant (P = .02). Combined treatment had no effect on hepatic T2* value (9.6 ± 2.8 ms to 9.5 ± 3.6 ms); difference between two groups was not significant (P = .2). In addition, a significant reduction was seen in serum ferritin levels in two groups. Mild gastrointestinal upset was the most common untoward effect. Addition of amlodipine to iron chelators has beneficial effects for reduction of iron loading in patients with thalassemia major. This combination therapy seems safe. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hypothalamic digoxin and hemispheric chemical dominance in relation to the pathogenesis of bronchial asthma.

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Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-08-01

The isoprenoid pathway produces three key metabolites--digoxin (membrane sodium-potassium ATPase inhibitor and regulator of neurotransmitter transport), dolichol (regulator of N-glycosylation of proteins), and ubiquinone (free radical scavenger). The isoprenoid pathway was assessed in patients with bronchial asthma. The pathway was also assessed in patients with right hemispheric, left hemispheric, and bihemispheric dominance to find out the role of hemispheric dominance in the pathogenesis of bronchial asthma. The pathway was upregulated with increase in digoxin synthesis in bronchial asthma. There was an increase in tryptophan catabolites and a reduction in tyrosine catabolites in patients with bronchial asthma. The ubiquinone levels were low and lipid peroxidation increased in these patients. There was increase in dolichol and glycoconjugate levels and reduction in lysosomal stability in these patients. The cholesterol:phospholipid ratio was increased and glycoconjugate levels were reduced in the membranes of these patients. The patterns noticed in bronchial asthma were similar to those in patients with right hemispheric chemical dominance. Bronchial asthma occurs in right hemispheric chemically dominant individuals. Ninety percent of the patients with bronchial asthma were right-handed and left hemispheric dominant by the dichotic listening test. But their biochemical patterns were similar to those obtained in right hemispheric chemical dominance. Hemispheric chemical dominance is a different entity and has no correlation with handedness or the dichotic listening test.

Development and validation of an in vitro–in vivo correlation (IVIVC model for propranolol hydrochloride extended-release matrix formulations

Directory of Open Access Journals (Sweden)

Chinhwa Cheng

2014-06-01

Full Text Available The objective of this study was to develop an in vitro–in vivo correlation (IVIVC model for hydrophilic matrix extended-release (ER propranolol dosage formulations. The in vitro release characteristics of the drug were determined using USP apparatus I at 100 rpm, in a medium of varying pH (from pH 1.2 to pH 6.8. In vivo plasma concentrations and pharmacokinetic parameters in male beagle dogs were obtained after administering oral, ER formulations and immediate-release (IR commercial products. The similarity factor f2 was used to compare the dissolution data. The IVIVC model was developed using pooled fraction dissolved and fraction absorbed of propranolol ER formulations, ER-F and ER-S, with different release rates. An additional formulation ER-V, with a different release rate of propranolol, was prepared for evaluating the external predictability. The results showed that the percentage prediction error (%PE values of Cmax and AUC0–∞ were 0.86% and 5.95%, respectively, for the external validation study. The observed low prediction errors for Cmax and AUC0–∞ demonstrated that the propranolol IVIVC model was valid.

Daily propranolol prevents prolonged mobilization of hematopoietic progenitor cells in a rat model of lung contusion, hemorrhagic shock, and chronic stress.

Science.gov (United States)

Bible, Letitia E; Pasupuleti, Latha V; Gore, Amy V; Sifri, Ziad C; Kannan, Kolenkode B; Mohr, Alicia M

2015-09-01

Propranolol has been shown previously to decrease the mobilization of hematopoietic progenitor cells (HPCs) after acute injury in rodent models; however, this acute injury model does not reflect the prolonged period of critical illness after severe trauma. Using our novel lung contusion/hemorrhagic shock/chronic restraint stress model, we hypothesize that daily administration of propranolol will decrease prolonged mobilization of HPCs without worsening lung healing. Male Sprague-Dawley rats underwent 6 days of restraint stress after undergoing lung contusion or lung contusion/hemorrhagic shock. Restraint stress consisted of a daily 2-hour period of restraint interrupted every 30 minutes by alarms and repositioning. Each day after the period of restraint stress, the rats received intraperitoneal propranolol (10 mg/kg). On day 7, peripheral blood was analyzed for granulocyte-colony stimulating factor (G-CSF) and stromal cell-derived factor 1 via enzyme-linked immunosorbent assay and for mobilization of HPCs using c-kit and CD71 flow cytometry. The lungs were examined histologically to grade injury. Seven days after lung contusion and lung contusion/hemorrhagic shock, the addition of chronic restraint stress significantly increased the mobilization of HPC, which was associated with persistently increased levels of G-CSF and increased lung injury scores. The addition of propranolol to lung contusion/chronic restraint stress and lung contusion/hemorrhagic shock/chronic restraint stress models greatly decreased HPC mobilization and restored G-CSF levels to that of naïve animals without worsening lung injury scores. The daily administration of propranolol after both lung contusion and lung contusion/hemorrhagic shock subjected to chronic restraint stress decreased the prolonged mobilization of HPC from the bone marrow and decreased plasma G-CSF levels. Despite the decrease in mobilization of HPC, lung healing did not worsen. Alleviating chronic stress with propranolol

The Efficacy of Propranolol in Retinopathy of Prematurity and its Correlation with the Platelet Mass Index.

Science.gov (United States)

Korkmaz, Levent; Baştuğ, Osman; Ozdemir, Ahmet; Korkut, Sabriye; Karaca, Cagatay; Akin, Mustafa Ali; Gunes, Tamer; Kurtoglu, Selim; Ozturk, Mehmet Adnan

2017-01-01

Retinopathy of Prematurity (ROP) is a proliferative vitreoretinopathy which is one of the most frequent causes of blindness in children. In an attempt to find a solution to this important problem in preterm children, the search for new, effective treatment modalities with fewer side effects is underway. In our study, which was planned for this reason, we aimed to investigate the effects of propranolol treatment applied to cases of ROP in various stages during the second phase (known as the neovascularization-hypoxia phase) and to determine the correlation of these effects with the platelet mass index (PMI). A total of 171 preterm infants at risk of ROP were selected randomly for inclusion in the study. All of the patients were classified according to their stage of ROP and were divided into control and treatment groups. While the cases in the control group were administered physiological saline solution, those in the treatment group were administered propranolol in the period that corresponded to the second stage of the disease. The thrombocyte and PMI values in the first and second stages of each study group were recorded. A significant difference was found between the control and treatment groups of the stage 2 ROP study subjects. In the stage 2 ROP study group, no significant difference was detected between the control and treatment cases in terms of platelet counts in phase 1 or in the PMI values and the thrombolytic counts in phase 2. On the other hand, in phase 2 of the stage 2 ROP study subjects significant differences were detected between the control and treatment group in terms of PMI values. In the study, it was found in the stage 2 ROP study group that propranolol reduced the need for laser photocoagulation significantly. Also, in parallel to the efficacy of propranolol in this study group, a decrease was observed in PMI values.

Effects of propranolol and pindolol on plasma ANP levels in humans at rest and during exercise.

Science.gov (United States)

Bouissou, P; Galen, F X; Richalet, J P; Lartigue, M; Devaux, F; Dubray, C; Atlan, G

1989-08-01

In attempt to elucidate whether the beta-adrenoceptor is involved in the control of atrial natriuretic peptide (ANP) secretion, plasma immunoreactive ANP level was measured at rest, in recumbent and upright positions, and during graded maximal ergocycle exercise in nine healthy male subjects (23 +/- 0.5 years of age) treated for 3 days with nonselective beta-blockers propranolol (150 mg/day) or pindolol (15 mg/day) or with placebo. The effects of beta-blockers, which differ by their hemodynamic actions at rest because of the intrinsic sympathomimetic activity of pindolol, were compared. Maximal O2 consumption (VO2max) during beta-blockade was not significantly different from the placebo value. Resting heart rate was not affected by pindolol treatment but was decreased with propranolol (-10 beats/min). Both beta-blockers caused a reduction in heart rate at all the exercise intensities. Mean blood pressure was not affected by beta-blockade at rest but was significantly reduced during exercise. During placebo treatment, plasma ANP increased in response to exercise intensities greater than 65% of VO2max. At 100% VO2max plasma ANP was nearly doubled (101.5 +/- 14 pg/ml) compared with the basal value in upright position (56.6 +/- 15 pg/ml). beta-Blockade caused a marked elevation in plasma ANP at all the levels of activity. Despite different hemodynamic responses to pindolol and propranolol, both beta-blockers produced similar increases in the basal level of plasma ANP. These rises were maintained in the course of exercise tests, and no significant difference was found between propranolol and pindolol. We conclude that beta-adrenoceptor mechanisms are not directly responsible for tonic and exercise-induced ANP secretion in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Propranolol, clonidine, urapidil and trazodone infusion in essential tremor: a double-blind crossover trial.

Science.gov (United States)

Caccia, M R; Osio, M; Galimberti, V; Cataldi, G; Mangoni, A

1989-05-01

Accelerometric tremorgrams were recorded from 25 subjects affected by essential tremor and analysed by a Berg-Fourier frequency analyser before and during venous infusion of the following drugs: propranolol (beta-blocker), clonidine (alpha-presynaptic adrenergic agonist), urapidil (alpha-postsynaptic blocker), trazodone (adrenolytic agent) and placebo. The washout interval between infusions was 3 days. Recordings and data analyses were performed in a double-blind crossover trial. Tremor was classified as: at rest; postural (arms hyperextended); and intention (finger-nose test). Analysis of the results showed that propranolol and clonidine reduced significantly (P = 0.01 and P = 0.009, respectively) the power spectrum of postural tremor, but left at rest and intention tremors unchanged. No significant effects on the tremor power spectrum were observed after placebo, urapidil or trazodone administration. None of the drugs had any effect on tremor frequency.

Digoxin-like immunoreactivity, endogeneous cardiac glycoside-like factors (s) and natriuretic hormone. More than a hypothesis. Review article

Energy Technology Data Exchange (ETDEWEB)

Clerico, A

1987-01-01

Endogenous factors crossreacting with antidigoxin antibodies (digoxin-like immunoreactive substances=DLIS) have been found in several tissues and body fluids of animals and humans, using commercially avaiable digoxin RIA or EIA methods. Detectable DLIS concentration were found in blood and urine extracts of adults (normal healthy controls, hypertensive patients and salt loaded healthy subjects), while higher levels were generally observed in plasma samples of pregnant women, newborns and patients with renal insufficiency. The chemical characteristics of this endogenous factor are, at present, unknown, although it has been suggested that DLIS could be a substance with low molecular weight. Experimental studies and theoretical consideration suggest that DLIS, in addition to reacting with antibodies, might also bind to the specific cellular receptor of the cardiac glycosides and thus inhibit the membrane Na/sup +//K/sup +/ ATPase (sodium pump). Therefore, it has been suggested that DLSI is an endogeneous modulator of the membrane sodium-potassium pump and it could play a role in the regulation of fluid and electrolytes muscular tone of myocardial and also in pathogenesis of hypertension. 91 refs.

Psychophysiological responding to emotional memories in healthy young men after cortisol and propranolol administration

NARCIS (Netherlands)

Tollenaar, M.S.; Elzinga, B.M.; Spinhoven, P.; Everaerd, W.

2009-01-01

Rationale: Propranolol is found to reduce physiological hyper-responsiveness in post traumatic stress disorder (PTSD), possibly by affecting reconsolidation after the reactivation of traumatic memories. Cortisol is found to attenuate declarative memory retrieval, but it is unknown whether it also

Psychophysiological responding to emotional memories in healthy young men after cortisol and propranolol administration

NARCIS (Netherlands)

Tollenaar, M.S.; Elzinga, B.M.; Spinhoven, P.; Everaerd, W.T.A.M.

2009-01-01

Propranolol is found to reduce physiological hyper-responsiveness in post traumatic stress disorder (PTSD), possibly by affecting reconsolidation after the reactivation of traumatic memories. Cortisol is found to attenuate declarative memory retrieval, but it is unknown whether it also reduces

Hypothalamic digoxin, hemispheric chemical dominance, and the tridosha theory.

Science.gov (United States)

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-05-01

Ayurveda, the traditional Indian System of Medicine, deals with the theory of the three tridosha states (both physical and psychological): Vata, Pitta, and Kapha. They are the three major human constitutional types that both depend on psychological and physical characteristics. The Pitta state is described as a critical, discriminative, and rational psychological state of mind, while the Kapha state is described as being dominant for emotional stimuli. The Vata state is an intermediate unstable shifting state. The Pitta types are of average height and built with well developed musculature. The Vata types are thin individuals with low body mass index. The Kapha types are short stocky individuals that tend toward obesity, and who are sedentary. The study assessed the biochemical differences between right hemispheric dominant, bihemispheric dominant, and left hemispheric dominant individuals, and then compared this with the patterns obtained in the Vata, Pitta, and Kapha states. The isoprenoid metabolites (digoxin, dolichol, and ubiquinone), glycoconjugate metabolism, free radical metabolism, and the RBC membrane composition were studied. The hemispheric chemical dominance in various systemic diseases and psychological states was also investigated. The results showed that right hemispheric chemically dominant/Kapha state had elevated digoxin levels, increased free radical production and reduced scavenging, increased tryptophan catabolites and reduced tyrosine catabolites, increased glycoconjugate levels and increased cholesterol: phospholipid ratio of RBC membranes. Left hemispheric chemically dominant/Pitta states had the opposite biochemical patterns. The patterns were normal or intermediate in the bihemispheric chemically dominant/Vata state. This pattern could be correlated with various systemic and neuropsychiatric diseases and personality traits. Right hemispheric chemical dominance/Kapha state represents a hyperdigoxinemic state with membrane sodium

Preparation and preliminary biological evaluation of radiogallium-labeled DTPA-amlodipine complex for possible L-type calcium channel imaging

Energy Technology Data Exchange (ETDEWEB)

Firuzyar, Tahereh; Shafiee-Ardestani, Mehdi; Khalaj, Ali [Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of). Faculty of Pharmacy; Jalilian, Amir R.; Fazaeli, Yousef; Aboudzadeh, Mohammad Reza [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of). Radiopharmacy Research Group

2014-07-01

A DTPA-conjugated amlodipine analog (DTPA-AMLO) 3, was prepared for possible voltage gated calcium channel imaging after radiolabeling with Ga-67. [{sup 67}Ga]-DTPA-AMLO complex was prepared starting [{sup 67}Ga]gallium chloride and DTPA-AMLO in 60-90 min at 50-60 C in phosphate buffer. The partition co-efficient and stability of the tracer was determined in final solution (25 C) and presence of human serum (37 C) up to 24 h. The biodistribution of the labeled compound in wild-type rats were determined up to 72 h using organ counting and SPECT. The radiolabled complex was prepared in high radiochemical purity (>96%, RTLC and >98% HPLC) and significant specific activity (7-10 GBq/mmol). The log P for the complex was calculated as -0.594, consistent with a water soluble complex. The tracer is mostly washed out through kidneys which were in full compliance with the amlodipine metabolism and imaging studies demonstrated the same behavior. The tracer uptake in organs with smooth muscles was observed in stomach, colon as well as intestine.

Myocardial scintigraphy with 16 123I hexadecene-9 oic acid. Study of the influence of isoproterenol, propranolol, dipyridamole and isoptine

International Nuclear Information System (INIS)

Comet, M.; Wolf, J.E.; Pilichowski, P.; Busquet, G.; Dubois, F.; Mathieu, J.P.; Pernin, C.; Riche, F.; Vidal, M.

1983-01-01

After I.V. injection of 123 I hexadecene-9 oic acid to dogs, the decreasing part of the myocardial activity curve is fitted with an exponential which period is calculated. Tacking the anesthetized dogs as his own reference, we study the influence of isoproterenol, propranolol, dipyridamole and isoptine on value of the period. None of the drugs modify significatively the period. Nevertheless, propranolol and isoptine and to a lesser extent dipyridamole have a tendancy to increase the value of the period [fr

Effect of ouabain, digoxin and digitoxigenin on potassium uptake and histamine release from rat peritoneal mast cells

DEFF Research Database (Denmark)

Knudsen, T; Ferjan, I; Johansen, Torben

1993-01-01

Rat peritoneal mast cells were used to study the effects of digitalis glycosides on potassium uptake and histamine release induced by compound 48/80, substance P and egg-albumin (immunological release). In the absence of calcium all glycosides inhibited potassium uptake. Ouabain and digoxin....... Hydrophilic digitalis glycosides seem to enhance histamine release secondary to an increase in intracellular sodium. Lipophilic glycosides have no effect on the release....

Uptake of propranolol, a cardiovascular pharmaceutical, from water into fish plasma and its effects on growth and organ biometry

Energy Technology Data Exchange (ETDEWEB)

Owen, Stewart F. [Institute for the Environment, Brunel University, Uxbridge, Middlesex, UB8 3PH (United Kingdom); Global Safety Health and Environment, AstraZeneca, Brixham Environmental Laboratory, Freshwater Quarry, Brixham, Devon, TQ5 8BA (United Kingdom); Huggett, Duane B. [Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340 (United States); Hutchinson, Thomas H.; Hetheridge, Malcolm J. [Global Safety Health and Environment, AstraZeneca, Brixham Environmental Laboratory, Freshwater Quarry, Brixham, Devon, TQ5 8BA (United Kingdom); Kinter, Lewis B. [AstraZeneca Pharmaceuticals US, 1800 Concord Pike, Wilmington, DE 19850 (United States); Ericson, Jon. F. [Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340 (United States); Sumpter, John P., E-mail: john.sumpter@brunel.ac.uk [Institute for the Environment, Brunel University, Uxbridge, Middlesex, UB8 3PH (United Kingdom)

2009-07-26

Pharmaceuticals in the environment (PIE) are of importance since these compounds are designed to affect biological receptors/enzymes that are often conserved across vertebrate families. Across-species extrapolation of these therapeutic targets suggests potential for impacting amphibia and fish in the aquatic environment. Due to the scarcity of relevant ecotoxicological data, the long-tem impact of PIE remains a research question. Efficient use of mammalian data has been proposed to better understand and predict the potential for a given pharmaceutical to impact the environment. Using a model cardiovascular pharmaceutical (propranolol, a non-specific {beta}{sub 1}/{beta}{sub 2}-adrenergic antagonist), the hypothesis that mammalian data can be used to predict toxicity in fish was tested. Rainbow trout (Oncorhynchus mykiss (Walbaum)) have {beta}-adrenergic signalling mechanisms analogous to human cardiovascular receptors that respond to pharmacological doses of agonists and antagonists. Trout absorbed propranolol from water such that after 40 days of exposure, the linear relationship was [plasma] = 0.59[water] (n = 31, r = 0.96). Growth rate was affected only at very high aqueous concentrations (10-day {sup growth}NOEC = 1.0 and {sup growth}LOEC = 10 mg/l). Growth recovered with time (40-day {sup growth}NOEC = 10 mg/l), suggesting possible adaptation to the pharmaceutical, although the internal plasma concentration in trout exposed to 10 mg propranolol/l of water was higher than the mammalian therapeutic plasma concentration. Additional endpoints suggested subtle changes of liver and heart size at much lower concentrations may have occurred, although these were not concentration-related. There was, however, a dose-dependent effect upon overall body condition. The trout plasma concentrations at these effective aqueous concentrations fell within the range of mammalian effective plasma concentrations, supporting the potential for developing 'read-across' from

Uptake of propranolol, a cardiovascular pharmaceutical, from water into fish plasma and its effects on growth and organ biometry

International Nuclear Information System (INIS)

Owen, Stewart F.; Huggett, Duane B.; Hutchinson, Thomas H.; Hetheridge, Malcolm J.; Kinter, Lewis B.; Ericson, Jon. F.; Sumpter, John P.

2009-01-01

Pharmaceuticals in the environment (PIE) are of importance since these compounds are designed to affect biological receptors/enzymes that are often conserved across vertebrate families. Across-species extrapolation of these therapeutic targets suggests potential for impacting amphibia and fish in the aquatic environment. Due to the scarcity of relevant ecotoxicological data, the long-tem impact of PIE remains a research question. Efficient use of mammalian data has been proposed to better understand and predict the potential for a given pharmaceutical to impact the environment. Using a model cardiovascular pharmaceutical (propranolol, a non-specific β 1 /β 2 -adrenergic antagonist), the hypothesis that mammalian data can be used to predict toxicity in fish was tested. Rainbow trout (Oncorhynchus mykiss (Walbaum)) have β-adrenergic signalling mechanisms analogous to human cardiovascular receptors that respond to pharmacological doses of agonists and antagonists. Trout absorbed propranolol from water such that after 40 days of exposure, the linear relationship was [plasma] = 0.59[water] (n = 31, r = 0.96). Growth rate was affected only at very high aqueous concentrations (10-day growth NOEC = 1.0 and growth LOEC = 10 mg/l). Growth recovered with time (40-day growth NOEC = 10 mg/l), suggesting possible adaptation to the pharmaceutical, although the internal plasma concentration in trout exposed to 10 mg propranolol/l of water was higher than the mammalian therapeutic plasma concentration. Additional endpoints suggested subtle changes of liver and heart size at much lower concentrations may have occurred, although these were not concentration-related. There was, however, a dose-dependent effect upon overall body condition. The trout plasma concentrations at these effective aqueous concentrations fell within the range of mammalian effective plasma concentrations, supporting the potential for developing 'read-across' from mammalian pharmacology safety data to fish

Differential effects of amlodipine and atorvastatin treatment and their combination on atherosclerosis in ApoE*3-Leiden transgenic mice

NARCIS (Netherlands)

Delsing, D.J.; Jukema, J.W.; van de Wiel, M.A.; Emeis, J.; van der Laarse, A.; Havekes, L.M.; Princen, H.M.G.

2003-01-01

This study was designed to investigate the potential antiatherosclerotic effects of the calcium antagonist amlodipine as compared with the HMG-CoA reductase inhibitor atorvastatin and the combination of both in ApoE*3-Leiden transgenic mice. Four groups of 15 ApoE*3-Leiden mice were put on a

Design and monitoring of photostability systems for amlodipine dosage forms.

Science.gov (United States)

Ragno, G; Cione, E; Garofalo, A; Genchi, G; Ioele, G; Risoli, A; Spagnoletta, A

2003-10-20

Photostability of amlodipine (AML) has been monitored in several pharmaceutical inclusion systems characterized by plurimolecular aggregation of the drug and excipients with high molecular weight. Several formulations including cyclodextrins, liposomes and microspheres have been prepared and characterized. The photodegradation process has been monitored according to the conditions suggested by the ICH Guideline for photostability testing, by using a light cabinet equipped with a Xenon lamp and monitored by spectrophotometry. The formulations herein tested have been found to be able to considerably increase drug stability, when compared with usual pharmaceutical forms. The residual concentration detected in the inclusion complexes with cyclodextrins and liposomes was 90 and 77%, respectively, while a very good value of 97% was found for microspheres, after a radiant exposure of 11,340 kJm(-2).

Enhancement of exposure therapy in participants with specific phobia: A randomized controlled trial comparing yohimbine, propranolol and placebo.

Science.gov (United States)

Meyerbröker, K; Morina, N; Emmelkamp, P M G

2018-05-04

Recent research indicates that pharmacological agents may enhance psychotherapeutic outcome. Yet, empirical results have not been conclusive with respect to two pharmacological agents, yohimbine hydrochloride (YOH) and propranolol. YOH is suggested to enhance emotional memory by elevating norepinephrine, whereas the β-adrenergic receptor antagonist propranolol might help better cope with feared situations by reducing accompanying bodily sensations. In this controlled trial, fifty-six participants with specific phobia were randomly assigned to either 1) virtual reality exposure therapy (VRET) plus YOH, 2) VRET plus Propranolol, or 3) VRET plus placebo. Participants in all conditions received three sessions of VRET over a period of two weeks. We conducted 2 × 3 repeated measures MANOVA's. Results showed a significant effect for time, with partial eta squared ranging from ηp2 = 0.647 to ηp2 = 0.692, for specific phobia, yet no significant interaction effects were found. No significant differences were found when VRET with YOH or a beta-blocker was compared to VRET with a non-active placebo. Implications for clinical practice and future research are discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Myocardial scintigraphy with 16 /sup 123/I hexadecene-9 oic acid. Study of the influence of isoproterenol, propranolol, dipyridamole and isoptine

Energy Technology Data Exchange (ETDEWEB)

Comet, M.; Wolf, J.E.; Pilichowski, P.; Busquet, G.; Dubois, F.; Mathieu, J.P.; Pernin, C.; Riche, F.; Vidal, M. ( Grenoble Universite, 38 - (France))

1983-01-01

After I.V. injection of /sup 123/I hexadecene-9 oic acid to dogs, the decreasing part of the myocardial activity curve is fitted with an exponential which period is calculated. Taking the anesthetized dog as reference, we study the influence of isoproterenol, propranolol, dipyridamole and isoptine on value of the period. None of the drugs modify significantly the period. Nevertheless, propranolol and isoptine and to a lesser extent dipyridamole have a tendancy to increase the value of the period.

Decreased absorption as a possible cause for the lower bioavailability of a sustained-release propranolol.

Science.gov (United States)

Takahashi, H; Ogata, H; Warabioka, R; Kashiwada, K; Ohira, M; Someya, K

1990-03-01

The influence of sustained absorption on the oral availability of propranolol (P) and the metabolic disposition of P were investigated by obtaining the partial metabolic clearances (CLm) following long-acting P (LA) dosing in comparison with the conventional propranolol tablet (CP). Ten healthy volunteers were given a single oral dose of an LA capsule (60 mg) and CP (20 mg x 3) using a crossover design. Blood and urine samples were collected over 24- and 48-h postdose periods, respectively. Concentrations of P, propranolol glucuronide (PG), 4-hydroxypropranolol (4P), 4-hydroxypropranolol glucuronide (4PG), 4-hydroxypropranolol sulfate (4PS), and naphthoxylactic acid (NLA) were determined by HPLC with fluorescence and UV detection. Significant differences were observed between LA and CP in the area under the plasma concentration-time curves (AUCs) for P, PG, and NLA and in the amounts excreted into urine (Ae) for all measured metabolites (i.e., PG, 4P, 4PG, 4PS, and NLA). The parallel decrease of the AUC for P and the excreted amounts of all measured metabolites following LA dosing resulted in partial metabolic clearances (CLm) and renal clearances (CL) for P and its metabolites that were similar to those observed for CP. Therefore, the hepatic metabolism of P would not be affected by the slower absorption at a single oral dose of 60 mg. These results indicate that the poor absorption of P from the gastrointestinal tract might be one of the factors causing the low bioavailability of P observed after administration of the sustained-release formulation.

Comparison of the efficacy and safety profiles of two fixed-dose combinations of antihypertensive agents, amlodipine/benazepril versus valsartan/hydrochlorothiazide, in patients with type 2 diabetes mellitus and hypertension: a 16-week, multicenter, randomized, double-blind, noninferiority study.

Science.gov (United States)

Lee, I-Te; Hung, Yi-Jen; Chen, Jung-Fu; Wang, Chih-Yuan; Lee, Wen-Jane; Sheu, Wayne Huey-Herng

2012-08-01

Hypertension is a prevalent condition that is closely associated with chronic complications in patients with diabetes. Fixed-dose combination therapy is currently recommended for the treatment of hypertension due to the advantage of reducing the pill burden. However, the effects of combination therapy may be diverse because of the different components. We examined blood pressure reduction and metabolic alterations after amlodipine/benazepril and valsartan/hydrochlorothiazide treatment in patients with type 2 diabetes mellitus and hypertension and microalbuminuria. This randomized, double-blind, parallel comparison, noninferiority clinical trial included patients with type 2 diabetes mellitus and hypertension and microalbuminuria detected within the past year. After a 2-week, placebo run-in period, patients were assigned to treatment with amlodipine/benazepril or valsartan/hydrochlorothiazide for 16 weeks. The primary end point was mean change in diastolic blood pressure. The prespecified boundary for noninferiority was 3.5 mm Hg of the mean change in diastolic blood pressure between treatments (amlodipine/benazepril minus valsartan/hydrochlorothiazide). If the upper limit of the 95% CI fell within 3.5 mm Hg, amlodipine/benazepril would be considered noninferior to valsartan/hydrochlorothiazide. Of the 226 patients assessed for eligibility, 169 satisfied the inclusion/exclusion criteria and were assigned to a treatment group; 83 patients (54.2% male, mean age of 60.5 [10.0] years) in the amlodipine/benazepril group and 84 patients (64.3% male, mean age of 59.0 [10.6] years) in the valsartan/hydrochlorothiazide group received at least 1 dose of study medication and were included in the intention-to-treat population. In the per-protocol population, amlodipine/benazepril (n = 74) was noninferior to valsartan/hydrochlorothiazide (n = 78) with regard to the mean change in diastolic blood pressure (difference, -0.9 mm Hg; 95% CI, -3.5 to 1.6). The mean change in systolic

Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF-TIMI 48 Trial

DEFF Research Database (Denmark)

Eisen, Alon; Ruff, Christian T; Braunwald, Eugene

2017-01-01

BACKGROUND: Digoxin is widely used in patients with atrial fibrillation despite the lack of randomized controlled trials. Observational studies report conflicting results regarding its association with mortality, perhaps because of residual confounding by the presence of heart failure (HF). METHO...

Dependence on the mobile phase pH of the adsorption behavior of propranolol enantiomers on a cellulase protein used as the chiral selector

Energy Technology Data Exchange (ETDEWEB)

Fornstedt, T.; Goetmar, G.; Andersson, M.; Guiochon, G.

1999-02-17

The authors reported previously on the unusual thermodynamic characteristics of the enantioselective interactions between the enantiomers of the {beta}-blocker propranolol and the protein cellobiohydrolase I immobilized on silica. The adsorption of the more retained enantiomer, (S)-propranolol, is endothermic while that of the (R)-propranolol is exothermic. This causes a rapid increase of the selectivity factor with increasing temperature. In this work, the complex dependence of the selectivity factor on the pH of the solvent is studied. They determined the equilibrium isotherms of (R)- and (S)-propranolol in a wide concentration range (0.25 {micro}M to 1.1 mM) at six different mobile-phase pHs (4.7, 5.0, 5.2, 5.5, 5.7, and 6.0) and fitted the data obtained to the bi-Langmuir model. This gave the saturation capacity and the binding constant of the nonselective contribution for the two enantiomers. It also gave these parameters for the enantioselective contributions of each of them. The dependence of these parameters on the pH is discussed and interpreted in terms of the retention mechanism. Conclusions are in excellent agreement with recent, independent results on the structure of the protein obtained by X-ray crystallography.

Comparison of valsartan and amlodipine on ambulatory blood pressure variability in hypertensive patients.

Science.gov (United States)

Eguchi, Kazuo; Imaizumi, Yuki; Kaihara, Toshiki; Hoshide, Satoshi; Kario, Kazuomi

We tested the hypothesis that calcium channel blockers (CCBs: amlodipine group, n = 38)) are superior to angiotensin receptor blockers (ARBs: valsartan group, n = 38) against ambulatory blood pressure variability (BPV) in untreated Japanese hypertensive patients. Both drugs significantly reduced ambulatory systolic and diastolic BP values. With regard to BPV, standard deviation (SD) in SBP did not change with the administration of either drug, but the ARB significantly increased SD in awake DBP (12 ± 4-14 ± 4 mmHg). The ARB also significantly increased the coefficients of variation (CVs)in awake and 24-h SBP/DBP (all P valsartan, especially in reducing maximum BP levels.

A qualitative study of amlodipine and its related compounds by electrospray ionization tandem mass spectrometry.

Science.gov (United States)

Gibbons, John; Pugh, Jonathan; Dimopoulos-Italiano, Gina; Pike, Richard

2006-01-01

A comprehensive structural analysis of amlodipine and certain related compounds was performed by electrospray ionization tandem mass spectrometry. Triple quadrupole and quadrupole time-of-flight instruments were used to provide collision-induced dissociation and accurate mass measurement for selected product and second-generation product ions. A unique ion rearrangement was observed, which was found to be characteristic of certain dihydropyridines. This study provides a fundamental understanding of the fragmentation of these compounds. The structural elucidation of an unknown impurity is presented as an example. Copyright (c) 2006 John Wiley & Sons, Ltd.

Substrate-Dependent Inhibition of P-glycoprotein Mediated Efflux Transport of Digoxin

DEFF Research Database (Denmark)

Saaby, Lasse; Ozgür, Burak; Brodin, Birger

, distribution and excretion of a wide range of structurally diverse drug compounds and P-gp therefore constitutes a potential site for drug-drug interactions. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) recommend that all new investigational drugs be screened...... for interactions with P-gp among other transporters in vitro. This includes an evaluation of new drug compounds as inhibitors of P-gp, preferably in competition with a clinically relevant probe substrate such as digoxin. However, increasing evidence indicates that the binding pocket of P-gp contains several...... overlapping binding sites for substrates. This suggests that drug-drug interactions may be pairwise specific and observations of interaction from a single drug-drug combination may therefore not apply to a second drug combination. At present, it is not known which drug combinations should be considered...

Reduction of FDG uptake in brown adipose tissue in clinical patients by a single dose of propranolol

Energy Technology Data Exchange (ETDEWEB)

Soederlund, Veli [Karolinska University Hospital, Department of Radiology, Stockholm (Sweden); Larsson, Stig A. [Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Jacobsson, Hans [Karolinska University Hospital, Department of Radiology, Stockholm (Sweden); Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden)

2007-07-15

Uptake in brown adipose tissue (hibernating fat) is sometimes seen at FDG-PET examinations. Despite a characteristic appearance, this may hide clinically relevant uptake. Stimulation of the sympathetic nervous system increases glucose uptake of brown fat. We now re-examine patients with brown fat activity that could disguise tumour uptake after pre-treatment with propranolol (a non-selective {beta}-blocker) in order to reduce the uptake. Our first examinations of this kind are reported. Eleven patients with strong brown fat uptake were studied. There was a mean of 5 days (range 2-8) between the examinations. At the second examination, 80 mg of propranolol was given orally 2 h before FDG administration. In addition to visual evaluation of the brown fat uptake, SUV assessments of the uptake in brown fat, lung, heart, liver, spleen and bone marrow were made. All patients showed complete or almost complete disappearance of the brown fat activity at the second examination (p < 0.001) both upon visual evaluation and when comparing SUVs. In seven patients there was also uptake in a known or strongly suspected malignancy, which remained unchanged between the examinations. Beyond an insignificant decrease in the myocardial uptake, there was no redistribution to the various examined organs at the second examination. Pre-treatment with a single dose of propranolol blocks the FDG uptake in brown adipose tissue, thereby increasing the specificity of the examination. The tumour uptake seems not to be impaired. (orig.)

DYNAMICS OF STRUCTURAL AND FUNCTIONAL STATUS OF MYOCARDIUM DUE TO COMBINATION THERAPY WITH AMLODIPINE AND BISOPROLOL IN PATIENTS WITH ARTERIAL HYPERTENSION

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I. L. Zapesochnaya

2015-09-01

Full Text Available Aim. To evaluate the effect of 6-month therapy with combination of amlodipine and bisoprolol on the structural and functional status of the myocardium in hypertensive patients who work in the Far North.Material and methods. 140 hypertensive patients who live in the Khanty-Mansiysk Autonomous District - Yugra were divided into two groups depending on arrangement of working time. The first group included 72 patients who work only day shift; the second group – 68 patients who work alternate (day/night shifts. Combination therapy with amlodipine and bisoprolol assigned to all patients. Echocardiography was performed at baseline, after 12 weeks, and after 6 months of therapy.Results. The target blood pressure (BP level in group 1 was achieved in 92.9%. A share of patients with normal left ventricular (LV geometry increased from 37.5 to 44.8%; a share of patients with concentric and eccentric LV hypertrophy (LVH decreased from 30.6 to 23.9% and 19.4 to 19.2%, respectively. Target BP level in group 2 was achieved in 87.9%. A share of patients with normal LV geometry increased from 23.5 to 33.3%; while share of patients with concentric and eccentric LVH decreased from 45.6 to 38.1% and from 19.1 to 17.4%, respectively. A positive correlation between LV myocardial index and average daily systolic and diastolic BP was found.Conclusion. Revealed changes in BP and in LV structure and function due to treatment with amlodipine and bisoprolol can be considered as cardioprotective effect of this combination in hypertensive patients who work in the Far North. This effect was more pronounced in hypertensive patients working alternate (day/night shifts.

DYNAMICS OF STRUCTURAL AND FUNCTIONAL STATUS OF MYOCARDIUM DUE TO COMBINATION THERAPY WITH AMLODIPINE AND BISOPROLOL IN PATIENTS WITH ARTERIAL HYPERTENSION

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I. L. Zapesochnaya

2014-01-01

Full Text Available Aim. To evaluate the effect of 6-month therapy with combination of amlodipine and bisoprolol on the structural and functional status of the myocardium in hypertensive patients who work in the Far North.Material and methods. 140 hypertensive patients who live in the Khanty-Mansiysk Autonomous District - Yugra were divided into two groups depending on arrangement of working time. The first group included 72 patients who work only day shift; the second group – 68 patients who work alternate (day/night shifts. Combination therapy with amlodipine and bisoprolol assigned to all patients. Echocardiography was performed at baseline, after 12 weeks, and after 6 months of therapy.Results. The target blood pressure (BP level in group 1 was achieved in 92.9%. A share of patients with normal left ventricular (LV geometry increased from 37.5 to 44.8%; a share of patients with concentric and eccentric LV hypertrophy (LVH decreased from 30.6 to 23.9% and 19.4 to 19.2%, respectively. Target BP level in group 2 was achieved in 87.9%. A share of patients with normal LV geometry increased from 23.5 to 33.3%; while share of patients with concentric and eccentric LVH decreased from 45.6 to 38.1% and from 19.1 to 17.4%, respectively. A positive correlation between LV myocardial index and average daily systolic and diastolic BP was found.Conclusion. Revealed changes in BP and in LV structure and function due to treatment with amlodipine and bisoprolol can be considered as cardioprotective effect of this combination in hypertensive patients who work in the Far North. This effect was more pronounced in hypertensive patients working alternate (day/night shifts.

Role of valsartan, amlodipine and hydrochlorothiazide fixed combination in blood pressure control: an update

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Maurizio Destro

2010-04-01

Full Text Available Maurizio Destro1, Francesca Cagnoni1, Antonio D’Ospina1, Alessandra Rossi Ricci1, Elena Demichele1, Emmanouil Peros1, Augusto Zaninelli2, Paola Preti31Internal Medicine, Ospedale Unificato Broni-Stradella, Stradella (PV, Italy; 2General Medicine, School of Medicine, University of Florence, Florence, Italy; 3Internal Medicine, University of Pavia, Pavia, ItalyAbstract: The treatment of moderate or severe hypertension in most cases requires the contemporaneous use of multiple antihypertensive agents. The most available two-drug combinations have an agent that addresses renin secretion and another one that is statistically more effective in renin-independent hypertension. The practice of combining agents that counteract different mechanisms is the most likely explanation for the fact that most available two-drug combinations have an agent that addresses renin secretion (beta-blocker, angiotensin converting enzyme inhibitor, angiotensin II receptor blocker or direct renin inhibitor and another one that is more effective in renin-independent hypertension (diuretic, dihydropyridine or non-dihydropyridine calcium channel blocker. Based on these considerations, addition of hydrochlorothiazide to the combination of an antagonist of the renin-angiotensin system with a calcium channel blocker would constitute a logical approach. Inclusion of a diuretic in the triple combination is based on the evidence that these agents are effective and cheap, enhance the effect of other antihypertensive agents, and add a specific effect to individuals with salt-sensitivity of blood pressure. The benefit of triple combination therapy with amlodipine, valsartan and hydrochlorothiazide over its dual component therapies has been demonstrated, and the use of a single pill will simplify therapy resulting in better blood pressure control.Keywords: valsartan, amlodipine, hydrochlorothiazide, HCTZ, blood pressure, hypertension

Pulmonary extraction of serotonin and propranolol in patients with adult respiratory distress syndrome

International Nuclear Information System (INIS)

Morel, D.R.; Dargent, F.; Bachmann, M.; Suter, P.M.; Junod, A.F.

1985-01-01

Because injury to the pulmonary vascular endothelium is associated with the development of the adult respiratory distress syndrome (ARDS), the authors assessed the metabolic function of pulmonary endothelial cells by the measurements of the first-pass pulmonary extraction of [ 14 C]serotonin and [ 3 H]propranolol in 15 patients with ARDS and 15 patients at risk for developing ARDS. Serotonin extraction ratio was lower in patients with ARDS (0.85 +/- 0.10, mean +/- SD) than in patients at risk (0.91 +/- 0.04) (p less than 0.025), and both values were significantly reduced (p less than 0.005) when compared with a control group value (0.97 +/- 0.01). The decrease in serotonin extraction was correlated with the severity of ARDS (r = -0.67) (p less than 0.001) and with pulmonary function changes over time. Propranolol extraction ratio was decreased in patients at risk (0.66 +/- 0.11) (p less than 0.005) but not in patients with ARDS (0.75 +/- 0.11), when compared with those in the control group (0.81 +/- 0.03). Low values in patients at risk were restored to normal by continuous positive airway pressure breathing. The authors conclude that pulmonary extraction of serotonin, an index of pulmonary endothelial cell function, correlates with the severity of ARDS

Ambulatory blood pressure monitoring after 1 year on valsartan or amlodipine-based treatment: a VALUE substudy

DEFF Research Database (Denmark)

Pedersen, Ole Lederballe; Mancia, Giuseppe; Pickering, Thomas

2007-01-01

OBJECTIVE: The ambulatory blood pressure (ABP) monitoring substudy of the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial was carried out in a subset of patients from USA, Italy and Denmark. ABP was measured after 1 year in the trial, with the aim of evaluating comparability...... of ABP levels on valsartan (VAL) and amlodipine (AML)-based regimens. METHODS: ABP was measured every 20 min during a 25-h period after morning administration of medicine; 659 patients were available for intention-to-treat analysis. RESULTS: Office blood pressure (BP) differences were smaller than...

Validation of an HPLC–UV method for the determination of digoxin residues on the surface of manufacturing equipment

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ZORAN B. TODOROVIĆ

2009-09-01

Full Text Available In the pharmaceutical industry, an important step consists in the removal of possible drug residues from the involved equipments and areas. The cleaning procedures must be validated and methods to determine trace amounts of drugs have, therefore, to be considered with special attention. An HPLC–UV method for the determination of digoxin residues on stainless steel surfaces was developed and validated in order to control a cleaning procedure. Cotton swabs, moistened with methanol were used to remove any residues of drugs from stainless steel surfaces, and give recoveries of 85.9, 85.2 and 78.7 % for three concentration levels. The precision of the results, reported as the relative standard deviation (RSD, were below 6.3 %. The method was validated over a concentration range of 0.05–12.5 µg mL-1. Low quantities of drug residues were determined by HPLC–UV using a Symmetry C18 column (150´4.6 mm, 5 µm at 20 °C with an acetonitrile–water (28:72, v/v mobile phase at a flow rate of 1.1 mL min-1, an injection volume of 100 µL and were detected at 220 nm. A simple, selective and sensitive HPLC–UV assay for the determination of digoxin residues on stainless steel was developed, validated and applied.

Assessment of Glomerular Filtration Rate Based on Alterations of Serum Brain-Derived Neurotrophic Factor in Type 2 Diabetic Subjects Treated with Amlodipine/Benazepril or Valsartan/Hydrochlorothiazide

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I-Te Lee

2015-01-01

Full Text Available Background. Brain-derived neurotrophic factor (BDNF is associated with sympathetic activation. However, the effects of BDNF on diabetic nephropathy are unknown. The aim of this study was to assess the estimated glomerular filtration rates (eGFRs and changes in serum BDNF levels in type 2 diabetic subjects treated with antihypertensive medications. Methods. In this randomized, double-blind clinical trial, type 2 diabetic subjects with hypertension were assigned to either the benazepril/amlodipine or valsartan/hydrochlorothiazide treatment groups for a 16-week period. The post hoc analyses were based on increased or decreased serum BDNF levels. Results. Of the 153 enrolled subjects, the changes in eGFR were significantly and inversely correlated with those in BDNF in the 76 subjects treated with valsartan/hydrochlorothiazide (r=-0.264, P=0.021 but not in the 77 subjects treated with benazepril/amlodipine (r=-0.025, P=0.862. The 45 subjects with increased BDNF following valsartan/hydrochlorothiazide treatment exhibited a significantly reduced eGFR (-8.8±14.9 mL/min/1.73 m2; P<0.001. Multivariate regression analysis revealed that increased serum BDNF represents an independent factor for reduced eGFR (95% confidence interval between −0.887 and −0.076, P=0.020. Conclusions. Increased serum BDNF is associated with reduced eGFR in type 2 diabetic subjects treated with valsartan/hydrochlorothiazide but not with amlodipine/benazepril.

A double blind, placebo-controlled study of the effects of post-retrieval propranolol on reconsolidation of memory for craving and cue reactivity in cocaine dependent humans.

Science.gov (United States)

Saladin, Michael E; Gray, Kevin M; McRae-Clark, Aimee L; Larowe, Steven D; Yeatts, Sharon D; Baker, Nathaniel L; Hartwell, Karen J; Brady, Kathleen T

2013-04-01

This study examined the effects of propranolol vs. placebo, administered immediately after a "retrieval" session of cocaine cue exposure (CCE), on craving and physiological responses occurring 24 h later during a subsequent "test" session of CCE. It was hypothesized that compared to placebo-treated cocaine-dependent (CD) individuals, propranolol-treated CD individuals would evidence attenuated craving and physiological reactivity during the test session. Secondarily, it was expected that group differences identified in the test session would be evident at a 1-week follow-up CCE session. Exploratory analyses of treatment effects on cocaine use were also performed at follow-up. CD participants received either 40 mg propranolol or placebo immediately following a "retrieval" CCE session. The next day, participants received a "test" session of CCE that was identical to the "retrieval" session except no medication was administered. Participants underwent a "follow-up" CCE session 1 week later. Craving and other reactivity measures were obtained at multiple time points during the CCE sessions. Propranolol- vs. placebo-treated participants evidenced significantly greater attenuation of craving and cardiovascular reactivity during the test session. Analysis of the follow-up CCE session data did not reveal any group differences. Although there was no evidence of treatment effects on cocaine use during follow-up, this study was insufficiently powered to rigorously evaluate differential cocaine use. This double-blind, placebo-controlled laboratory study provides the first evidence that propranolol administration following CCE may modulate memories for learning processes that subserve cocaine craving/cue reactivity in CD humans. Alternative interpretations of the findings were considered, and implications of the results for treatment were noted.

DOUBLE-BLIND PLACEBO-CONTROLLED STUDY OF IBOPAMINE AND DIGOXIN IN PATIENTS WITH MILD-TO-MODERATE HEART-FAILURE - RESULTS OF THE DUTCH IBOPAMINE MULTICENTER TRIAL (DIMT)

NARCIS (Netherlands)

VANVELDHUISEN, DJ; MANINTVELD, AJ; DUNSELMAN, PHJM; LOK, DJA; DOHMEN, HJM; POORTERMANS, JC; WITHAGEN, AJAM; PASTEUNING, WH; BROUWER, J; LIE, KI

1993-01-01

Objectives. This study was conducted to determine the efficacy and safety of long-term treatment with the orally active dopamine agonist ibopamine in patients with mild to moderate chronic congestive heart failure and to compare the results with those of treatment with digoxin and placebo.

Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension.

Science.gov (United States)

Hilleman, D E; Reyes, A P; Wurdeman, R L; Faulkner, M

2001-08-01

Recent hypertension trials have demonstrated the importance of achieving goal blood pressures to reduce the risk of target organ damage. In patients with moderate to severe hypertension, the use of high-dose monotherapy and/or combinations of drugs are necessary to achieve these goals. Fixed-dose combination products may be useful in these patients by reducing the number of daily doses required to control blood pressure. The objective of the present study was to evaluate the efficacy and safety of a therapeutic interchange between high-dose calcium channel blocker therapy and a fixed-dose combination of amlodipine/ benazepril (Lotrel; Novartis Pharmaceuticals, USA) in patients with moderate to severe hypertension. A total of 75 patients were switched from amlodipine (n = 25), felodipine (n = 25), and nifedipine-GITS (n = 25) to amlodipine/benazepril. Twenty-eight of the 75 patients (37%) were taking either a beta-blocker or a diuretic in addition to the high-dose calcium channel blocker prior to the switch. Blood pressure control, side effects and the cost of the therapeutic interchange were evaluated in the year following the therapeutic interchange. Sixty-six of the 75 (88%) patients were successfully switched with maintenance of blood pressure control and without the development of new dose-limiting side effects. Reasons for treatment failure after the therapeutic interchange included loss of blood pressure control in five patients and the development of new dose-limiting side effects in four patients. These side effects included cough in three patients and rash in one patient. After accounting for differences in drug acquisition cost and costs related to the switch (clinic and emergency room and laboratory tests), a cost savings of $16030 for all 75 patients was realised in the first year. The per patient-per year cost savings was $214. Our data indicate that a therapeutic interchange from selected high-dose calcium channel blockers to a fixed-dose combination

Simultaneous determination of amlodipine, valsartan and hydrochlorothiazide by LC–ESI-MS/MS and its application to pharmacokinetics in rats

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Shankar Ganesh Gadepalli

2014-12-01

Full Text Available Polypill is a fixed-dose combination that contains three or more active ingredients used as a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects. A novel and accurate liquid chromatography tandem mass spectrometry method using electrospray ionization mode has been developed and validated for the simultaneous determination of amlodipine (AMD, valsartan (VAL using losartan (LOS as an internal standard (IS, and hydrochlorothiazide (HCT using furosemide (FSD as an IS. The separation was carried on Aquasil C18 (50 mm×2.1 mm, 5 µm reversed phase column using acetonitrile and water containing 0.1% formic acid (50:50, v/v as the mobile phase. The method was validated in terms of linearity, accuracy and precision over the concentration range of 1–1000 ng/mL. The intra and inter-day precision and accuracy, stability and extraction recoveries of all the analytes were in the acceptable range. This method can be successfully applied to the pharmacokinetic study of AMD, VAL and HCT when given as a polypill. Keywords: Amlodipine, Valsartan, Hydrochlorothiazide, Exforge HCT, Polypill

The "3"2P applicator combined with propranolol in the treatment of large area skin capillary hemangiomain children

International Nuclear Information System (INIS)

Duan Yongqiang; Wu Zhenfu; Wu Min; Qiu Xuan; Fei Shinuan

2016-01-01

Objective: To investigate the clinical efficacy of "3"2P applicator plus propranolol in children with a large area of skin capillary hemangioma. Methods: Forty five cases of large hemangioma were divided into two groups. Control group of 20 patients recieved the conventional "3"2P application therapy. Of 20 cases in control group, there were 10 cases ≤3 years old children with hemangiomas, and 10 cases > 3 years old children with Port Wine Stain(PWS). Observation group of 25 cases recieved "3"2P applicator plus propranolol. Of 25 cases in observation group 10 cases werer ≤3 years old children with hemangiomas, 15 cases of children with PWS. Comparison was made between two different types of vascular tumors, treatment in ≤3 years old children and > 3 years old children, and adverse reactions. Data statistical analysis used χ"2 test and zero reaction test. P 0.05). The treatment efficacy in ≤3 years old children with infant hemangioma was 90.0% in control group and 100% in observation group (P > 0.05 ). The treatment efficacy for PWS in > 3 years old children was 40.0% in control group and 80% in observation group. Here the difference is statistically significant(P 3 years old children in control group,the treatment efficacy was 90.0% and 40.0%, respectively P 3 years old children in observation group, the treatment efficacy was 100.0% and 80.0% with no significant difference(P > 0.05). Complication of moist dermatitis was 25.0% in control group and 40.0% in observation group. Occurrence of depigmentation was 75.0% and 84.0% in control and observation group with no significant difference(P > 0.05). Changing in heart rate occurs in ≤3 years old children and > 3 years old children, 50.0% and 40.0%, respectively, with no significant difference(P > 0.05). Conclusion: "3"2P applicator plus propranolol treatment of refractory large hemangioma is simple, safe, and effective. But close attention needs to be paid to both "3"2P and propranolol on adverse reactions

Concurrent hyperthyroidism and papillary thyroid cancer: a fortuitous and ambiguous case report from a resource-poor setting.

Science.gov (United States)

Kadia, Benjamin Momo; Dimala, Christian Akem; Bechem, Ndemazie Nkafu; Aroke, Desmond

2016-07-26

Concurrent thyroid cancer (TC) and hyperthyroidism (HT) is rare though increasingly being reported. HT due to TC is much rarer and more challenging especially in Africa where TC and HT have significant case fatality rates. We present a 37-year-old Cameroonian female who had been on irregular regimens of propranolol and digoxin as treatment for worsening palpitations for 12 months. She came to our district hospital for her propranolol medication refill. We fortuitously identified features of HT and found a left uninodular goiter with no cervical lymphadenopathy. She was referred for thyroid assessment which suggested primary HT and an enlarged heterogeneous left lobe with a well-defined homogenous solid mass. We restarted her on propranolol and referred her for a course of methimazole. At the referral hospital, she also underwent a left thyroid lobectomy. The resected lobe was sent for histopathology which revealed a neoplastic nodule with features suggestive of a papillary thyroid cancer (PTC) causing HT. The patient's clinical progress postoperatively was good and there was regression of hyperthyroid symptoms. The historical, clinical, and laboratory findings were suggestive of HT due to PTC. A high index of suspicion, prompt referral and counter-referral lead to a positive outcome of such a rare case in a resource poor setting. We advocate for systematic and careful evaluation of all thyroid nodules.

Efficacy and safety of long-term treatment with the combination of amlodipine besylate and olmesartan medoxomil in patients with hypertension.

Science.gov (United States)

Chrysant, Steven G; Oparil, Suzanne; Melino, Michael; Karki, Sulekha; Lee, James; Heyrman, Reinilde

2009-09-01

J Clin Hypertens (Greenwich). 2009;11:475-482. (c) 2009 Wiley Periodicals, Inc.The authors report on the 44-week open-label extension of the 8-week, double-blind Combination of Olmesartan Medoxomil and Amlodipine Besylate in Controlling High Blood Pressure (COACH) trial in 1684 patients. Initial therapy was amlodipine (AML) plus olmesartan medoxomil (OM) 5+40 mg/d, up-titrated to AML+OM 10+40 mg/d plus hydrochlorothiazide (HCTZ) 12.5 mg then 25 mg if patients did not achieve blood pressure (BP) goal (<140/90 mm Hg or <130/80 mm Hg in patients with diabetes). Baseline mean BP decreased from 164/102 mm Hg to 131/82 mm Hg at end of study, with an overall 66.7% of patients, including those with diabetes, achieving BP goal. The BP goal achievement was 80% for AML+OM 5+40 mg/d, 70.6% for AML+OM 10+40 mg/d, 66.6% for AML+OM+HCTZ 10+40+12.5 mg/d, and 46.3% for AML+OM+HCTZ 10+40+25 mg/d. Study medication was safe and well tolerated. Combination antihypertensive therapy with AML+OM+/-HTCZ, up-titrated as necessary, allowed a majority of patients to achieve BP goal.

Are patients reliable when self-reporting medication use? Validation of structured drug interviews and home visits by drug analysis and prescription data in acutely hospitalized patients

DEFF Research Database (Denmark)

Glintborg, Bente; Hillestrøm, Peter René; Olsen, Lenette Holm

2007-01-01

were compared to the patients' self-reported medication history. Information on prescribed drugs dispensed from any Danish pharmacy was collected from nationwide real-time pharmacy records. The authors performed home visits in a subgroup of 115 patients 4 weeks after their discharge. Stored drugs were......The medication history among hospitalized patients often relies on patients' self-reports due to insufficient communication between health care professionals. The aim of the present study was to estimate the reliability of patients' self-reported medication use. Five hundred patients admitted...... to an acute medical department at a Danish university hospital were interviewed on the day of admission about their recent medication use. Blood samples drawn immediately after admission were screened for contents of 5 drugs (digoxin, bendroflumethiazide, amlodipine, simvastatin, glimepiride), and the results...

Terazosin and propranolol as blockers to the deleterious effect of nicotine in a random skin flap, in the rat Terazosina e propanolol como bloqueadores do efeito deletério da nicotina em um retalho cutâneo randômico, no rato

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Andre V. Fonseca

2004-06-01

Full Text Available PURPOSE: To evaluate the effect of Terazosin and Propranolol on the prevention of necrosis induced by nicotine, in a random skin flap. METHODS: This study utilized 32 adult male Wistar-EPM rats divided, at random, into four groups of eight animals each. All the 32 animals received nicotine (2 mg/kg/day subcutaneously, for one week before and one week after flap elevation. CG (Control group received distilled water (0.2 ml/day by gavage and saline (0.5 ml intraperitoneally, for seven days in the postoperative period. TG (Terazosin group received terazosin hydrochloride (3 mg/day by gavage and saline, intraperitoneally, for seven days in the postoperative period. PG (Propranolol group received propranolol (1.5 mg/day intraperitoneally and distilled water, by gavage, following the stablished pattern. TPG (Terazosin + Propranolol group received both drugs. On the seventh postoperative day, the distal necrotic area of the flaps was determined via the paper template method. Blood and skin samples were collected in order to allow determination of Malondialdehyde (MDA levels RESULTS: The control group had a mean value of 39.5 % of necrosis; the Terazosin group 25.1 %; the Propranolol group 34.5 % and the Terazosin + Propranolol group 26.2 % of necrosis. MDA levels in the serum and in the skin samples behave similarly, with an exception regarding Propranolol group in this case. CONCLUSION: Terazosin is effective in the prevention of necrosis in this animal model and Propranolol is not effective in this case.OBJETIVO: O objetivo deste estudo experimental foi avaliar o efeito da Terazosina e do Propranolol na prevenção da necrose induzida pela nicotina, em um retalho cutâneo randômico. MÉTODOS: Este estudo utilizou 32 ratos machos adultos Wistar-EPM divididos, ao acaso, em quatro grupos de oito animais. Todos os 32 animais receberam nicotina (2 mg/kg/dia, por via subcutânea, por uma semana antes e uma semana após a elevação do retalho. O grupo CG

Comparative Study of the Clonidin and Propranolol Effect in the Prevention of Hemodynamic Changes after Electroconvulsive Therapy

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A. Moradi

2009-04-01

Full Text Available Introduction & Objective: ECT is an inevitable therapy for many of psychiatric patients. During ECT severe hemodynamic changes occur which may cause dangerous cardiovascular complications especially in elderly patients with cardiac disease and may lead to arrhythmia,ischemia and myocardial infarction. The purpose of this study was to show the effect of clonidin and propranolol on the prevention of hemodynamic changes following the ECT.Materials & Methods: This study was a controlled double blind clinical trial which was carried out on 31 patients ASA I, II hospitalized in psychiatry ward of Hamadan Sina hospital who were in need of ECT. In order to increase the accuracy of the study the personal factors on the drug metabolism were omitted and the chosen patients were given ECT three times separately with the interval of 48 hours. Two hours before every ECT clonidin (0.2 mg, propranolol (40 mg and placebo (vitamin c were administered and after each ECT the hemodynamic parameters including systolic blood pressure, diastolic blood pressure, rate pressure product and ECG were measured at certain intervals and recorded on information forms and then analyzed by SPSS 9 soft ware. Results: The result of this study showed that the average changes of hemodynamic parameters in different times occurred in all groups significantly(p<0.001. Following ECT, arrhythmia in control group has been plentiful in comparison with the other two groups, and the changes were statistically meaningful (p=0.001.Conclusion: We concluded that the modifying hemodynamic changes and decrease of arrhythmia taking the drugs in comparison with placebo have been more effective and of the two drugs, propranolol has been more effective on the prevention of hemodynamic changes after ECT.

Effect of long-term propranolol administration on specific binding of 3H-WB-4101 with rat mesenteric vascular membranes

International Nuclear Information System (INIS)

Ismailov, S.I.; Rozhanets, V.V.; Val'dman, A.V.

1985-01-01

The aim of this investigation was, first, to study the affinity of certain beta-adrenoblockers for specific binding sites of 3 H-WB-4101 (identifiable as alpha-adrenoreceptors) of brain membranes and, second, to study the characteristics of these same receptors in membranes of mesenteric vessels of rats during long-term administration of propranolol. Isotherms of specific binding, because of the limited quantity of vascular membranes, were determined by the use of three concentrations of 3 H-WB-4101: 0.1, 0.5, and 1.0 nM. It is shown that some beta-adrenoblockers have weak affinity for alpha-adrenoreceptors of brain synaptic membranes exhibited only when these compounds are present in relatively high concentrations. It is also shown that administration of propranolol for 15 days led to a significant decrease in affinity of the alpha-adrenorecptors for their specific antagonist WB-4101

Structures and characterization of digoxin- and bufalin-bound Na+,K+-ATPase compared with the ouabain-bound complex.

Science.gov (United States)

Laursen, Mette; Gregersen, Jonas Lindholt; Yatime, Laure; Nissen, Poul; Fedosova, Natalya U

2015-02-10

Cardiotonic steroids (CTSs) are specific and potent inhibitors of the Na(+),K(+)-ATPase, with highest affinity to the phosphoenzyme (E2P) forms. CTSs are comprised of a steroid core, which can be glycosylated, and a varying number of substituents, including a five- or six-membered lactone. These functionalities have specific influence on the binding properties. We report crystal structures of the Na(+),K(+)-ATPase in the E2P form in complex with bufalin (a nonglycosylated CTS with a six-membered lactone) and digoxin (a trisaccharide-conjugated CTS with a five-membered lactone) and compare their characteristics and binding kinetics with the previously described E2P-ouabain complex to derive specific details and the general mechanism of CTS binding and inhibition. CTSs block the extracellular cation exchange pathway, and cation-binding sites I and II are differently occupied: A single Mg(2+) is bound in site II of the digoxin and ouabain complexes, whereas both sites are occupied by K(+) in the E2P-bufalin complex. In all complexes, αM4 adopts a wound form, characteristic for the E2P state and favorable for high-affinity CTS binding. We conclude that the occupants of the cation-binding site and the type of the lactone substituent determine the arrangement of αM4 and hypothesize that winding/unwinding of αM4 represents a trigger for high-affinity CTS binding. We find that the level of glycosylation affects the depth of CTS binding and that the steroid core substituents fine tune the configuration of transmembrane helices αM1-2.

Clinical utility of fixed-combination telmisartan–amlodipine in the treatment of hypertension

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Segura J

2011-05-01

Full Text Available Julian Segura, Luis M RuilopeHypertension Unit, Hospital 12 de Octubre, Madrid, SpainAbstract: The majority of hypertensive patients, especially those with target organ damage, are likely to require multiple-drug therapy in order to reach blood pressure (BP targets and reduce their risk of adverse vascular outcomes. The rationale for combination therapy with agents that block the renin–angiotensin system (RAS and a calcium channel blocker (CCB or diuretic is well founded in growing evidence. Recent published trials have shown that the combination of an RAS suppressor and a dihydropiridinic CCB would offer additional benefits independently of BP reduction. A telmisartan–amlodipine combination has demonstrated significantly greater BP reductions compared with each monotherapy component in the overall population, and in particular in patients with moderate to severe hypertension and high-risk patients. This combination is well tolerated with a safety profile similar to placebo and is consistent with the known safety profile of its monotherapy components.Keywords: hypertensive patients, monotherapy, stroke, antihypertensive

Effect of oral propranolol on circulating catecholamines in cirrhosis: relationship to severity of liver disease and splanchnic haemodynamics

DEFF Research Database (Denmark)

Bendtsen, Flemming; Henriksen, Jens Henrik; Sørensen, T I

1990-01-01

propranolol. A borderline significant correlation was observed between the decrease in azygos blood flow and the increase in NA (r = 0.64, p = 0.06). Our results suggest that besides a relationship to liver function and severity of disease, sympathetic nervous activity, as reflected by circulating NA.......01). Azygos blood flow was increased (0.75 l/min) and positively related to plasma NA (r = 0.57, p = 0.05, n = 12). After propranolol intake, plasma NA increased from 0.52 to 0.59 ng/ml (p less than 0.01). This response was found in all Child-Turcotte classes (A: 0.37 to 0.43; B: 0.49 to 0.56; C: 0.78 to 0.......88 ng/ml), and in patients with as well as without ascites. Plasma adrenaline increased in the same way (p less than 0.01). Hepatic blood flow (from 1.10 to 0.93 l/min, p less than 0.01) and azygos blood flow (from 0.75 to 0.55 l/min, n = 9, p less than 0.05) decreased significantly after oral...

Are patients reliable when self-reporting medication use? Validation of structured drug interviews and home visits by drug analysis and prescription data in acutely hospitalized patients

DEFF Research Database (Denmark)

Glintborg, Bente; Hillestrøm, Peter René; Olsen, Lenette Holm

2007-01-01

inspected, and patients were interviewed about their drug use. Additional blood samples were drawn for drug analysis. The median age of included patients was 72 years, and 298 patients (60%) were women. Patients reported use of 3 (median) prescription-only medications (range, 0-14) during the structured...... interview. The congruence between self-report and drug analysis was high for all 5 drugs measured (all kappa >0.8). However, 9 patients (2%) reported use of drugs that were not detected in their blood samples. In 29 patients (6%), the blood samples contained drugs not reported during the structured...... to an acute medical department at a Danish university hospital were interviewed on the day of admission about their recent medication use. Blood samples drawn immediately after admission were screened for contents of 5 drugs (digoxin, bendroflumethiazide, amlodipine, simvastatin, glimepiride), and the results...

A multibiomarker approach to explore interactive effects of propranolol and fluoxetine in marine mussels

International Nuclear Information System (INIS)

Franzellitti, Silvia; Buratti, Sara; Du, Bowen; Haddad, Samuel P.; Chambliss, C. Kevin; Brooks, Bryan W.; Fabbri, Elena

2015-01-01

A multi-biomarker approach, including several lysosomal parameters, activity and mRNA expression of antioxidant enzymes, and DNA damage, was employed to investigate the nominal effects of 0.3 ng/L fluoxetine (FX) and 0.3 ng/L propranolol (PROP) alone or in combination (0.3 ng/L FX + 0.3 ng/L PROP) on Mediterranean mussels after a 7 day treatment. FX co-exposure appears to facilitate PROP bioaccumulation because PROP only accumulated in digestive gland of FX + PROP treated mussels. Lysosomal parameters were significantly impaired by FX + PROP treatment, while no clear antioxidant responses at the catalytic and transcriptional levels were observed. Biomarker responses led to a “medium stress level” diagnosis in FX + PROP treated mussels, according to the Expert System, whereas 0.3 ng/L PROP or FX alone did not induce consistent stress conditions. These findings suggest vulnerability of coastal marine mussels to FX and PROP contamination at environmentally relevant levels. - Highlights: • FX and PROP combined effects were assessed in marine mussels using biomarkers. • PROP bioaccumulation was observed in digestive gland of FX + PROP treated mussels. • Lysosomal parameters were significantly impaired by FX + PROP treatment. • No clear antioxidant responses at the catalytic and mRNA levels were observed. • FX + PROP treatment increased stress levels of mussels compared with the single chemicals. - Fluoxetine and propranolol induce interactive effects on marine mussels biomarker responses and pharmaceutical bioaccumulation

Effect of propranolol on myocardial imaging with radioiodinated hexadecenoic acid in the dog heart

International Nuclear Information System (INIS)

Comet, M.; Wolf, J.E.; Pilichowfski, P.

1982-01-01

After I.V. injection of 16- 123 I 9-hexadecenoic acid, the following is noted: among dogs, there are important differences in the values of the half-life of the myocardial radioactivity curves without any significant differences in the biological constants; for a given dog, the value of the half-life is reproducible when there are no modifications in the physiological condition; propranolol brings about twofold increase in the value of the half-life of the myocardial radioactivity curve. On the myocardial scintigraphy, performed after an I.V. injection of a fatty acid (F.A.) labelled with 123 I, ischaemia appears as an hypoactive area which reveals a failure in the capture of the F.A. and also an abnormal lengthening of the half-life of the myocardial activity curve. It is probable that, in some cases, on the evolution curve of myocardial activity would allow a detection of metabolism anomalies of the F.A. The cause of variation of the half-life are poorly understood. Given the influence of catecholamines on normal and pathological myocardial metabolism, the influence of a #betta# blocker Propranolol, on the curve half-life after the injection of 16 123 I 9-hexadecenoic acid (I.F.A.) was studied in the dog. In order to assess the effect of the drug, the reproducibility of the curve half-lives was tested, in the absence of marked variations in the physiological condition of the animal

Assessment of glomerular filtration rate based on alterations of serum brain-derived neurotrophic factor in type 2 diabetic subjects treated with amlodipine/benazepril or valsartan/hydrochlorothiazide.

Science.gov (United States)

Lee, I-Te; Sheu, Wayne Huey-Herng; Hung, Yi-Jen; Chen, Jung-Fu; Wang, Chih-Yuan; Lee, Wen-Jane

2015-01-01

Brain-derived neurotrophic factor (BDNF) is associated with sympathetic activation. However, the effects of BDNF on diabetic nephropathy are unknown. The aim of this study was to assess the estimated glomerular filtration rates (eGFRs) and changes in serum BDNF levels in type 2 diabetic subjects treated with antihypertensive medications. In this randomized, double-blind clinical trial, type 2 diabetic subjects with hypertension were assigned to either the benazepril/amlodipine or valsartan/hydrochlorothiazide treatment groups for a 16-week period. The post hoc analyses were based on increased or decreased serum BDNF levels. Of the 153 enrolled subjects, the changes in eGFR were significantly and inversely correlated with those in BDNF in the 76 subjects treated with valsartan/hydrochlorothiazide (r = -0.264, P = 0.021) but not in the 77 subjects treated with benazepril/amlodipine (r = -0.025, P = 0.862). The 45 subjects with increased BDNF following valsartan/hydrochlorothiazide treatment exhibited a significantly reduced eGFR (-8.8 ± 14.9 mL/min/1.73 m(2); P benazepril.

Prevalence of Self-prescribing Propranolol Among Medical and Dental Students in Riyadh, Saudi Arabia: A Cross-sectional Study

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Omar A. Al-Mohrej

2018-03-01

Conclusions: The overall results showed a slightly high rate of propanol misuse among medical and dental students. The majority of users are aware of the risks and potential side effects of self-prescribing medications, however; the anxiety relieving effect of propranolol increased its use prior to oral exams and presentations. Educational activity targeting students must be implemented.

A comparison of automated and manual radioimmunoassays for the estimation of serum digoxin

International Nuclear Information System (INIS)

Tuttlebee, J.W.

1984-01-01

Digoxin was assayed manually (SPAC kit) and by an automated radioimmunoassay instrument (ARIA II). There was good correlation between the methods (r=0.964; n=120). Carryover by the automated method was marginally significant from low to high level samples (5.2%), but insignificant from high to low level samples (1.4%). The precision on the ARIA II was far better in spite of the fact that assays were performed only in singlets compared with duplicates on the manual procedure. Best precision was obtained at the high level (3.76 nmol/l; between-batch CV: 2.4% ARIA; 5.5% SPAC). All values for control samples (manual and automated) fell within 6% of the all-method means. Using the ARIA II is marginally quicker and significantly cheaper. However, some back-up procedure is required for 'down time' with the machine, for what can be an urgent investigation. Patient results correlated well with clinical data. (orig.) [de

No Dose Adjustment is Recommended for Digoxin, Warfarin, Atorvastatin or a Combination Oral Contraceptive When Coadministered with Dulaglutide.

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de la Peña, Amparo; Cui, Xuewei; Geiser, Jeanne; Loghin, Corina

2017-11-01

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the treatment of type 2 diabetes mellitus are known to delay gastric emptying (GE). The potential effect of the GLP-1 RA dulaglutide on the pharmacokinetics (PK) of four orally administered drugs and on the pharmacodynamic (PD) effect of warfarin was investigated. In four separate clinical pharmacology studies, digoxin, warfarin, atorvastatin and Ortho-Cyclen ® were orally administered to healthy subjects with and without a subcutaneous dose of dulaglutide 1.5 mg. The effect of dulaglutide coadministration was assessed based on the PK parameters of key analytes. For warfarin PD, the effect of dulaglutide on the international normalized ratio (INR) was evaluated. Areas under the concentration-time curves (AUCs) with and without dulaglutide were similar for all analytes except atorvastatin, where it was reduced by 21%. Maximum concentrations (C max ) were generally lower following coadministration with dulaglutide, with statistically significant reductions (90% confidence intervals of geometric least squares means ratios outside 0.80-1.25) for all analytes except R-warfarin. For all analytes, there was a general trend for the time to C max (t max ) to increase following coadministration with dulaglutide. For warfarin, dulaglutide coadministration had no statistically significant effect on the maximum INR (INR max ); however, a 2% increase in area under the INR curve (AUC INR ) was observed. Dulaglutide did not affect the absorption of the tested medications to a clinically relevant degree. Based on the PK and PD evaluations, no dose adjustments for digoxin, warfarin, atorvastatin and Ortho-Cyclen ® are recommended when coadministered with dulaglutide. NCT01458210, NCT01436201, NCT01432938, and NCT01250834.

Contextualizando reações ácido-base de acordo com a teoria protônica de Brönsted-Lowry usando comprimidos de propranolol e nimesulida

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Arlan de Assis Gonsalves

2013-01-01

Full Text Available This paper reports the use of alternative materials for teaching experimental chemistry. In this context, nimesulide and propranolol tablets were used to teach chemical concepts about acid-base reactions according to Brönsted-Lowry protonic Theory. Important topics of Organic, Analytical and Pharmaceutical Chemistry were discussed, such as purification by acid-base extraction, solubility of organic compounds in aqueous solutions, buffers, the dissociation constant (pKa, potentiometric titration and ionization of drugs in biological fluids. The purification of propranolol and nimesulide from tablets produced yields of 75% and 90%, respectively. The experimental values of pKa for both drugs were in agreement with those from the literature.

Liquid chromatography-tandem mass spectrometry method for simultaneous quantification of bisoprolol, ramiprilat, propranolol and midazolam in rat dried blood spots.

Science.gov (United States)

Cvan Trobec, Katja; Trontelj, Jurij; Springer, Jochen; Lainscak, Mitja; Kerec Kos, Mojca

2014-05-01

Dried blood spot (DBS) sampling represents a suitable method for pharmacokinetic studies in rats, particularly if serial sampling is needed. To study the pharmacokinetics of drugs in a rat heart failure (HF) model, we developed and validated a method for the simultaneous determination of bisoprolol, ramiprilat, propranolol and midazolam in DBS samples. Bisoprolol and ramipril are widely used in the treatment of HF, and midazolam and propranolol are markers of hepatic metabolism, which can be altered in HF. A 20μL sample of rat blood was pipetted onto Whatman 903 Protein Saver Card and allowed to dry. The whole spot was excised and 300μL of solvent (methanol with 10% ultrapure water and 0.1% formic acid) was added. After mixing and incubating the sample in an ultrasonic bath, a mixture of isotopically labeled internal standards was added. After centrifugation, the extracts were cleaned on an Ostro™ plate and analyzed using liquid chromatography-tandem mass spectroscopy. The method was successfully validated. No significant interference was observed in the retention times of analytes or internal standards. The intraday and interday accuracy and precision were within a ±15% interval. The method was linear in the range 5-250μg/L and the lower limit of quantification was 5μg/L for all four analytes. The absolute matrix effect ranged from 98.7% for midazolam to 121% for ramiprilat. The recovery was lowest for ramiprilat and highest for propranolol. Samples were stable at all tested temperatures. The method has been used successfully in a real-time pharmacokinetic study in rats. Copyright © 2014 Elsevier B.V. All rights reserved.

Enantioselective biotransformation of propranolol to the active metabolite 4-hydroxypropranolol by endophytic fungi

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Keyller Bastos Borges

2011-01-01

Full Text Available The enantioselective biotransformation of propranolol (Prop by the endophytic fungi Phomopsis sp., Glomerella cingulata, Penicillium crustosum, Chaetomium globosum and Aspergillus fumigatus was investigated by studying the kinetics of the aromatic hydroxylation reaction with the formation of 4-hydroxypropranolol (4-OH-Prop. Both Prop enantiomers were consumed by the fungi in the biotransformation process, but the 4-hydroxylation reaction yielded preferentially (--(S-4-OH-Prop. The quantity of metabolites biosynthesized varied slightly among the evaluated endophytic fungi. These results show that all investigated endophytic fungi could be used as biosynthetic tools in biotransformation processes to obtain the enantiomers of 4-OH-Prop.

Phototransformation of Amlodipine in Aqueous Solution: Toxicity of the Drug and Its Photoproduct on Aquatic Organisms

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Marina DellaGreca

2007-01-01

Full Text Available The phototransformation of amlodipine in water was investigated under various conditions. A quantum yield ΦS2.2×10−4 and a half-life time t1/2 0.419 days were calculated when the drug in water (10−4 M was exposed to sunlight. The only photoproduct found was its pyridine derivative. Formation of this product was explained on the basis of a radical cation intermediate. The acute and chronic toxicity of the drug and its photoproduct were evaluated on different organisms of the freshwater chain (Brachionus calyciflorus, Thamnocephalus platyurus, Daphnia magna, Ceriodaphnia dubia. The photoproduct exhibited a stronger toxic potential than the parent drug on the long time for C. dubia.

Development of (acrylic acid/ polyethylene glycol)-zinc oxide mucoadhesive nanocomposites for buccal administration of propranolol HCl

Science.gov (United States)

Mahmoud, Ghada A.; Ali, Amr El-Hag; Raafat, Amany I.; Badawy, Nagwa A.; Elshahawy, Mai. F.

2018-06-01

A series of mucoadhesive nanocomposites with self disinfection properties composed of acrylic acid, polyethylene glycol and ZnO nanoparticles (AAc/PEG)-ZnO were developed for localized buccal Propranolol HCl delivery. γ-irradiation as a clean tool for graft copolymerization process was used for the preparation of (AAc/PEG) hydrogels. In suite precipitation technique was used for ZnO nanoparticles immobilization within (AAc/PEG) hydrogels. The developed (AAc/PEG)-ZnO nanocomposites were characterized by X-ray diffraction (XRD), UV-Vis spectrophotometer, energy dispersive X-ray spectroscopy (EDX) and scanning electron microscopy (SEM) to confirm the success of ZnO nanoparticles formation within the (AAc/PEG) matrices. The presence of ZnO nanoparticles improves the thermal stability as indicated using thermogravimetric analysis (TGA). The mucoadhesion characteristics such as hydration degree, surface pH, and mucoadhesive strength were evaluated in artificial saliva solution. The self disinfection property of the developed (AAc/PEG)-ZnO nanocomposites was investigated by examining their resistance to pathogenic microorganisms such as Staphylococcus aureus, Bacillus subtilis, and Escherichia coli using disc diffusion method. The release of Propranolol -HCl drug in artificial saliva was found to obey a non-Fickian diffusion mechanism. The obtained results suggests that (AAc/PEG)-ZnO nanocomposites could be used as mucoadhesive carrier for buccal drug delivery with efficient antibacterial properties.

Comparison of effects of valsartan and amlodipine on cognitive functions and auditory p300 event-related potentials in elderly hypertensive patients.

Science.gov (United States)

Katada, Eiichi; Uematsu, Norihiko; Takuma, Yuko; Matsukawa, Noriyuki

2014-01-01

We compared the antihypertensive effect of valsartan (VAL) and amlodipine (AML) treatments in elderly hypertensive patients by examining the long-term changes in cognitive function and auditory P300 event-related potentials. We enrolled 20 outpatients, including 12 men and 8 women in the age group of 56 to 81 years who had mild to moderate essential hypertension. The subjects were randomly allocated to receive either 80 mg VAL once a day (10 patients) or 5 mg AML once a day (10 patients). Neuropsychological assessment and auditory P300 event-related potentials were obtained before initiation of VAL or AML treatment and after 6 months of the treatment with VAL or AML. Neuropsychological assessment was evaluated by conducting the Mini-Mental State Examination, the verbal fluency, word-list memory, word-list recall test, word-list recognition, and Trails B tests. Both the groups showed significantly reduced-blood pressure after 6 months of treatment, and the intergroup difference was not significant. The mean baseline Mini-Mental State Examination scores of the VAL and AML groups were not significantly different. Amlodipine treatment did not significantly affect any test score, but VAL treatment significantly increased the word-list memory and word-list recall test scores. Valsartan, and not AML, significantly reduced the mean P300 latency after 6 months. These results suggest that VAL exerts a positive effect on cognitive functions, independent of its antihypertensive effect.

Assessing the environmental hazard of individual and combined pharmaceuticals: acute and chronic toxicity of fluoxetine and propranolol in the crustacean Daphnia magna.

Science.gov (United States)

Varano, Valentina; Fabbri, Elena; Pasteris, Andrea

2017-08-01

Pharmaceuticals are widespread emerging contaminants and, like all pollutants, are present in combination with others in the ecosystems. The aim of the present work was to evaluate the toxic response of the crustacean Daphnia magna exposed to individual and combined pharmaceuticals. Fluoxetine, a selective serotonin re-uptake inhibitor widely prescribed as antidepressant, and propranolol, a non-selective β-adrenergic receptor-blocking agent used to treat hypertension, were tested. Several experimental trials of an acute immobilization test and a chronic reproduction test were performed. Single chemicals were first tested separately. Toxicity of binary mixtures was then assessed using a fixed ratio experimental design. Five concentrations and 5 percentages of each substance in the mixture (0, 25, 50, 75, and 100%) were tested. The MIXTOX model was applied to analyze the experimental results. This tool is a stepwise statistical procedure that evaluates if and how observed data deviate from a reference model, either concentration addition (CA) or independent action (IA), and provides significance testing for synergism, antagonism, or more complex interactions. Acute EC50 values ranged from 6.4 to 7.8 mg/L for propranolol and from 6.4 to 9.1 mg/L for fluoxetine. Chronic EC50 values ranged from 0.59 to 1.00 mg/L for propranolol and from 0.23 to 0.24 mg/L for fluoxetine. Results showed a significant antagonism between chemicals in both the acute and the chronic mixture tests when CA was adopted as the reference model, while absence of interactive effects when IA was used.

Ansiedade social e abuso de propranolol: relato de caso

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Fontanella Bruno José Barcellos

2003-01-01

Full Text Available Paciente com grave ansiedade social automedicou-se com propranolol durante seis anos, em doses de até 320 mg/d. Além do tratamento psicanalítico que já havia iniciado, foi tratada com tranilcipromina, apresentando melhora parcial do quadro fóbico e do abuso do betabloqueador. Após introdução de paroxetina, houve melhora ainda mais pronunciada. Apesar da automedicação com uma substância potencialmente eficaz em alguns casos, perpetuou-se durante anos um grave padrão fóbico de comportamento. O caso exemplifica as dificuldades de procura de tratamento específico pela população de fóbicos sociais. Levanta-se a hipótese da existência de uma prática crescente de automedicação com betabloqueadores entre fóbicos sociais e pessoas com ansiedade de desempenho, problema cuja relevância para a saúde pública ainda não foi pesquisada.

Quantification of pulmonary thallium-201 activity after upright exercise in normal persons: importance of peak heart rate and propranolol usage in defining normal values

International Nuclear Information System (INIS)

Brown, K.A.; Boucher, C.A.; Okada, R.D.; Strauss, H.W.; Pohost, G.M.

1984-01-01

Fifty-nine normal patients (34 angiographically normal and 25 clinically normal by Bayesian analysis) underwent thallium-201 imaging after maximal upright exercise. Lung activity was quantitated relative to myocardial activity and a lung/myocardial activity ratio was determined for each patient. Stepwise regression analysis was then used to examine the influence of patient clinical characteristics and exercise variables on the lung/myocardium ratio. Peak heart rate during exercise and propranolol usage both showed significant negative regression coefficients (p less than 0.001). No other patient data showed a significant relation. Using the regression equation and the estimated variance, a 95% confidence level upper limit of normal could be determined for a give peak heart rate and propranolol status. Sixty-one other patients were studied to validate the predicted upper limits of normal based on this model. None of the 27 patients without coronary artery disease had an elevated lung/myocardial ratio, compared with 1 of 8 with 1-vessel disease (difference not significant), 6 of 14 with 2-vessel disease (p less than 0.005), and 6 of 12 with 3-vessel disease (p less than 0.0001). Thus, lung activity on upright exercise thallium-201 studies can be quantitated relative to myocardial activity, and is inversely related to peak heart rate and propranolol use. Use of a regression analysis allows determination of a 95% confidence upper limit of normal to be anticipated in an individual patient

Evaluation of Plantago major L. seed mucilage as a rate controlling matrix for sustained release of propranolol hydrochloride.

Science.gov (United States)

Saeedi, Majid; Morteza-Semnani, Katayoun; Sagheb-Doust, Mehdi

2013-03-01

Polysaccharide mucilage derived from the seeds of Plantago major L. (family Plantaginaceae) was investigated for use in matrix formulations containing propranolol hydrochloride. HPMC K4M and tragacanth were used as standards for comparison. The hardness, tensile strength, and friability of tablets increased as the concentration of mucilage increased, indicating good compactibility of mucilage powders. The rate of release of propranolol hydrochloride from P. major mucilage matrices was mainly controlled by the drug/mucilage ratio. Formulations containing P. major mucilage were found to exhibit a release rate comparable to HPMC containing matrices at a lower drug/polymer ratio (drug/HPMC 2:1). These results demonstrated that P. major mucilage is a better release retardant compared to tragacanth at an equivalent content. The results of kinetic analysis showed that in F3 (containing 1:2 drug/mucilage) the highest correlation coefficient was achieved with the zero order model. The swelling and erosion studies revealed that as the proportion of mucilage in tablets was increased, there was a corresponding increase in percent swelling and a decrease in percent erosion of tablets. The DSC and FT-IR studies showed that no formation of complex between the drug and mucilage or changes in crystallinity of the drug had occurred.

Evaluation of Ocimum basilicum L. seed mucilage as rate controlling matrix for sustained release of propranolol HCl

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Majid Saeedi

2015-01-01

Full Text Available Polysaccharide mucilage derived from the seeds of Ocimum basilicum L. (family Lamiaceae was investigated for use in matrix formulations containing propranolol hydrochloride. Basil mucilage was extracted and several tablets were formulated. The effect of mucilage on drug release rate was evaluated in comparison with tablets containing two kinds of hydroxypropyl methylcellulose (HPMC K4M and HPMC K100M as standard polymer. The release data were fitted to several models for kinetic evaluation. The results showed that hardness decreased and friability of tablets increased as the concentration of mucilage increased. The rate of release of propranolol HCl from O. basilicm mucilage matrices was mainly controlled by the drug: mucilage ratio. Drug release was slower from the HPMC K4M and HPMCK100M containing tablets compared to the mucilage containing matrices than the drug release from matrices containing O. basilicum seed mucilage in similar ratios.  Formulations containing O. basilicm mucilage were found to exhibit suitable release pattern. The results of kinetic analysis showed that in tablets containing O. basilicm mucilage the highest correlation coefficient was achieved with the zero order model. The swelling and erosion studies revealed that, as the proportion of mucilage in tablets was increased, there was a corresponding increase in percent swelling and a decrease in percent erosion of tablets.

A study of the relationship between serum bile acids and propranolol pharmacokinetics and pharmacodynamics in patients with liver cirrhosis and in healthy controls

NARCIS (Netherlands)

Taegtmeyer, Anne B.; Haschke, Manuel; Tchambaz, Lydia; Buylaert, Mirabel; Tschöpl, Martin; Beuers, Ulrich; Drewe, Jürgen; Krähenbühl, Stephan

2014-01-01

The main objectives of the study were to determine the exposure and bioavailability of oral propranolol and to investigate their associations with serum bile acid concentration in patients with liver cirrhosis and in healthy controls. A further objective was to study the pharmacodynamics of

Three different spectrophotometric methods manipulating ratio spectra for determination of binary mixture of Amlodipine and Atorvastatin

Science.gov (United States)

Darwish, Hany W.; Hassan, Said A.; Salem, Maissa Y.; El-Zeiny, Badr A.

2011-12-01

Three simple, specific, accurate and precise spectrophotometric methods manipulating ratio spectra are developed for the simultaneous determination of Amlodipine besylate (AM) and Atorvastatin calcium (AT) in tablet dosage forms. The first method is first derivative of the ratio spectra ( 1DD), the second is ratio subtraction and the third is the method of mean centering of ratio spectra. The calibration curve is linear over the concentration range of 3-40 and 8-32 μg/ml for AM and AT, respectively. These methods are tested by analyzing synthetic mixtures of the above drugs and they are applied to commercial pharmaceutical preparation of the subjected drugs. Standard deviation is <1.5 in the assay of raw materials and tablets. Methods are validated as per ICH guidelines and accuracy, precision, repeatability and robustness are found to be within the acceptable limit.

A review of the benefits of early treatment initiation with single-pill combinations of telmisartan with amlodipine or hydrochlorothiazide

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Segura J

2013-09-01

Full Text Available Julian Segura, Luis Miguel Ruilope Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain Abstract: This review discusses the rationale for earlier use of single-pill combinations (SPCs of antihypertensive drugs, with a focus on telmisartan/amlodipine (T/A and telmisartan/hydrochlorothiazide (T/H SPCs. Compared with the respective monotherapies, the once-daily T/A and T/H SPCs have been shown to result in significantly higher blood pressure (BP reductions, BP goal rates, and response rates in patients at all stages of hypertension. As expected, BP reductions are highest with the highest dose (T80/A10 and T80/H25 SPCs. Subgroup analyses of the telmisartan trials have reported the efficacy of both SPCs to be consistent, regardless of the patients' age, race, and coexisting diabetes, obesity, or renal impairment. In patients with mild-to-moderate hypertension, the T/A combination provides superior 24-hour BP-lowering efficacy compared with either treatment administered as monotherapy. Similarly, the T/H SPC treatment provides superior 24-hour BP-lowering efficacy, especially in the last 6 hours relative to other renin–angiotensin system inhibitor-based SPCs. The T/A SPC is associated with a lower incidence of edema than amlodipine monotherapy, and the T/H SPC with a lower incidence of hypokalemia than hydrochlorothiazide monotherapy. Existing evidence supports the use of the T/A SPC for the treatment of hypertensive patients with prediabetes, diabetes, or metabolic syndrome, due to the metabolic neutrality of both component drugs, and the use of the T/H SPC for those patients with edema or in need of volume reduction. Keywords: calcium-channel blocker, essential hypertension, diuretic, primary care physician, renin-angiotensin system inhibitor

Propranolol plasma monitoring in children submitted to surgery of tetralogy of Fallot by a micromethod using high performance liquid chromatography Monitoramento do propranolol plasmático em crianças operadas da tetralogia de Fallot através de micrométodo utilizando a cromatografia líquida de alta eficiência

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Cristina Sanches

2007-01-01

Full Text Available OBJECTIVE: To evaluate the analytical micromethod using liquid chromatography for the quantification of propranolol in children submitted to surgery of tetralogy of Fallot (TLF. Methods: Only 0.2 mL of plasma is required for the assay. Peaks eluted at 8.4 (Propranolol and 17.5 min (verapamil, internal standard from a C18 column, with a mobile phase 0.1 M acetate buffer, pH 5.0, and acetonitrile (60:40, v/v at flow rate 0.7 mL/min, detected at 290 nm (excitation and 358 nm (emission. Surgery was started 776 min of drug administration (8.7mg, mean; seven blood samples were collected from six patients (4M/2F; 2.1yrs;11.5kg; 0.80m; 18.9kg/m². RESULTS: Confidence limits of the method showed high selectivity and recovery, sensitivity of 0.02ng/mL, good linearity (0.05-1000ng/mL, precision of 8.6% and accuracy of 3.1%. The mean duration of surgery was 283.2min, with the patients remaining under cardiopulmonary bypass (CPB for 114min. A declining curve of propranolol plasma concentration was obtained after the last dose in the night that preceded the day of surgery. Plasma concentration also was normalized with hematocrit due to the hemodilution caused by the CPB procedure. On the other hand a decrease on drug plasma concentration was obtained between periods, the beginning of surgery to the postoperative day 2 (7.09 ng/mL and 0.05 ng/mL, pOBJETIVO: Avaliar o micrométodo analítico empregando a cromatografia líquida para quantificação de propranolol em crianças operadas de tetralogia de Fallot (TLF. MÉTODO: Requereu-se apenas volumes de 0,2mL de plasma para a realização do ensaio. Os picos foram eluídos em 8.4 (Propranolol e 17.5 min (verapamil, padrão interno de uma coluna C18, com fase móvel (tampão acetato 0,1 M pH 5,0 e acetonitrila, 60:40, v/v em fluxo de 0,7 mL/min, sendo detectados em 290 nm (excitação e em 358 nm (emissão. A cirurgia iniciou-se 776 min depois da dose administrada (8,7mg, média e sete amostras de sangue foram

Host-Guest Inclusion Complexes between Amlodipine Enantiomers in Biphasic Recognition Chiral Extraction System using Tartaric Acid and β-Cyclodextrin Derivatives as Positive Confirmation Using of their Enantioselective Extraction

OpenAIRE

AZZAM, Khaldun; ABDALLAH, Hassan; HALIM, Hairul; AHMAD, Maizatul; SHAIBAH, Hassan

2015-01-01

The current work reports an extended theoretical study from our previous experimental work for the enantioselective extraction of amlodipine enantiomers in a biphasic recognition chiral extraction system (BRCES) consisting of hydrophobic D-diisopropyl tartrate dissolved in organic phase (n-decanol) and hydrophilic hydroxypropyl-?-cyclodextrin (HP-?-CD) in aqueous phase (acetate buffer) which preferentially recognize the R-enantiomer and S-enantiomer, respectively. The calculations were simula...

Hypothalamic digoxin, hemispheric chemical dominance, and peptic ulcer disease.

Science.gov (United States)

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-10-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin-like factor (EDLF) (membrane sodium-potassium ATPase inhibitor and regulator of neurotransmitter transport), ubiquinone (free radical scavenger), and dolichol (regulator of glycoconjugate metabolism). The pathway was assessed in peptic ulcer and acid peptic disease and its relation to hemispheric dominance studied. The activity of HMG CoA reductase, serum levels of EDLF, magnesium, tryptophan catabolites, and tyrosine catabolites were measured in acid peptic disease, right hemispheric dominant, left hemispheric dominant, and bihemispheric dominant individuals. All the patients with peptic ulcer disease were right-handed/left hemispheric dominant by the dichotic listening test. The pathway was upregulated with increased EDLF synthesis in peptic ulcer disease (PUD). There was increase in tryptophan catabolites and reduction in tyrosine catabolites in these patients. The ubiquinone levels were low and free radical production increased. Dolichol and glycoconjugate levels were increased and lysosomal stability reduced in patients with acid peptic disease (APD). There was increase in cholesterol:phospholipid ratio with decreased glyco conjugate levels in membranes of patients with PUD. Acid peptic disease represents an elevated EDLF state which can modulate gastric acid secretion and the structure of the gastric mucous barrier. It can also lead to persistence of Helicobacter pylori infection. The biochemical pattern obtained in peptic ulcer disease is similar to those obtained in left-handed/right hemispheric chemically dominant individuals. But all the patients with peptic ulcer disease were right-handed/left hemispheric dominant by the dichotic listen ing test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Peptic ulcer disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

Effect of oral propranolol administration on azygos, renal and hepatic uptake and output of catecholamines in cirrhosis

DEFF Research Database (Denmark)

Bendtsen, F; Christensen, N J; Sørensen, T I

1991-01-01

Circulating catecholamines are increased in cirrhosis with portal hypertension, and increase further after propranolol. In 23 cirrhotic patients, plasma norepinephrine and epinephrine were determined in an artery, the azygos vein, the right renal vein and a hepatic vein before and after an oral 80...... to the circulation) and clearance of epinephrine remained unaltered. Hepatointestinal clearance showed no significant change for norepinephrine, but showed a borderline-significant decrease for epinephrine (-23%, p = 0.08). Our results show a net production of norepinephrine in the prehepatic splanchnic area drained...

Application of a colorimetric technique in quality control for printed pediatric orodispersible drug delivery systems containing propranolol hydrochloride

DEFF Research Database (Denmark)

Vakili, Hossein; Nyman, Johan O; Genina, Natalja

2016-01-01

and the excipients. The inkjet printing technique deposited precise and uniform escalating doses (0.08-3.16mg) of the active pharmaceutical ingredient onto the substrates (R(2)≥0.9934). A disintegration test with clear end-point detection confirmed that all the substrates meet the requirements of the Ph. Eur....... to disintegrate within 180s. The colorimetric technique proved to be a reliable method to distinguish the small color differences between formulations containing an escalating dose of propranolol hydrochloride....

Enantiomers Recognition of Propranolol Based on Organic-Inorganic Hybrid Open-Tubular MIPs-CEC Column Using 3-(Trimethoxysilyl)Propyl Methacrylate as a Cross-Linking Monomer.

Science.gov (United States)

Chen, Guo-Ning; Li, Ning; Luo, Tian; Dong, Yu-Ming

2017-04-01

In this study, 3-(trimethoxysilyl)propyl methacrylate (γ-MPS), a bifunctional group compound, was used as a single cross-linking agent to prepare molecular imprinted inorganic-organic hybrid polymers by in situ polymerization for open-tubular capillary electro chromatography (CEC) column. The optimal preparation conditions were: the ratio between template molecule and functional monomer was 1:4; the volume proportion of porogen toluene and methanol was 1:1 and the volume of cross-linking agent γ-MPS was 69 μL. The optimal separation conditions were separation voltage of 15 kV; detection wavelength at 215 nm and background electrolyte composed of 70% acetonitrile/20 mmol/L boric acid salt (pH 6.9). Under the optimized conditions, the propranolol enantiomers can be separated well by CEC. The method is simple and fast, it can be a potentially useful approach for propranolol enantiomers separation. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Degradation of the beta-blocker propranolol by electrochemical advanced oxidation processes based on Fenton's reaction chemistry using a boron-doped diamond anode

Energy Technology Data Exchange (ETDEWEB)

Isarain-Chavez, Eloy; Rodriguez, Rosa Maria; Garrido, Jose Antonio; Arias, Conchita; Centellas, Francesc; Cabot, Pere Lluis [Laboratori d' Electroquimica dels Materials i del Medi Ambient, Departament de Quimica Fisica, Facultat de Quimica, Universitat de Barcelona, Marti i Franques 1-11, 08028 Barcelona (Spain); Brillas, Enric, E-mail: brillas@ub.ed [Laboratori d' Electroquimica dels Materials i del Medi Ambient, Departament de Quimica Fisica, Facultat de Quimica, Universitat de Barcelona, Marti i Franques 1-11, 08028 Barcelona (Spain)

2010-12-15

The electro-Fenton (EF) and photoelectro-Fenton (PEF) degradation of solutions of the beta-blocker propranolol hydrochloride with 0.5 mmol dm{sup -3} Fe{sup 2+} at pH 3.0 has been studied using a single cell with a boron-doped diamond (BDD) anode and an air diffusion cathode (ADE) for H{sub 2}O{sub 2} electrogeneration and a combined cell containing the above BDD/ADE pair coupled in parallel to a Pt/carbon felt (CF) cell. This naphthalene derivative can be mineralized by both methods with a BDD anode. Almost overall mineralization is attained for the PEF treatments, more rapidly with the combined system due to the generation of higher amounts of hydroxyl radical from Fenton's reaction by the continuous Fe{sup 2+} regeneration at the CF cathode, accelerating the oxidation of organics to Fe(III)-carboxylate complexes that are more quickly photolyzed by UVA light. The homologous EF processes are less potent giving partial mineralization. The effect of current density, pH and Fe{sup 2+} and drug concentrations on the oxidation power of PEF process in combined cell is examined. Propranolol decay follows a pseudo first-order reaction in most cases. Aromatic intermediates such as 1-naphthol and phthalic acid and generated carboxylic acids such as maleic, formic, oxalic and oxamic are detected and quantified by high-performance liquid chromatography. The chloride ions present in the starting solution are slowly oxidized at the BDD anode. In PEF treatments, all initial N of propranolol is completely transformed into inorganic ions, with predominance of NH{sub 4}{sup +} over NO{sub 3}{sup -} ion.

A double-blind randomized controlled trial of low doses of propranolol, nortriptyline, and the combination of propranolol and nortriptyline for the preventive treatment of migraine Estudo controlado, randomizado e duplo cego do uso de baixas doses de propranolol, nortriptilina e a combinação destas duas drogas no tratamento preventivo da migrânea

Directory of Open Access Journals (Sweden)

Renan B. Domingues

2009-12-01

Full Text Available Few trials have evaluated combination of two or more drugs in the preventive treatment of migraine. In this study three therapeutic regimens were compared: (a propranolol, at a dose of 40 mg per day, (b nortriptyline, at a dose of 20 mg per day, and (c the combination of these two drugs in these dosages. The groups were matched according to age, gender, and frequency of migraine attacks prior to treatment. The period of treatment was two months and the frequency and intensity of headache attacks of the 30 days pre-treatment period were compared with the frequency of headaches in the treatment period. Fourteen patients in groups A and B and sixteen patients in group C have completed the study. Treatment with propranolol, alone or in combination, was shown to be effective. Treatment with nortriptyline alone was not effective. All three therapeutic regimens were safe and side effects were minimal. The frequency of discontinuation of the study was the same in the 3 groups but no patient left the study due to adverse reactions. The combined therapy proved to be as safe as the monotherapy. Further studies evaluating this and other possible combinations of drugs in higher doses and for longer periods, should more clearly elucidate the role of combined therapy in the treatment of migraine.Poucos ensaios clínicos têm avaliado o tratamento preventivo da migrânea através da combinação de drogas. Neste estudo, três regimes terapêuticos foram comparados: (a popranolol, na dose de 40 mg por dia, (b nortriptilina, na dose de 20 mg por dia e (c combinação destas duas drogas nestas dosagens. Os grupos foram pareados de acordo com idade, sexo e freqüência de crises previamente ao tratamento. O período de tratamento foi de dois meses e a frequência e a intensidade das crises de cefaléia do período pré-tratamento foram comparadas com as do período de tratamento. Concluíram o estudo 14 pacientes do grupo A, 14 do grupo B e 16 do grupo C. Os

Development of dissolution test method for a telmisartan/amlodipine besylate combination using synchronous derivative spectrofluorimetry

Directory of Open Access Journals (Sweden)

Panikumar Durga Anumolu

2014-04-01

Full Text Available The dissolution process is considered an important in vitro tool to evaluate product quality and drug release behavior. Single dissolution methods for the analysis of combined dosage forms are preferred to simplify quality control testing. The objective of the present work was to develop and validate a single dissolution test for a telmisartan (TEL and amlodipine besylate (AML combined tablet dosage form. The sink conditions, stability and specificity of both drugs in different dissolution media were tested to choose a discriminatory dissolution method, which uses an USP type-II apparatus with a paddle rotating at 75 rpm, with 900 mL of simulated gastric fluid (SGF without enzymes as the dissolution medium. This dissolution methodology provided good dissolution profiles for both TEL and AML and was able to discriminate changes in the composition and manufacturing process. To quantify both drugs simultaneously, a synchronous first derivative spectrofluorimetric method was developed and validated. Drug release was analyzed by a fluorimetric method at 458 nm and 675 nm for AML and TEL, respectively. The dissolution method was validated as per ICH guidance.

Effects of tham, isoprenaline and propranolol on blood flow and vascular resistances of the liver after in- and outflow occlusion. Relation with the splanchnic shock.

Science.gov (United States)

Stoitchcov, E; Kawai, T; Bleser, F; Benichoux, R

1976-01-01

The responsibility of the portal and the hepatic artery circulations during shock states has been established by studying the effects of a 15-min occlusion of two of the following blood vessels on 23 dogs: inferior vena cava below the diaphragm, portal vein and hepatic artery. Intrahepatic vascular resistances were computed from blood pressure records in these vessels and transhepatic blood flow studies using the 133Xe clearance method. The animals were treated with THAM, plasmagel, isoprenaline, and propranolol. The tolerance of the occlusion is significantly improved when the animals are treated with the association of the four drugs. The portal and the systemic arterial blood pressures return to normal more promptly. Sinusoid and peribiliary resistances are remarkably stable if compared to the changes occurring in the control animals. The well-known benefit of THAM is improved by the apparently paradoxical association of isoprenaline and propranolol. In fact, at the doses which have been used, they counterbalance their mutual disadvantages. Finally, the analysis of the hepatic blood flow rates and vascular resistances suggests that the splanchnic shock has two components: hepatic and visceral.

Study on the inclusion behavior of p-sulfonatocalix[6]arene with propranolol by spectrofluorometry

Science.gov (United States)

Li, Hui; Song, Jin-Ping; Chao, Jian-Bin; Shuang, Shao-Min; Dong, Chuan

2012-11-01

The inclusion interaction between propranolol (PPL) and p-sulfonatocalix[6]arene (SCX6) was investigated by fluorescence and 1H NMR spectroscopy. Influences of pH, temperature, ionic strength and the concentration of SCX6 were examined in detail. In phosphate buffer solution with pH 7.5, the fluorescence of PPL dramatically quenched upon addition of SCX6 revealing the formation of inclusion complexes between PPL and SCX6. The stoichiometric ratio was verified to be 1:1 by the continuous variation method. The inclusion constant of PPL-SCX6 complexes was calculated as 2.2 × 104 L/mol by the nonlinear curve fitting method. 1H NMR titration spectra testified that the aliphatic chain of PPL may be partially penetrated into the hydrophobic cavity of SCX6. This was confirmed by molecular dynamics calculations.

Comparative study between derivative spectrophotometry and multivariate calibration as analytical tools applied for the simultaneous quantitation of Amlodipine, Valsartan and Hydrochlorothiazide

Science.gov (United States)

Darwish, Hany W.; Hassan, Said A.; Salem, Maissa Y.; El-Zeany, Badr A.

2013-09-01

Four simple, accurate and specific methods were developed and validated for the simultaneous estimation of Amlodipine (AML), Valsartan (VAL) and Hydrochlorothiazide (HCT) in commercial tablets. The derivative spectrophotometric methods include Derivative Ratio Zero Crossing (DRZC) and Double Divisor Ratio Spectra-Derivative Spectrophotometry (DDRS-DS) methods, while the multivariate calibrations used are Principal Component Regression (PCR) and Partial Least Squares (PLSs). The proposed methods were applied successfully in the determination of the drugs in laboratory-prepared mixtures and in commercial pharmaceutical preparations. The validity of the proposed methods was assessed using the standard addition technique. The linearity of the proposed methods is investigated in the range of 2-32, 4-44 and 2-20 μg/mL for AML, VAL and HCT, respectively.

Assessment of Pharmacokinetic Interactions Between Obeticholic Acid and Caffeine, Midazolam, Warfarin, Dextromethorphan, Omeprazole, Rosuvastatin, and Digoxin in Phase 1 Studies in Healthy Subjects.

Science.gov (United States)

Edwards, Jeffrey E; Eliot, Lise; Parkinson, Andrew; Karan, Sharon; MacConell, Leigh

2017-09-01

Obeticholic acid (OCA), a potent and selective farnesoid X receptor agonist, is indicated for the treatment of primary biliary cholangitis (PBC). We investigated the potential drug-drug interaction effect of OCA on metabolic CYP450 enzymes and drug transporters. Five phase 1 single-center, open-label, fixed-sequence, inpatient studies were conducted in healthy adult subjects to evaluate the effect of oral daily doses of 10 or 25 mg OCA on single-dose plasma pharmacokinetics of specific probe substrates for enzymes CYP1A2 (caffeine, R-warfarin), CYP3A (midazolam, R-warfarin), CYP2C9 (S-warfarin), CYP2D6 (dextromethorphan), CYP2C19 (omeprazole), and drug transporters, BCRP/OATP1B1/OATP1B3 (rosuvastatin), and P-gp (digoxin). OCA showed no substantial suppression/inhibition of S-warfarin, digoxin, and dextromethorphan and weak interactions with caffeine, omeprazole, rosuvastatin, and midazolam. The maximal pharmacodynamic responses (E max ) to warfarin-based INR, PT, and aPTT were reduced by 11%, 11%, and 1%, respectively, for the 10-mg dose group and by 7%, 7% and 0%, respectively, for the 25-mg dose group. Overall, drugs dosed in combination with OCA were well tolerated, and most adverse events were mild in severity. No clinically important trends were noted in laboratory evaluations, vital signs, or 12-lead ECGs. In these studies, OCA showed weak to no suppression/inhibition of metabolic enzymes and drug transporters at the highest recommended therapeutic dose in patients with PBC. On the basis on these analyses, monitoring and maintenance of target INR range are required during coadministration of OCA with drugs that are metabolized by CYP1A2 (R-warfarin). Intercept Pharmaceuticals, Inc.

Effect of combination tablets containing amlodipine 10 mg and irbesartan 100 mg on blood pressure and cardiovascular risk factors in patients with hypertension

Directory of Open Access Journals (Sweden)

Yagi S

2015-01-01

Full Text Available Shusuke Yagi,1 Akira Takashima,1 Minoru Mitsugi,2 Toshihiro Wada,2 Junko Hotchi,1 Ken-ichi Aihara,3 Tomoya Hara,1 Masayoshi Ishida,1 Daiju Fukuda,4 Takayuki Ise,1 Koji Yamaguchi,1 Takeshi Tobiume,1 Takashi Iwase,1 Hirotsugu Yamada,1 Takeshi Soeki,1 Tetsuzo Wakatsuki,1 Michio Shimabukuro,4 Masashi Akaike,5 Masataka Sata11Department of Cardiovascular Medicine, Graduate School of Health Biosciences, University of Tokushima, Tokushima, 2Department of Internal Medicine, Shikoku Central Hospital, Shikokuchuo, 3Department of Medicine and Bioregulatory Sciences, 4Department of Cardio-Diabetes Medicine, 5Department of Medical Education, Graduate School of Health Biosciences, University of Tokushima, Tokushima, JapanBackground: Hypertension is one of the major risk factors for cardiovascular and cerebrovascular disease and mortality. Patients who receive insufficient doses of antihypertensive agents or who are poorly adherent to multidrug treatment regimens often fail to achieve adequate blood pressure (BP control. The aim of this study was to determine the efficacy of an angiotensin II receptor blocker (ARB and calcium channel blocker (CCB combination tablet containing a regular dose of irbesartan (100 mg and a high dose of amlodipine (10 mg with regard to lowering BP and other risk factors for cardiovascular disease.Methods: We retrospectively evaluated data from 68 patients with essential hypertension whose treatment regimen was changed either from combination treatment with an independent ARB and a low-dose or regular-dose CCB or from a combination tablet of ARB and a low-dose or regular-dose CCB to a combination tablet containing amlodipine 10 mg and irbesartan 100 mg, because of incomplete BP control. Previous treatments did not include irbesartan as the ARB.Results: The combination tablet decreased systolic and diastolic BP. In addition, it significantly decreased serum uric acid, low-density lipoprotein cholesterol, and increased high

Evaluation by N-terminal prohormone of brain natriuretic peptide concentrations and ross scoring of the efficacy of digoxin in the treatment of heart failure secondary to congenital heart disease with left-to-right shunts.

Science.gov (United States)

Elkiran, Ozlem; Sandikkaya, Ayse; Kocak, Gulendam; Karakurt, Cemsit; Taskapan, Cagatay; Yologlu, Saim

2013-10-01

This study aimed to evaluate the effectiveness of digoxin in children with heart failure secondary to left-to-right shunt lesions and normal left ventricular systolic function. The study registered 37 such patients (ages 10 days to 24 months, groups 1 and 2) and used 20 healthy children as a control group (group 3). Left ventricular systolic function, as assessed by conventional echocardiography, was normal in all the subjects. Congestive heart failure was diagnosed by clinical evaluation and modified Ross scoring. Plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentrations and complete blood counts were assessed in all the children. Group 1 was treated with digoxin, enalapril, and furosemide and group 2 with enalapril and furosemide. Approximately 1 month after starting treatment, the patients were reevaluated by physical and echocardiographic examinations, modified Ross scoring, plasma NT-proBNP concentrations, and complete blood counts. The pre- and posttreatment Ross scores of group 1 (p = 0.377) and group 2 (p = 0.616) did not differ significantly. The NT-proBNP values in both groups decreased after treatment (p = 0.0001). The pre- and posttreatment NT-proBNP values did not differ significantly in group 1 (p = 0.094)) and group 2 (p = 0.372). The pretreatment NT-proBNP values in groups 1 and 2 (p = 0.0001) were significantly higher than in the control group (p = 0.003). A smaller difference was observed between posttreatment NT-proBNP values in group 1 and the control group (p = 0.045). We found no significant difference between the posttreatment NT-proBNP values of group 2 and those of the control group (p = 0.271). The study showed that both treatments currently used to treat heart failure secondary to congenital heart disease with left-to-right shunts and preserved left ventricular systolic function are effective and do not differ significantly. Thus, digoxin does not provide any extra benefit in the treatment of such patients.

[Two news drugs (ivacaftor & bedaquiline), one biomarker (florbetapir) and a re-positioned drug (propranolol) on the market].

Science.gov (United States)

Monneret, C

2014-07-01

Among the new molecular entities approved by the EMEA and the FDA in 2012, four have caught our attention for their significant contribution to the health of patient. First of all, among the notable 2012 approvals, is ivacaftor or Kalydeco®. This is the first treatment that targets one of the gene defects that is underlying cause of cystic fibrosis. This is also an example of the promise of personalized medicine. The benefits with bedaquiline or Sirturo® are its ability to likely provide clinically relevant activity as part of multi-drug regimens against tuberculosis (TB) based on clinical data in multi-drug resistant tuberculosis (MDR TB) patients, who were defined as being at least resistant against the two major tuberculostatic medicines (isaoniazide and rifampicine). On December 2012 and then, on December 2013, the FDA and European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended granting a conditional marketing authorization for Sirturo® (bedaquiline), respectively, for use as part of a combination therapy for pulmonary multidrug resistant tuberculosis in adult patients when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability. Amyvid®, which is a solution for injection that contains the active substance florbetapir (18F), is a radiopharmaceutical that emits low amounts of radiation and works by targeting and attaching to β-amyloid plaques in the brain. This enables doctors to know whether or not significant amount of plaques are present in order to know if the patient is unlikely or not, to have Alzheimer's disease. Finally, the last topics addresses the propranolol, which is a beta-blocker, used alone or together with other medicines to treat high blood pressure. Propranolol is gaining a new lease of life for treating infantile hemangioma. Copyright © 2014. Published by Elsevier Masson SAS.

Comparative study between derivative spectrophotometry and multivariate calibration as analytical tools applied for the simultaneous quantitation of Amlodipine, Valsartan and Hydrochlorothiazide.

Science.gov (United States)

Darwish, Hany W; Hassan, Said A; Salem, Maissa Y; El-Zeany, Badr A

2013-09-01

Four simple, accurate and specific methods were developed and validated for the simultaneous estimation of Amlodipine (AML), Valsartan (VAL) and Hydrochlorothiazide (HCT) in commercial tablets. The derivative spectrophotometric methods include Derivative Ratio Zero Crossing (DRZC) and Double Divisor Ratio Spectra-Derivative Spectrophotometry (DDRS-DS) methods, while the multivariate calibrations used are Principal Component Regression (PCR) and Partial Least Squares (PLSs). The proposed methods were applied successfully in the determination of the drugs in laboratory-prepared mixtures and in commercial pharmaceutical preparations. The validity of the proposed methods was assessed using the standard addition technique. The linearity of the proposed methods is investigated in the range of 2-32, 4-44 and 2-20 μg/mL for AML, VAL and HCT, respectively. Copyright © 2013 Elsevier B.V. All rights reserved.

Transplacental and mammary passage of radioactivity in rats treated vaginally and orally with [14C]propranolol

International Nuclear Information System (INIS)

Buttar, H.S.; Moffatt, J.H.; Bura, C.

1988-01-01

Single doses (10 mg/kg) of an aqueous solution of [14C]propranolol were administered either orally (po) or intravaginally (ivg) on gestational d 15, or on postpartum d 7-10. Upon ivg administration, [14C]propranolol was quickly transferred to systemic circulation and the mean blood [14C] concentrations were significantly greater during the first 0.25-2 h than in po dosed counterparts. About 98% of the ivg applied dose was absorbed after 6 h in gravid rats, and the combined 6-h excretions of radioactivity in the urine (ivg = 24.6%; po = 22.9%) and feces (ivg = 16.8%; po = 14.6%) were equivalent in both groups. At the end of 6 h, the levels of [14C] in the urinary bladder, adrenal, uterus, ovary, spleen, skeletal muscle, brain, heart, lung and fat were significantly higher in ivg treated rats than po dosed animals. Compared with the maternal plasma (ivg = 0.76; po = 0.88 microgram/ml), the mean concentrations of [14C] in the placentas were similar in both groups, while the amounts of [14C] were three to five times lower in the amniotic fluids and the fetuses of both po and ivg treated dams. In lactating rats, over 99% of the administered radioactivity was absorbed from the vagina within 6 h. The blood concentrations of [14C] were significantly elevated at 0.5 and 1 h in the per vaginam treated animals, and afterward the disappearance rate of [14C] followed a similar course in both groups. Following ivg application, the milk radioactivity peaked at 0.5 h and declined rapidly. However, the appearance of [14C] in milk was rather slow after oral dosing: the milk [14C] peaked between 2 and 3 h posttreatment and remained steady thereafter. The milk to blood (M/B) [14C] concentration ratios were markedly greater during 0.5 to 1 h in the ivg group than in their po dosed counterparts

Host-Guest Inclusion Complexes between Amlodipine Enantiomers in the Biphasic Recognition Chiral Extraction System using Tartaric Acid and β-Cyclodextrin Derivatives as Positive Confirmation by using their Enantioselective Extraction.

Science.gov (United States)

Al Azzam, Khaldun M; Abdallah, Hassan H; Halim, Hairul N Abdul; Ahmad, Maizatul Akmam; Shaibah, Hassan

2015-01-01

The current work reports an extended theoretical study from our previous experimental work for the enantioselective extraction of amlodipine enantiomers in a biphasic recognition chiral extraction system (BRCES) consisting of hydrophobic D-diisopropyl tartrate dissolved in organic phase (n-decanol) and hydrophilic hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous phase (acetate buffer) which preferentially recognize the R-enantiomer and S-enantiomer, respectively. The calculations were simulated using a semi-empirical PM3 method as a part of the Gaussian09 software package and were used to optimize the structures of the hosts, guests, and host-guest complexes in the gas phase without any restrictions. It was found that HP-β-CD has the strongest recognition ability among the three β-CD derivatives studied, namely HP-β-CD, hydroxyethyl-β-cyclodextrin (HE-β-CD), and methylated-β-cyclodextrin (Me-β-CD), due to the large interaction energies (Ecomp = -14.3025 kcal/ mol), while D-diisopropyl tartrate has the strongest ability among the four tartaric acid derivatives studied namely; L-diisopropyl tartrate, D-diisopropyl tartrate, L-diethyl tartrate, and D-diethyl tartrate (Ecomp = -5.9964 kcal/ mol). The computational calculations for the enantioselective partitioning of amlodipine enantiomers rationalized the reasons for the different behaviors for this extraction. The present theoretical results may be informative to scientists who are devoting themselves to developing models for their experimental parts or for enhancing the hydrophobic drug solubility in drug delivery systems.

Host-Guest Inclusion Complexes between Amlodipine Enantiomers in the Biphasic Recognition Chiral Extraction System using Tartaric Acid and β-Cyclodextrin Derivatives as Positive Confirmation by using their Enantioselective Extraction

Science.gov (United States)

Al Azzam, Khaldun M.; Abdallah, Hassan H.; Halim, Hairul N. Abdul; Ahmad, Maizatul Akmam; Shaibah, Hassan

2015-01-01

The current work reports an extended theoretical study from our previous experimental work for the enantioselective extraction of amlodipine enantiomers in a biphasic recognition chiral extraction system (BRCES) consisting of hydrophobic D-diisopropyl tartrate dissolved in organic phase (n-decanol) and hydrophilic hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous phase (acetate buffer) which preferentially recognize the R-enantiomer and S-enantiomer, respectively. The calculations were simulated using a semi-empirical PM3 method as a part of the Gaussian09 software package and were used to optimize the structures of the hosts, guests, and host-guest complexes in the gas phase without any restrictions. It was found that HP-β-CD has the strongest recognition ability among the three β-CD derivatives studied, namely HP-β-CD, hydroxyethyl-β-cyclodextrin (HE-β-CD), and methylated-β-cyclodextrin (Me-β-CD), due to the large interaction energies (Ecomp = −14.3025 kcal/ mol), while D-diisopropyl tartrate has the strongest ability among the four tartaric acid derivatives studied namely; L-diisopropyl tartrate, D-diisopropyl tartrate, L-diethyl tartrate, and D-diethyl tartrate (Ecomp = −5.9964 kcal/ mol). The computational calculations for the enantioselective partitioning of amlodipine enantiomers rationalized the reasons for the different behaviors for this extraction. The present theoretical results may be informative to scientists who are devoting themselves to developing models for their experimental parts or for enhancing the hydrophobic drug solubility in drug delivery systems. PMID:26839848

Simultaneous Detemination of Atorvastatin Calcium and Amlodipine Besylate by Spectrophotometry and Multivariate Calibration Methods in Pharmaceutical Formulations

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Amir H. M. Sarrafi

2011-01-01

Full Text Available Resolution of binary mixture of atorvastatin (ATV and amlodipine (AML with minimum sample pretreatment and without analyte separation has been successfully achieved using a rapid method based on partial least square analysis of UV–spectral data. Multivariate calibration modeling procedures, traditional partial least squares (PLS-2, interval partial least squares (iPLS and synergy partial least squares (siPLS, were applied to select a spectral range that provided the lowest prediction error in comparison to the full-spectrum model. The simultaneous determination of both analytes was possible by PLS processing of sample absorbance between 220-425 nm. The correlation coefficients (R and root mean squared error of cross validation (RMSECV for ATV and AML in synthetic mixture were 0.9991, 0.9958 and 0.4538, 0.2411 in best siPLS models respectively. The optimized method has been used for determination of ATV and AML in amostatin commercial tablets. The proposed method are simple, fast, inexpensive and do not need any separation or preparation methods.

Propranolol y sus ésteres: detección y resolución enantiomérica

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Ritsie Ruiz Caballero

1998-08-01

Full Text Available Se realizó una revisión bibliográfica sobre el racemato del clorhidrato de propranolol y sus ésteres, con el objetivo de recopilar los métodos más actuales para su detección y la resolución de su mezcla racémica, de forma que se mantengan informados los farmacéuticos, químicos sintetizadores y otros profesionales relacionados con la temática. Se consultaron las bases de datos MEDLINE (1986-1994, Analytical Abstracts (1985-1994, Chemicals Abstracts (1990-1992 y los Current Contents (Life Science y Physical, Chemical & Earth Sciences desde 1990-1996. Se reportan como técnicas de análisis para su detección: espectrofluorometría, colorimetría, cromatografía de placa delgada y cromatografía líquida de alta resolución. Se reflejan diferentes métodos de resolución de enantiómeros, como: cromatografía de fluido supercrítico, electroforesis capilar, cromatografía de placa delgada y cromatografía líquida de alta resolución utilizando fases y/o aditivos quirales, empleados estos 2 últimos tanto para la detección como para la resolución del clorhidrato de propranolol y sus ésteres.A bibliographic review on the raceme of propanolol chlorhydrate and its esters was made aimed at compiling the latest methods for its detection and the resolution of its racemic mix in order to provide information to pharmacists, synthesizer chemistry and other professionals connected with this topic. Reference was made to the MEDLINE (1986-1994, Analytical Abstracts (1985-1994, and Chemical Abstracts (1990-1992 data bases, as well as to Current Contents (Life Science & Physical, Chemical & Earth Sciences form 1990 to 1996. The spectrofluorometry, the colorimetry, the thinlayer chromatography, and the high oressure liquid chromatography are reported as analysis techniques used for its detection. The following methods of resolution of enantiomers are considered: supercritical fluid chromatography, capillary electrophoresis, thin

Adherence to Treatment, Safety, Tolerance, and Effectiveness of Perindopril/Amlodipine Fixed-Dose Combination in Greek Patients with Hypertension and Stable Coronary Artery Disease: A Pan-Hellenic Prospective Observational Study of Daily Clinical Practice.

Science.gov (United States)

Liakos, Charalampos I; Papadopoulos, Dimitrios P; Kotsis, Vasilios T

2017-10-01

Initiation of antihypertensive therapy with a two-drug fixed-dose combination (FDC) in a single tablet may be recommended in patients at high risk of cardiovascular events to improve adherence and effectiveness. Preferred combinations include an angiotensin-converting enzyme inhibitor with a dihydropyridine calcium antagonist. This study assessed adherence to and the safety, tolerance, and effectiveness of the perindopril/amlodipine FDC in Greek patients with hypertension and stable coronary artery disease (CAD) over a 4-month period. A total of 1907 patients with hypertension and CAD (59.1% males) who had recently (≤2 weeks) commenced treatment with the perindopril/amlodipine FDC (5/5, 5/10, 10/5, or 10/10 mg) were studied at baseline and at 1 and 4 months. Adherence to treatment was assessed with the Morisky Medication-taking Adherence Scale (MMAS). Seven patients (0.4%) did not attend the scheduled visits. In total, 1607 (84.6%) patients received a constant treatment dose throughout the study. High adherence (MMAS score = 0) was reported by 1592 (83.6%), 1628 (85.7%), and 1477 (77.7%) patients at the second and the third visit and at both visits, respectively. Adverse reactions were reported by only 13 (0.7%) patients, were all minor, and did not result in treatment discontinuation. Office blood pressure (BP) was significantly decreased at the third visit (130.8 ± 8.4/78.2 ± 6.4 mmHg) compared with baseline (156.5 ± 15.0/89.9 ± 9.6 mmHg; p < 0.001), regardless of previous antihypertensive treatment. Patients with grade 1, 2, and 3 hypertension at baseline showed a reduction in BP of 19.3/9.4, 31.5/13.5, and 47.8/22.2 mmHg, respectively (p < 0.001). Uncontrolled hypertension (≥140/90 mmHg) was notably reduced from 90.3% at baseline to 18.5% at the third visit. The perindopril/amlodipine FDC is characterized by high adherence and effectiveness, regardless of previous treatment. Degree of BP reduction was related to baseline BP levels

Development and Evaluation of Mouth Dissolving Films of Amlodipine Besylate for Enhanced Therapeutic Efficacy

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K. M. Maheswari

2014-01-01

Full Text Available The present investigation was undertaken with an objective of formulating mouth dissolving films (MDFs of Amlodipine Besylate (AMLO to enhance convenience and compliance of the elderly and pediatric patients for better therapeutic efficacy. Film formers like hydroxy propyl methyl cellulose (HPMC and methyl cellulose (MC along with film modifiers like poly vinyl pyrrolidone K30 (PVP K30, and sodium lauryl sulphate (SLS as solubilizing agents were evaluated. The prepared MDFs were evaluated for in vitro dissolution characteristics, in vitro disintegration time, and their physicomechanical properties. All the prepared MDFs showed good mechanical properties like tensile strength, folding endurance, and % elongation. MDFs were evaluated by means of FTIR, SEM, and X-RD studies. MDFs with 7.5% (w/w of HPMC E3 gave better dissolution properties when compared to HPMC E5, HPMC E15, and MC. MDFs with PVP K30 and SLS gave superior dissolution properties when compared to MDFs without PVP K30 and SLS. The dissolution properties of MDFs with PVP K30 were superior when compared to MDFs with SLS. In the case of F3 containing 7.5% of HPMC E3 and 0.04% of PVP K30, complete and faster release was observed within 60 sec when compared to other formulations. Release kinetics data reveals diffusion is the release mechanism.

Electro-Fenton and photoelectro-Fenton degradations of the drug beta-blocker propranolol using a Pt anode: Identification and evolution of oxidation products

Energy Technology Data Exchange (ETDEWEB)

Isarain-Chavez, Eloy; Cabot, Pere Lluis; Centellas, Francesc; Rodriguez, Rosa Maria; Arias, Conchita; Garrido, Jose Antonio [Laboratori d' Electroquimica dels Materials i del Medi Ambient, Departament de Quimica Fisica, Facultat de Quimica, Universitat de Barcelona, Marti i Franques 1-11, 08028 Barcelona (Spain); Brillas, Enric, E-mail: brillas@ub.edu [Laboratori d' Electroquimica dels Materials i del Medi Ambient, Departament de Quimica Fisica, Facultat de Quimica, Universitat de Barcelona, Marti i Franques 1-11, 08028 Barcelona (Spain)

2011-01-30

The beta-blocker propranolol hydrochloride has been degraded by electrochemical advanced oxidation processes like electro-Fenton (EF) and photoelectro-Fenton (PEF) using a single cell with a Pt anode and an air diffusion cathode (ADE) for H{sub 2}O{sub 2} electrogeneration and a combined system containing the above Pt/ADE pair coupled in parallel to a Pt/carbon-felt (CF) cell. Organics are mainly oxidized with hydroxyl radical ({center_dot}OH) formed from Fenton's reaction between added Fe{sup 2+} and electrogenerated H{sub 2}O{sub 2}. The PEF treatment in Pt/ADE-Pt/CF system yields almost total mineralization because {center_dot}OH production is enhanced by Fe{sup 2+} regeneration from Fe{sup 3+} reduction at the CF cathode and Fe(III) complexes with generated carboxylic acids are rapidly photodecarboxylated under UVA irradiation. Lower mineralization degree is found for PEF in Pt/ADE cell due to the little influence of UVA light on Fe{sup 2+} regeneration. The homologous EF processes are much less potent as a result of the persistence of Fe(III)-carboxylate complexes. Aromatic intermediates such as 1-naphthol, 1,4-naphthoquinone and phthalic acid and generated carboxylic acids such as pyruvic, glycolic, malonic, maleic, oxamic, oxalic and formic are identified. While chloride ion remains stable, NH{sub 4}{sup +} and NO{sub 3}{sup -} ions are released to the medium. A reaction sequence for propranolol hydrochloride mineralization is proposed.

Radioactive iodine therapy in a case of Graves' disease with allergy to antithyroid drugs (ATD) and propranolol

International Nuclear Information System (INIS)

Bahri, I.M.; San Luis, T.O.L.

2007-01-01

Full text: This is a case of V.C., 56 year old, female, from Las Pinas City, Philippines, diagnosed as a case of Graves' disease. During the course of therapy, the patient had allergy to antithyroid drugs (ATDs) and beta blocker (Propranolol). She developed rashes all over the body, sparing the face the day after taking her ATDs as well as Propranolol, thus all medications were discontinued. Other options, such as RAI therapy and surgery, with their respective advantages and disadvantages were fully explained to the patient who then opted to undergo RAI therapy. In our institution, we usually compute the dose based on the size of the gland and radioactive Iodine-131 uptake measurements (RAIU) rather than using fixed doses. Thyroid scintigraphy and RAIU were done which revealed poorly visualized thyroid gland and markedly diminished 24-hour uptake but normal 4-hour uptake [RAIU 4 hour uptake: 26% (NV= 15-25%); 24 hour uptake: 6% (NV25-45%)]. * Note: Variations in normal uptake values compared to US are due to iodine deficiency still existing in some regions. Because of the very low 24-hour uptake, we reviewed the probable causes which can result in low uptake values. All causes were ruled out and the patient was advised to undergo two weeks of strict low-iodine diet prior to repeat thyroid scintigraphy and RAIU. Thereafter, the result of repeat study showed diffuse thyromegaly with elevated uptake values indicating rapid trapping and organification processes [RAIU 4 hour uptake: 82% (NV= 15-25%); 24 hour uptake: 68% (NV25-45%)]. The day after the study, the patient was given 10 mCi I-131 based on the estimated weight of the gland, rapid thyroid iodine turnover ('small pool') and 24-hour uptake. This was considered to be the highest allowable dose of RAI to decrease the probability of relapse and the need for re-treatment. Approximately 4 weeks after the therapy, the patient is noted to have responded satisfactorily to therapy with resolution of symptoms. (author)

Combinação de anlodipino e enalaprila em pacientes hipertensos com doença coronariana Combinación de amlodipino y enalapril en pacientes hipertensos con enfermedad coronaria Combination of amlodipine and enalapril in hypertensive patients with coronary disease

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Marcos Rienzo

2009-03-01

Full Text Available FUNDAMENTO: Pacientes (pts com doença coronariana (DAC estável podem se beneficiar de menor pressão arterial (PA, conforme estudos recentes. OBJETIVO: Avaliar a eficácia e a tolerabilidade da combinação fixa anlodipino + enalaprila, comparada a anlodipino na normalização da PA diastólica (PAD ( 90 e 110 mmHg durante o wash-out de quatro semanas, em uso só de atenolol. Após wash-out randomizamos para combinação (A ou anlodipino (B e seguimos de quatro em quatro semanas até 98 dias. As doses (mg iniciais foram, respectivamente: A- 2,5/10 e B- 2,5, sendo incrementadas se PAD> 85mmHg, nas visitas. Estatística com χ2, Fischer e análise de variância, para pFUNDAMENTO: Pacientes (pts con enfermedad coronaria (EAC estable pueden beneficiarse con una menor presión arterial (PA, de acuerdo con estudios recientes. OBJETIVO: Evaluar la eficacia y la tolerancia de la combinación fija amlodipino + enalapril, comparada a el amlodipino en la normalización de la PA diastólica (PAD (90 y 110 mmHg durante el wash-out de cuatro semanas, en uso sólo de atenolol. Después del wash-out randomizamos para combinación (A o amlopidino (B y seguimos de cuatro en cuatro semanas hasta 98 días. Las dosis (mg iniciales fueron, respectivamente: A- 2,5/10 y B- 2,5, siendo incrementadas si PAD> 85mmHg, en las visitas. Estadística con χ2, Fischer y análisis de varianza, para pBACKGROUND: Patients (pts with stable coronary artery disease (CAD can benefit from a decrease in the blood pressure (BP, according to recent studies. OBJECTIVE: To evaluate the efficacy and tolerability of the fixed combination: amlodipine + enalapril, when compared to amlodipine in the normalization of the diastolic arterial pressure (DAP (90 and 110 mmHg during the four-week wash-out with atenolol treatment alone, were excluded. After the wash-out, pts were randomly distributed for the use of the combination (A or amlodipine (B and were followed every four weeks up to 98 days

Physicochemical characterization and evaluation of buccal adhesive patches containing propranolol hydrochloride.

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Patel, V M; Prajapati, B G; Patel, J K; Patel, M M

2006-07-01

Buccal adhesive patches containing 20 mg of propranolol hydrochloride were prepared using solvent casting method. Chitosan was used as a natural bioadhesive polymer. Patches were prepared at different ratios of PVP K-30 and evaluated for various physicochemical characteristics such as weight variation, drug content uniformity, folding endurance, surface pH, ex-vivo mucoadhesive strength, ex-vivo residence time, in vitro drug release and in vitro buccal permeation study. Patches exhibited sustained release over a period of 7 hours. The mechanism of drug release was found to be Non-Fickian diffusion. Addition of PVP K-30 generally enhanced the releasing rate. The ex-vivo mucoadhesive strength was performed using sheep buccal mucosa on modified physical balance. Optimized patches (batch F4) showed satisfactory bioadhesive strength (9.6 degrees 2.0 gram) and ex vivo residence time (272 degrees 0.25 minutes). Swelling index was proportional to PVP K-30. The surface pH of all batches was within satisfactory limit (7.0+/-1.5) and hence patches would not cause irritation in the buccal cavity. Good correlation was observed between in vitro drug release and in vitro drug permeation with correlation coefficient of 0.9364. Stability of optimized patches was performed in natural human saliva showed that both drug and dosage forms were stable in human saliva.

Contextualizando reações ácido-base de acordo com a teoria protônica de Brönsted-Lowry usando comprimidos de propranolol e nimesulida

OpenAIRE

Gonsalves, Arlan de Assis; Araújo, Cleônia Roberta Melo; Leite Filho, Carlos Alberto; Medeiros, Felipe Santana de

2013-01-01

This paper reports the use of alternative materials for teaching experimental chemistry. In this context, nimesulide and propranolol tablets were used to teach chemical concepts about acid-base reactions according to Brönsted-Lowry protonic Theory. Important topics of Organic, Analytical and Pharmaceutical Chemistry were discussed, such as purification by acid-base extraction, solubility of organic compounds in aqueous solutions, buffers, the dissociation constant (pKa), potentiometric titrat...

Effect of oral propranolol on splanchnic oxygen uptake and haemodynamics in patients with cirrhosis

DEFF Research Database (Denmark)

Bendtsen, Flemming; Henriksen, Jens Henrik; Becker, Povl Ulrik

1987-01-01

.01), azygos venous oxygen saturation (76 vs. 67%, P less than 0.05), ICG clearance (263 vs. 226 ml/min, P less than 0.01), wedged-to-free hepatic vein pressure (16 vs. 13.5 mm Hg, P less than 0.01), hepatic blood flow (1.18 vs. 0.78 l/min, P less than 0.01), cardiac index (3.42 vs. 2.53 l/min . min 2, P less...... mg propranolol. All patients underwent hepatic vein catheterization and had a primed continuous intravenous infusion of ICG. Azygos vein catheterization was performed in six patients. Splanchnic (hepatic-intestinal) oxygen uptake (median control 68 ml/min vs. beta-blockade 56 ml/min, P less than 0...... than 0.01), and heart rate (72 vs. 56 beats per min, P less than 0.01) decreased significantly after oral beta-blockade. The hepatic extraction ratio of ICG increased significantly (0.32 vs. 0.45, P less than 0.01), whereas estimated 'intrinsic' ICG clearance (289 vs. 300 ml/min, n.s.), arterial blood...

Uso del propranolol como modulador de la memoria y el aprendizaje en modelos animales

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Mariana Psyrdellis

2016-09-01

Full Text Available El propranolol es un antagonista β-adrenérgico no selectivo de los receptores adrenérgicos β1y β2. El rol de este sistema de neurotransmisión sobre la memoria ha sido demostrado en diversas investigaciones, ya sea tanto en la fase de codificación, consolidación y evocación como en la reconsolidación. El objetivo de este trabajo es realizar una revisión sobre los efectos de este β-bloqueante en diversos aprendizajes con paradigmas animales, entendiendo por medio de esto las implicaciones del sistema noradrenérgico en los procesos de memoria. El fármaco muestra resultados particulares dependiendo del momento de su aplicación y del diseño experimental empleado. En el trabajo se discuten los efectos de la droga sobre las distintas fases de la memoria en paradigmas animales con contenido espacial, estímulos gustativos y aversivos, con entrenamientos complejos, y con aprendizajes de un solo ensayo.

Experimental and clinical study on the digitalis in renal function disturbance

International Nuclear Information System (INIS)

Okubo, Mitsuru

1977-01-01

By using radioimmunoassay, movement of digoxin in the bodies of normal rabbits and dogs was discussed experimentally, and pathophysiology digoxin excretion in renal function disturbance was also discussed experimentally and clinically. The concentration of digoxin in each organ 30 minutes after intravenous administration of digoxin of 0.5 mg/kg to normal rabbits was the highest in the kidney, and it was high in order of skeletal muscles, ventricular muscles, and auricular muscles. A significant positive correlation was recognized between concentration of digoxin in blood and that in ventricular muscles. Digoxin clearance showed high values in normal dogs and dogs whose single kidney were extracted, when the concentration of digoxin in blood was low. A significant correlation between the concentration of digoxin in blood and BUN or creatinine was not recognized in patients with renal diseases, but a significant negative correlation between the concentration of digoxin in blood and creatinine clearance and between urinary excretion of digoxin and creatinine clearance was recognized. Therefore, creatinine clearance was thought to be useful for index to determine the administration dose of digoxin in renal dysfunction. In the patients who received external dialysis, decrease of the concentration of digoxin in blood after intravenous administration of digoxin delayed significantly in contrast to that of normal control group. (Tsunoda, M.)

A dose–response study of the effects of pre-test administration of beta-adrenergic receptor antagonist propranolol on the learning of active place avoidance, a spatial cognition task, in rats

Czech Academy of Sciences Publication Activity Database

Stuchlík, Aleš; Petrásek, Tomáš; Valeš, Karel

2009-01-01

Roč. 200, č. 1 (2009), s. 144-149 ISSN 0166-4328 R&D Projects: GA ČR(CZ) GA309/07/0341; GA ČR(CZ) GA309/09/0286 Institutional research plan: CEZ:AV0Z50110509 Keywords : propranolol * learning * spatial memory Subject RIV: FH - Neuro logy Impact factor: 3.220, year: 2009

Adaptation of a T3-uptake test and of radioimmunoassays for serum digoxin, thyroxine, and triiodothyronine to an automated radioimmunoassay system: ''Centria''

International Nuclear Information System (INIS)

Ertingshausen, G.; Shapiro, S.I.; Green, G.; Zborowski, G.

1975-01-01

We report the adaptation of four radioassays to the prototype of an automated radioimmunoassay system (''Centria,'' Union Carbide). The system consists of three integrated modules: an automated pipettor, which dispenses samples and reagents; the key module, an incubator/separator, in which centrifugal force is used to initiate and terminate multiple radioassay incubations and separations simultaneously; and a gamma-counter/computer, which counts three tubes simultaneously and converts counts into concentration units. Radioimmunoassays for thyroxine, triiodothyronine, and digoxin were developed with use of well-characterized antibodies and of prepackaged Sephadex-containing columns to separate bound and free radioactive ligand. A triiodothyronine-uptake test in which the same kind of columns were used was also adapted to the instrument. Results for clinical samples compared favorably with those obtained by manual procedures. We report data on correlation between different methods and preliminary data on precision of the prototype system

Estudo "LOTHAR": avaliação de eficácia e tolerabilidade da combinação fixa de anlodipino e losartana no tratamento da hipertensão arterial primária The "LOTHAR" study: evaluation of efficacy and tolerability of the fixed combination of amlodipine and losartan in the treatment of essential hypertension

Directory of Open Access Journals (Sweden)

Osvaldo Kohlmann Jr

2006-01-01

Full Text Available OBJETIVO: O estudo LOTHAR avaliou a eficácia, tolerabilidade e os efeitos metabólicos em médio e longo prazo (um ano da combinação fixa de anlodipino e losartana versus anlodipino e losartana isoladamente. MÉTODOS: Estudo multicêntrico brasileiro, randomizado, duplo-cego e comparativo realizado com 198 pacientes com hipertensão arterial primária em estágios 1 e 2. RESULTADOS: A combinação fixa apresenta alta eficácia anti-hipertensiva que se mantém em longo prazo com percentual reduzido de escape do controle pressórico, inferior a dos dois regimes monoterápicos de comparação. Em longo prazo, mais de 60% dos pacientes tratados com a combinação fixa permaneceram com níveis da PAD OBJECTIVE: The LOTHAR study evaluated medium and long term (one year efficacy, tolerability and metabolic effects of the fixed combination of amlodipine and losartan compared to amlodipine or losartan alone. METHODS: Brazilian multicenter, randomized, double-blind and comparative trial performed with 198 patients in stage 1 and 2 essential hypertension. RESULTS: The fixed combination has a high antihypertensive efficacy that is sustained in the long term with very low percentage of loss of blood pressure control. This percentage is incidentally lower than that of the two monotherapy comparative regimens. In the long term, more than 60% of the patients treated with the fixed combination remained with DBP < 85 mmHg, and the antihypertensive effect, when assessed by ABPM persisted for 24 hours with a trough-to-peak ratio of 76.7%. The frequency of adverse events was quite low in this group, and the long-term incidence of leg edema was approximately four-fold lower than that observed with amlodipine alone. The fixed combination did not change glucose and lipid metabolism in the medium or in the long term. CONCLUSION: Based on these results, we can say that the combination of amlodipine and losartan - the first fixed combination of a calcium channel

Minoxidil-associated anorexia in an infant with refractory hypertension.

Science.gov (United States)

Vesoulis, Zachary A; Attarian, Stephanie J; Zeller, Brandy; Cole, Francis Sessions

2014-12-01

Minoxidil is a potent antihypertensive used as an adjunctive agent in refractory hypertension. It exerts an antihypertensive effect through two mechanisms: selective arterial vasodilation by activation of potassium channels in the vascular smooth muscle and stimulation of carotid and aortic baroreceptors, leading to downstream release of renin and norepinephrine. Although frequently cited in reviews of antihypertensive agents, limited data about the use of minoxidil in neonates are available. We describe an infant girl, born at 35 weeks of gestation, who was diagnosed with idiopathic hypertension after extensive diagnostic evaluation. Adequate blood pressure control was not achieved with captopril, amlodipine, and clonidine. Oliguria secondary to captopril and rapid-onset congestive heart failure due to persistent hypertension led to the introduction of intravenous agents labetalol and nitroprusside. Although adequate blood pressure control was achieved, attempts to transition back to oral agents were unsuccessful, prompting the use of minoxidil as an alternative agent. Although good blood pressure control was achieved, the infant's oral intake plummeted from 210 to 63 ml/kg/day. The anorexia quickly resolved after stopping minoxidil, and she was discharged home at 5 months of age receiving propranolol, amlodipine, and doxazosin. Use of the Naranjo adverse drug reaction probability scale indicated a definite relationship (score of 10) between the patient's development of anorexia and minoxidil therapy. To our knowledge, there have been no previous reports of minoxidil-associated anorexia in preterm or term infants. Clinicians should be aware that anorexia is a possible adverse effect of minoxidil in this patient population when initiating the drug in similar patients. © 2014 Pharmacotherapy Publications, Inc.

Enhanced down regulation of cortical ±-propranolol sensitive [3H]-DHA binding sites by co-administration of DMI and 5-HT1A partial agonist gepirone

International Nuclear Information System (INIS)

Geissler, M.A.; Yocca, F.D.

1990-01-01

The putative interrelationship between the noradrenergic and serotonergic systems has been supported by numerous studies. Recently, Dudley et al. (1989) demonstrated significant down regulation of cortical β-adrenergic receptors by co-administration of desipramine (DMI), a norepinephrine uptake inhibitor, and the full 5-HT 1A agonist 8-OH-DPAT. To this end, the effects of acute and chronic (4 and 14 day) administration of DMI, gepirone, a selective 5-HT 1A post-synaptic partial agonist, as well as a combination of the two, on cortical (±)-propranolol sensitive [ 3 H]-DHA binding sites were examined in rats. Down regulation was apparent after 4 and 14 day treatment with DMI. However, this was not the case with gepirone. Of particular importance is the demonstration of a greater magnitude of down regulation with co-administration of a greater magnitude of down regulation with co-administration of DMI and gepirone. These results suggests that alteration in rat cortical (±)-propranolol sensitive [ 3 H]-DHA binding sites by noradrenergic uptake inhibitors can be further modulated by selective partial agonist activity at central 5-HT 1A postsynaptic receptors. Further data on the co-administration of DMI and BMY 7378 (7,9-dioxo-8-[2-(4-o-methoxyphenylpiperazinyl)ethyl]-8-azaspiro[4,5]decane dihydrochloride), a weak partial agonist at postsynaptic 5-HT 1A receptors, are also presented

Use of beta-adrenoceptor blocking drugs in hyperthyroidism.

Science.gov (United States)

Feely, J; Peden, N

1984-05-01

There is an increasing use and variety of beta-adrenoceptor blocking agents (beta-blockers) available for the treatment of hyperthyroidism. Recent comparative studies suggest that atenolol (200mg daily), metoprolol (200mg daily); acebutolol (400mg daily), oxprenolol ( 160mg daily), nadolol ( 80mg daily) and timolol (20mg daily) produce a beneficial clinical response equal to that seen with propranolol ( 160mg daily). Most beta-blockers reduce resting heart rate by approximately 25 to 30 beats/min, although a lesser reduction is seen with those possessing intrinsic sympathomimetic activity such as oxprenolol and pindolol. While earlier studies employing large doses of intravenous propranolol concluded that beta-blockade reduced myocardial contractility, more recent non-invasive studies suggest that the predominant cardiac effect is on heart rate. In patients with cardiac failure, beta-blockers may, however, produce a profound fall in cardiac output. Nevertheless, in combination with digoxin they may be useful in controlling the atrial fibrillation of thyrocardiac disease. beta-Blockers improve nervousness and tremor (although to a lesser extent with cardioselective agents) and severe myopathy, and they also reduce the frequency of paralysis in patients with thyrotoxic periodic paralysis. There is often subjective improvement in sweating but usually no major effect on eye signs. Recent studies show a 10% reduction in oxygen consumption/basal metabolic rate with long term oral use of selective or nonselective beta-blockers. In addition, many agents (propranolol, metoprolol, nadolol and sotalol but not acebutolol, atenolol or oxprenolol) reduce circulating tri-iodothyronine (T3) concentration by between 10 and 40%, although the clinical significance of this effect (if any) is not established. beta-Blockers may also have endocrinological effects on gastrin, cyclic AMP, catecholamines and other hormone levels. Given in adequate dosage, propranolol has been shown to

Reduction of non-specific adsorption of drugs to plastic containers used in bioassays or analyses.

Science.gov (United States)

Fukazawa, Tominaga; Yamazaki, Yuri; Miyamoto, Yohei

2010-01-01

Non-specific adsorption (NSA) of drugs to plastic or glass containers used in clinical use is well known, but methods for reducing NSA have been rarely reported. We assessed the NSA to various containers and then investigated methods to reduce NSA. Probe drugs (methotrexate, warfarin, chloroquine, propranolol, verapamil, digoxin and paclitaxel) dissolved in water were incubated in conventional or low-adsorption containers for 4h at 4 degrees C and the NSA was determined by HPLC. They were also dissolved in aqueous methanol or acetonitrile and the NSA to a conventional polypropylene microplate was determined. Finally, tissue culture microplates were coated with silane coupling agents and the effects of the coatings were evaluated. Hydrophobic drugs (paclitaxel, verapamil and digoxin) were highly adsorbed to conventional plastic microplates, but in addition to hydrophobic drugs, positively charged drugs were well adsorbed to the tissue culture microplate. Low-adsorption microplates could reduce NSA below 15%, but positively charged or neutral hydrophobic drugs showed relatively higher adsorption. Acetonitrile showed stronger NSA inhibition than that of methanol, but the peak shapes of methotrexate and chloroquine were broadened and split. Among the silane coupling agents, GPTMS suppressed the NSA below 10%. Also, AATMS resembled the NSA pattern of GPTMS, but it increased the adsorption of methotrexate to 29%. On conventional plastic microplates, NSA is mainly driven by hydrophobic interactions, but on tissue culture microplates and low-adsorption microplates, in addition to hydrophobic interactions, ionic interactions play a role in the NSA. Therefore, to reduce the NSA to plastic containers, both hydrophobic and ionic interactions should be reduced using amphiphilic organic solvents or neutral and hydrophilic coatings. 2010 Elsevier Inc. All rights reserved.

Comparative study of excipients for propanolol hydrochloryde tablets prepared by means of diferent techniques Estudo comparativo de excipientes em diferentes técnicas de preparação de comprimidos de cloridrato de propranolol

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Cinara Maistro Mamprim

2001-11-01

Full Text Available Systemic arterial hipertension (SAH is one of the major factors in cardiovascular risk, since it contributes to the existence of more than 500 thousand cases of cerebral vascular accidents (CVA, 150 thousand deaths by cerebral hemorrhage and approximately a million myocardium infarctions (IAM. In Brazil, it is estimated that about 15% of the adult population can be considered hypertensive. Hypertension can be prevented by changes in lifestyle, although in most cases, the treatment with drugs becomes necessary. Propranolol hydrochloride is the drug chosen for the hypertensive elderly population who has had myocardium infarctation previously. The drug is commercially available as injections, solutions, capsules and tablets. Tablets can be prepared using three different techniques. The most used technique is the granulation by moisture. With the advance of new excipients available in the market for the Pharmaceutical Industry, a more simple and economical technique became possible, improving the physical and chemical stability of the product, reaching the goal of getting more efficient and safer medicine. The purpose of this study was to develop formulations of propranolol hydrochloride tablets through the variation of excipients and manufacture techniques. The propranolol hydrochloryde tablets were stored at 37o C and 50o C with 90% UR for 90 days, and analysed in pre-established time intervals the formulations were evaluated as for the physical and physical-chemical aspects.   A hipertensão arterial sistêmica (HAS é um dos mais importantes fatores de risco cardiovascular uma vez que contribui, mundialmente, com mais de 500 mil casos de acidentes cerebrovasculares (AVC, 150 mil mortes por hemorragia cerebral e aproximadamente um milhão de infartos de miocárdio (IAM. No Brasil estima-se que cerca de15% dos indivíduos adultos possam ser rotulados como hipertensos. A hipertensão pode ser prevenida com a mudança no estilo de vida, embora na

Efficacy of an amlodipine/olmesartan treatment algorithm in patients with or without type 2 diabetes and hypertension (a secondary analysis of the BP-CRUSH study).

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Nesbitt, S D; Shojaee, A; Maa, J-F; Weir, M R

2013-07-01

A prespecified subgroup analysis of an open-label, multicenter, single-arm, dose-titration study is presented. The efficacy and safety of 20-week treatment with an amlodipine (AML)/olmesartan medoxomil (OM)±hydrochlorothiazide (HCTZ) algorithm were assessed in patients with hypertension and type 2 diabetes mellitus (T2DM) who were uncontrolled by antihypertensive monotherapy. Eligible patients received AML/OM 5/20 mg for 4 weeks, followed by stepwise uptitration to AML/OM 5/40 mg, AML/OM 10/40 mg, AML/OM 10/40 mg+HCTZ 12.5 mg and AML/OM 10/40 mg+HCTZ 25 mg at 4-week intervals if blood pressure (BP) remained uncontrolled. The primary end point was the achievement of the seated cuff systolic BP (SeSBP) goal (hypertension and T2DM.

Effect of Propranolol on Thyroxine-Induced Changes in Body Temperature and Metabolism During Exercise in Dogs

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Kaciuba-Uscilko, Hanna; Brzezinska, Zofia; Greenleaf, John E.

1976-01-01

Effects of thyroxine on temperature and metabolism during exercise were studied in dogs after beta-adrenergic blockade. Dogs performed 60 min treadmill exercise of moderate intensity 5 and 72 h following thyroxine injected s. c. in a single dose of 0.1 mg/kg b.w. Thyroxine increased significantly the lipolytic response to exercise as well as blood lactate (LA) concentrations and rectal temperature (T(sub re)) during exercise as early as 5 h following the hormone administration. The changes became more pronounced 72 h after the injection. At rest T(sub re), blood FFA (free fatty acid) and LA levels in the thyroxine-treated dogs did not differ from the control values, and blood glucose was slightly, but significantly higher. Propranolol given intravenously in a dose of 0.25 mg/kg at 30 min of the exercise performed 72 h following thyroxine injection abolished the plasma FFA rise, and inhibited to a certain extent increases in T(sub re) and blood LA concentrations during the next 30 min of exercise.

Formulation, characterization and clinical evaluation of propranolol hydrochloride gel for transdermal treatment of superficial infantile hemangioma.

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Zhou, Wenhu; He, Shiying; Yang, Yijun; Jian, Dan; Chen, Xiang; Ding, Jinsong

2015-01-01

The objective of the present study is to formulate and characterize propranolol hydrochloride (PPL · HCl) gel, and to evaluate the efficacy of this formulation in transdermal treatment for superficial infantile hemangioma (IH). The transdermal PPL · HCl gel was prepared by a direct swelling method, which chose hydroxypropyl methylcellulose (HPMC) as the matrix and used terpenes plus alcohols as permeation enhancer. Permeation studies of PPL · HCl were carried out with modified Franz diffusion cells through piglet skin. Our results pointed to that among all studied permeation enhancers, farnesol plus isopropanol was the most effective combination (Q24, 6027.4 ± 563.1 μg/cm(2), ER, 6.8), which was significantly higher than that of control gel (p homemade PPL · HCl oral solution as a control. Clinical studies also confirmed the excellent therapeutic response and few side effects of the PPL · HCl gel. These results suggest that transdermal application of the PPL · HCl gel is an effective and safe formulation in treating superficial IH.

Propranolol, but not naloxone, enhances spinal reflex bladder activity and reduces pudendal inhibition in cats.

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Rogers, Marc J; Xiao, Zhiying; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

2015-01-01

This study examined the role of β-adrenergic and opioid receptors in spinal reflex bladder activity and in the inhibition induced by pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS). Spinal reflex bladder contractions were induced by intravesical infusion of 0.25% acetic acid in α-chloralose-anesthetized cats after an acute spinal cord transection (SCT) at the thoracic T9/T10 level. PNS or TNS at 5 Hz was applied to inhibit these spinal reflex contractions at 2 and 4 times the threshold intensity (T) for inducing anal or toe twitch, respectively. During a cystrometrogram (CMG), PNS at 2T and 4T significantly (P reflex bladder contractions. After administering propranolol (3 mg/kg iv, a β₁/β₂-adrenergic receptor antagonist), the effects of 2T and 4T PNS on bladder capacity were significantly (P reflex bladder contractions or PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly (P reflex bladder contractions. This study indicates an important role of β₁/β₂-adrenergic receptors in pudendal inhibition and spinal reflex bladder activity. Copyright © 2015 the American Physiological Society.

Remobilization Dynamics of Caffeine, Ciprofloxacin, and Propranolol following Evaporation-Induced Immobilization in Porous Media.

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Normile, Hayley J; Papelis, Charalambos; Kibbey, Tohren C G

2017-06-06

Changing weather conditions can cause cycles of wetting and drying in the unsaturated zone. When porewater evaporates, any nonvolatile solutes present in the pores will be driven to adsorb and ultimately precipitate on solid surfaces. When media are subsequently resaturated through rainfall infiltration, the remobilization of solutes likely depends on both the hydraulics of resaturation and the dynamics of dissolution processes. The focus of this work was to study the dynamics of remobilization of three different emerging contaminants (caffeine, ciprofloxacin, and propranolol) and two model compounds (fluorescein and sulforhodamine B) from porous media following evaporation of porewater. Remobilization column experiments were conducted to study this phenomenon and were evaluated using a finite difference model developed to simulate the adsorption-desorption dynamics during resaturation and elution. Results indicate that dissolution dynamics become increasingly important with increasing adsorption affinity for solid surfaces. Trends in observed elution behavior are not well-predicted from chemical properties, such as solubility. One of the most significant observations of the work is the presence of spikes in elution concentrations well above initial porewater concentration, resulting from the hydraulics of the resaturation process. The effect is most significant in highly mobile compounds that exhibit low adsorption affinity for solid surfaces.

Formulation, evaluation, and comparison of bilayered and multilayered mucoadhesive buccal devices of propranolol hydrochloride.

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Patel, Vishnu M; Prajapati, Bhupendra G; Patel, Madhabhai M

2007-03-16

The purpose of this research work was to establish mucoadhesive buccal devices of propranolol hydrochloride (PRH) in the forms of bilayered and multilayered tablets. The tablets were prepared using sodium carboxymethylcellulose (SCMC) and Carbopol-934 (CP) as bioadhesive polymers to impart mucoadhesion and ethyl cellulose (EC) to act as an impermeable backing layer. Buccal devices were evaluated by different parameters such as weight uniformity, content uniformity, thickness, hardness, surface pH, swelling index, ex vivo mucoadhesive strength, ex vivo mucoadhesion time, in vitro drug release, and in vitro drug permeation. As compared with bilayered tablets, multilayered tablets showed slow release rate of drug with improved ex vivo bioadhesive strength and enhanced ex vivo mucoadhesion time. The mechanism of drug release was found to be non-Fickian diffusion (value of n between 0.5 and 1.0) for both the buccal devices. The stability of drug in both the optimized buccal devices was tested for 6 hours in natural human saliva; both the buccal devices were found to be stable in natural human saliva. The present study concludes that mucoadhesive buccal devices of PRH can be a good way to bypass the extensive hepatic first-pass metabolism and to improve the bioavailability of PRH.

Bilateral blindness secondary to optic nerve ischemia from severe amlodipine overdose: a case report.

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Kao, Raymond; Landry, Yves; Chick, Genevieve; Leung, Andrew

2017-08-03

Calcium channel blockers are commonly prescribed medications; calcium channel blocker overdose is becoming increasingly prevalent. The typical presentation of a calcium channel blocker overdose is hypotension and decreased level of consciousness. We describe a case of a calcium channel blocker overdose that led to bilateral cortical blindness, a presentation that has not previously been reported. A 49-year-old white woman with known bilateral early optic atrophy presented to our hospital with hypotension and obtundation following a known ingestion of 150 mg of amlodipine. She was transferred to our intensive care unit where she was intubated, mechanically ventilated, and required maximal vasopressor support (norepinephrine 40 mcg/minute, epinephrine 40 mcg/minute, and vasopressin 2.4 units/hour) along with intravenously administered crystalloid boluses. Despite these measures, she continued to deteriorate with persistent hypotension and tachycardia, as well as anuria. Intralipid emulsion therapy was subsequently administered to which no initial response was observed. A chest X-ray revealed diffuse pulmonary edema; intravenous diuresis as well as continuous renal replacement therapy was initiated. Following the initiation of continuous renal replacement therapy, her oxygen requirements as well as urine output began to improve, and 3 days later she was liberated from mechanical ventilation. Following extubation, she complained of new onset visual impairment, specifically seeing only red-green colors, but no objects. An ophthalmologic examination revealed that this was due to bilateral optic atrophy from prolonged hypotension during the first 24 hours after the overdose. Persistent hypotension in the setting of a calcium channel blocker overdose can lead to worsening optic atrophy resulting in bilateral cortical blindness.

Pre-training administration of tianeptine, but not propranolol, protects hippocampus-dependent memory from being impaired by predator stress.

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Campbell, Adam M; Park, Collin R; Zoladz, Phillip R; Muñoz, Carmen; Fleshner, Monika; Diamond, David M

2008-02-01

Extensive research has shown that the antidepressant tianeptine blocks the adverse effects of chronic stress on hippocampal functioning. The current series of experiments extended this area of investigation by examining the influence of tianeptine on acute stress-induced impairments of spatial (hippocampus-dependent) memory. Tianeptine (10 mg/kg, ip) administered to adult male rats before, but not after, water maze training blocked the amnestic effects of predator stress (occurring between training and retrieval) on memory. The protective effects of tianeptine on memory occurred in rats which had extensive pre-stress training, as well as in rats which had only a single day of training. Tianeptine blocked stress effects on memory without altering the stress-induced increase in corticosterone levels. Propranolol, a beta-adrenergic receptor antagonist (5 and 10 mg/kg, ip), in contrast, did not block stress-induced amnesia. These findings indicate that treatment with tianeptine, unlike propanolol, provides an effective means with which to block the adverse effects of stress on cognitive functions of the hippocampus.

Different approaches in Partial Least Squares and Artificial Neural Network models applied for the analysis of a ternary mixture of Amlodipine, Valsartan and Hydrochlorothiazide

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Darwish, Hany W.; Hassan, Said A.; Salem, Maissa Y.; El-Zeany, Badr A.

2014-03-01

Different chemometric models were applied for the quantitative analysis of Amlodipine (AML), Valsartan (VAL) and Hydrochlorothiazide (HCT) in ternary mixture, namely, Partial Least Squares (PLS) as traditional chemometric model and Artificial Neural Networks (ANN) as advanced model. PLS and ANN were applied with and without variable selection procedure (Genetic Algorithm GA) and data compression procedure (Principal Component Analysis PCA). The chemometric methods applied are PLS-1, GA-PLS, ANN, GA-ANN and PCA-ANN. The methods were used for the quantitative analysis of the drugs in raw materials and pharmaceutical dosage form via handling the UV spectral data. A 3-factor 5-level experimental design was established resulting in 25 mixtures containing different ratios of the drugs. Fifteen mixtures were used as a calibration set and the other ten mixtures were used as validation set to validate the prediction ability of the suggested methods. The validity of the proposed methods was assessed using the standard addition technique.

Dgroup: DG01925 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available amlodipine besilate mixt ... D07569 ... Candesartan cilexetil and anmlodipine besylate tablets (JP17) ... D10286 ... Amlodipine - valsartan... -hydrochlorothiazide mixt ... D10287 ... Aliskiren hemifumarate - valsartan... mixt D10288 ... Olmesartan medoxomil - amlodipine besylate - hydrochlorothiazide mixt ... D10226 ... Sacubitril valsartan

MANAGEMENT OF HYPERTENSION- INSIGHTS INTO REAL-WORLD CLINICAL PRACTICE FOR DIFFERENTIAL USAGE OF CALCIUM CHANNEL BLOCKERS (CCBS

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Arup Dasbiswas

2017-05-01

Full Text Available BACKGROUND Calcium channel blockers (CCB like amlodipine, S (- amlodipine and cilnidipine, etc. have established place in the treatment of hypertension (HTN. As perceived by most of the physicians, they have comparative antihypertensive efficacy. However, available evidences suggest varied differences in incidence of pedal oedema. Aim- This survey was planned to understand real-world clinical practice pattern of Indian physicians for usage of various antihypertensive agents with emphasis on CCBs and whether differential incidence of oedema with CCBs is encountered in their clinical practice. MATERIALS AND METHODS Survey questionnaire consisting of 10 questions about preferred antihypertensive choice for different subsets of patients with HTN and efficacy and safety of S (- amlodipine was prepared and validated in small group of physicians. Overall, 494 general physicians and cardiologists practising in India were approached for seeking their opinion on usage of various CCBs. Statistical Analysis- Data were expressed in percentage. Design- Prospective, cross sectional, questionnaire-based survey. RESULTS Amongst various anti-hypertensive agents, majority of the physicians preferred CCB as their initial drug of choice for patients with HTN (53.8%, HTN with CKD (41.1%, elderly (55.3%, and young (30.8% patients. Though amlodipine was preferred by 75.7% physicians, pedal oedema was observed in >10% patients by 40.5% physicians. Most of the physicians rated S (- amlodipine to have better efficacy (79.4% and safety profile (88.3% with decreased incidence of pedal oedema than racemic Amlodipine. CONCLUSION Available evidences suggest comparative efficacy of S (- amlodipine and racemic amlodipine with varied differences in incidence of pedal oedema. However, our survey suggests better efficacy and safety of S (- amlodipine over racemic amlodipine as opined by most of the physicians of India. The survey findings need to be further evaluated in randomised

ACHIEVEMENT OF TARGET BLOOD PRESSURE LEVEL IN HYPERTENSIVE PATIENTS WITH AMLODIDINE: ORIGINAL DRUG VERSUS GENERIC

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S. Yu. Martsevich

2009-01-01

Full Text Available Aim. To evaluate antihypertensive effects of new generic amlodipine (Stamlo M in comparison with original amlodipine (Norvasc in monotherapy and in combination with angiotensin converting enzyme (ACE inhibitor and diuretic in patients with arterial hypertension (HT of 1-2 degree.Material and methods. 60 patients with HT of 1-2 degree were included in the open randomized parallel comparative study. Patients were split into 2 groups. Study duration was 10 weeks. Efficacy control, dose correction, addition of ACE inhibitor and diuretic was performed each 2 weeks.Results. The significant antihypertensive effect of monotherapy was observed in both groups already by the 2-4 weeks of therapy. Significant differences between amlodipines in influence on blood pressure (BP level and heart rate was not found. Monotherapy with generic amlodipine (10 mg OD provided target BP level more than in half of patients. Achievement of target BP levels was found in 89% and 96% of patients treated with generic and original amlodipine, respectively, when they were combined with lisinopril (10 mg OD and hydrochlorothiazide (12,5 mg OD.Conclusion. New generic amlodipine (Stamlo M is an effective and safe antihypertensive drug comparable with original amlodipine in clinical efficacy.

pH-independent release of propranolol hydrochloride from HPMC-based matrices using organic acids

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2008-08-01

Full Text Available Background and purpose of the study: Propranolol HCl, a widely used drug in the treatment of cardiac arrhythmias and hypertension, is a weak basic drug with pH-dependent solubility that may show release problems from sustained release dosage forms at higher pH of small intestine. This might decrease drug bioavailability and cause variable oral absorption. Preparation of a sustained release matrix system with a pH-independent release profile was the aim of the present study. Methods: Three types of organic acids namely tartaric, citric and fumaric acid in the concentrations of 5, 10 and 15 % were added to the matrices prepared by hydroxypropyl methylcellulose (HPMC and dicalcium phosphate. The drug release studies were carried out at pH 1.2 and pH 6.8 separately and mean dissolution time (MDT as well as similarity factor (¦2 were calculated for all formulations. Results and discussion: It was found that incorporation of 5 and 10 % tartaric acid in tablet formulations with 30 % HPMC resulted in a suitable pH-independent release profiles with significant higher ¦2 values (89.9 and 87.6 respectively compared to acid free tablet (58.03. The other two acids did not show the desirable effects. It seems that lower pKa of tartaric acid accompanied by its higher solubility were the main factors in the achievement of pH-independent release profiles.

Olmesartan/amlodipine/hydrochlorothiazide in participants with hypertension and diabetes, chronic kidney disease, or chronic cardiovascular disease: a subanalysis of the multicenter, randomized, double-blind, parallel-group TRINITY study

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Kereiakes Dean J

2012-10-01

Full Text Available Abstract Background Patients with hypertension and cardiovascular disease (CVD, diabetes, or chronic kidney disease (CKD usually require two or more antihypertensive agents to achieve blood pressure (BP goals. Methods The efficacy/safety of olmesartan (OM 40 mg, amlodipine besylate (AML 10 mg, and hydrochlorothiazide (HCTZ 25 mg versus the component dual-combinations (OM 40/AML 10 mg, OM 40/HCTZ 25 mg, and AML 10/HCTZ 25 mg was evaluated in participants with diabetes, CKD, or chronic CVD in the Triple Therapy with Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in Hypertensive Patients Study (TRINITY. The primary efficacy end point was least squares (LS mean reduction from baseline in seated diastolic BP (SeDBP at week 12. Secondary end points included LS mean reduction in SeSBP and proportion of participants achieving BP goal ( Results At week 12, OM 40/AML 10/HCTZ 25 mg resulted in significantly greater SeBP reductions in participants with diabetes (−37.9/22.0 mm Hg vs −28.0/17.6 mm Hg for OM 40/AML 10 mg, −26.4/14.7 mm Hg for OM 40/HCTZ 25 mg, and −27.6/14.8 mm Hg for AML 10/HCTZ 25 mg, CKD (−44.3/25.5 mm Hg vs −39.5/23.8 mm Hg for OM 40/AML 10 mg, −25.3/17.0 mm Hg for OM 40/HCTZ 25 mg, and −33.4/20.6 mm Hg for AML 10/HCTZ 25 mg, and chronic CVD (−37.8/20.6 mm Hg vs −31.7/18.2 mm Hg for OM 40/AML 10 mg, −30.9/17.1 mm Hg for OM 40/HCTZ 25 mg, and −27.5/16.1 mm Hg for AML 10/HCTZ 25 mg (P Conclusions In patients with diabetes, CKD, or chronic CVD, short-term (12 weeks and long-term treatment with OM 40/AML 10/HCTZ 25 mg was well tolerated, lowered BP more effectively, and enabled more participants to reach BP goal than the corresponding 2-component regimens. Trial Identification Number NCT00649389

Antagonism of the Sodium-Potassium ATPase Impairs Chikungunya Virus Infection

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Alison W. Ashbrook

2016-05-01

Full Text Available Chikungunya virus (CHIKV is a reemerging alphavirus that has caused epidemics of fever, arthralgia, and rash worldwide. There are currently no licensed vaccines or antiviral therapies available for the prevention or treatment of CHIKV disease. We conducted a high-throughput, chemical compound screen that identified digoxin, a cardiac glycoside that blocks the sodium-potassium ATPase, as a potent inhibitor of CHIKV infection. Treatment of human cells with digoxin or a related cardiac glycoside, ouabain, resulted in a dose-dependent decrease in infection by CHIKV. Inhibition by digoxin was cell type-specific, as digoxin treatment of either murine or mosquito cells did not diminish CHIKV infection. Digoxin displayed antiviral activity against other alphaviruses, including Ross River virus and Sindbis virus, as well as mammalian reovirus and vesicular stomatitis virus. The digoxin-mediated block to CHIKV and reovirus infection occurred at one or more postentry steps, as digoxin inhibition was not bypassed by fusion of CHIKV at the plasma membrane or infection with cell surface-penetrating reovirus entry intermediates. Selection of digoxin-resistant CHIKV variants identified multiple mutations in the nonstructural proteins required for replication complex formation and synthesis of viral RNA. These data suggest a role for the sodium-potassium ATPase in promoting postentry steps of CHIKV replication and provide rationale for modulation of this pathway as a broad-spectrum antiviral strategy.

Bidirectional Tachycardia after an Acute Intravenous Administration of Digitalis for a Suicidal Gesture

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Diletta Sabatini

2014-01-01

Full Text Available Acute digoxin intoxication is a life-threating condition associated with severe cardiotoxicity. Female gender, age, low lean body mass, hypertension, and renal insufficiency may worsen the prognosis. Arrhythmias caused by digitalis glycosides are characterized by an increased automaticity coupled with concomitant conduction delay. Bidirectional tachycardia is pathognomonic of digoxin intoxication, but it is rarely observed. An 83-year-old woman was admitted to the Emergency Department after self-administration of 5 mg of digoxin i.v. for suicidal purpose. Her digoxin serum concentration was 17.4 ng/mL. The patient developed a bidirectional tachycardia and the Poison Control Center of the hospital provided digoxin immune fab. Bidirectional tachycardia quickly reversed and the patient remained stable throughout the hospital stay. This case shows that a multiple disciplinary approach, involving cardiologists and toxicologists, is essential for the management of digoxin intoxication. The optimal treatment of this rare event depends on the clinical conditions and on the serum drug concentration of the patient. Digoxin immune fab represents a safe, effective, and specific method for rapidly reversing digitalis cardiotoxicity and should be started as soon as the diagnosis is defined.

Catalytic degradation of Amlodipine Besylate using ZnO, Cu doped ZnO, and Fe doped ZnO nanoparticles from an aqueous solution: Investigating the effect of different parameters on degradation efficiency

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Alizadeh, Elahe; Baseri, Hadi

2018-04-01

Some common nanoparticles, such as Zinc Oxide have been used as nanocatalysts in many processes, but they also have an important application in water purification processes. In this research, ZnO based nanoparticles were used for the degradation of Amlodipine Besylate (AMB) and the effect of some main parameters, e.g. initial concentration of AMB, nanocatalysts dose, pH of the solution, temperature of the solution, H2O2 dose, and the time of visible light irradiation, were investigated. The destruction amount was determined by UV-Vis spectroscopy. The synthesized nanoparticles were characterized by FE-SEM, XRD, FT-IR, BET, BJH, EDS, XRF and UV-Vis techniques. The maximum degradation of AMB was about 90% in 60 min of visible light irradiation with 100 μL of H2O2.

Management of congestive heart failure (CHF): a case report on ...

African Journals Online (AJOL)

A case report on the management of Congestive Heart Failure is presented with emphasis on the use of DIGOXIN. Keywords: Congestive heart failure, Failing heart syndrome, Digoxin, Digoxin Toxicity. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

Comparative study between univariate spectrophotometry and multivariate calibration as analytical tools for quantitation of Benazepril alone and in combination with Amlodipine.

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Farouk, M; Elaziz, Omar Abd; Tawakkol, Shereen M; Hemdan, A; Shehata, Mostafa A

2014-04-05

Four simple, accurate, reproducible, and selective methods have been developed and subsequently validated for the determination of Benazepril (BENZ) alone and in combination with Amlodipine (AML) in pharmaceutical dosage form. The first method is pH induced difference spectrophotometry, where BENZ can be measured in presence of AML as it showed maximum absorption at 237nm and 241nm in 0.1N HCl and 0.1N NaOH, respectively, while AML has no wavelength shift in both solvents. The second method is the new Extended Ratio Subtraction Method (EXRSM) coupled to Ratio Subtraction Method (RSM) for determination of both drugs in commercial dosage form. The third and fourth methods are multivariate calibration which include Principal Component Regression (PCR) and Partial Least Squares (PLSs). A detailed validation of the methods was performed following the ICH guidelines and the standard curves were found to be linear in the range of 2-30μg/mL for BENZ in difference and extended ratio subtraction spectrophotometric method, and 5-30 for AML in EXRSM method, with well accepted mean correlation coefficient for each analyte. The intra-day and inter-day precision and accuracy results were well within the acceptable limits. Copyright © 2013 Elsevier B.V. All rights reserved.

Bilayered buccal films as child-appropriate dosage form for systemic administration of propranolol.

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Abruzzo, Angela; Nicoletta, Fiore Pasquale; Dalena, Francesco; Cerchiara, Teresa; Luppi, Barbara; Bigucci, Federica

2017-10-05

Buccal mucosa has emerged as an attractive site for systemic administration of drug in paediatric patients. This route is simple and non-invasive, even if the saliva wash-out effect and the relative permeability of the mucosa can reduce drug absorption. Mucoadhesive polymers represent a common employed strategy to increase the contact time of the formulation at the application site and to improve drug absorption. Among the different mucoadhesive dosage forms, buccal films are particularly addressed for paediatric population since they are thin, adaptable to the mucosal surface and able to offer an exact and flexible dose. The objective of the present study was to develop bilayered buccal films for the release of propranolol hydrochloride. A primary polymeric layer was prepared by casting and drying of solutions of film-forming polymers, such as polyvinylpyrrolidone (PVP) or polyvinylalcohol (PVA), added with different weight ratios of gelatin (GEL) or chitosan (CH). In order to achieve unidirectional drug delivery towards buccal mucosa, a secondary ethylcellulose layer was applied onto the primary layer. Bilayered films were characterized for their physico-chemical (morphology, thickness, drug content and solid state) and functional (water uptake, mucoadhesion, drug release and permeation) properties. The inclusion of CH into PVP and PVA primary layer provided the best mucoadhesion ability. Films containing CH provided a lower drug release with respect to films containing GEL and increased the amount of permeated drug through buccal mucosa, thanks to its ability of interfering with the lipid organization. The secondary ethylcellulose layer did not interfere with drug permeation, but it could limit drug release in the buccal cavity. Copyright © 2017 Elsevier B.V. All rights reserved.

No upregulation of digitalis glycoside receptor (Na,K-ATPase) concentration in human heart left ventricle samples obtained at necropsy after long term digitalisation.

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Schmidt, T A; Holm-Nielsen, P; Kjeldsen, K

1991-08-01

The aim was to evaluate the hypothesis that digitalis glycosides increase the concentration of their specific receptor (Na,K-ATPase) in human myocardial tissue, thereby possibly reducing the inotropic effect of long term digitalis treatment. Intact samples of left ventricle were obtained at necropsy from patients who had been on long term treatment with digoxin and from patients not previously given digoxin. Digitalis glycoside receptors were quantified using vanadate facilitated 3H-ouabain binding before and after washing samples in buffer containing excess digoxin antibody fragments for 16 h at 30 degrees C. This washing procedure has previously been shown to reduce prior specific digoxin binding in human left ventricle by 95% and to allow subsequent vanadate facilitated complete quantification of 3H-ouabain binding sites. In this context it was performed to reduce occupancy of digitalis glycoside receptors by digoxin, caused by digitalisation before 3H-ouabain binding. 11 patients who had been on long term treatment with digoxin and eight who had not previously been given digoxin were studied. Left ventricle samples were obtained at necropsy at around 15 h after death. Standard 3H-ouabain binding was 39% less in samples from digitalised than from undigitalised subjects (p less than 0.001). Washing samples in buffer containing excess digoxin antibody fragments induced an increase in 3H-ouabain binding from 174(SEM 10) to 265(20) pmol.g-1 wet weight (n = 11, p less than 0.001) in samples from digitalised patients. After washing, the digitalis glycoside receptor concentration in left ventricle samples showed a tendency to a lower value (14%, p greater than 0.10) in patients exposed to digoxin compared to left ventricle samples from individuals unexposed to digitalis glycoside treatment. Calculating 3H-ouabain binding relative to dry ventricular muscle weight confirmed the results obtained using wet weight as reference. The results suggest that digoxin treatment in

Quantification of amlodipine and atorvastatin in human plasma by UPLC-MS/MS method and its application to a bioequivalence study.

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Rezk, Mamdouh R; Badr, Kamal A

2018-07-01

A robust, rapid and sensitive UPLC-MS/MS method has been developed, optimized and validated for the determination of amlodipine (AML) and atorvastatin (ATO) in human plasma using eplerenone as an internal standard (IS). Multiple-reaction monitoring in positive electrospray ionization mode was utilized in Xevo TQD LC-MS/MS. Double extraction was used in sample preparation using diethyl ether and ethyl acetate. The prepared samples were analyzed using an Acquity UPLC BEH C 18 (50 × 2.1 mm, 1.7 μm) column. Ammonium formate and acetonitrile, pumped isocraticaly at a flow rate of 0.25 mL/min, were used as a mobile phase. Method validation was done as per the US Food and Drug Administration guidelines. Linearity was achieved in the range of 0.1-10 ng/mL for AML and 0.05-50 ng/mL for ATO. Intra-day and inter-day accuracy and precision were calculated and found to be within the acceptable range. A short run time, of <1.5 min, permits analysis of a large number of plasma samples per batch. The developed and validated method was applied to estimate AML and ATO in a bioequivalence study in healthy human volunteers. Copyright © 2018 John Wiley & Sons, Ltd.

Evaluation of safety and efficacy of telmisartan-amlodipine combination in treating hypertension.

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Faruqui, Arif A

2008-09-01

The objective of this open, non-comparative, prospective postmarketing surveillance (PMS) study was to identify, validate and quantify the safety and efficacy associated with the use of fixed dose combination (FDC) of telmisartan 40 mg + amlodipine 5 mg (T40+A5) in hypertensive patients with or without concomitant diabetes. The data was collected from 72 centres from all over India during the period of June 2007 to February 2008. A total of 251 patients of either sex and those who were newly diagnosed stage II hypertension, or those who were uncontrolled on monotherapy with or without diabetes mellitus were included in this study. Patients were prescribed with T40+A5 combination orally. Systolic BP (SBP), diastolic BP (DBP) and heart rate (HR) were measured at the start and at the end of 2, 4 and 8 weeks of treatment. Primary efficacy end points were reduction in clinical SBP/ DBP from baseline to study end and number of patients achieving JNC VII goals. Tolerability was assessed by treatment-emergent adverse events. Out of 251 patients, 208 patients had completed the study (120 males and 88 females), 42 were lost to follow-up the study and one patient was withdrawn due to adverse effects. The mean age of the patients was 54.5 +/- 0.98 years for males and 52.94 +/- 1.078 years for females. Diabetes mellitus was seen in 64.9% of cases, dyslipidaemia in 2.88%, previous IHD in 7.2% cases and chronic obstructive pulmonary disease (COPD) in 0.50% of cases. Reduction in the mean SBP was found to be 12.08%, 18.92% and 22.90% at the end of 2, 4 and 8 weeks respectively (p hypertensive patients and 70% diabetic hypertensive patients achieved the JNC VII recommended goals. The overall incidence of ADRs was 7.69% with headache (1.92%) and vertigo (1.44%), as the commonest side-effect. According to physician's assessment of efficacy and tolerability 99.5% of total cases showed good to excellent response. In the treatment of stage II hypertensive patient the FDC of T40+A5

Radioimmunoassay of diagoxin with the aid of the solid phase - microtitre plating technique

International Nuclear Information System (INIS)

Scheidt, C.

1982-01-01

Preliminary results are reported here on the development of a digoxin-radioimmunoassay with an anti-digoxin antibody (goat) in a solid phase technique (mictrotitre plate). The advantages compared to conventional RIAs are: Cross reactions towards digoxin is minimal, both in vitro and in vivo. The calibraton range extends from 0.25 to 8 ng/ml. The radioactive load could be reduced significantly by use of smaller amounts of tracer (0.004 μCi/single determination) and by reduction of waste volume (solid), waste weight (solid) and liquid waste. The DIGOXIN RIA BIOTEST MTP is, in addition, the only digoxin radioimmunoassay where radioactive waste is produced in a sealed form. The test is a simple one and can be carried out without the need for complicated apparatus and techniques. (orig./MG) [de

Dissolution Behavior and Content Uniformity of An Improved Tablet Formulation Assayed by Spectrofluorometric and RIA Methods

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Morteza Rafiee-Tehrani

1990-06-01

Full Text Available Digoxin 0.25 mg tablets were manufactured by pregranulation of lactose-fcorn starch with 10% corn starch paste and deposition of solvent on pregranules to make digoxin granules. In the preparation of tablet A, granules of lactose-corn Starch was uniformly moistened with a 5% chloroform-ethanol solution (2:lv/vof digoxin by a simple blending. Tablet B was produced by spray granulation system on which the solvent was sprayed on the granules of lactose-corn starch by utilization of a laboratory size fluidized bed drier (Uniglatt . The content uniformity and dissolution of both tablets were determined by the spectrofluorometric and radio¬immunoassay (RIA method modified for the assay of tablet solutious. One available commercially brand of digoxin tablet (C was included in dissolution study for comparison. For the spectrofluorometric method the technique is based on the fluor-ometric measurenent of the dehydration product of the cardiotonic steroid resulting from its reaction with hydrogen peroxide in concentrated hydrochloric acid. For the RIA method, the filtrate was diluted to theoretical concentration of 2.5 ng/ml."nAliquots of this dilution were then assayed for digoxin content using a commercial digoxin125 I RIA kit. Results from both assay methods were extrapolated to the total tablet content and compared with the labeled amount of 20 individual tablets. All tablet assay results were within the USP standards for the content uniformity and"ndissolution of individual. The individual tablet deviations from labeled amount by RIA method were smaller when compared with the spectrofluorometric method.There was no significant difference between the release of digoxin from three products, and thus it is suggested that the Procedure B could be easily applied for manufacturing"nof digoxin tablets in industrial scales.It was also concluded that,the RIA method could be used for the digoxin tablet determination.

Influence of hydralazine on the pharmacokinetics of orally administered d-propranolol and lidocaine in conscious dogs.

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Heinzow, B G; Somogyi, A; McLean, A J

1987-03-01

A study was conducted on the influence of oral coadministration of hydralazine (H) on the pharmacokinetics of d-propranolol (P) and lidocaine (L) in 6 conscious dogs. They were given an oral solution containing P (2 mg/kg) and L (15 mg/kg) alone or together with 25 mg H. Plasma concentrations of P and L and the metabolites monoethylglycinexylidide (MEGX) and glycinexylidide (GX) were measured by specific HPLC methods. Concomitant administration of H caused a significant (p less than 0.05) increase in P peak concentrations (Cmax, 34 +/- 5: 73 +/- 10 ng/ml) and the area under plasma concentration time curve (AUC, 142 +/- 18: 254 +/- 56 ng/ml X hr) of P with significant (p less than 0.05) 24% reduction of the apparent oral clearance. The time to reach peak concentrations (Tmax) and the terminal half life (t1/2 beta) were not altered. In contrast to the pattern seen with P the disposition of L was not affected by H. The change in presystemic clearance of P by H cannot be explained by a general underlying mechanism such as an alteration in liver blood flow alone or portal-systemic shunting, since then the pharmacokinetics of L should parallel those of P. It is speculated that other mechanisms, most likely alteration of P metabolism, are primarily responsible for the observed interaction between P and H.

Biointerfacial phenomena of amlodipine buccomucosal tablets of HPMC matrix system containing polyacrylate polymer/β-cyclodextrin: Correlation of swelling and drug delivery performance.

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Panda, Brajabihari; Subhadarsini, Rajalaxmi; Mallick, Subrata

2016-01-01

This study focuses on the development of amlodipine bilayer buccal tablets of hydroxypropyl methylcellulose (HPMC) matrix system containing polyacrylate polymer (Carbopol(®))/β-cyclodextrin as the drug layer and ethylcellulose as the non-swellable backing layer, and their biointerfacial phenomena. Tablets were evaluated for swelling, erosion and mucoadhesion using buccal mucosal tissue ex vivo. In vitro drug release and ex vivo drug transport across mucosal tissue were also performed in phosphate buffer (pH 6.8). The relationship of swelling with buccoadhesion and buccal permeation of various bilayer tablet formulations containing HPMC alone and in combination with Carbopol or drug-β-cyclodextrin complex has been prepared. Overall buccoadhesion of the tablet with combination of HPMC and Carbopol was increased significantly compared with that of HPMC alone. Presence of cyclodextrin did not change bioadhesion force and swelling behavior significantly. Ex vivo permeation was increased with the increase of HPMC proportion in other formulations as observed in in vitro dissolution. Drug-cyclodextrin complexes in the tablet improved permeation due to its improved dissolution at the site of biointerface of tablet and buccomucosa. Correlations of ex vivo and in vitro data have been established to predict the buccomucosal permeation from the swelling index or drug release alone.

Semisolid matrix-filled hard gelatin capsules for rapid dissolution of amlodipine besilate: Development and assessment

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Vijay K Tyagi

2013-01-01

Full Text Available The objective of the study was to prepare semisolid capsules (SSCs of poorly water-soluble drug amlodipine besilate (AB using a combination of technologies involving solid dispersion (SD preparation and converting it into semisolid matrix filled in hard gelatin capsules (termed as SSCs with the aim of reducing lag time in drug release and to improve the dissolution rate. AB is used for its anti-arrhythmic, anti-anginal, and anti-hypertensive activity. These are the emergency activities which should be treated as fast as possible like in the case of angina attack (heart attack. Any lag time that is generated due to its poor dissolution can add on in this emergency and that can be avoided by developing a readily dissolvable formulation: SDs of AB. SD of AB was prepared by fusion method using varying combinations of Poloxamer 407 and Plasdone S630. A total of nine batches (SD1−SD9 were characterized for the in vitro dissolution behavior in phosphate buffer pH7.4. SD8 with 95.8% cumulative drug release in 60 min, t50% = 4.1 min and DE 30 Min = 84.2% were selected for the development of the semisolid matrix. Differential scanning calorimetry of SD8 revealed molecular dispersion of AB and Plasdone S630 in Poloxamer 407. SD8 was then formulated as SSCs using gelucire 44/14 and PEG 400 as semisolid components and PEG 6000 as a suspending agent to achieve the reduction in lag time for drug release. A total of seven SSC formulations were prepared and evaluated for drug release. Formulation of SSC4 showed maximum cumulative drug release (CDR of 98.9% within 20 min that was almost a threefold reduction in the time required to achieve similar CDR by SD of AB. Thus, SSCs present an excellent approach to enhance the dissolution as well as to reduce the lag time of dissolution for poor water-soluble drugs especially to those therapeutic classes that are intended for faster onset of action.

Human skeletal muscle digitalis glycoside receptors (Na,K-ATPase)--importance during digitalization.

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Schmidt, T A; Holm-Nielsen, P; Kjeldsen, K

1993-02-01

The aims of the present study were to evaluate in humans the putative importance of skeletal muscle digitalis glycoside receptors (Na,K-ATPase) in the volume of distribution of digoxin and to assess whether therapeutic digoxin exposure might cause digitalis receptor upregulation in skeletal muscle. Samples of the vastus lateralis were obtained postmortem from 11 long-term (9 months to 9 years) digitalized (125-187.5 micrograms daily) and eight undigitalized subjects. In intact samples from digitalized patients, vanadate-facilitated 3H-ouabain binding increased 15% (p 0.30) before and after washing in specific digoxin antibody fragments, respectively. Thus, the present study indicates a approximately 13% occupancy of skeletal muscle digitalis glycoside receptors with digoxin during digitalization. In light of the large skeletal muscle contribution to body mass, this indicates that the skeletal muscle Na,K-ATPase pool constitutes a major volume of distribution for digoxin during digitalization. The results gave no indication of skeletal muscle digitalis glycoside receptor upregulation in response to digoxin treatment. On the contrary, there was evidence of significantly lower (37%, p digitalized patients, which may be of importance for skeletal muscle incapacity in heart failure.

Amlodipine+benazepril is superior to hydrochlorothiazide+benazepril irrespective of baseline pulse pressure: subanalysis of the ACCOMPLISH trial.

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Skoglund, Per H; Svensson, Per; Asp, Joline; Dahlöf, Björn; Kjeldsen, Sverre E; Jamerson, Kenneth A; Weber, Michael A; Jia, Yan; Zappe, Dion H; Östergren, Jan

2015-02-01

Pulse pressure (PP) is an independent risk factor for cardiovascular (CV) disease and death but few studies have investigated the effect of antihypertensive treatments in relation to PP levels before treatment. The Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial showed that the combination of benazepril+amlodipine (B+A) is superior to benazepril+hydrochlorothiazide (B+H) in reducing CV events. We aimed to investigate whether the treatment effects in the ACCOMPLISH trial were dependent on baseline PP. High-risk hypertensive patients (n=11,499) were randomized to double-blinded treatment with single-pill combinations of either B+A or B+H and followed for 36 months. Patients were divided into tertiles according to their baseline PP and events (CV mortality/myocardial infarction or stroke) were compared. Hazard ratios (HRs) for the treatment effect (B+A over B+H) were calculated in a Cox regression model with age, coronary artery disease, and diabetes mellitus as covariates and were compared across the tertiles. The event rate was increased in the high tertile of PP compared with the low tertile (7.2% vs 4.4% P<.01). In the high and medium PP tertiles, HRs were 0.75 (95% confidence interval [CI], 0.60-0.95; P=.018) and 0.74 (CI, 0.56-0.98, P=.034), respectively, in favor of B+A. There was no significant difference between the treatments in the low tertile and no significant differences in treatment effect when comparing the HRs between tertiles of PP. B+A has superior CV protection over B+H in high-risk hypertensive patients independent of baseline PP although the absolute treatment effect is enhanced in the higher tertiles of PP where event rates are higher. © 2014 Wiley Periodicals, Inc.

Prophylactic digitalisation in pulmonary surgery.

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Ritchie, A J; Danton, M; Gibbons, J R

1992-01-01

Prophylactic digoxin is widely used in patients undergoing pulmonary surgery to prevent or control cardiac arrhythmias, but whether it is helpful or not is uncertain. An open, controlled randomised prospective clinical study of 111 patients was undertaken to compare the incidence of cardiac arrhythmias in the 58 patients who received preoperative digoxin and the 53 who did not. Cardiac arrhythmia occurred in half (29/58) of those given prophylactic digoxin and in 36% (19/53) of those who were not. The overall incidence of arrhythmia was 43%, with no statistically significant difference between the groups. Cardiac arrhythmias remain an important complication of pulmonary surgery and the incidence is not reduced by prophylactic digoxin.

Liposomal Encapsulation for Systemic Delivery of Propranolol via Transdermal Iontophoresis Improves Bone Microarchitecture in Ovariectomized Rats.

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Teong, Benjamin; Kuo, Shyh Ming; Tsai, Wei-Hsin; Ho, Mei-Ling; Chen, Chung-Hwan; Huang, Han Hsiang

2017-04-13

The stimulatory effects of liposomal propranolol (PRP) on proliferation and differentiation of human osteoblastic cells suggested that the prepared liposomes-encapsulated PRP exerts anabolic effects on bone in vivo. Iontophoresis provides merits such as sustained release of drugs and circumvention of first pass metabolism. This study further investigated and evaluated the anti-osteoporotic effects of liposomal PRP in ovariectomized (OVX) rats via iontophoresis. Rats subjected to OVX were administered with pure or liposomal PRP via iontophoresis or subcutaneous injection twice a week for 12 weeks. Changes in the microarchitecture at the proximal tibia and the fourth lumbar spine were assessed between pure or liposomal PRP treated and non-treated groups using micro-computed tomography. Administration of liposomal PRP at low dose (0.05 mg/kg) via iontophoresis over 2-fold elevated ratio between bone volume and total tissue volume (BV/TV) in proximal tibia to 9.0% whereas treatment with liposomal PRP at low and high (0.5 mg/kg) doses via subcutaneous injection resulted in smaller increases in BV/TV. Significant improvement of BV/TV and bone mineral density (BMD) was also found in the fourth lumbar spine when low-dose liposomal PRP was iontophoretically administered. Iontophoretic low-dose liposomal PRP also elevated trabecular numbers in tibia and trabecular thickness in spine. Enhancement of bone microarchitecture volumes has highlighted that liposomal formulation with transdermal iontophoresis is promising for PRP treatment at the lower dose and with longer duration than its clinical therapeutic range and duration to exhibit optimal effects against bone loss in vivo.

Enantioselective analysis of propranolol and 4-hydroxypropranolol by CE with application to biotransformation studies employing endophytic fungi.

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Borges, Keyller Bastos; Pupo, Mônica Tallarico; Bonato, Pierina Sueli

2009-11-01

A CE method is described for the enantioselective analysis of propranolol (Prop) and 4-hydroxypropranolol (4-OH-Prop) in liquid Czapek medium with application in the study of the enantioselective biotransformation of Prop by endophytic fungi. The electrophoretic conditions previously optimized were as follows: an uncoated fused-silica capillary, 4% w/v carboxymethyl-beta-CD in 25 mmol/L triethylamine/phosphoric acid (H(3)PO(4)) buffer at pH 9 as running electrolyte and 17 kV of voltage. UV detection was carried out at 208 nm. Liquid-liquid extraction using diethyl ether: ethyl acetate (1:1 v/v) as extractor solvent was employed for sample preparation. The calibration curves were linear over the concentration range of 0.25-10.0 microg/mL for each 4-OH-Prop enantiomer and 0.10-10.0 microg/mL for each Prop enantiomer (r>or=0.995). Within-day and between-day relative standard deviations and relative errors for precision and accuracy were lower than 15% for all the enantiomers. Finally, the validated method was used to evaluate Prop biotransformation in its mammalian metabolite 4-OH-Prop by some selected endophytic fungi. The screening of five strains of endophytic fungi was performed and all of them could biotransform Prop to some extent. Specifically, Glomerella cingulata (VA1) biotransformed 47.8% of (-)-(S)-Prop to (-)-(S)-4-OH-Prop with no formation of (+)-(R)-4-OH-Prop in 72 h of incubation.

Stability-Indicating RP-UPLC Method for the Simultaneous Determination of Potential Degradation and Process Impurities of Amlodipine Basylate and Benazepril HCl in Pharmaceutical Dosage Form

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Gajanan B. Kasawar

2014-10-01

Full Text Available A stability-indicating RP-UPLC method was developed for the quantification of related impurities of amlodipine basylate (AB and Benazepril hydrochloride (BH in solid pharmaceutical dosages form. The chromatographic separation employs a C18 column using a gradient elution, being solvent-A (1.36 g of potassium dihydrogen phosphate dissolved in one liter of water, adjusted to pH 3.0 with orthophosphoric acid and solvent-B (acetonitrile delivered at a flow rate of 0.3 mL min-1. The analytes were detected and quantified at 217 nm and 240 nm using photo diode-array detector. The method was validated demonstrating to be accurate and precise within the corresponding linear range of all components. The stability of the method was investigated under different stress conditions including hydrolytic, oxidative, exposed to photolytic, humidity and thermal as recommended by ICH guidelines. Relevant degradation was found under hydrolytic and oxidative conditions. Robustness against small modification in mobile phase pH, column oven temperature, flow rate and percentage of the mobile phase composition was ascertained. Lower limit of quantification and detection was also determined. The peak purity indices (purity angle < purity threshold obtained with the aid of PDA detector and satisfactory resolution between related impurities established the specificity of the determination.

Digitalisation and digitalis detoxication in the elderly.

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Caird, F I; Kennedy, R D

1977-02-01

Twenty-three elderly patients with normal renal function were studied during digitalisation for cardiac failure or atrial fibrillation. Mean serum digoxin concentrations were in the therapeutic range from the fourth day in seven patients given digoxin 0.25 mg daily, from the second day in seven patients given 0.5 mg followed by 0.25 mg daily, and from the first day in nine patients given 0.75 mg followed by 0.25 mg daily. Toxic effects were not encountered in any patient. Serial measurement of serum digoxin concentrations in six patients recovering from digitalis intoxication, all of whom had severe renal impairment, allowed calculation of serum half-times (62 to 189 hours), and elimination constants (9 to 27% per day). The apparent volumes of distribution of digoxin were around 300 litres, and the apparent body contents of the drugs around 20-25 mug/kg body weight. Differences between these figures and those determined by others for younger patients seem mainly to reflect the consequences of renal impairment. If reasonable assumptions are made for fractional absorption, volume of distribution, and elimination constant, serum digoxin levels during digitalisation can be predicted, and are found to agree well with those observed.

Detection of endogenous lithium in neuropsychiatric disorders--a model for biological transmutation.

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Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2002-01-01

The human hypothalamus produces an endogenous membrane Na(+)-K(+) ATPase inhibitor, digoxin. A digoxin induced model of cellular/neuronal quantal state and perception has been described by the authors. Biological transmutation has been described in microbial systems in the quantal state. The study focuses on the plasma levels of digoxin, RBC membrane Na(+)-K(+) ATPase activity, plasma levels of magnesium and lithium in neuropsychiatric and systemic disorders. Inhibition of RBC membrane Na(+)-K(+) ATPase activity was observed in most cases along with an increase in the levels of serum digoxin and lithium and a decrease in the level of serum Mg(++). The generation of endogenous lithium would obviously occur due to biological transmutation from magnesium. Digoxin and lithium together can produce added membrane Na(+)-K(+) ATPase inhibition. The role of membrane Na(+)-K(+) ATPase inhibition in the pathogenesis of neuropsychiatric and systemic disorders is discussed. The inhibition of membrane Na(+)-K(+) ATPase can contribute to an increase in intracellular calcium and a decrease in magnesium, which can result in a defective neurotransmitter transport mechanism, mitochondrial dysfunction and apoptosis, defective golgi body function and protein processing dysfunction, immune dysfunction and oncogenesis. Copyright 2002 John Wiley & Sons, Ltd.

Oxidation of atenolol, propranolol, carbamazepine and clofibric acid by a biological Fenton-like system mediated by the white-rot fungus Trametes versicolor.

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Marco-Urrea, Ernest; Radjenović, Jelena; Caminal, Gloria; Petrović, Mira; Vicent, Teresa; Barceló, Damià

2010-01-01

Biological advanced oxidation of the pharmaceuticals clofibric acid (CA), carbamazepine (CBZP), atenolol (ATL) and propranolol (PPL) is reported for the first time. Extracellular oxidizing species were produced through a quinone redox cycling mechanism catalyzed by an intracellular quinone reductase and any of the ligninolytic enzymes of Trametes versicolor after addition of the lignin-derived quinone 2,6-dimethoxy-1,4-benzoquinone (DBQ) and Fe(3+)-oxalate in the medium. Time-course experiments with approximately 10mg L(-1) of initial pharmaceutical concentration resulted in percent degradations above 80% after 6h of incubation. Oxidation of pharmaceuticals was only observed under DBQ redox cycling conditions. A similar degradation pattern was observed when CBZP was added at the environmentally relevant concentration of 50 microg L(-1). Depletion of DBQ due to the attack of oxidizing agents was assumed to be the main limiting factor of pharmaceutical degradation. The main degradation products, that resulted to be pharmaceutical hydroxylated derivatives, were structurally elucidated. The detected 4- and 7-hydroxycarbamazepine intermediates of CBZP degradation were not reported to date. Total disappearance of intermediates was observed in all the experiments at the end of the incubation period. (c) 2009 Elsevier Ltd. All rights reserved.

Decreasing adrenergic or sympathetic hyperactivity after severe traumatic brain injury using propranolol and clonidine (DASH After TBI Study: study protocol for a randomized controlled trial

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Patel Mayur B

2012-09-01

Full Text Available Abstract Background Severe TBI, defined as a Glasgow Coma Scale ≤ 8, increases intracranial pressure and activates the sympathetic nervous system. Sympathetic hyperactivity after TBI manifests as catecholamine excess, hypertension, abnormal heart rate variability, and agitation, and is associated with poor neuropsychological outcome. Propranolol and clonidine are centrally acting drugs that may decrease sympathetic outflow, brain edema, and agitation. However, there is no prospective randomized evidence available demonstrating the feasibility, outcome benefits, and safety for adrenergic blockade after TBI. Methods/Design The DASH after TBI study is an actively accruing, single-center, randomized, double-blinded, placebo-controlled, two-arm trial, where one group receives centrally acting sympatholytic drugs, propranolol (1 mg intravenously every 6 h for 7 days and clonidine (0.1 mg per tube every 12 h for 7 days, and the other group, double placebo, within 48 h of severe TBI. The study uses a weighted adaptive minimization randomization with categories of age and Marshall head CT classification. Feasibility will be assessed by ability to provide a neuroradiology read for randomization, by treatment contamination, and by treatment compliance. The primary endpoint is reduction in plasma norepinephrine level as measured on day 8. Secondary endpoints include comprehensive plasma and urine catecholamine levels, heart rate variability, arrhythmia occurrence, infections, agitation measures using the Richmond Agitation-Sedation Scale and Agitated Behavior scale, medication use (anti-hypertensive, sedative, analgesic, and antipsychotic, coma-free days, ventilator-free days, length of stay, and mortality. Neuropsychological outcomes will be measured at hospital discharge and at 3 and 12 months. The domains tested will include global executive function, memory, processing speed, visual-spatial, and behavior. Other assessments include

Combination With Low-dose Dextromethorphan Improves the Effect of Amlodipine Monotherapy in Clinical Hypertension

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Yin, Wei-Hsian; Chen, Pei; Yeh, Hung-I; Wang, Kuo-Yang; Hung, Yi-Jen; Tseng, Wei-Kung; Wen, Ming-Shien; Wu, Tao-Cheng; Wu, Chau-Chung; Cheng, Shu-Meng; Chen, Jaw-Wen

2016-01-01

Abstract The combination of low rather than high dose of dextromethorphan (DXM) with amlodipine (AM) could improve blood pressure (BP) reduction in hypertensive animals. The study aimed to evaluate the feasibility of different doses of DXM combined with standard AM treatment in clinical hypertension. This was a prospective, 14-week, dose-escalation, multicenter study. After 2-week run-in period with AM 5 mg/day, hypertensive patients who got the BP goal of 140/90 mmHg kept receiving AM monotherapy for another 12 weeks. The nonresponders, while kept on AM 5 mg/day, received additional DXM treatment for 3 sequential dose-titrated periods with initially 2.5 mg/day, followed by 7.5 mg/day, and finally 30 mg/day. Each period was for 4 weeks. The patients at BP goal after each treatment period were defined as the responders and kept on the same combination till the end of the study. The responder rate of each treatment period was recorded. The changes of BP and serum antioxidant/endothelial markers between week 14 and week 2 were evaluated. Of the 103 patients initially enrolled, 89 entered the treatment period. In the 78 patients completing the study, 31 (40%) at BP goal after 2-week AM run-in kept on AM monotherapy (DXM0). The addition of 2.5 (DXM2.5) and 7.5 mg/day (DXM7.5) of DXM enabled BP goal achievement in 22 (47%) nonresponders to AM monotherapy including 16 (29%) with DXM2.5 and 6 (18%) with DXM7.5. Only 4 patients (16%) reached BP goal with the combination of DXM 30 mg/day (DXM30). Overall, 73% of the 78 patients reached BP goal at the end of the 14-week study. Mean systolic BP was reduced by 7.9% ± 7.0% with DXM2.5 (P < 0.001) and by 5.4% ± 2.4% with DXM7.5 (P = 0.003) respectively at week 14 from that at week 2, which was unchanged in either DXM0 or DXM30 group. Besides, the effects of combination treatment were particularly significant in the patients with impaired endothelial function suggested by reduced serum NOx level

Severe symptomatic bradycardia after a dinner of spicy oleander soup

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Andrea Tampieri

2016-10-01

Full Text Available Cardiac glycosides similar to digoxin are produced by different plants in nature. Nerium oleander, commonly grown as an ornamental shrub, can be found worldwide in temperate countries. Intentional or accidental ingestion of any part of the plant can lead to clinically relevant intoxication. A 63-year-old woman came to the emergency department with acute dyspeptic symptoms after eating vegetable soup flavored with unfamiliar flowers she have collected herself. However, the electrocardiography (ECG showed abnormalities that raised suspicions for an overdose of digoxin-like cardiac glycosides. The patient was not on treatment with digoxin and a careful anamnesis revealed that she had eaten oleander leaves. Digoxin specific Fab antibody fragments were administered for marked bradycardia that was not responding to atropine administration, after counseling with the reference toxicology center. The patient was also treated with activated charcoal and magnesium sulphate, intravenous fluids and pantoprazole. Four days later she was discharged as asymptomatic, with normal sinus rhythm. Emergency physicians should be aware of this type of poisoning, especially in cases with typical ECG alterations in patients not treated with digoxin and medical history of plants ingestion. Cardio-active glycosides are present in different plants, often used inappropriately, with potential toxic effects and harmful drug interactions.

Tablet splitting and weight uniformity of half-tablets of 4 medications in pharmacy practice.

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Tahaineh, Linda M; Gharaibeh, Shadi F

2012-08-01

Tablet splitting is a common practice for multiple reasons including cost savings; however, it does not necessarily result in weight-uniform half-tablets. To determine weight uniformity of half-tablets resulting from splitting 4 products available in the Jordanian market and investigate the effect of tablet characteristics on weight uniformity of half-tablets. Ten random tablets each of warfarin 5 mg, digoxin 0.25 mg, phenobarbital 30 mg, and prednisolone 5 mg were weighed and split by 6 PharmD students using a knife. The resulting half-tablets were weighed and evaluated for weight uniformity. Other relevant physical characteristics of the 4 products were measured. The average tablet hardness of the sampled tablets ranged from 40.3 N to 68.9 N. Digoxin, phenobarbital, and prednisolone half-tablets failed the weight uniformity test; however, warfarin half-tablets passed. Digoxin, warfarin, and phenobarbital tablets had a score line and warfarin tablets had the deepest score line of 0.81 mm. Splitting warfarin tablets produces weight-uniform half-tablets that may possibly be attributed to the hardness and the presence of a deep score line. Digoxin, phenobarbital, and prednisolone tablet splitting produces highly weight variable half-tablets. This can be of clinical significance in the case of the narrow therapeutic index medication digoxin.

Separate and simultaneous binding effects of aspirin and amlodipine to human serum albumin based on fluorescence spectroscopic and molecular modeling characterizations: A mechanistic insight for determining usage drugs doses

International Nuclear Information System (INIS)

Abdollahpour, Nooshin; Asoodeh, Ahmad; Saberi, Mohammad Reza; Chamani, JamshidKhan

2011-01-01

The binding of aspirin (ASA) and amlodipine (AML) to human serum albumin (HSA) in aqueous solution was investigated by multiple techniques such as fluorescence quenching, resonance light scattering (RLS), three-dimensional fluorescence spectroscopy, FT-IR and zeta-potential measurements in an aqueous solution at pH=7.4. For the protein-ligand association reaction, fluorescence measurements can give important clues as to the binding of ligands to proteins, e.g., the binding mechanism, binding mode, binding constants, binding sites, etc. Fluorescence spectroscopy showed that ASA and AML could quench the HSA fluorescence spectra, and this quenching effect became more significant when both ASA and AML coexisted. The results pointed at the interaction between HSA and both drugs as ternary systems decreasing the binding constant and binding stability of the HSA-drug complex as a binary system. Therefore, by reducing the amount of drugs transported to their targets, the free drug concentration of the target would be reduced, lowering the efficacy of the drugs. It was demonstrated that there exists antagonistic behavior between the two drugs when it comes to binding of HSA. Furthermore, the fluorescence results also showed that the quenching mechanism of HSA-drug complexes as binary and ternary systems is a static procedure. The number of binding sites of HSA-ASA, (HSA-AML)ASA, HSA-AML and (HSA-ASA) AML were 1.31, 0.92, 1 and 0.93, respectively. Due to the existence of the antagonistic action between ASA and AML, the binding distance r was reduced. The results of synchronous fluorescence and three-dimensional fluorescence spectra showed that the antagonistic action between ASA and AML would alter the micro-environment around Trp and Tyr residues. Moreover, the simultaneous presence of ASA and AML during binding to HSA should be taken into account in multidrug therapy, as it induces the necessity of a monitoring therapy owing to the possible increase of uncontrolled toxic

Separate and simultaneous binding effects of aspirin and amlodipine to human serum albumin based on fluorescence spectroscopic and molecular modeling characterizations: A mechanistic insight for determining usage drugs doses

Energy Technology Data Exchange (ETDEWEB)

Abdollahpour, Nooshin [Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad (Iran, Islamic Republic of); Asoodeh, Ahmad [Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad (Iran, Islamic Republic of); Saberi, Mohammad Reza [Department of Medical Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Chamani, JamshidKhan, E-mail: chamani@ibb.ut.ac.ir [Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad (Iran, Islamic Republic of)

2011-09-15

The binding of aspirin (ASA) and amlodipine (AML) to human serum albumin (HSA) in aqueous solution was investigated by multiple techniques such as fluorescence quenching, resonance light scattering (RLS), three-dimensional fluorescence spectroscopy, FT-IR and zeta-potential measurements in an aqueous solution at pH=7.4. For the protein-ligand association reaction, fluorescence measurements can give important clues as to the binding of ligands to proteins, e.g., the binding mechanism, binding mode, binding constants, binding sites, etc. Fluorescence spectroscopy showed that ASA and AML could quench the HSA fluorescence spectra, and this quenching effect became more significant when both ASA and AML coexisted. The results pointed at the interaction between HSA and both drugs as ternary systems decreasing the binding constant and binding stability of the HSA-drug complex as a binary system. Therefore, by reducing the amount of drugs transported to their targets, the free drug concentration of the target would be reduced, lowering the efficacy of the drugs. It was demonstrated that there exists antagonistic behavior between the two drugs when it comes to binding of HSA. Furthermore, the fluorescence results also showed that the quenching mechanism of HSA-drug complexes as binary and ternary systems is a static procedure. The number of binding sites of HSA-ASA, (HSA-AML)ASA, HSA-AML and (HSA-ASA) AML were 1.31, 0.92, 1 and 0.93, respectively. Due to the existence of the antagonistic action between ASA and AML, the binding distance r was reduced. The results of synchronous fluorescence and three-dimensional fluorescence spectra showed that the antagonistic action between ASA and AML would alter the micro-environment around Trp and Tyr residues. Moreover, the simultaneous presence of ASA and AML during binding to HSA should be taken into account in multidrug therapy, as it induces the necessity of a monitoring therapy owing to the possible increase of uncontrolled toxic

Pharmacokinetics of digoxin cross-reacting substances in patients with acute yellow oleander (Thevetia peruviana) poisoning, including the effect of activated charcoal.

Science.gov (United States)

Roberts, Darren M; Southcott, Emma; Potter, Julia M; Roberts, Michael S; Eddleston, Michael; Buckley, Nick A

2008-01-01

Intentional self-poisonings with seeds from the yellow oleander tree (Thevetia peruviana) are widely reported. Activated charcoal has been suggested to benefit patients with yellow oleander poisoning by reducing absorption and/or facilitating elimination. Two recent randomised controlled trials (RCTs) assessing the efficacy of activated charcoal reported conflicting outcomes in terms of mortality. The effect of activated charcoal on the pharmacokinetics of Thevetia cardenolides has not been assessed. This information may be useful for determining whether further studies are necessary. Serial blood samples were obtained from patients enrolled in a RCT assessing the relative efficacy of single dose (SDAC) and multiple doses (MDAC) of activated charcoal compared to no activated charcoal (NoAC). The concentration of Thevetia cardenolides was estimated using a digoxin immunoassay. The effect of activated charcoal on cardenolide pharmacokinetics was compared between treatment groups using the AUC24, the 24h Mean Residence Time (MRT24), and regression lines obtained from serial concentration points adjusted for exposure. Erratic and prolonged absorption patterns were noted in each patient group. The apparent terminal half-life was highly variable, with a median time of 42.9h. There was a reduction in MRT24 and the apparent terminal half-life estimated from linear regression in patients administered activated charcoal compared to the control group (NoAC). This effect was approximately equal in patients administered MDAC or SDAC. Activated charcoal appears to favourably influence the pharmacokinetic profile of Thevetia cardenolides in patients with acute self-poisoning, which may have clinical benefits. Given the conflicting clinical outcomes noted in previous RCTs, this mechanistic data supports the need for further studies to determine whether a subgroup of patients (eg. those presenting soon after poisoning) will benefit from activated charcoal. PMID:17164695

Clinical course of acute atrial fibrillation treated with rapid digitalization.

Science.gov (United States)

Weiner, P; Bassan, M M; Jarchovsky, J; Iusim, S; Plavnick, L

1983-02-01

Forty-seven episodes of acute atrial fibrillation (AF) in 45 patients were examined prospectively to determine the course of the disorder treated with rapid digitalization. Patients received 1.5 mg of digoxin intravenously over 12 hours. In 40 of the 47 attacks, reversion to sinus rhythm occurred with no additional therapy at 1 to 96 hours (median 4 hours) after beginning digoxin. In thirty-two patients, conversion occurred within 8 hours; only one patient showed important ventricular slowing before conversion. Thus, if digoxin facilitates conversion, it does not do so by slowing the ventricular response. Of the 11 patients still in AF at 16 hours, conversion subsequently occurred in only four who were receiving digoxin alone. We conclude that the prognosis for quick reversion to sinus rhythm in patients with acute AF treated with rapid digitalization alone is excellent. If reversion does not occur by 16 to 24 hours, additional measures to restore sinus rhythm are indicated.

Comparison of benazepril plus amlodipine or hydrochlorothiazide in high-risk patients with hypertension and coronary artery disease.

Science.gov (United States)

Bakris, George; Briasoulis, Alexandros; Dahlof, Bjorn; Jamerson, Kenneth; Weber, Michael A; Kelly, Roxzana Y; Hester, Allen; Hua, Tsushung; Zappe, Dion; Pitt, Bertram

2013-07-15

Combination therapy with benazepril 40 mg and amlodipine 10 mg (B+A) has been shown to be more effective than benazepril 40 mg and hydrochlorothiazide (HCTZ) 25 mg (B+H) in reducing cardiovascular (CV) events in high-risk patients with stage 2 hypertension with similar blood pressure reductions. In the present post hoc analysis, we evaluated whether B+A is more effective than B+H for reducing CV events in patients with known coronary artery disease (CAD) at baseline in a subgroup analysis of the Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) study. The main trial randomized 11,506 patients. Of those, 5,744 received B+A and 5,762 received B+H. Of the 11,506 patients, 5,314 (46%) were classified as having CAD at baseline. The mean patient follow-up period was 35.7 months for the B+A group and 35.6 months for the B+H group. The primary end point was the interval to the first event of composite CV morbidity and mortality. At baseline, significant differences were present between the 5,314 with CAD and the 6,192 without CAD. The patients with CAD had a lower systolic blood pressure and heart rate, a lower incidence of diabetes, and greater incidence of dyslipidemia. However, no baseline differences were found between the randomized B+A and B+H groups. In the patients with CAD, an 18% reduction occurred in the hazard ratio for CV events (primary end point) with B+A versus B+H (p = 0.0016). In a prespecified secondary analysis of the composite end point, including only CV death, myocardial infarction, and stroke, the hazard ratio in the patients with CAD was reduced by 25% (p = 0.0033) in the B+A group compared with the B+H group. B+A was more effective than B+H at comparable blood pressure reductions for reducing CV events in patients, regardless of the presence of CAD. In conclusion, our findings suggest that the combination of B+A should be preferentially used for older patients with high

Lack of effect of spinal anesthesia on drug metabolism

International Nuclear Information System (INIS)

Whelan, E.; Wood, A.J.; Shay, S.; Wood, M.

1989-01-01

The effect of spinal anesthesia on drug disposition was determined in six dogs with chronically implanted vascular catheters using propranolol as a model compound. On the first study day, 40 mg of unlabeled propranolol and 200 microCi of [3H]propranolol were injected into the portal and femoral veins respectively. Arterial blood samples were taken for 4 hr for measurement of plasma concentrations of labeled and unlabeled propranolol by high-pressure liquid chromatography (HPLC) and of [3H]propranolol by liquid scintillation counting of the HPLC eluant corresponding to each propranolol peak. Twenty-four hr later, spinal anesthesia was induced with tetracaine (mean dose 20.7 +/- 0.6 mg) with low sacral to midthoracic levels and the propranolol infusions and sampling were then repeated. Spinal anesthesia had no significant effect on either the intrinsic clearance of propranolol (2.01 +/- 0.75 L/min before and 1.9 +/- 0.7 L/min during spinal anesthesia), or on mean hepatic plasma flow (2.01 +/- 0.5 L/min before and 1.93 +/- 0.5 L/min during spinal anesthesia). The systemic clearance and elimination half-life of propranolol were also unchanged by spinal anesthesia (0.9 +/- 0.23 L/min on the first day, 0.7 +/- 0.1 L/min during spinal anesthesia; and 101 +/- 21 min on the first day, 115 +/- 16 min during spinal anesthesia, respectively). The volume of distribution (Vd) of propranolol was similarly unaffected by spinal anesthesia