prescription pattern of anti-hypertensive drugs in a tertiary health

African Journals Online (AJOL)

Emmanuel Ameh

co.uk, Tel.: +234-8054693770. Abstract. Objective: This study examined the pattern of physicians' prescription of antihypertensive drugs and its possible effects on blood pressure control as well as physicians' compliance with recommended.

Cerebral blood flow autoregulation in hypertension and effects of antihypertensive drugs

DEFF Research Database (Denmark)

Barry, David; Lassen, N A

1984-01-01

If antihypertensive treatment, especially emergency blood pressure lowering, is always to be safe, more thought should be given to autoregulation of cerebral blood in the hypertensive patient. This topic is reviewed in the present article, in the hypertensive patient. This topic is reviewed...... in the present article, particular emphasis being placed on the resetting of the lower limit of autoregulation to higher pressure in hypertension and the effects of acute administration of anti-hypertensive drugs on CBF and CBF-autoregulation....

Current prescription status of antihypertensive drugs with special reference to the use of diuretics in Japan.

Science.gov (United States)

Ibaraki, Ai; Goto, Wataru; Iura, Rie; Tominaga, Mitsuhiro; Tsuchihashi, Takuya

2017-02-01

The guidelines for the management of hypertension recommend the inclusion of diuretics, especially when three or more antihypertensive drugs are used. The present study investigated the current prescription status of antihypertensive drugs with a particular focus on the use of diuretics in a local district in Japan. Prescriptions, including antihypertensive drugs, were collected from a dispensing pharmacy of the Yahata Pharmacist Association, located in Kitakyushu City, in October 2014. Of the 10 585 prescriptions, calcium channel blockers (CCBs) were prescribed in 73.5%, followed by angiotensin II receptor blockers (ARB, 62.7%), diuretics (16.5%) and β-blockers (13.6%). The average number of drugs used was 1.80. The rates of prescription of diuretics for patients with one, two, three and four drugs were 0.6%, 13.1%, 55.2% and 82.6%, respectively. Diuretics were more frequently prescribed in elderly patients, and the prescription rate of doctors in hospitals was significantly higher than that of general practitioners (19.1% vs. 15.7%, Pdiuretics were prescribed combination tablets of hydrochlorothiazide with ARB, whereas trichlormethiazide (34.9%) and indapamide (19.8%) were used in other patients. Based on these findings, the use of diuretics remains limited, even among patients taking multiple antihypertensive drugs.

Antihypertensive regimen and blood pressure control in patients ...

African Journals Online (AJOL)

Hypertension is a major public health problem worldwide. In Nigeria, records have shown an increasing prevalence with suboptimal evaluation of blood pressure (BP) control. Generally, antihypertensives have recorded significant successes in BP control over the years. This study was aimed at investigating ...

Assessment of postoperative changes in antihypertensive drug consumption in patients with primary aldosteronism using the defined daily dose

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Takanobu Utsumi

2014-10-01

Conclusion: The defined daily dose is a useful tool for assessing total changes in the consumption of antihypertensive drugs in patients with primary aldosteronism. Using the defined daily dose, clinicians could explain in detail to patients with primary aldosteronism the predicted postoperative change in antihypertensive drug consumption.

Effect of a Modest Weight Loss in Normalizing Blood Pressure in Obese Subjects on Antihypertensive Drugs

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Luisa Gilardini

2016-07-01

Full Text Available Objective: To assess the effect of a lifestyle intervention in lowering/normalizing blood pressure (BP levels in hypertensive (controlled or not obese patients. Methods: In this prospective observational study, 490 obese hypertensive patients, 389 controlled (BP Results: 18.9% of CH and 20.0% of UH were on ≥ 3 antihypertensive drugs. Weight change (average -4.9 ± 2.7% was independent of the antihypertensive drugs employed. Systolic BP (SBP decreased by 23 mm Hg and diastolic BP (DBP by 9 mm Hg, in patients with UH most of whom (89% normalized BP levels (in 49% after a weight loss Conclusion: Lifestyle interventions are useful for all obese hypertensive patients in most of whom a modest weight loss is sufficient to normalize BP levels avoiding the aggressive use of multiple antihypertensive drugs.

[The problems of antihypertensive balneotherapy].

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Vladimirskiĭ, E V; Fil'tsagina, T N

2013-01-01

This review is devoted to the challenging problems of balneotherapeutics, such as the mechanisms of antihypertensive balneotherapy and its optimization. The experience of the authors with the practical application of chloride - sodium, iodine - bromide, and hydrogen sulfide mineral baths is analysed in comparison with the literature data. The role, dosage regimen, and duration of balneotherapeutic treatment as well as the effectiveness of its combination with medicamental therapy are considered. The authors hope that the discussion of these issues will be conducive to the solution of problems currently facing modern antihypertensive balneotherapy.

Efficacy and tolerability of antihypertensive drugs in diabetic and nondiabetic patients

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Maria Aslam

2017-01-01

Full Text Available Objectives of the Study: The aim of the study was to compare the efficacy and tolerability of different classes of antihypertensive drugs in diabetic and nondiabetic patients (NDPs with essential hypertension. Material and Methods: The study was conducted in Mayo Hospital, Punjab Institute of Cardiology, and National Defence Hospital, Lahore, Pakistan, on 200 hypertensive patients with diabetes and 230 hypertensive patients without (Three hospitals diabetes. Both male and female patients of age between 30 and 80 years with systolic blood pressure (SBP above 130 mmHg and diastolic blood pressure (DBP above 80 mmHg were enrolled in the study. Angiotensin converting enzyme inhibitors (ACEI, beta-blocker (βB, calcium-channel blocker (CCB, diuretics (D, angiotensin receptor blocker (ARB as well as α-blocker classes of antihypertensive drugs were used. These drugs were used as monotherapy as well as combination therapy. The study was conducted for 4 months (July–October. After 4 months, patients were assessed for efficacy by monitoring blood pressure (BP and tolerability by assessing safety profile on renal function, liver function as well as lipid profile. Results: Significant control in mean BP by all drug groups was observed in “both groups that is patients with diabetes and without diabetes.” The efficacy and tolerability data revealed that in diabetic patients with hypertension, the highest decrease in SBP and DBP was observed using monotherapy with ACEI, two-drug combination therapy with ACEI plus diuretic, ARBs plus diuretic, ACEI plus CCBs, three-drug combination therapy with ACEI plus CCBs plus diuretic, and four drug combination therapy with ACEI plus CCBs plus diuretic plus βBs, ARB's plus CCBs plus diuretic plus βBs while in NDPs, monotherapy with diuretic, two-drug combination therapy with ACEI plus CCBs, ACEI plus βBs, three-drug combination therapy with βBs plus ACEI plus D was found more effective in controlling SBP as well

New drugs and perspectives for new anti-tuberculosis regimens

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S. Tiberi

2018-03-01

Full Text Available Tuberculosis (TB is the ninth cause of global death, more than any other infectious disease. With growing drug resistance the epidemic remains and will require significant attention and investment for the elimination of this disease to occur. With susceptible TB treatment not changing over the last four decades and the advent of drug resistance, new drugs and regimens are required.Recently, through greater collaboration and research networks some progress with significant advances has taken place, not withstanding the comparatively low amount of resources invested. Of late the availability of the new drugs bedaquiline, delamanid and repurposed drugs linezolid, clofazimine and carbapenems are being used more frequently in drug-resistant TB regimens.The WHO shorter multidrug-resistant tuberculosis regimen promises to reach more patients and treat them more quickly and more cheaply.With this new enthusiasm and hope we this review gives an update on the new drugs and perspectives for the treatment of drug-susceptible and drug-resistant tuberculosis. Keywords: Bedaquiline, Delamanid, Linezolid, MDR, XDR-TB, TB

Patterns of prescription antihypertensive drug utilization and adherence to treatment guidelines in the city of Novi Sad.

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Tomas, Ana; Tomić, Zdenko; Milijasević, Boris; Ban, Milica; Horvat, Olga; Vukmirović, Sasa; Sabo, Ana

2016-06-01

Hypertension is one of the leading causes of cardiovascular morbidity and mortality and more than a half of all health insurance expenditures for reimbursed medicines are allocated to antihypertensive drugs in Serbia. The aim of this study was to identify the antihypertensive drug utilization patterns among hypertensive outpatients in the city of Novi Sad, Serbia, determine the adherence to clinical guidelines and address the economic aspects of current prescribing practices. This retrospective observational study was conducted in Novi Sad over a period of six months. The data on the number of packages, size their, and retail price of antihypertensives issued on prescription in outpatients with the diagnosis of essential arterial hypertension was collected from all state-owned pharmacies in Novi Sad. Drug consumption was analyzed using the Anatomical Therapeutic Chemical (ATC)/ defined daily dose (DDD) methodology. Total consumption of antihypertensives issued on prescription over a 6-month period in the city of Novi sad, Serbia was 283.48 DDD per 1,000 inhabitans per day (DID). Angiotensin converting enzyme inhibitors (ACEi) were most commonly prescribed drugs, and were used 3 times more often than calcium channel blockers and 5 times more than beta-blockers. The consumption of diuretics and angiotensin receptor antagonists was low within all the groups of outpatients. Both national and international guidelines state superiority and effectiveness of diuretics in treatment of hypertension in the elderly, but their consumption was unreasonable low despite the fact that over 70% of all antihypertensive drugs in the city of Novi Sad were dispensed in people aged > 60. The use of more expensive ACEi was observed despite the guidelines deeming all the drugs of this class equally effective in treatment of hypertension. Large differences in utilization of different groups of antihypertensive agents were noted in this study. Underutilization of valuable, efficacious, and

Antihypertensives in dermatology Part I - Uses of antihypertensives in dermatology

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P. S. S. Ranugha

2018-01-01

Full Text Available Hypertension is a global health problem. Antihypertensives are the mainstay of treatment for hypertension. Some of them were accidentally found to be useful in alopecias and infantile hemangiomas and have now become standard treatment for these conditions as well. Antihypertensives are also being studied for other dermatological indications, where they have shown promising efficacy. This review focuses on the dermatological indications for antihypertensives, discussing the drugs that have been tried, as well as their efficacy, dosage, duration of therapy, and adverse effects.

Layered double hydroxides as supports for intercalation and sustained release of antihypertensive drugs

International Nuclear Information System (INIS)

Xia Shengjie; Ni Zheming; Xu Qian; Hu Baoxiang; Hu Jun

2008-01-01

Zn/Al layered double hydroxides (LDHs) were intercalated with the anionic antihypertensive drugs Enalpril, Lisinopril, Captopril and Ramipril by using coprecipitation or ion-exchange technique. TG-MS analyses suggested that the thermal stability of Ena - , Lis - (arranged with monolayer, resulted from X-ray diffraction (XRD) and Fourier transform infrared spectra (FT-IR) analysis was enhanced much more than Cap - and Ram - (arranged with bilayer). The release studies show that the release rate of all samples markedly decreased in both pH 4.25 and 7.45. However, the release time of Ena - , Lis - were much longer compared with Cap - , Ram - in both pH 4.25 and 7.45, it is possible that the intercalated guests, arranged with monolayer in the interlayer, show lesser repulsive force and strong affinity with the LDH layers. And the release data followed both the Higuchi-square-root law and the first-order equation well. Based on the analysis of batch release, intercalated structural models as well as the TG-DTA results, we conclude that for drug-LDH, stronger the affinity between intercalated anions and the layers is, better the thermal property and the stability to the acid attack of drug-LDH, and the intercalated anions are easier apt to monolayer arrangement within the interlayer, were presented. - Graphical abstract: A series of antihypertensive drugs including Enalpril, Lisinopril, Captopril and Ramipril were intercalated into Zn/Al-NO 3 -LDHs successfully by coprecipitation or ion-exchange technique. We focus on the structure, thermal property and low/controlled release property of as-synthesized drug-LDH composite intended for the possibility of applying these LDH-antihypertensive nanohybrids in drug delivery and controlled release systems

Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials

DEFF Research Database (Denmark)

Bangalore, Sripal; Kumar, Sunil; Kjeldsen, Sverre E

2011-01-01

The risk of cancer from antihypertensive drugs has been much debated, with a recent analysis showing increased risk with angiotensin-receptor blockers (ARBs). We assessed the association between antihypertensive drugs and cancer risk in a comprehensive analysis of data from randomised clinical tr...

Blood pressure reduction, persistence and costs in the evaluation of antihypertensive drug treatment – a review

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Hasford Joerg

2009-03-01

Full Text Available Abstract Background Blood pressure lowering drugs are usually evaluated in short term trials determining the absolute blood pressure reduction during trough and the duration of the antihypertensive effect after single or multiple dosing. A lack of persistence with treatment has however been shown to be linked to a worse cardiovascular prognosis. This review explores the blood pressure reduction and persistence with treatment of antihypertensive drugs and the cost consequences of poor persistence with pharmaceutical interventions in arterial hypertension. Methods We have searched the literature for data on blood pressure lowering effects of different antihypertensive drug classes and agents, on persistence with treatment, and on related costs. Persistence was measured as patients' medication possession rate. Results are presented in the form of a systematic review. Results Angiotensin II receptor blocker (ARBs have a competitive blood pressure lowering efficacy compared with ACE-inhibitors (ACEi and calcium channel blockers (CCBs, beta-blockers (BBs and diuretics. 8 studies describing the persistence with treatment were identified. Patients were more persistent on ARBs than on ACEi and CCBs, BBs and diuretics. Thus the product of blood pressure lowering and persistence was higher on ARBs than on any other drug class. Although the price per tablet of more recently developed drugs (ACEi, ARBs is higher than that of older ones (diuretics and BBs, the newer drugs result in a more favourable cost to effect ratio when direct drug costs and indirect costs are also considered. Conclusion To evaluate drugs for the treatment of hypertension several key variables including the blood pressure lowering effect, side effects, compliance/persistence with treatment, as well as drug costs and direct and indirect costs of medical care have to be considered. ARBs, while nominally more expensive when drug costs are considered only, provide substantial cost savings

[Variations in antihypertensive drug utilization among primary care areas in the autonomous region of Valencia (Spain)].

Science.gov (United States)

Sanfélix-Gimeno, Gabriel; Peiró, Salvador; Librero, Julián

2010-01-01

To estimate consumption of five subgroups of antihypertensive drugs by primary care areas and to analyze its variation. We performed an ecological, descriptive study of antihypertensive consumption in 239 primary care areas in the autonomous region of Valencia in 2005 followed by analysis of the variability observed. The 239 primary care areas were studied by descriptive analysis of dispensation [defined daily dose (DDD) per 1,000 inhabitants/day in pensioners (DDD/1000p/day) and in the active population (DDD/1000a/day)] and standardized consumption ratios. Small-area variation analysis was used to analyze the observed variability. Associations among dispensations of the distinct therapeutic subgroups were also analyzed. Overall antihypertensive use in the autonomous region of Valencia in 2005 was 235.6DDD/1000/day. This consumption was concentrated in pensioners (800DDD/1000p/day vs. 73DDD/1000a/day). Consumption of antihypertensive subgroups oscillated from 442DDD/1000p/day for drugs with action on the renin-angiotensin system to 32DDD/1000p/day for doxazosin. The active population showed similar patterns. Variation in consumption was moderate, with coefficients of variation from 0.20 to 0.40 (slightly greater for the active population). Associations among dispensations of the different therapeutic subgroups were strong. This study shows major variations in the overall consumption of antihypertensive drugs among primary care areas of the autonomous region of Valencia. These results suggest that variation may be associated with problems of underutilization in areas with lower consumption. Copyright © 2010 SESPAS. Published by Elsevier Espana. All rights reserved.

NSAID-antihypertensive drug interactions: Which outpatients are at risk for a rise in systolic blood pressure?

NARCIS (Netherlands)

Floor-Schreudering, Annemieke; De Smet, Peter Agm; Buurma, Henk; Kramers, Cornelis; Tromp, P. Chris; Belitser, Svetlana V.; Bouvy, Marcel L.

2015-01-01

Background: Management guidelines for drug-drug interactions between non-steroidal anti-inflammatory drugs (NSAIDs) and antihypertensives recommend blood pressure monitoring in hypertensive patients. We measured the short-term effect of initiating NSAIDs on systolic blood pressure (SBP) in users of

NSAID-antihypertensive drug interactions: which outpatients are at risk for a rise in systolic blood pressure?

NARCIS (Netherlands)

Floor-Schreudering, A.; Smet, P.A.G.M. de; Buurma, H.; Kramers, C.; Tromp, P.C.; Belitser, S.V.; Bouvy, M.L.

2015-01-01

BACKGROUND: Management guidelines for drug-drug interactions between non-steroidal anti-inflammatory drugs (NSAIDs) and antihypertensives recommend blood pressure monitoring in hypertensive patients. We measured the short-term effect of initiating NSAIDs on systolic blood pressure (SBP) in users of

Effectiveness of malic acid 1% in patients with xerostomia induced by antihypertensive drugs

Science.gov (United States)

Guardia, Javier; Aguilar-Salvatierra, Antonio; Cabrera-Ayala, Maribel; Maté-Sánchez de-Val, José E.; Calvo-Guirado, José L.

2013-01-01

Objectives: Assessing the clinical effectiveness of a topical sialogogue on spray (malic acid, 1%) in the treatment of xerostomia induced by antihypertensive drugs. Study Design: This research has been carried out through a randomized double-blind clinical trial. 45 patients suffering from hypertensive drugs-induced xerostomia were divided into 2 groups: the first group (25 patients) received a topical sialogogue on spray (malic acid, 1%) whereas the second group (20 patients) received a placebo. Both of them were administered on demand for 2 weeks. Dry Mouth Questionnaire (DMQ) was used in order to evaluate xerostomia levels before and after product/placebo application. Unstimulated and stimulated salivary flows rates, before and after application, were measured. All the statistical analyses were performed by using SPSS software v17.0. Different DMQ scores at the earliest and final stage of the trial were analysed by using Mann-Whitney U test, whereas Student’s T-test was used to analyse salivary flows. Critical p-value was established at p0.05) after placebo application. After two weeks of treatment with malic acid, unstimulated salivary flow increased from 0.17 to 0.242 mL/min whereas the stimulated one increased from 0.66 to 0.92 mL/min (p0.05). Conclusions: Malic acid 1% spray improved antihypertensive-induced xerostomia and stimulated the production of saliva. Key words:Xerostomia, hyposialia, malic acid, antihypertensive drugs. PMID:22926481

Immediate or deferred adjustment of drug regimens in multidose drug dispensing systems.

Science.gov (United States)

Mertens, Bram J; Kwint, Henk-Frans; van Marum, Rob J; Bouvy, Marcel L

2018-05-18

Multidose drug dispensing (MDD) is used to help patients take their medicines appropriately. Little is known about drug regimen changes within these MDD systems and how they are effectuated by the community pharmacist. Manual immediate adjustments of the MDD system could introduce dispensing errors. MDD guidelines therefore recommend to effectuate drug regimen changes at the start of a new MDD system. The aim of this study was to investigate the frequency, type, procedure followed, immediate necessity, and time taken to make MDD adjustments. This was a cross-sectional study in eight community pharmacies in the Netherlands. All adjustments to MDD systems were systematically documented for 3 weeks by the community pharmacist. Overall, 261 MDD adjustments involving 364 drug changes were documented for 250 patients: 127 (35%) drug changes involved the addition of a new drug, 124 (34%) a change in dosage, and 95 (26%) drug discontinuation. Of the MDD adjustments, 135 (52%) were effectuated immediately: 81 (31%) by adjusting the MDD system manually, 49 (19%) by temporarily dispensing the drug separately from the MDD system, and 5 (2%) by ordering a new MDD system. Pharmacists considered that 36 (27%) of the immediate MDD adjustments could have been deferred until the next MDD system was produced. Immediate adjustment took significantly longer than deferred adjustment (p < 0.001). This study shows that in patients using MDD systems, over half of the drug regimen changes are adjusted immediately. The necessity of these immediate changes should be critically evaluated. Copyright © 2018. Published by Elsevier Inc.

Compliance to antihypertensive drugs, salt restriction, exercise and control of systemic hypertension in hypertensive patients at abbottabad

International Nuclear Information System (INIS)

Ahmed, N.; Waqas, A.; Khaliq, M.A.

2008-01-01

Hypertension is one of the most important cardiovascular risk factor but its control is still a challenge for physicians all around the world. Control of blood pressure can reduce cardiovascular morbidity and mortality, so the compliance to antihypertensive drugs and life style modification play an important role for the control of hypertension. This analytical (cross-sectional) study was conducted to assess prevalence of control of hypertension among hypertensive patients and to assess the relationship of control of hypertension with factors like compliance to antihypertensive drugs, salt restriction and exercise among the hypertensive patients. This study was conducted at outpatient clinic of medicine at Shahina Jamil Hospital Abbottabad from April 2007 to September 2007. Eighty-nine patients seen in the outpatient clinic of medicine were enrolled in the study. All the patients with age 15 years or above, diagnosed as a case of systemic hypertension were included. Among eighty nine patients, 67 were female and 22 were male with mean age of 55.8+-13.4 years, mean systolic and diastolic blood pressure of 160+-28.6 and 97.8+-14.1 mm Hg respectively, and pulse rate of 85.9+-11.4 per minutes. Out of 89 patients, 25.8% were having controlled hypertension, 48.3% were compliant and 51.7% were not compliant to antihypertensive drugs, 55.1% were having salt restriction and 44.9% were having no salt restriction and 23.6% were used to do physical activity while 76.4% were not used to do physical activity. In group A consisted of patients with controlled hypertension, 95.7% patients were compliant to antihypertensive patients, 95.7% were having salt restriction and 43.5% were used to do physical activity. In group B consisted of patients with uncontrolled hypertension, only 31.8% were compliant to antihypertensive drugs, 40.9% were having salt restriction, 16.7% were used to do physical activity. Hypertension can be controlled if the hypertensive patients have good compliance

Using Clinical Data, Hypothesis Generation Tools and PubMed Trends to Discover the Association between Diabetic Retinopathy and Antihypertensive Drugs

Energy Technology Data Exchange (ETDEWEB)

Senter, Katherine G [ORNL; Sukumar, Sreenivas R [ORNL; Patton, Robert M [ORNL; Chaum, Ed [University of Tennessee, Knoxville (UTK)

2015-01-01

Diabetic retinopathy (DR) is a leading cause of blindness and common complication of diabetes. Many diabetic patients take antihypertensive drugs to prevent cardiovascular problems, but these drugs may have unintended consequences on eyesight. Six common classes of antihypertensive drug are angiotensin converting enzyme (ACE) inhibitors, alpha blockers, angiotensin receptor blockers (ARBs), -blockers, calcium channel blockers, and diuretics. Analysis of medical history data might indicate which of these drugs provide safe blood pressure control, and a literature review is often used to guide such analyses. Beyond manual reading of relevant publications, we sought to identify quantitative trends in literature from the biomedical database PubMed to compare with quantitative trends in the clinical data. By recording and analyzing PubMed search results, we found wide variation in the prevalence of each antihypertensive drug in DR literature. Drug classes developed more recently such as ACE inhibitors and ARBs were most prevalent. We also identified instances of change-over-time in publication patterns. We then compared these literature trends to a dataset of 500 diabetic patients from the UT Hamilton Eye Institute. Data for each patient included class of antihypertensive drug, presence and severity of DR. Graphical comparison revealed that older drug classes such as diuretics, calcium channel blockers, and -blockers were much more prevalent in the clinical data than in the DR and antihypertensive literature. Finally, quantitative analysis of the dataset revealed that patients taking -blockers were statistically more likely to have DR than patients taking other medications, controlling for presence of hypertension and year of diabetes onset. This finding was concerning given the prevalence of -blockers in the clinical data. We determined that clinical use of -blockers should be minimized in diabetic patients to prevent retinal damage.

Physician adherence to hypertension treatment guidelines and drug acquisition costs of antihypertensive drugs at the cardiac clinic: a pilot study

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Abdulameer SA

2012-01-01

Full Text Available Shaymaa Abdalwahed Abdulameer1, Mohanad Naji Sahib1, Noorizan Abd Aziz1,2, Yahaya Hassan1,2, Hadeer Akram Abdul AlRazzaq1, Omar Ismail31School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia; 2Faculty of Pharmacy, Universiti Teknologi MARA (UiTM, 42300 Puncak Alam, Selangor, Malaysia; 3Hospital Pulau Pinang, 10900, Penang, MalaysiaAbstract: Prescribing pattern surveys are one of the pharmacoepidemiological techniques that provide an unbiased picture of prescribing habits. Prescription surveys permit the identification of suboptimal prescribing patterns for further evaluation. The aims of this study were to determine the prescribing trend, adherence of the prescribers to the guideline, and the impact of drug expenditure on drug utilization at the cardiac clinic of Penang Hospital, Malaysia. This was a cross-sectional study. Demographic data of the patients, diagnoses and the drugs prescribed were recorded. The average drug acquisition costs (ADAC were calculated for each antihypertensive drug class on a daily and annual basis. Adherence to the guideline was calculated as a percentage of the total number of patients. A total of 313 individuals fulfilled the inclusion criteria. The average age of the study population was 59.30 ± 10.35 years. The mean number of drugs per prescription in the study was 2.09 ± 0.78. There were no significant differences in the demographic data. Antihypertensive drugs were used in monotherapy and polytherapy in 20.8% and 79.2% of the patients, respectively. Adherence to the guideline regarding prescription occurred in 85.30% of the patients. The lowest priced drug class was diuretics and the highest was angiotensin-receptor blockers. In conclusion, the total adherence to the guideline was good; the adherence percentage only slightly decreased with a co-existing comorbidity (such as diabetes mellitus. The use of thiazide diuretics was encouraged because they are well tolerated and

Effect of lipid-lowering and anti-hypertensive drugs on plasma homocysteine levels

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Jutta Dierkes

2007-03-01

Full Text Available Jutta Dierkes, Claus Luley, Sabine WestphalInstitute of Clinical Chemistry and Biochemistry, University Hospital Magdeburg, Germany Abstract: Elevated plasma concentrations of homocysteine, a sulfur-containing amino acid, are a risk factor for coronary, cerebral and peripheral artery disease. Next to other factors, drugs used for the prevention or treatment of cardiovascular disease may modulate plasma homocysteine levels. Thus, a drug induced homocysteine increase may counteract the desired cardioprotective effect. The aim is to summarize the current knowledge on the effect of two important classes of drugs, lipid-lowering drugs and anti-hypertensive drugs, on homocysteine metabolism. Among the lipid-lowering drugs, especially the fibric acid derivatives, which are used for treatment of hypertriglyceridemia and low HDL-cholesterol, are associated with an increase of homocysteine by 20%–50%. This increase can be reduced, but not totally avoided by the addition of folic acid, vitamin B12 and B6 to fibrates. HMG-CoA reductase inhibitors (statins do not influence homocysteine concentrations substantially. The effects of nicotinic acid and n3-fatty acids on the homocysteine concentrations are less clear, more studies are necessary to clarify their influence on homocysteine. Antihypertensive drugs have also been studied with respect to homocysteine metabolism. A homocysteine increase has been shown after treatment with hydrochlorothiazide, a lowering was observed after treatment with ß-blockers, but no effect with ACE-inhibitors. The clinical significance of the homocysteine elevation by fibrates and thiazides is not clear. However, individual patients use these drugs for long time, indicating that even moderate increases may be important.Keywords: homocysteine, fibrates, diuretics, cardiovascular disease

In Silico Investigations of Chemical Constituents of Clerodendrum colebrookianum in the Anti-Hypertensive Drug Targets: ROCK, ACE, and PDE5.

Science.gov (United States)

Arya, Hemant; Syed, Safiulla Basha; Singh, Sorokhaibam Sureshkumar; Ampasala, Dinakar R; Coumar, Mohane Selvaraj

2017-06-16

Understanding the molecular mode of action of natural product is a key step for developing drugs from them. In this regard, this study is aimed to understand the molecular-level interactions of chemical constituents of Clerodendrum colebrookianum Walp., with anti-hypertensive drug targets using computational approaches. The plant has ethno-medicinal importance for the treatment of hypertension and reported to show activity against anti-hypertensive drug targets-Rho-associated coiled-coil protein kinase (ROCK), angiotensin-converting enzyme, and phosphodiesterase 5 (PDE5). Docking studies showed that three chemical constituents (acteoside, martinoside, and osmanthuside β6) out of 21 reported from the plant to interact with the anti-hypertensive drug targets with good glide score. In addition, they formed H-bond interactions with the key residues Met156/Met157 of ROCK I/ROCK II and Gln817 of PDE5. Further, molecular dynamics (MD) simulation of protein-ligand complexes suggest that H-bond interactions between acteoside/osmanthuside β6 and Met156/Met157 (ROCK I/ROCK II), acteoside and Gln817 (PDE5) were stable. The present investigation suggests that the anti-hypertensive activity of the plant is due to the interaction of acteoside and osmanthuside β6 with ROCK and PDE5 drug targets. The identified molecular mode of binding of the plant constituents could help to design new drugs to treat hypertension.

Factors associated with false-positive self-reported adherence to antihypertensive drugs.

Science.gov (United States)

Tedla, Y G; Bautista, L E

2017-05-01

Self-reported medication adherence is known to overestimate true adherence. However, little is known about patient factors that may contribute to the upward bias in self-reported medication adherence. The objective of this study is to examine whether demographic, behavioral, medication and mood factors are associated with being a false-positive self-reported adherer (FPA) to antihypertensive drug treatment. We studied 175 patients (mean age: 50 years; 57% men) from primary-care clinics starting antihypertensive drug treatment. Self-reported adherence (SRA) was measured with the Medication Adherence Report Scale (MARS) and by the number of drug doses missed in the previous week/month, and compared with pill count adherence ratio (PCAR) as gold standard. Data on adherence, demographic, behavioral, medication and mood factors were collected at baseline and every 3 months up to 1 year. FPA was defined as being a non-adherer by PCAR and an adherer by self-report. Mixed effect logistic regression was used for the analysis. Twenty percent of participants were FPA. Anxiety increased (odds ratio (OR): 3.00; P=0.01), whereas smoking (OR: 0.40; P=0.03) and drug side effects (OR: 0.46, P=0.03) decreased the probability for FPA by MARS. Education below high-school completion increased the probability of being an FPA as measured by missing doses in the last month (OR: 1.66; P=0.04) and last week (OR: 1.88; P=0.02). The validity of SRA varies significantly according to drug side effects, behavioral factors and patient's mood. Careful consideration should be given to the use of self-reported measures of adherence among patients likely to be false-positive adherers.

Nanotechnology Based Approaches for Enhancing Oral Bioavailability of Poorly Water Soluble Antihypertensive Drugs

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Mayank Sharma

2016-01-01

Full Text Available Oral administration is the most convenient route among various routes of drug delivery as it offers high patient compliance. However, the poor aqueous solubility and poor enzymatic/metabolic stability of drugs are major limitations in successful oral drug delivery. There are several approaches to improve problems related to hydrophobic drugs. Among various approaches, nanotechnology based drug delivery system has potential to overcome the challenges associated with the oral route of administration. Novel drug delivery systems are available in many areas of medicine. The application of these systems in the treatment of hypertension continues to broaden. The present review focuses on various nanocarriers available in oral drug administration for improving solubility profile, dissolution, and consequently bioavailability of hydrophobic antihypertensive drugs.

Efficacy, safety and tolerability of sildenafil in Brazilian hypertensive patients on multiple antihypertensive drugs

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Denilson C. Albuquerque

2005-08-01

Full Text Available OBJECTIVE: To evaluate the efficacy, safety and tolerability of sildenafil among Brazilian patients with hypertension treated with combinations of anti-hypertensive drugs. MATERIALS AND METHODS: One hundred twenty hypertensive men aged 30 to 81 years old under treatment with 2 or more anti-hypertensive drugs and with erectile dysfunction (ED lasting for at least 6 months were enrolled at 7 research centers in Brazil. Patients were randomized to receive treatment with either sildenafil or placebo taken 1 hour before sexual intercourse (initial dose of 50 mg, adjusted to 25 mg or 100 mg according to efficacy and toxicity. During the following 8 weeks, patients were evaluated regarding vital signs, adverse events, therapeutic efficacy, satisfaction with treatment and use of concurrent medications. RESULTS: The primary evaluation of efficacy, which was based on responses to questions 3 and 4 of the International Index of Erectile Function, showed significant differences regarding treatment with sildenafil (p = 0.0002 and p < 0.0001, respectively. In the assessment of global efficacy, 87% of the patients treated with sildenafil reported improved erections, as compared with 37% of patients given placebos (p < 0.0001. The other secondary evaluations supported the results favoring sildenafil. The most frequent adverse events among patients treated with sildenafil were headaches (11.4%, vasodilation (11.4% and dyspepsia (6.5%. There were no significant changes in blood pressure measurements in both groups. CONCLUSION: Sildenafil is efficacious and safe for the treatment of hypertensive patients with ED who receive concurrent combinations of anti-hypertensive drugs.

Sex differences in antihypertensive drug use : determinants of the choice of medication for hypertension

NARCIS (Netherlands)

Klungel, O.H.; de Boer, A; Paes, A.H.P.; Seidell, J C; Bakker, A

1998-01-01

OBJECTIVE: To describe and explain sex differences in antihypertensive drug use. DESIGN AND METHODS: From 1987 to 1995, two cross-sectional population-based surveys of cardiovascular disease risk factors in The Netherlands were carried out among 56026 men and women aged 20-59 years. Polytomous

Drug-gene interaction between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and antihypertensive therapy

NARCIS (Netherlands)

Schelleman, Hedi; Klungel, Olaf H; van Duijn, Cornelia M; Witteman, Jacqueline C M; Hofman, Albert; de Boer, Anthonius; Stricker, Bruno H Ch

BACKGROUND: Despite the availability of a variety of effective drugs, inadequate control of blood pressure is common. There are some indications that the angiotensin-converting enzyme (ACE) gene modifies the response to antihypertensive drugs, but the results have been inconclusive. OBJECTIVE: To

Anti-hypertensive drugs and skin cancer risk: a review of the literature and meta-analysis.

Science.gov (United States)

Gandini, Sara; Palli, Domenico; Spadola, Giuseppe; Bendinelli, Benedetta; Cocorocchio, Emilia; Stanganelli, Ignazio; Miligi, Lucia; Masala, Giovanna; Caini, Saverio

2018-02-01

Several anti-hypertensive drugs have photosensitizing properties, however it remains unclear whether long-term users of these drugs are also at increased risk of skin malignancies. We conducted a literature review and meta-analysis on the association between use of anti-hypertensive drugs and the risk of cutaneous melanoma and non-melanoma skin cancer (NMSC). We searched PubMed, EMBASE, Google Scholar and the Cochrane Library, and included observational and experimental epidemiological studies published until February 28th, 2017. We calculated summary relative risk (SRR) and 95% confidence intervals (95% CI) through random effect models to estimate the risk of skin malignancies among users of the following classes of anti-hypertensive drugs: thiazide diuretics, angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), calcium channel blockers (CCB) and β-blockers. We conducted sub-group and sensitivity analysis to explore causes of between-studies heterogeneity, and assessed publication bias using a funnel-plot based approach. Nineteen independent studies were included in the meta-analysis. CCB users were at increased skin cancer risk (SRR 1.14, 95% CI 1.07-1.21), and β-blockers users were at increased risk of developing cutaneous melanoma (SRR 1.21, 95% CI 1.05-1.40), with acceptable between-studies heterogeneity (I 2  skin cancer risk. We found no evidence of publication bias affecting the results. Family doctors and clinicians should inform their patients about the increased risk of skin cancer associated with the use of CCB and β-blockers and instruct them to perform periodic skin self-examination. Further studies are warranted to elucidate the observed associations. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of Antihypertensive Drugs and Ischemic Stroke Severity - Is There a Role for Angiotensin-II?

NARCIS (Netherlands)

Hwong, Wen Yea; Bots, Michiel L.; Selvarajah, Sharmini; Aziz, Zariah Abdul; Sidek, Norsima Nazifah; Spiering, Wilko; Kappelle, L. Jaap; Vaartjes, Ilonca

2016-01-01

BACKGROUND: The increase in angiotensin II (Ang II) formation by selected antihypertensive drugs is said to exhibit neuroprotective properties, but this translation into improvement in clinical outcomes has been inconclusive. We undertook a study to investigate the relationship between types of

Utilization of Antihypertensive Drugs: A Comparison of Tertiary and ...

African Journals Online (AJOL)

To compare the quality of antihypertensive prescriptions at 2 different health care levels in a hypertensive Nigerian population.We carried out a retrospective comparative analysis of the quality and pattern of antihypertensive and low-dose aspirin prescription in a tertiary and two secondary health care institutions providing ...

Mobile phone text messaging improves antihypertensive drug adherence in the community.

Science.gov (United States)

Varleta, Paola; Acevedo, Mónica; Akel, Carlos; Salinas, Claudia; Navarrete, Carlos; García, Ana; Echegoyen, Carolina; Rodriguez, Daniel; Gramusset, Lissette; Leon, Sandra; Cofré, Pedro; Retamal, Raquel; Romero, Katerine

2017-12-01

Antihypertensive drug adherence (ADA) is a mainstay in blood pressure control. Education through mobile phone short message system (SMS) text messaging could improve ADA. The authors conducted a randomized study involving 314 patients with hypertension with Text messaging intervention improved ADA (risk ratio, 1.3; 95% confidence interval, 1.0-1.6 [Ptext messaging resulted in an increase in reporting ADA in this hypertensive Latino population. This approach could become an effective tool to overcome poor medication adherence in the community. ©2017 Wiley Periodicals, Inc.

How Ghanaian, African-Surinamese and Dutch patients perceive and manage antihypertensive drug treatment: a qualitative study

NARCIS (Netherlands)

Beune, Erik J. A. J.; Haafkens, Joke A.; Agyemang, Charles; Schuster, John S.; Willems, Dick L.

2008-01-01

OBJECTIVES: To explore and compare how Ghanaian, African-Surinamese (Surinamese), and White-Dutch patients perceive and manage antihypertensive drug treatment in Amsterdam, the Netherlands. METHODS: Qualitative study was conducted using detailed interviews with a purposive sample of 46 hypertensive

How Ghanaian, African-Surinamese and Dutch patients percieve and manage antihypertensive drug treatment: A qualitive study

NARCIS (Netherlands)

Beune, E.J.; Haafkens, J.; Agyeman, Ch.; Schuster, J.; Willems, D.

2008-01-01

OBJECTIVES: To explore and compare how Ghanaian, African-Surinamese (Surinamese), and White-Dutch patients perceive and manage antihypertensive drug treatment in Amsterdam, the Netherlands. METHODS: Qualitative study was conducted using detailed interviews with a purposive sample of 46 hypertensive

Evaluation Of Prescription Pattern And Medication Adherence Of Antihypertensive Drugs In Stage 1 Essential Hypertensive Patients At Rural Tertiary Care Teaching Hospital Of Central India.

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Chetan S. Urade

2016-09-01

Full Text Available Objectives- To study the prescription pattern of antihypertensive drugs and analyze the medication adherence to antihypertensive drugs at rural tertiary care teaching hospital.Materials and Methods- Prospective, observational, 12 weeks, questionnaire based study, conducted in rural tertiary care teaching hospital of central India. 214 antihypertensive prescriptions were analyzed by Morisky medication adherence scale. Statistical analysis was done by MS Excel and Graph pad prism 6.0.Results- 28.03% patients were not aware about the medicines taken, 29.90% patients were unacquainted about dose and route of administration whereas 32.71% patients were unfamiliar about frequency of administration of medicines. 53.27% patients were unaware about precautions to be taken while consuming medicines.  58.68% & 12.67% patients consumed amlodipine & atenolol respectively. In 16.43% patients, atenolol + amlodipine combination therapy was prescribed.  Amongst 214 patients 12, 58 & 144 showed high, medium & low adherence respectively.  No significant difference was found on gender basis at any level of adherence.Conclusion- In this study, physicians given preference to amlodipine than other antihypertensive drugs. However, thiazide is a first line drug in stage 1 hypertension, recommended by JNC VII guideline. This indicates that there is need of creating awareness about current management of hypertension to clinicians by organizing various workshops. We observed only 5.60% patients showed high adherence to antihypertensive therapy. Therefore educational strategies must be carried out for physicians focusing on causes for nonadherence to antihypertensive medications. Also raising patient trust in their physicians may improve patient motivation to prescribed medication. 

Effect of a Modest Weight Loss in Normalizing Blood Pressure in Obese Subjects on Antihypertensive Drugs.

Science.gov (United States)

Gilardini, Luisa; Redaelli, Gabriella; Croci, Marina; Conti, Antonio; Pasqualinotto, Lucia; Invitti, Cecilia

2016-01-01

To assess the effect of a lifestyle intervention in lowering/normalizing blood pressure (BP) levels in hypertensive (controlled or not) obese patients. In this prospective observational study, 490 obese hypertensive patients, 389 controlled (BP < 140/90 mm Hg; CH) and 101 uncontrolled (BP ≥ 140/90 mm Hg; UH) attended a 3-month lifestyle intervention. Before and after the intervention we assessed weight, waist circumference, fat mass, BP, metabolic and renal variables, and physical activity. A multivariate regression model was used to determine the predictors of BP changes. 18.9% of CH and 20.0% of UH were on ≥ 3 antihypertensive drugs. Weight change (average -4.9 ± 2.7%) was independent of the antihypertensive drugs employed. Systolic BP (SBP) decreased by 23 mm Hg and diastolic BP (DBP) by 9 mm Hg, in patients with UH most of whom (89%) normalized BP levels (in 49% after a weight loss < 5%). Age, gender, whole and central obesity, concomitance of type 2 diabetes, chronic renal disease, physical activity intensification, and pharmacological therapy did not affect BP lowering. In the regression analysis with SBP change as dependent variable, weight reduction (β = 0.523, p = 0.005) and group (UH vs. CH, β = -19.40, p = 0.0005) remained associated with SBP reduction. When DBP change was entered as dependent variable, baseline uric acid remained associated with DBP reduction (β = 0.824, p < 0.05). Lifestyle interventions are useful for all obese hypertensive patients in most of whom a modest weight loss is sufficient to normalize BP levels avoiding the aggressive use of multiple antihypertensive drugs. © 2016 The Author(s) Published by S. Karger GmbH, Freiburg.

Monitoring of Adverse Drug Reactions Associated with Antihypertensive Medicines at a University Teaching Hospital in New Delhi

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Fowad Khurshid

2012-09-01

Full Text Available Aim To monitor the adverse drug reactions (ADRs caused by antihypertensive medicines prescribed in a university teaching hospital.Methods:he present work was an open, non-comparative, observational study conducted on hypertensive patients attending the Medicine OPD of Majeedia Hospital, Jamia Hamdard, New Delhi, India by conducting patient interviews and recording the data on ADR monitoring form as recommended by Central Drugs Standard Control Organization (CDSCO, Government of India.Results:A total of 21 adverse drug reactions were observed in 192 hypertensive patients. Incidence of adverse drug reactions was found to be higher in patients more than 40 years in age, and females experienced more ADRs (n = 14, 7.29 % than males, 7 (3.64 %. Combination therapy was associated with more number of adverse drug reactions (66.7 % as against monotherapy (33.3 %. Calcium channel blockers were found to be the most frequently associated drugs with adverse drug reactions (n = 7, followed by diuretics (n = 5, and beta- blockers (n = 4. Among individual drugs, amlodipine was found to be the commonest drug associated with adverse drug reactions (n = 7, followed by torasemide (n = 3. Adverse drug reactions associated with central nervous system were found to be the most frequent (42.8 % followed by musculo-skeletal complaints (23.8 % and gastro-intestinal disorders (14.3 %. Conclusions:The present pharmacovigilance study represents the adverse drug reaction profile of the antihypertensive medicines prescribed in our university teaching hospital. The above findings would be useful for physicians in rational prescribing. Calcium channel blockers were found to be the most frequently associated drugs with adverse drug reactions.

Metabolic drug interactions - the impact of prescribed drug regimens on the medication safety.

NARCIS (Netherlands)

Fialova, D.; Vrbensky, K.; Topinkova, E.; Vlcek, J.; Soerbye, L.W.; Wagner, C.; Bernabei, R.

2005-01-01

Background and objective: Risk/benefit profile of prescribed drug regimens is unkown. Over 60% of commonly used medications interact on metabolic pathways (cytochrom P450 (CYP450), uridyl-glucuronyl tranferasis (UGT I, II) and P-glycoprotein (PGP) transport). Using an up-to-date knowledge on

Economic evaluation of 3-drug antiretroviral regimens for the prevention of mother-to-child HIV transmission in Thailand.

Science.gov (United States)

Werayingyong, Pitsaphun; Phanuphak, Nittaya; Chokephaibulkit, Kulkunya; Tantivess, Sripen; Kullert, Nareeluk; Tosanguan, Kakanang; Butchon, Rukmanee; Voramongkol, Nipunporn; Boonsuk, Sarawut; Pilasant, Songyot; Kulpeng, Wantanee; Teerawattananon, Yot

2015-03-01

The current program for prevention of mother-to-child HIV transmission in Thailand recommends a 2-drugs regimen for HIV-infected pregnant women with a CD4 count >200 cells/mm(3). This study assesses the value for money of 3 antiretroviral drugs compared with zidovudine (AZT)+single-dose nevirapine (sd-NVP). A decision tree was constructed to predict costs and outcomes using the governmental perspective for assessing cost-effectiveness of 3-drug regimens: (1) AZT, lamivudine, and efavirenz and (2) AZT, 3TC, and lopinavir/ritonavir, in comparison with the current protocol, AZT+sd-NVP. The 3-drug antiretroviral regimens yield lower costs and better health outcomes compared with AZT+sd-NVP. Although these 3-drug regimens offer higher program costs and health care costs for premature birth, they save money significantly in regard to pediatric HIV treatment and treatment costs for drug resistance in mothers. The 3-drug regimens are cost-saving interventions. The findings from this study were used to support a policy change in the national recommendation. © 2013 APJPH.

Antihypertensive medication postpones the onset of glaucoma

DEFF Research Database (Denmark)

Horwitz, Anna; Klemp, Marc; Jeppesen, Jørgen

2017-01-01

The aim was to investigate the impact of antihypertensive medication on the onset of glaucoma. Data from the complete Danish population between 40 and 95 years of age were used in the period from 1996 to 2012, covering >2.6 million individuals. The National Danish Registry of Medicinal Products...... Statistics was used to identify all claimed prescriptions for glaucoma medication and antihypertensive drugs. We first investigated basic correlations in the data and found that patients treated with antihypertensive medication, at any time during the study period, had a significantly higher overall relative...... risk (RR) of glaucoma, even when controlling for age and sex (with a RR of 1.31 and Pglaucoma. To investigate the causal effect of antihypertensive treatment on the onset of treatment for glaucoma, we used...

Interactions between the adducin 2 gene and antihypertensive drug therapies in determining blood pressure in people with hypertension

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Barkley Ruth

2007-09-01

Full Text Available Abstract Background As part of the NHLBI Family Blood Pressure Program, the Genetic Epidemiology Network of Arteriopathy (GENOA recruited 575 sibships (n = 1583 individuals from Rochester, MN who had at least two hypertensive siblings diagnosed before age 60. Linkage analysis identified a region on chromosome 2 that was investigated using 70 single nucleotide polymorphisms (SNPs typed in 7 positional candidate genes, including adducin 2 (ADD2. Method To investigate whether blood pressure (BP levels in these hypertensives (n = 1133 were influenced by gene-by-drug interactions, we used cross-validation statistical methods (i.e., estimating a model for predicting BP levels in one subgroup and testing it in a different subgroup. These methods greatly reduced the chance of false positive findings. Results Eight SNPs in ADD2 were significantly associated with systolic BP in untreated hypertensives (p-value Conclusion Our findings suggest that hypertension candidate gene variation may influence BP responses to specific antihypertensive drug therapies and measurement of genetic variation may assist in identifying subgroups of hypertensive patients who will benefit most from particular antihypertensive drug therapies.

CLINICAL AND PHARMACOLOGICAL APPROACHES TO OPTIMIZE THE DOSING REGIMEN OF ANTIBACTERIAL DRUGS IN PEDIATRICS

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Natal’ya B. Lazareva

2018-01-01

Full Text Available The rational use of antibacterial drugs in children implies an adequate choice of the necessary medication, its dosing regimen, and the duration of treatment in order to achieve maximum efficacy and minimize toxic effects. The knowledge of pharmacokinetic and pharmacodynamic profiles of the antibacterial drug plays a crucial role for optimizing the dosing regimen. The strategy of individual choice of the dosing regimen, taking into account the principles of pharmacokinetics and pharmacodynamics, can be especially effective in patients with the expectedly changed parameters of pharmacokinetics and in infections caused by bacteria strains with low sensitivity to antibiotics. The review presents a contemporary view of pharmacokinetic and pharmacodynamic profiles of antibacterial drugs most commonly used in pediatrics and their relationship to the clinical efficacy of the administered therapy.

Healthy lifestyle status, antihypertensive treatment and the risk of heart failure among Finnish men and women.

Science.gov (United States)

Wang, Yujie; Tuomilehto, Jaakko; Jousilahti, Pekka; Antikainen, Riitta; Mähönen, Markku; Katzmarzyk, Peter T; Hu, Gang

2013-11-01

To compare the association between antihypertensive drug treatment and heart failure (HF) risk with the association between engaging in a healthy lifestyle and HF risk. We prospectively investigated the single and joint associations of lifestyle factors and awareness, treatment, blood pressure control status with HF risk among 38 075 Finns, who were 25-74 years old and free of HF at baseline. During a median follow-up of 14.1 years, 638 men and 445 women developed HF. Engaging in a healthy lifestyle was associated with an decreased risk of HF. Compared with normotensive people, hypertensive patients with and without antihypertensive treatment had a higher risk of HF. Hypertensive patients who used antihypertensive drugs but did not engage in a healthy lifestyle had a significantly higher risk of HF [HR 1.75; 95% confidence interval (CI) 1.39-2.21] than hypertensive patients who did not use antihypertensive drugs but engaged in a healthy lifestyle. In addition, compared with hypertensive patients who used antihypertensive drugs and engaged in a healthy lifestyle, hypertensive patients who did not use antihypertensive drug or engage in a healthy lifestyle had a significantly higher risk of HF (HR 1.55; 95% CI 1.24-1.95). The present study demonstrates that HF risk was lower in hypertensive patients who engaged in a healthy lifestyle but higher in hypertensive people using antihypertensive drug treatment.

Continuing versus Stopping Prestroke Antihypertensive Therapy in Acute Intracerebral Hemorrhage

DEFF Research Database (Denmark)

Krishnan, Kailash; Scutt, Polly; Woodhouse, Lisa

2016-01-01

BACKGROUND AND PURPOSE: More than 50% of patients with acute intracerebral hemorrhage (ICH) are taking antihypertensive drugs before ictus. Although antihypertensive therapy should be given long term for secondary prevention, whether to continue or stop such treatment during the acute phase of ICH...... remains unclear, a question that was addressed in the Efficacy of Nitric Oxide in Stroke (ENOS) trial. METHODS: ENOS was an international multicenter, prospective, randomized, blinded endpoint trial. Among 629 patients with ICH and systolic blood pressure between 140 and 220 mmHg, 246 patients who were...... taking antihypertensive drugs were assigned to continue (n = 119) or to stop (n = 127) taking drugs temporarily for 7 days. The primary outcome was the modified Rankin Score at 90 days. Secondary outcomes included death, length of stay in hospital, discharge destination, activities of daily living, mood...

Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium.

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Joshua C Bis

Full Text Available Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD, including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals.Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases.Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four

Blocking epithelial-to-mesenchymal transition in glioblastoma with a sextet of repurposed drugs: the EIS regimen.

Science.gov (United States)

Kast, Richard E; Skuli, Nicolas; Karpel-Massler, Georg; Frosina, Guido; Ryken, Timothy; Halatsch, Marc-Eric

2017-09-22

This paper outlines a treatment protocol to run alongside of standard current treatment of glioblastoma- resection, temozolomide and radiation. The epithelial to mesenchymal transition (EMT) inhibiting sextet, EIS Regimen, uses the ancillary attributes of six older medicines to impede EMT during glioblastoma. EMT is an actively motile, therapy-resisting, low proliferation, transient state that is an integral feature of cancers' lethality generally and of glioblastoma specifically. It is believed to be during the EMT state that glioblastoma's centrifugal migration occurs. EMT is also a feature of untreated glioblastoma but is enhanced by chemotherapy, by radiation and by surgical trauma. EIS Regimen uses the antifungal drug itraconazole to block Hedgehog signaling, the antidiabetes drug metformin to block AMP kinase (AMPK), the analgesic drug naproxen to block Rac1, the anti-fibrosis drug pirfenidone to block transforming growth factor-beta (TGF-beta), the psychiatric drug quetiapine to block receptor activator NFkB ligand (RANKL) and the antibiotic rifampin to block Wnt- all by their previously established ancillary attributes. All these systems have been identified as triggers of EMT and worthy targets to inhibit. The EIS Regimen drugs have a good safety profile when used individually. They are not expected to have any new side effects when combined. Further studies of the EIS Regimen are needed.

What role does African ancestry play in how hypertensive patients respond to certain antihypertensive drug therapy?

Science.gov (United States)

Seedat, Yackoob K; Brewster, Lizzy M

2014-02-01

This article is a summary of the response of the four commonly used antihypertensive agents in African ancestry patients. They are thiazide like diuretics or indapamide, calcium channel blockers (CCB), angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers, and β-adrenergic blockers (ARB). Response was superior in African ancestry patients on a thiazide like diuretic or indapamide and CCB, while the response to β-adrenergic blockers and ACEI are attenuated. Available data are very limited but self-defined ancestry seems to be the best predictor of individual responses to antihypertensive drugs. Knowledge of the factors like economic and social consideration affect the lower rate of detection, treatment and control of hypertension in the African ancestry population of the USA. For regions in which health care resources are particularly scarce, investment in population-based primary prevention strategies may yield the largest benefit.

Design and Characterization of Buccoadhesive Liquisolid System of an Antihypertensive Drug

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Nilesh P. Kala

2015-01-01

Full Text Available Nifedipine is an antihypertensive BCS class II drug which has poor bioavailability when given orally. The objective of the present study was to increase the bioavailability of nifedipine, by formulation and evaluation of a buccoadhesive liquisolid system using magnesium aluminium silicate (Neusilin as both carrier and coating material and dissolution media were selected based on the solubility studies. A mixture of carboxymethylcellulose sodium and carbomer was used as mucoadhesive polymers. Buccoadhesive tablets were prepared by direct compression. FTIR studies confirmed no interaction between drug and excipients. XRD studies indicated change/reduction in crystallinity of drug. The powder characteristics were evaluated by different flow parameters to comply with pharmacopoeial specifications. The dissolution studies for liquisolid compacts and tablet formulations were carried out and it was found that nifedipine liquisolid tablets formulated from bioadhesive polymers containing 49% liquisolid system, 17.5% carbomer, and 7.5% carboxymethylcellulose sodium showed the best results in terms of dissolution properties. Prepared formulation batches were evaluated for swelling, bioadhesion strength, ex vivo residence time, and permeability studies. The optimized batch was showing promising features of the system. Formulating nifedipine as a buccoadhesive tablet allows reduction in dose and offers better control over the plasma levels.

COMPARISON OF DIFFERENT STRATEGIES OF ANTIHYPERTENSIVE THERAPY IN OUT-PATIENT CLINIC

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O. A. Plejko

2008-01-01

Full Text Available Aim. To compare different strategies of start antihypertensive therapy in out-patients.Material and methods. 120 out-patients with arterial hypertension (HT 1-2 stages were included in the study and randomized in 3 groups. Patients of group «A» received start treatment in compliance with age, clinical features and mechanisms of hypertension. Patients of group «B» received step-by-step start antihypertensive therapy based on doses titration and addition of the second (third drug if necessary. Patients of group «C» received fixed drug combination with addition of other antihypertensive medicines if necessary. Decrease of BP level and number of visits were used as criteria of therapy efficacy. Pharmacoeconomic analysis of antihypertensive therapy was done in all groups.Results. Strategy of HT start therapy in group «C» had advantages in speed of blood pressure normalization, number of necessary visits and in pharmacoeconomic efficacy in comparison with the strategies in group «A» and «B».Conclusion. HT start therapy with implementation of fixed low dose combination leads to the best result in comparison with other strategy based on step-by-step drug replacement (as well as their combining or monotherapy dose titration.

Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy.

Science.gov (United States)

Etiebet, Mary-Ann A; Shepherd, James; Nowak, Rebecca G; Charurat, Man; Chang, Harry; Ajayi, Samuel; Elegba, Olufunmilayo; Ndembi, Nicaise; Abimiku, Alashle; Carr, Jean K; Eyzaguirre, Lindsay M; Blattner, William A

2013-02-20

In resource-limited settings, HIV-1 drug resistance testing to guide antiretroviral therapy (ART) selection is unavailable. We retrospectively conducted genotypic analysis on archived samples from Nigerian patients who received targeted viral load testing to confirm treatment failure and report their drug resistance mutation patterns. Stored plasma from 349 adult patients on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens was assayed for HIV-1 RNA viral load, and samples with more than 1000 copies/ml were sequenced in the pol gene. Analysis for resistance mutations utilized the IAS-US 2011 Drug Resistance Mutation list. One hundred and seventy-five samples were genotyped; the majority of the subtypes were G (42.9%) and CRF02_AG (33.7%). Patients were on ART for a median of 27 months. 90% had the M184V/I mutation, 62% had at least one thymidine analog mutation, and 14% had the K65R mutation. 97% had an NNRTI resistance mutation and 47% had at least two etravirine-associated mutations. In multivariate analysis tenofovir-based regimens were less likely to have at least three nucleoside reverse transcriptase inhibitor (NRTI) mutations after adjusting for subtype, previous ART, CD4, and HIV viral load [P < 0.001, odds ratio (OR) 0.04]. 70% of patients on tenofovir-based regimens had at least two susceptible NRTIs to include in a second-line regimen compared with 40% on zidovudine-based regimens (P = 0.04, OR = 3.4). At recognition of treatment failure, patients on tenofovir-based first-line regimens had fewer NRTI drug-resistant mutations and more active NRTI drugs available for second-line regimens. These findings can inform strategies for ART regimen sequencing to optimize long-term HIV treatment outcomes in low-resource settings.

Analysis of drug-drug interactions among patients receiving antiretroviral regimens using data from a large open-source prescription database.

Science.gov (United States)

Patel, Nimish; Borg, Peter; Haubrich, Richard; McNicholl, Ian

2018-06-14

Results of a study of contraindicated concomitant medication use among recipients of preferred antiretroviral therapy (ART) regimens are reported. A retrospective study was conducted to evaluate concomitant medication use in a cohort of previously treatment-naive, human immunodeficiency virus (HIV)-infected U.S. patients prescribed preferred ART regimens during the period April 2014-March 2015. Data were obtained from a proprietary longitudinal prescription database; elements retrieved included age, sex, and prescription data. The outcome of interest was the frequency of drug-drug interactions (DDIs) associated with concomitant use of contraindicated medications. Data on 25,919 unique treatment-naive patients who used a preferred ART regimen were collected. Overall, there were 384 instances in which a contraindicated medication was dispensed for concurrent use with a recommended ART regimen. Rates of contraindicated concomitant medication use differed significantly by ART regimen; the highest rate (3.2%) was for darunavir plus ritonavir plus emtricitabine-tenofovir disoproxil fumarate (DRV plus RTV plus FTC/TDF), followed by elvitegravir-cobicistat-emtricitabine-tenofovir disoproxil fumarate (EVG/c/FTC/TDF)(2.8%). The highest frequencies of DDIs were associated with ART regimens that included a pharmacoenhancing agent: DRV plus RTV plus FTC/TDF (3.2%) and EVG/c/FTC/TDF (2.8%). In a large population of treatment-naive HIV-infected patients, ART regimens that contained a pharmacoenhancing agent were involved most frequently in contraindicated medication-related DDIs. All of the DDIs could have been avoided by using therapeutic alternatives within the same class not associated with a DDI. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Consumption of antihypertensive drugs dispensed under the pharmacy benefit management program

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Aline Pereira Rocha

2011-12-01

Full Text Available Pharmacy benefit management (PBM programs provide attractive discounts for drug purchase, a relevant measure to address costs, mainly of drugs for the treatment of chronic diseases. This study investigated whether PBM may be used as a tool to provide information about the use of antihypertensive medications when they are purchased. The profile of medicines taken to treat high blood pressure by large IT company employees and their dependents was evaluated from January to December 2009. The mean rate of drug boxes purchased to control hypertension was 9.4 ± 10.0 in 2009. Men purchased more drugs than women. The number of drugs purchased for the treatment of hypertension was lower than expected in all age groups except for individuals aged 54-58 and >59 years. Among men, the purchase of drugs to treat hypertension was higher than expected in the 24-28, 34-38 and 54-58 age groups. Among women, results matched expectations, except for the age group 34-38 years, in which purchase was lower than expected. Individuals in the age group 0-18 years were found to consume antihypertensive drugs. Although the PBM system may be used to identify drugs purchased by users, it does not ensure patient adherence to recommended drug treatment to control hypertension.O objetivo do Programa de Benefícios em Medicamentos (PBM é proporcionar descontos atraentes para aquisição de medicamentos, um fator relevante para o custo, principalmente no tratamento de doenças crônicas. O objetivo deste estudo é comprovar se o PBM pode ser utilizado como ferramenta para o fornecimento de informações sobre o consumo de medicamentos antihipertensivos através da aquisição dos mesmos. Foi realizada análise do perfil de medicamentos adquiridos para o tratamento de hipertensão arterial sistêmica por funcionários e seus dependentes de uma empresa de grande porte na área de tecnologia de informação (TI no período compreendido entre janeiro a dezembro de 2009. A taxa de

Analysis of combination drug therapy to develop regimens with shortened duration of treatment for tuberculosis.

Directory of Open Access Journals (Sweden)

George L Drusano

Full Text Available Tuberculosis remains a worldwide problem, particularly with the advent of multi-drug resistance. Shortening therapy duration for Mycobacterium tuberculosis is a major goal, requiring generation of optimal kill rate and resistance-suppression. Combination therapy is required to attain the goal of shorter therapy.Our objective was to identify a method for identifying optimal combination chemotherapy. We developed a mathematical model for attaining this end. This is accomplished by identifying drug effect interaction (synergy, additivity, antagonism for susceptible organisms and subpopulations resistant to each drug in the combination.We studied the combination of linezolid plus rifampin in our hollow fiber infection model. We generated a fully parametric drug effect interaction mathematical model. The results were subjected to Monte Carlo simulation to extend the findings to a population of patients by accounting for between-patient variability in drug pharmacokinetics.All monotherapy allowed emergence of resistance over the first two weeks of the experiment. In combination, the interaction was additive for each population (susceptible and resistant. For a 600 mg/600 mg daily regimen of linezolid plus rifampin, we demonstrated that >50% of simulated subjects had eradicated the susceptible population by day 27 with the remaining organisms resistant to one or the other drug. Only 4% of patients had complete organism eradication by experiment end.These data strongly suggest that in order to achieve the goal of shortening therapy, the original regimen may need to be changed at one month to a regimen of two completely new agents with resistance mechanisms independent of the initial regimen. This hypothesis which arose from the analysis is immediately testable in a clinical trial.

The impact of serum potassium-influencing antihypertensive drugs on the risk of out-of-hospital cardiac arrest : A case–control study

NARCIS (Netherlands)

Alharbi, Fawaz F; Souverein, Patrick C.; de Groot, Mark C.H.; Blom, Marieke T.; de Boer, Anthonius; Klungel, Olaf H.; Tan, Hanno L.

2017-01-01

Aims: Sudden cardiac arrest (SCA) is a complex multifactorial event and most commonly caused by ventricular tachycardia/ fibrillation (VT/ VF). Some antihypertensive drugs could induce hypokalaemia or hyperkalaemia, which may increase susceptibility to VT/VF and SCA. Objective: To assess the

In silico analysis of the anti-hypertensive drugs impact on myocardial oxygen balance.

Science.gov (United States)

Guala, A; Leone, D; Milan, A; Ridolfi, L

2017-06-01

Hypertension is a very common pathology, and its clinical treatment largely relies on different drugs. Some of these drugs exhibit specific protective functions in addition to those resulting from blood pressure reduction. In this work, we study the impact of commonly used anti-hypertensive drugs (RAAS, [Formula: see text] and calcium channel blockers) on myocardial oxygen supply-consumption balance, which plays a crucial role in type 2 myocardial infarction. To this aim, 42 wash-out hypertensive patients were selected, a number of measured data were used to set a validated multi-scale cardiovascular model to subject-specific conditions, and the administration of different drugs was suitably simulated. Our results ascribe the well-known major cardioprotective efficiency of [Formula: see text] blockers compared to other drugs to a positive change of myocardial oxygen balance due to the concomitant: (1) reduction in aortic systolic, diastolic and pulse pressures, (2) decrease in left ventricular work, diastolic cavity pressure and oxygen consumption, (3) increase in coronary flow and (4) ejection efficiency improvement. RAAS blockers share several positive outcomes with [Formula: see text] blockers, although to a reduced extent. In contrast, calcium channel blockers seem to induce some potentially negative effects on the myocardial oxygen balance.

The impact of serum potassium-influencing antihypertensive drugs on the risk of out-of-hospital cardiac arrest: A case-control study

NARCIS (Netherlands)

Alharbi, Fawaz F.; Souverein, Patrick C.; de Groot, Mark C. H.; Blom, Marieke T.; de Boer, Anthonius; Klungel, Olaf H.; Tan, Hanno L.

2017-01-01

AimsSudden cardiac arrest (SCA) is a complex multifactorial event and most commonly caused by ventricular tachycardia/ fibrillation (VT/ VF). Some antihypertensive drugs could induce hypokalaemia or hyperkalaemia, which may increase susceptibility to VT/VF and SCA. ObjectiveTo assess the association

[Predictive factors of clinically significant drug-drug interactions among regimens based on protease inhibitors, non-nucleoside reverse transcriptase inhibitors and raltegravir].

Science.gov (United States)

Cervero, Miguel; Torres, Rafael; Jusdado, Juan José; Pastor, Susana; Agud, Jose Luis

2016-04-15

To determine the prevalence and types of clinically significant drug-drug interactions (CSDI) in the drug regimens of HIV-infected patients receiving antiretroviral treatment. retrospective review of database. Centre: Hospital Universitario Severo Ochoa, Infectious Unit. one hundred and forty-two participants followed by one of the authors were selected from January 1985 to December 2014. from their outpatient medical records we reviewed information from the last available visit of the participants, in relation to HIV infection, comorbidities, demographics and the drugs that they were receiving; both antiretroviral drugs and drugs not related to HIV infection. We defined CSDI from the information sheet and/or database on antiretroviral drug interactions of the University of Liverpool (http://www.hiv-druginteractions.org) and we developed a diagnostic tool to predict the possibility of CSDI. By multivariate logistic regression analysis and by estimating the diagnostic performance curve obtained, we identified a quick tool to predict the existence of drug interactions. Of 142 patients, 39 (29.11%) had some type of CSDI and in 11.2% 2 or more interactions were detected. In only one patient the combination of drugs was contraindicated (this patient was receiving darunavir/r and quetiapine). In multivariate analyses, predictors of CSDI were regimen type (PI or NNRTI) and the use of 3 or more non-antiretroviral drugs (AUC 0.886, 95% CI 0.828 to 0.944; P=.0001). The risk was 18.55 times in those receiving NNRTI and 27,95 times in those receiving IP compared to those taking raltegravir. Drug interactions, including those defined as clinically significant, are common in HIV-infected patients treated with antiretroviral drugs, and the risk is greater in IP-based regimens. Raltegravir-based prescribing, especially in patients who receive at least 3 non-HIV drugs could avoid interactions. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Effectiveness of a triple-drug regimen for global elimination of lymphatic filariasis: A modelling study

NARCIS (Netherlands)

M.A. Irvine (Michael A.); W.A. Stolk (Wilma); Smith, M.E. (Morgan E); S.V. Subramanian; B.K. Singh (Brajendra K.); G.J. Weil (Gary); E. Michael (Edwin); T.D. Hollingsworth (T. Déirdre)

2017-01-01

textabstractBackground: Lymphatic filariasis is targeted for elimination as a public health problem by 2020. The principal approach used by current programmes is annual mass drug administration with two pairs of drugs with a good safety profile. However, one dose of a triple-drug regimen

NAGD regimen for the coma of drug-related overdose.

Science.gov (United States)

Rappolt, R T; Gay, G R; Decker, W J; Inaba, D S

1980-07-01

A specific arousal therapy with NAGD (Naloxone, Activated Charcoal, Glucagon, Doxapram) is outlined for victims of drug overdose in comatose and semi-comatose states. Several direct benefits accrue if early awakening or lightening of such patients is safely accomplished. There are: 1) elimination of need for prolonged intubation or tracheostomy; 2) patient's ability to tell which drug(s) were taken; 3) excessively frantic and vigorous supportive treatment is obviated; and 4) the overall hospital stay is shortened. The NAGD regimen has been found to effectively, safely, and predictably reverse coma. Therapy consists of: naloxone 0.8 mg to 1.6 mg intravenously; large-bore orogastric tube instillation of 100 gm to 120 gm activated charcoal slurry; glucagon 1 mg to 2 mg intravenously; and, in selected cases, doxapram 1 mg/kg to 2 mg/kg intravenously.

[Implementation of ontology-based clinical decision support system for management of interactions between antihypertensive drugs and diet].

Science.gov (United States)

Park, Jeong Eun; Kim, Hwa Sun; Chang, Min Jung; Hong, Hae Sook

2014-06-01

The influence of dietary composition on blood pressure is an important subject in healthcare. Interactions between antihypertensive drugs and diet (IBADD) is the most important factor in the management of hypertension. It is therefore essential to support healthcare providers' decision making role in active and continuous interaction control in hypertension management. The aim of this study was to implement an ontology-based clinical decision support system (CDSS) for IBADD management (IBADDM). We considered the concepts of antihypertensive drugs and foods, and focused on the interchangeability between the database and the CDSS when providing tailored information. An ontology-based CDSS for IBADDM was implemented in eight phases: (1) determining the domain and scope of ontology, (2) reviewing existing ontology, (3) extracting and defining the concepts, (4) assigning relationships between concepts, (5) creating a conceptual map with CmapTools, (6) selecting upper ontology, (7) formally representing the ontology with Protégé (ver.4.3), (8) implementing an ontology-based CDSS as a JAVA prototype application. We extracted 5,926 concepts, 15 properties, and formally represented them using Protégé. An ontology-based CDSS for IBADDM was implemented and the evaluation score was 4.60 out of 5. We endeavored to map functions of a CDSS and implement an ontology-based CDSS for IBADDM.

More hypotension in patients taking antihypertensives preoperatively during shoulder surgery in the beach chair position.

Science.gov (United States)

Trentman, Terrence L; Fassett, Sharon L; Thomas, Justin K; Noble, Brie N; Renfree, Kevin J; Hattrup, Steven J

2011-11-01

Hypotension is common in patients undergoing surgery in the sitting position under general anesthesia, and the risk may be exacerbated by the use of antihypertensive drugs taken preoperatively. The purpose of this study was to compare hypotensive episodes in patients taking antihypertensive medications with normotensive patients during shoulder surgery in the beach chair position. Medical records of all patients undergoing shoulder arthroscopy during a 44-month period were reviewed retrospectively. The primary endpoint was the number of moderate hypotensive episodes (systolic blood pressure ≤ 85 mmHg) during the intraoperative period. Secondary endpoints included the frequency of vasopressor administration, total dose of vasopressors, and fluid administered. Values are expressed as mean (standard deviation). Of 384 patients who underwent shoulder surgery, 185 patients were taking no antihypertensive medication, and 199 were on at least one antihypertensive drug. The antihypertensive medication group had more intraoperative hypotensive episodes [1.7 (2.2) vs 1.2 (1.8); P = 0.01] and vasopressor administrations. Total dose of vasopressors and volume of fluids administered were similar between groups. The timing of the administration of angiotensin-converting enzyme inhibitors and of angiotensin receptor antagonists (≤ 10 hr vs > 10 hr before surgery) had no impact on intraoperative hypotension. Preoperative use of antihypertensive medication was associated with an increased incidence of intraoperative hypotension. Compared with normotensive patients, patients taking antihypertensive drugs preoperatively are expected to require vasopressors more often to maintain normal blood pressure.

Advancing tuberculosis drug regimen development through innovative quantitative translational pharmacology methods and approaches.

Science.gov (United States)

Hanna, Debra; Romero, Klaus; Schito, Marco

2017-03-01

The development of novel tuberculosis (TB) multi-drug regimens that are more efficacious and of shorter duration requires a robust drug development pipeline. Advances in quantitative modeling and simulation can be used to maximize the utility of patient-level data from prior and contemporary clinical trials, thus optimizing study design for anti-TB regimens. This perspective article highlights the work of seven project teams developing first-in-class translational and quantitative methodologies that aim to inform drug development decision-making, dose selection, trial design, and safety assessments, in order to achieve shorter and safer therapies for patients in need. These tools offer the opportunity to evaluate multiple hypotheses and provide a means to identify, quantify, and understand relevant sources of variability, to optimize translation and clinical trial design. When incorporated into the broader regulatory sciences framework, these efforts have the potential to transform the development paradigm for TB combination development, as well as other areas of global health. Copyright © 2016. Published by Elsevier Ltd.

Evolution of drug resistance in HIV infected patients remaining on a virologically failing cART regimen

DEFF Research Database (Denmark)

Cozzi-Lepri, A; Phillips, AN; Ruiz, L

2007-01-01

OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points...... (t0 and t1) when viral load was > 400 copies/ml. METHODS: Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1...... January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0). RESULTS: At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance...

Outcomes after chemotherapy with WHO category II regimen in a population with high prevalence of drug resistant tuberculosis.

Directory of Open Access Journals (Sweden)

Francine Matthys

Full Text Available Standard short course chemotherapy is recommended by the World Health Organization to control tuberculosis worldwide. However, in settings with high drug resistance, first line standard regimens are linked with high treatment failure. We evaluated treatment outcomes after standardized chemotherapy with the WHO recommended category II retreatment regimen in a prison with a high prevalence of drug resistant tuberculosis (TB. A cohort of 233 culture positive TB patients was followed through smear microscopy, culture, drug susceptibility testing and DNA fingerprinting at baseline, after 3 months and at the end of treatment. Overall 172 patients (74% became culture negative, while 43 (18% remained positive at the end of treatment. Among those 43 cases, 58% of failures were determined to be due to treatment with an inadequate drug regimen and 42% to either an initial mixed infection or re-infection while under treatment. Overall, drug resistance amplification during treatment occurred in 3.4% of the patient cohort. This study demonstrates that treatment failure is linked to initial drug resistance, that amplification of drug resistance occurs, and that mixed infection and re-infection during standard treatment contribute to treatment failure in confined settings with high prevalence of drug resistance.

Evolution of drug resistance in HIV infected patients remaining on a virologically failing cART regimen

DEFF Research Database (Denmark)

Cozzi-Lepri, A; Phillips, AN; Ruiz, L

2007-01-01

OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points...

Are SGLT2 inhibitors reasonable antihypertensive drugs and renoprotective?

Science.gov (United States)

Lovshin, J A; Gilbert, R E

2015-06-01

By eliminating glucose in the urine, the sodium-glucose-linked cotransporter-2 (SGLT2) inhibitors act as osmotic diuretics to lower blood pressure in addition to reducing plasma glucose and assisting with weight loss. While not approved as antihypertensive agents, the ability of this new class of antihyperglycemic agents to lower blood pressure is not insubstantial, and while not used primarily for this indication, they may assist diabetic individuals in attaining currently recommended blood pressure targets. In addition to lowering systemic pressure, preclinical and exploratory human studies suggest that SGLT2 inhibitors may also lower intraglomerular pressure, potentially reducing the rate of GFR decline in patients with diabetic nephropathy. However, given the lack of clinically meaningful endpoint data, the use of SGLT2 inhibitors, primarily, as either antihypertensive or renoprotective agents would, at present, be premature. Fortunately, further insight will be garnered from large, randomized controlled trials that will assess the effects of various SGLT2 inhibitors on cardiovascular and renal outcomes.

Effectiveness of multi-drug regimen chemotherapy treatment in osteosarcoma patients: a network meta-analysis of randomized controlled trials.

Science.gov (United States)

Wang, Xiaojie; Zheng, Hong; Shou, Tao; Tang, Chunming; Miao, Kun; Wang, Ping

2017-03-29

Osteosarcoma is the most common malignant bone tumour. Due to the high metastasis rate and drug resistance of this disease, multi-drug regimens are necessary to control tumour cells at various stages of the cell cycle, eliminate local or distant micrometastases, and reduce the emergence of drug-resistant cells. Many adjuvant chemotherapy protocols have shown different efficacies and controversial results. Therefore, we classified the types of drugs used for adjuvant chemotherapy and evaluated the differences between single- and multi-drug chemotherapy regimens using network meta-analysis. We searched electronic databases, including PubMed (MEDLINE), EmBase, and the Cochrane Library, through November 2016 using the keywords "osteosarcoma", "osteogenic sarcoma", "chemotherapy", and "random*" without language restrictions. The major outcome in the present analysis was progression-free survival (PFS), and the secondary outcome was overall survival (OS). We used a random effect network meta-analysis for mixed multiple treatment comparisons. We included 23 articles assessing a total of 5742 patients in the present systematic review. The analysis of PFS indicated that the T12 protocol (including adriamycin, bleomycin, cyclophosphamide, dactinomycin, methotrexate, cisplatin) plays a more critical role in osteosarcoma treatment (surface under the cumulative ranking (SUCRA) probability 76.9%), with a better effect on prolonging the PFS of patients when combined with ifosfamide (94.1%) or vincristine (81.9%). For the analysis of OS, we separated the regimens to two groups, reflecting the disconnection. The T12 protocol plus vincristine (94.7%) or the removal of cisplatinum (89.4%) is most likely the best regimen. We concluded that multi-drug regimens have a better effect on prolonging the PFS and OS of osteosarcoma patients, and the T12 protocol has a better effect on prolonging the PFS of osteosarcoma patients, particularly in combination with ifosfamide or vincristine

Antihypertensive drug Valsartan promotes dendritic spine density by altering AMPA receptor trafficking

Science.gov (United States)

Sohn, Young In; Lee, Nathanael J.; Chung, Andrew; Saavedra, Juan M.; Turner, R. Scott; Pak, Daniel T. S.; Hoe, Hyang-Sook

2013-01-01

Recent studies demonstrated that the antihypertensive drug Valsartan improved spatial and episodic memory in mouse models of Alzheimer’s Disease (AD) and human subjects with hypertension. However, the molecular mechanism by which Valsartan can regulate cognitive function is still unknown. Here, we investigated the effect of Valsartan on dendritic spine formation in primary hippocampal neurons, which is correlated with learning and memory. Interestingly, we found that Valsartan promotes spinogenesis in developing and mature neurons. In addition, we found that Valsartan increases the puncta number of PSD-95 and trends toward an increase in the puncta number of synaptophysin. Moreover, Valsartan increased the cell surface levels of AMPA receptors and selectively altered the levels of spinogenesis-related proteins, including CaMKIIα and phospho-CDK5. These data suggest that Valsartan may promote spinogenesis by enhancing AMPA receptor trafficking and synaptic plasticity signaling. PMID:24012668

Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen

DEFF Research Database (Denmark)

Cozzi-Lepri, Alessandro; Phillips, Andrew N; Ruiz, Lidia

2007-01-01

OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points...... (t0 and t1) when viral load was > 400 copies/ml. METHODS: Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1...... January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0). RESULTS: At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance...

Drug susceptibility of Mycobacterium tuberculosis in a rural area of Bangladesh and its relevance to the national treatment regimens.

Science.gov (United States)

Van Deun, A; Aung, K J; Chowdhury, S; Saha, S; Pankaj, A; Ashraf, A; Rigouts, L; Fissette, K; Portaels, F

1999-02-01

Greater Mymensingh District, a rural area of Bangladesh, at the start of the National Tuberculosis Programme (NTP). To determine the prevalence of initial and acquired drug resistance of Mycobacterium tuberculosis, and to assess the appropriateness of the NTP's standard regimens. Sampling of pre-treatment sputum from all newly registered smear-positive cases in five centres covering the area. Culture and susceptibility testing in a supra-national reference laboratory. Initial resistance to isoniazid (H) was 5.4%, and to rifampicin (R) 0.5%. Acquired H and R resistance were 25.9% and 7.4%, respectively. Multidrug resistance (MDR) was observed in one new case only and in 5.6% of previously treated patients. Changing the present NTP indication for retreatment regimen to one month of previous H intake would increase coverage of H-resistant cases from 52% to 89%, adding 6% to drug costs. The prevalence of drug resistance is surprisingly low in Bangladesh, but could rise with improving economic conditions. The NTP regimens for smear-positive cases are appropriate, all the more so since the human immunodeficiency virus is virtually absent. Indications for the retreatment regimen should be extended to include all patients treated for at least one month with any drug. The NTP regimen for smear-negative cases runs the risk of leading to MDR under present field conditions.

Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe

NARCIS (Netherlands)

Hofstra, L. Marije; Sauvageot, Nicolas; Albert, Jan; Alexiev, Ivailo; Garcia, Federico; Struck, Daniel; Van De Vijver, David A M C; Åsjö, Birgitta; Beshkov, Danail; Coughlan, Suzie; Descamps, Diane; Griskevicius, Algirdas; Hamouda, Osamah; Horban, Andrzej; Van Kasteren, Marjo; Kolupajeva, Tatjana; Kostrikis, Leontios G.; Liitsola, Kirsi; Linka, Marek; Mor, Orna; Nielsen, Claus; Otelea, Dan; Paraskevis, Dimitrios; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elisabeth; Sönnerborg, Anders; Staneková, Danica; Stanojevic, Maja; Van Laethem, Kristel; Zazzi, Maurizio; Lepej, Snjezana Zidovec; Boucher, Charles A B; Schmit, Jean Claude; Wensing, Annemarie M J; Puchhammer-Stockl, E.; Sarcletti, M.; Schmied, B.; Geit, M.; Balluch, G.; Vandamme, A. M.; Vercauteren, J.; Derdelinckx, I.; Sasse, A.; Bogaert, M.; Ceunen, H.; De Roo, A.; De Wit, S.; Echahidi, F.; Fransen, K.; Goffard, J. C.; Goubau, P.; Goudeseune, E.; Yombi, J. C.; Lacor, P.; Liesnard, C.; Moutschen, M.; Pierard, D.; Rens, R.; Schrooten, Y.; Vaira, D.; Vandekerckhove, L. P R; Van Den Heuvel, A.; Van Der Gucht, B.; Van Ranst, M.; Van Wijngaerden, E.; Vandercam, B.; Vekemans, M.; Verhofstede, C.; Clumeck, N.; Van Laethem, K.; Beshkov, D.; Alexiev, I.; Lepej, S. Zidovec; Begovac, J.; Kostrikis, Leontios G.; Demetriades, I.; Kousiappa, I.; Demetriou, V.; Hezka, J.; Linka, M.; Maly, M.; Machala, L.; Nielsen, C.; Jørgensen, L. B.; Gerstoft, J.; Mathiesen, L.; Pedersen, C.; Nielsen, H.; Laursen, A.; Kvinesdal, B.; Liitsola, K.; Ristola, M.; Suni, J.; Sutinen, J.; Descamps, D.; Assoumou, L.; Castor, G.; Grude, M.; Flandre, P.; Storto, A.; Hamouda, O.; Kücherer, C.; Berg, T.; Braun, P.; Poggensee, G.; Däumer, M.; Eberle, J.; Heiken, H.; Kaiser, R.; Knechten, H.; Korn, K.; Müller, H.; Neifer, S.; Schmidt, B.; Walter, H.; Gunsenheimer-Bartmeyer, B.; Harrer, T.; Paraskevis, D.; Hatzakis, A.; Zavitsanou, A.; Vassilakis, A.; Lazanas, M.; Chini, M.; Lioni, A.; Sakka, V.; Kourkounti, S.; Paparizos, V.; Antoniadou, A.; Papadopoulos, A.; Poulakou, G.; Katsarolis, I.; Protopapas, K.; Chryssos, G.; Drimis, S.; Gargalianos, P.; Xylomenos, G.; Lourida, G.; Psichogiou, M.; Daikos, G. L.; Sipsas, N. V.; Kontos, A.; Gamaletsou, M. N.; Koratzanis, G.; Sambatakou, E.; Mariolis, H.; Skoutelis, A.; Papastamopoulos, V.; Georgiou, O.; Panagopoulos, P.; Maltezos, E.; Coughlan, S.; De Gascun, C.; Byrne, C.; Duffy, M.; Bergin, C.; Reidy, D.; Farrell, G.; Lambert, J.; O'Connor, E.; Rochford, A.; Low, J.; Coakely, P.; O'Dea, S.; Hall, W.; Mor, O.; Levi, I.; Chemtob, D.; Grossman, Z.; Zazzi, M.; De Luca, A.; Balotta, C.; Riva, C.; Mussini, C.; Caramma, I.; Capetti, A.; Colombo, M. C.; Rossi, C.; Prati, F.; Tramuto, F.; Vitale, F.; Ciccozzi, M.; Angarano, G.; Rezza, G.; Kolupajeva, T.; Kolupajeva, T.; Vasins, O.; Griskevicius, A.; Lipnickiene, V.; Schmit, J. C.; Struck, D.; Sauvageot, N.; Hemmer, R.; Arendt, V.; Michaux, C.; Staub, T.; Sequin-Devaux, C.; Wensing, A. M J; Boucher, C. A B; Van Kessel, A.; Van Bentum, P. H M; Brinkman, K.; Connell, B. J.; Van Der Ende, M. E.; Hoepelman, I. M.; Van Kasteren, M.; Kuipers, M.; Langebeek, N.; Richter, C.; Santegoets, R. M W J; Schrijnders-Gudde, L.; Schuurman, R.; Van De Ven, B. J M; Åsjö, B.; Kran, A. M Bakken; Ormaasen, V.; Aavitsland, P.; Horban, A.; Stanczak, J. J.; Stanczak, G. P.; Firlag-Burkacka, E.; Wiercinska-Drapalo, A.; Jablonowska, E.; Maolepsza, E.; Leszczyszyn-Pynka, M.; Szata, W.; Camacho, R.; Palma, C.; Borges, F.; Paixão, T.; Duque, V.; Araújo, F.; Otelea, D.; Paraschiv, S.; Tudor, A. M.; Cernat, R.; Chiriac, C.; Dumitrescu, F.; Prisecariu, L. J.; Stanojevic, M.; Jevtovic, Dj; Salemovic, D.; Stanekova, D.; Habekova, M.; Chabadová, Z.; Drobkova, T.; Bukovinova, P.; Shunnar, A.; Truska, P.; Poljak, M.; Lunar, M.; Babic, D.; Tomazic, J.; Vidmar, L.; Vovko, T.; Karner, P.; Garcia, F.; Paredes, R.; Monge, S.; Moreno, S.; Del Amo, J.; Asensi, V.; Sirvent, J. L.; De Mendoza, C.; Delgado, R.; Gutiérrez, F.; Berenguer, J.; Garcia-Bujalance, S.; Stella, N.; De Los Santos, I.; Blanco, J. R.; Dalmau, D.; Rivero, M.; Segura, F.; Elías, M. J Pérez; Alvarez, M.; Chueca, N.; Rodríguez-Martín, C.; Vidal, C.; Palomares, J. C.; Viciana, I.; Viciana, P.; Cordoba, J.; Aguilera, A.; Domingo, P.; Galindo, M. J.; Miralles, C.; Del Pozo, M. A.; Ribera, E.; Iribarren, J. A.; Ruiz, L.; De La Torre, J.; Vidal, F.; Clotet, B.; Albert, J.; Heidarian, A.; Aperia-Peipke, K.; Axelsson, M.; Mild, M.; Karlsson, A.; Sönnerborg, A.; Thalme, A.; Navér, L.; Bratt, G.; Karlsson, A.; Blaxhult, A.; Gisslén, M.; Svennerholm, B.; Bergbrant, I.; Björkman, P.; Säll, C.; Lindholm, A.; Kuylenstierna, N.; Montelius, R.; Azimi, F.; Johansson, B.; Carlsson, M.; Johansson, E.; Ljungberg, B.; Ekvall, H.; Strand, A.; Mäkitalo, S.; Öberg, S.; Holmblad, P.; Höfer, M.; Holmberg, H.; Josefson, P.; Ryding, U.

2016-01-01

Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline

Non-compliance to anti-hypertensive medication and its associated factors among hypertensives

International Nuclear Information System (INIS)

Bilal, A.; Riaz, M.; Shafiq, N.U.; Ahmed, M.; Sheikh, S.; Rasheed, S.

2015-01-01

Non-compliance to anti-hypertensive drugs can have negative impact on cardiovascular outcome. Various studies have been conducted on the issue but the factors are not yet explored properly, particularly in Pakistan. This study was conducted to determine the frequency and factors associated with non-compliance to anti-hypertensive medications in Karachi. Methods: This descriptive cross sectional study was conducted on 113 indoor hypertensive patients included by purposive sampling, aged 30 years and above diagnosed at least 6 months back in public sector tertiary care institutes of Karachi from March to October 2011. Data was collected through a questionnaire in Urdu. Demographic data, hypertension diagnosis, medical co-morbidity, current number of anti-hypertensive medicines, frequency of missing prescribed antihypertensive therapy and other factors affecting compliance pertaining to medicines, patient, physician and health care centre were included in the questionnaire. Results: This study revealed that 68.14% patients were non-compliant. Non-compliance was found to be associated with gender and socioeconomic status. Duration of hypertension, duration between follow up visits to physician, number of drugs, careless attitude, role of physician and limiting access to health care center are found to be important factors in non-compliance. Conclusions: Multiple factors including patients, medicine and health care system related, which can be prevented with simple measures, were found responsible for higher prevalence of non-compliance against anti-hypertensive medicines. (author)

Ambulatory Blood Pressure Monitoring for the Effective Management of Antihypertensive Drug Treatment.

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O'Brien, Eoin; Dolan, Eamon

2016-10-01

This purpose of this article is to review the current recommendations for ambulatory blood pressure measurement (ABPM) and the use of ABPM in assessing treatment. We review current international guidelines and undertake a critical review of evidence supporting the clinical use of ABPM in effectively managing antihypertensive drug treatment. Current guidelines emphasize the diagnostic superiority of ABPM, mainly from the ability of the technique to identify sustained hypertension by allowing for the exclusion of white-coat hypertension and by demonstrating the presence of masked hypertension. ABPM also offers diagnostic insights into nocturnal patterns of blood pressure, such as dipping and nondipping, reverse dipping, and excessive dipping, and the presence of nocturnal hypertension; although less attention is given to the nocturnal behavior of blood pressure in clinical practice, the nocturnal patterns of blood pressure have particular relevance in assessing the response to blood pressure-lowering medication. Surprisingly, although the current guidelines give detailed recommendations on the diagnostic potential and use of ABPM, there are scant recommendations on the benefits and application of the technique for the initiation of blood pressure-lowering therapy in clinical practice and virtually no recommendations on how it might be used to assess the efficacy of drug treatment. In view of a deficiency in the literature on the role of ABPM in assess the efficacy of drug treatment, we put forward proposals to correct this deficiency and guide the prescribing physician on the most appropriate drug administration and dosage over time. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Antihypertensive drug prescription patterns and their impact on outcome of blood pressure in Ethiopia: a hospital-based cross-sectional study.

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Abegaz, Tadesse Melaku; Tefera, Yonas Getaye; Abebe, Tamrat Befekadu

2017-01-01

Irrational prescription is strongly associated with poor control of hypertension. The present study aimed to evaluate antihypertensive drug prescription trends and to measure their impact on the level of blood pressure (BP) control in Gondar University Hospital, Gondar, Ethiopia. A hospital-based retrospective cross-sectional study was conducted from May 30 to June 30, 2016. All hypertensive patients on medication were included. A structured data abstraction form was prepared to gather the necessary information. The prescription patterns and BP level were measured retrospectively. A binary logistic regression was computed to determine the effect of different prescription patterns on BP control. A total of 596 hypertension patients were recruited for the study; of them, 561(94%) met the study criteria. The mean age of the respondents was 55.96±14.6 years. Females constituted 58.2% of the study population. Approximately fifty percent of the prescriptions were monotherapies. Twice-daily dosing was associated with lower risk of uncontrolled hypertension (crude odds ratio [COR] =0.51[0.15-0.73], adjusted odds ratio [AOR] =0.69[0.163-0.91]). Monthly appointment was linked with a nearly 90% reduced incidence of uncontrolled BP (COR =0.15[0.04-0.73], AOR =0.093[0.024-0.359]). Monotherapies were the most frequently prescribed regimens. Twice-daily dosing and monthly appointments were associated with low incidence of uncontrolled BP. Clinicians should be vigilant in adjusting the frequency of dosing and should fix appointment date in consultation with their patients.

Interaction between anti-hypertensive and non-steroidal anti ...

African Journals Online (AJOL)

AKS Publication

Department of Physiotherapy, College of Medicine, University College Hospital,. University of Ibadan, Nigeria. (Received 19 ... that NSAIDs diminish the effects of anti-hypertensive drugs and may lead to an ineffective hypertension therapy. ..... repair, regeneration and transplantation. Instr Course Lect. 1998;47:487-504. 15.

Priority-Setting for Novel Drug Regimens to Treat Tuberculosis: An Epidemiologic Model.

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Emily A Kendall

2017-01-01

Full Text Available Novel drug regimens are needed for tuberculosis (TB treatment. New regimens aim to improve on characteristics such as duration, efficacy, and safety profile, but no single regimen is likely to be ideal in all respects. By linking these regimen characteristics to a novel regimen's ability to reduce TB incidence and mortality, we sought to prioritize regimen characteristics from a population-level perspective.We developed a dynamic transmission model of multi-strain TB epidemics in hypothetical populations reflective of the epidemiological situations in India (primary analysis, South Africa, the Philippines, and Brazil. We modeled the introduction of various novel rifampicin-susceptible (RS or rifampicin-resistant (RR TB regimens that differed on six characteristics, identified in consultation with a team of global experts: (1 efficacy, (2 duration, (3 ease of adherence, (4 medical contraindications, (5 barrier to resistance, and (6 baseline prevalence of resistance to the novel regimen. We compared scale-up of these regimens to a baseline reflective of continued standard of care. For our primary analysis situated in India, our model generated baseline TB incidence and mortality of 157 (95% uncertainty range [UR]: 113-187 and 16 (95% UR: 9-23 per 100,000 per year at the time of novel regimen introduction and RR TB incidence and mortality of 6 (95% UR: 4-10 and 0.6 (95% UR: 0.3-1.1 per 100,000 per year. An optimal RS TB regimen was projected to reduce 10-y TB incidence and mortality in the India-like scenario by 12% (95% UR: 6%-20% and 11% (95% UR: 6%-20%, respectively, compared to current-care projections. An optimal RR TB regimen reduced RR TB incidence by an estimated 32% (95% UR: 18%-46% and RR TB mortality by 30% (95% UR: 18%-44%. Efficacy was the greatest determinant of impact; compared to a novel regimen meeting all minimal targets only, increasing RS TB treatment efficacy from 94% to 99% reduced TB mortality by 6% (95% UR: 1%-13%, half the

ADVERSE PREGNANCY OUTCOMES ASSOCIATED WITH MATERNAL ENALAPRIL ANTIHYPERTENSIVE TREATMENT

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Enalapril, one of several antihypertensive drugs that act as angiotensin-converting enzyme (ACE) inhibitors, is often used for treatment of hypertension in women of reproductive age. Adverse birth outcomes following the use of ACE inhibitors, including enalapril, during pregnanc...

Interaction of antihypertensive drug amiloride with metal ions in micellar medium using fluorescence spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Gujar, Varsha; Pundge, Vijaykumar; Ottoor, Divya, E-mail: divya@chem.unipune.ac.in

2015-05-15

Steady state and life time fluorescence spectroscopy have been employed to study the interaction of antihypertensive drug amiloride with biologically important metal ions i.e. Cu{sup 2+}, Fe{sup 2+}, Ni{sup 2+} and Zn{sup 2+} in various micellar media (anionic SDS (sodium dodecyl sulfate), nonionic TX-100 (triton X-100) and cationic CTAB (cetyl trimethyl ammonium bromide)). It was observed that fluorescence properties of drug remain unaltered in the absence of micellar media with increasing concentration of metal ions. However, addition of Cu{sup 2+}, Fe{sup 2+} and Ni{sup 2+} caused fluorescence quenching of amiloride in the presence of anionic micelle, SDS. Binding of drug with metal ions at the charged micellar interface could be the possible reason for this pH-dependent metal-mediated fluorescence quenching. There were no remarkable changes observed due to metal ions addition when drug was present in cationic and nonionic micellar medium. The binding constant and bimolecular quenching constant were evaluated and compared for the drug–metal complexes using Stern–Volmer equation and fluorescence lifetime values. - Highlights: • Interaction of amiloride with biologically important metal ions, Fe{sup 2+}, Cu{sup 2+}, Ni{sup 2+} and Zn{sup 2+}. • Monitoring the interaction in various micelle at different pH by fluorescence spectroscopy. • Micelles acts as receptor, amiloride as transducer and metal ions as analyte in the present system. • Interaction study provides pH dependent quenching and binding mechanism of drug with metal ions.

Interaction of antihypertensive drug amiloride with metal ions in micellar medium using fluorescence spectroscopy

International Nuclear Information System (INIS)

Gujar, Varsha; Pundge, Vijaykumar; Ottoor, Divya

2015-01-01

Steady state and life time fluorescence spectroscopy have been employed to study the interaction of antihypertensive drug amiloride with biologically important metal ions i.e. Cu 2+ , Fe 2+ , Ni 2+ and Zn 2+ in various micellar media (anionic SDS (sodium dodecyl sulfate), nonionic TX-100 (triton X-100) and cationic CTAB (cetyl trimethyl ammonium bromide)). It was observed that fluorescence properties of drug remain unaltered in the absence of micellar media with increasing concentration of metal ions. However, addition of Cu 2+ , Fe 2+ and Ni 2+ caused fluorescence quenching of amiloride in the presence of anionic micelle, SDS. Binding of drug with metal ions at the charged micellar interface could be the possible reason for this pH-dependent metal-mediated fluorescence quenching. There were no remarkable changes observed due to metal ions addition when drug was present in cationic and nonionic micellar medium. The binding constant and bimolecular quenching constant were evaluated and compared for the drug–metal complexes using Stern–Volmer equation and fluorescence lifetime values. - Highlights: • Interaction of amiloride with biologically important metal ions, Fe 2+ , Cu 2+ , Ni 2+ and Zn 2+ . • Monitoring the interaction in various micelle at different pH by fluorescence spectroscopy. • Micelles acts as receptor, amiloride as transducer and metal ions as analyte in the present system. • Interaction study provides pH dependent quenching and binding mechanism of drug with metal ions

The SPYRAL HTN Global Clinical Trial Program: Rationale and design for studies of renal denervation in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications.

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Kandzari, David E; Kario, Kazuomi; Mahfoud, Felix; Cohen, Sidney A; Pilcher, Garrett; Pocock, Stuart; Townsend, Raymond; Weber, Michael A; Böhm, Michael

2016-01-01

Renal sympathetic activation plays a key role in the pathogenesis of hypertension, as demonstrated by high renal norepinephrine spillover into plasma of patients with essential hypertension. Renal denervation has demonstrated a significant reduction in blood pressure in unblinded studies of hypertensive patients. The SYMPLICITY HTN-3 trial, the first prospective, masked, randomized study of renal denervation versus sham control, failed its primary efficacy end point and raised important questions around potentially confounding factors, such as drug changes and adherence, study population, and procedural methods. The SPYRAL HTN Global Clinical Trial Program is designed to address limitations associated with predicate studies and provide insight into the impact of pharmacotherapy on renal denervation efficacy. The 2 initial trials of the program focus on the effect of renal denervation using the Symplicity Spyral multielectrode renal denervation catheter in hypertensive patients in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications. The SPYRAL HTN ON-MED study requires patients to be treated with a consistent triple therapy antihypertensive regimen, whereas the SPYRAL HTN OFF-MED study includes a 3- to 4-week drug washout period followed by a 3-month efficacy and safety end point in the absence of antihypertensive medications. The studies will randomize patients with combined systolic-diastolic hypertension to renal denervation or sham procedure. Both studies allow renal denervation treatments in renal artery branches and accessories. These studies will inform the design of the second pivotal phase of the program, which will more definitively analyze the antihypertensive effect of renal denervation. Copyright © 2015 Elsevier Inc. All rights reserved.

Investigation of the Relationship of Some Antihypertensive Drugs with Oxidant/Antioxidant Parameters and DNA Damage on Rat Uterus Tissue

OpenAIRE

Mustafa Talip Sener; Hamit Hakan Alp; Beyzagul Polat; Bunyamin Borekci; Yakup Kumtepe; Nesrin Gursan; Serkan Kumbasar; Suleyman Salman; Halis Suleyman

2011-01-01

Background In this study, we investigated the effects of treatment with chronic antihypertensive drugs (clonidine, methyldopa, amlodipine, ramipril and rilmenidine) on oxidant-antioxidant parameters and toxic effects on DNA in rat uterus tissue. In addition, uterus tissues were examined histopathologically. Materials and Methods A total of 36 albino Wistar rats were divided into the following six groups: 0.075 mg/kg clonidine group; 100 mg/kg methyldopa group; 2 mg/kg amlodipine group; 2.5 mg...

Viral resuppression and detection of drug resistance following interruption of a suppressive non-nucleoside reverse transcriptase inhibitor-based regimen

DEFF Research Database (Denmark)

Fox, Zoe; Phillips, Andrew; Cohen, Cal

2008-01-01

the NRTIs, or by replacing the NNRTI with another drug before interruption. Simultaneous interruption of all antiretrovirals was discouraged. Resuppression rates 4-8 months after reinitiating NNRTI-therapy were assessed, as was the detection of drug-resistance mutations within 2 months of the treatment...... regimen. NNRTI drug-resistance mutations were observed in a relatively high proportion of patients. These data provide additional support for a staggered or switched interruption strategy for NNRTI drugs.......BACKGROUND: Interruption of a non-nucleoside reverse transcriptase inhibitor (NNRTI)-regimen is often necessary, but must be performed with caution because NNRTIs have a low genetic barrier to resistance. Limited data exist to guide clinical practice on the best interruption strategy to use...

Antihypertensive drug treatment and circadian blood pressure rhythm: a review of the role of chronotherapy in hypertension.

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Schillaci, Giuseppe; Battista, Francesca; Settimi, Laura; Schillaci, Luca; Pucci, Giacomo

2015-01-01

Elevated nighttime blood pressure (BP) and a reduced day-night BP fall ("nondipping" condition) are strong predictors of cardiovascular complications, both in hypertension and in the general population. A reduced or inverted nocturnal BP fall might also be theoretically used to define the most appropriate timing for drug administration. In a systematic review of the available evidence, we show that bedtime dosing of antihypertensive medication reduces nocturnal BP and increases day-night BP fall more than standard morning dosing. The effects of such an approach on average 24-hour BP are more modest and less univocal, with a considerable between-center heterogeneity. Admittedly, the mechanisms underlying non-dipping condition have not been fully understood yet, and it is still a matter of debate whether restorating a dipping pattern may reduce the cardiovascular risk associated with non-dipping independently from the effects on 24-hour BP. Under this regard, evidence from a single trial strongly suggests that bedtime dosing of antihypertensive medications may greatly reduce cardiovascular morbidity in hypertensive patients. The provocative results of that trial deserve to be explored further in larger intervention trials.

Does the rising placebo response impact antihypertensive clinical trial outcomes? An analysis of data from the Food and Drug Administration 1990-2016.

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Arif Khan

Full Text Available Recent studies show that placebo response has grown significantly over time in clinical trials for antidepressants, ADHD medications, antiepileptics, and antidiabetics. Contrary to expectations, trial outcome measures and success rates have not been impacted. This study aimed to see if this trend of increasing placebo response and stable efficacy outcome measures is unique to the conditions previously studied or if it occurs in trials for conditions with physiologically-measured symptoms, such as hypertension.For this reason, we evaluated the efficacy data reported in the US Food and Drug Administration Medical and Statistical reviews for 23 antihypertensive programs (32,022 patients, 63 trials, 142 treatment arms. Placebo and medication response, effect sizes, and drug-placebo differences were calculated for each treatment arm and examined over time using meta-regression. We also explored the relationship of sample size, trial duration, baseline blood pressure, and number of treatment arms to placebo/drug response and efficacy outcome measures.Like trials of other conditions, placebo response has risen significantly over time (R2 = 0.093, p = 0.018 and effect size (R2 = 0.013, p = 0.187 drug-placebo difference (R2 = 0.013, p = 0.182 and success rate (134/142, 94.4% have remained unaffected, likely due to a significant compensatory increase in antihypertensive response (R2 = 0.086, p<0.001. Treatment arms are likely overpowered with sample sizes increasing over time (R2 = 0.387, p<0.0001 and stable, large effect sizes (0.78 ±0.37. The exploratory analysis of sample size, trial duration, baseline blood pressure, and number of treatment arms yielded mixed results unlikely to explain the pattern of placebo response and efficacy outcomes over time. The magnitude of placebo response had no relationship to effect size (p = 0.877, antihypertensive-placebo differences (p = 0.752, or p-values (p = 0.963 but was correlated with antihypertensive response

Does the rising placebo response impact antihypertensive clinical trial outcomes? An analysis of data from the Food and Drug Administration 1990-2016

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Fahl Mar, Kaysee; Schilling, Joshua; Brown, Walter A.

2018-01-01

Background Recent studies show that placebo response has grown significantly over time in clinical trials for antidepressants, ADHD medications, antiepileptics, and antidiabetics. Contrary to expectations, trial outcome measures and success rates have not been impacted. This study aimed to see if this trend of increasing placebo response and stable efficacy outcome measures is unique to the conditions previously studied or if it occurs in trials for conditions with physiologically-measured symptoms, such as hypertension. Method For this reason, we evaluated the efficacy data reported in the US Food and Drug Administration Medical and Statistical reviews for 23 antihypertensive programs (32,022 patients, 63 trials, 142 treatment arms). Placebo and medication response, effect sizes, and drug-placebo differences were calculated for each treatment arm and examined over time using meta-regression. We also explored the relationship of sample size, trial duration, baseline blood pressure, and number of treatment arms to placebo/drug response and efficacy outcome measures. Results Like trials of other conditions, placebo response has risen significantly over time (R2 = 0.093, p = 0.018) and effect size (R2 = 0.013, p = 0.187) drug-placebo difference (R2 = 0.013, p = 0.182) and success rate (134/142, 94.4%) have remained unaffected, likely due to a significant compensatory increase in antihypertensive response (R2 = 0.086, parms are likely overpowered with sample sizes increasing over time (R2 = 0.387, pblood pressure, and number of treatment arms yielded mixed results unlikely to explain the pattern of placebo response and efficacy outcomes over time. The magnitude of placebo response had no relationship to effect size (p = 0.877), antihypertensive-placebo differences (p = 0.752), or p-values (p = 0.963) but was correlated with antihypertensive response (R2 = 0.347, p<0.0001). Conclusions As hypothesized, this study shows that placebo response is increasing in clinical

Heterogeneity of Clinical Trials for Antihypertensive Drugs in Japan: Exploratory Analysis of Confirmatory Phase III Trials Used for Marketing Approval.

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Kaneko, Reina; Sano, Kota; Ono, Shunsuke

2018-07-01

The results of pivotal trials, which provide a rationale for marketing approval decisions for new drugs, are considered for various comparative purposes in postmarketing analyses. Using meta-regression analysis of 91 randomized controlled trials of 61 approved antihypertensive drugs in Japan, we show that mean baseline blood pressure (BP) of each arm was associated with predetermined entry criteria (EC), age, and trial start year (TSY). BP changes following treatment were associated with EC, subject characteristics (e.g., age, complications, baseline BP), study design (e.g., concomitant drug use), and TSY. Effect sizes were generally larger in trials for the first and second drugs in the same class than in trials for follow-on drugs. Results of pivotal trials may vary depending on many factors, suggesting possible challenges associated with the comparison of these results indirectly. Due to the heterogeneity in pivotal trials, caution should be exercised when comparing approved drugs and conducting meta-analyses retrospectively. © 2017, The American Society for Clinical Pharmacology and Therapeutics.

Antihypertensive drug use in resistant and nonresistant hypertension and in controlled and uncontrolled resistant hypertension.

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de la Sierra, Alejandro; Armario, Pedro; Oliveras, Anna; Banegas, José R; Gorostidi, Manuel; Vinyoles, Ernest; de la Cruz, Juan J; Segura, Julián; Ruilope, Luis M

2018-07-01

Treatment-resistant hypertension (TRH) is associated with particular clinical features, nonadherence, and suboptimal treatment. We assessed possible associations of antihypertensive drug classes, specific agents inside each class, and types of combinations, with the presence of non-TRH vs. TRH, and with controlled vs. uncontrolled TRH. Comparisons were done in 14 264 patients treated with three drugs (non-TRH: 2988; TRH: 11 276) and in 6974 treated with at least four drugs (controlled TRH: 1383; uncontrolled TRH: 5591). Associations were adjusted for age, sex, and previous cardiovascular event. In both groups of patients treated with three or with at least four drugs, aldosterone antagonists among drug classes [adjusted odds ratio (OR): 1.82 and 1.41, respectively], and ramipril (OR: 1.28 and 1.30), olmesartan (OR: 1.31 and 1.37), and amlodipine (OR: 1.11 and 1.41) inside each class were significantly associated with blood pressure control (non-TRH or controlled TRH). In patients treated with three drugs, non-TRH was also associated with the use of chlorthalidone (OR: 1.50) and bisoprolol (OR: 1.19), whereas in patients treated with at least four drugs, controlled TRH was significantly associated with the triple combination of a renin-angiotensin system blocker, a calcium channel blocker, and a diuretic (OR: 1.17). The use of aldosterone antagonists is associated with blood pressure control in patients treated with three or more drugs. Similar results are observed with specific agents inside each class, being ramipril, olmesartan, chlorthalidone, amlodipine, and bisoprolol those exhibiting significant results. An increased use of these drugs might probably reduce the burden of TRH.

Influence of drug load and physical form of cinnarizine in new SNEDDS dosing regimens

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Siqueira, Scheyla D V S; Müllertz, Anette; Gräeser, Kirsten

2017-01-01

The aim of this work was to evaluate the influence of drug load and physical form of cinnarizine (CIN) in self-nanoemulsifying drug delivery systems (SNEDDS) on absorption in rats. Further, the predictivity of the dynamic in vitro lipolysis model was evaluated. The following dosing regimens were......, compared to the aqueous suspension. Since the drug level in the aqueous phase is traditionally considered as the fraction available for absorption, a lack of in vitro-in vivo relation was observed. This study revealed that the physical form of CIN in the current SNEDDS does not affect CIN absorption...

PP042. Anti-hypertensive drugs hydralazine, clonidine and labetalol improve trophoblast integration into endothelial cellular networks in vitro.

Science.gov (United States)

Xu, B; Charlton, F; Makris, A; Hennessy, A

2012-07-01

Preeclampsia is an exaggerated maternal inflammatory state with over-expression of placental soluble fms-like tyrosine kinase 1 (sFlt-1). It is also associated with shallow trophoblast invasion and inadequate transformation of uterine spiral arteries. Antihypertensive drugs administrated in preeclampsia to control blood pressure have been reported to regulate placental and circulating cytokine production from women with preeclampsia. Whether they could modulate the interaction between trophoblast and endothelial cells are not investigated. This study is to examine the effect of pharmacological dose of anti-hypertensive hydralazine, clonidine and labetalol on trophoblast cell integration into inflammatory TNF-a pre-exposed endothelial cellular networks. Human uterine myometrial microvascular endothelial cells (UtMVECs) were pre-incubated with (or without) low dose (0.5ng/ml) inflammatory TNF-a or TNF-a plus sFlt-1 (100ng/ml) for 24hours. These cells were labelled with red fluorescence and seeded on a 24-well culture plate coated with Matrigel. Endothelial tubular structures appeared within 4hours. Green fluorescent-labelled HTR-8/SVneo trophoblast cells were then co-cultured with endothelial cells, with (or without) hydralazine (10μg/ml), clonidine (1.0μg/ml) or labetalol (0.5μg/ml). Red and green fluorescent images were captured after 24hours. Drug effect on HTR-8 cells integration into endothelial cellular networks was quantified by Image Analysis software. The conditioned media were also collected to measure concentrations of free VEGF, PLGF and sFlt-1 by ELISA. When HTR-8/SVneo trophoblast cells were co-cultured with TNF-a pre-incubated endothelial cells, hydralazine and clonidine can significantly increase the trophoblast integration into endothelial cellular networks. This increase was not seen if co-cultured with normal endothelial cells (without TNF-a pre-incubation) or with TNF-a plus sFlt-1 treated endothelial cells. Labetalol could increase the HTR-8

Similarity between generic and brand-name antihypertensive drugs for primary prevention of cardiovascular disease: evidence from a large population-based study.

Science.gov (United States)

Corrao, Giovanni; Soranna, Davide; Merlino, Luca; Mancia, Giuseppe

2014-10-01

Although generic and earlier brand-name counterparts are bioequivalent, their equivalence in preventing relevant clinical outcomes is of concern. To compare effectiveness of generic and brand-name antihypertensive drugs for preventing the onset of cardiovascular (CV) outcomes. A population-based, nested case-control study was carried out by including the cohort of 78 520 patients from Lombardy (Italy) aged 18 years or older who were newly treated with antihypertensive drugs during 2005. Cases were the 2206 patients who experienced a hospitalization for CV disease from initial prescription until 2011. One control for each case was randomly selected from the same cohort that generated cases. Logistic regression was used to model the CV risk associated with starting on and/or continuing with generic or brand-name agents. There was no evidence that patients who started on generics experienced different CV risk than those on brand-name product (OR 0·86; 95% CI 0·63-1·17). Patients at whom generics were main dispensed had not significantly difference in CV outcomes than those mainly on brand-name agents (OR 1·19; 95% CI 0·86-1·63). Compared with patients who kept initial brand-name therapy, those who experienced brand-to-generic or generic-to-brand switches, and those always on generics, did not show differential CV risks, being the corresponding ORs (and 95% CIs), 1·18 (0·96-1·47), 0·87 (0·63-1·21) and 1·08 (0·80-1·46). Our findings do not support the notion that brand-name antihypertensive agents are superior to generics for preventing CV outcomes in the real-world clinical practice. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

Workplace social capital and adherence to antihypertensive medication: a cohort study.

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Tuula Oksanen

Full Text Available While hypertension is a common and treatable health problem, adherence to antihypertensive medication remains a challenge. This study examines the hypothesis that workplace social capital may influence adherence to antihypertensive medication among hypertensive employees.We linked survey responses to nationwide pharmacy records for a cohort of 3515 hypertensive employees (mean age 53.9 years, 76% women who required continuous antihypertensive drug therapy (the Finnish Public Sector study. A standard scale was used to measure workplace social capital from co-workers' assessments and self-reports in 2000-2004. Non-adherence to antihypertensive medication was determined based on the number of days-not-treated at the year following the survey using comprehensive prescription records. Negative binomial regression models were conducted adjusting for socio-demographic characteristics, duration of hypertension, behaviour-related risk factors, and co-morbid conditions. The overall rate of days-not-treated was 20.7 per person-year (78% had no days-not-treated. Higher age, obesity, and presence of somatic co-morbidities were all associated with better adherence, but this was not the case for co-worker-assessed or self-reported workplace social capital. The rate of days-not-treated was 19.7 per person-year in the bottom fourth of co-worker-assessed workplace social capital, compared to 20.4 in the top fourth. The corresponding rate ratio from the fully-adjusted model was 0.95 (95% confidence interval (CI 0.58-1.56. In a subgroup of 907 new users of antihypertensive medication this rate ratio was 0.98 (95% CI 0.42-2.29.We found no consistent evidence to support the hypothesized effect of workplace social capital on adherence to drug therapy among employees with chronic hypertension.

Voltammetric Determination of Anti-Hypertensive Drug Hydrochlorothiazide Using Screen-Printed Electrodes Modified with L-Glutamic Acid

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Camilo González-Vargas

2017-09-01

Full Text Available This work deals with the development of screen-printed carbon electrodes modified with L-glutamic acid via two different approaches: electropolymerization (SPCE/PGA and aryl diazonium electrochemical grafting (SPCE/EGA. SPCE/PGA and SPCE/EGA were analytically compared in the determination of hydrochlorothiazide (HCTZ by differential pulse voltammetry. Both electrochemical characterization and analytical performance indicate that SPCE/EGA is a much better sensor for HCTZ. The detection and quantification limits were at the level of μmol L−1 with a very good linearity in the studied concentration range. In addition, the proposed SPCE/EGA was successfully applied for the determination of HCTZ in an anti-hypertensive drug with high reproducibility and good trueness.

THE ANALYSIS OF DIFFERENCES IN DOCTORS PREFERENCES IN THE PRESCRIPTIONS OF ANTIHYPERTENSIVE DRUGS IN FOUR REGIONS OF THE FAR EASTERN FEDERAL DISTRICT

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M. S. Soboleva

2018-01-01

Full Text Available Aim. To study regional features and preferences of specialists in the choice of drug therapy of arterial hypertension in four subjects of the Far Eastern Federal District.Material and methods. Statistical data, demographic indicators, state and municipal drug procurements in Chukotka Autonomous Okrug, the Sakha Republic (Yakutia, the Magadan Region, and Kamchatka Krai were analyzed. The studied period was 2012-2016. Dynamics of the use (procurements of five main therapeutic classes of antihypertensive drugs was studied.Results. Among β-blockers the leaders were metoprolol (from 2% to 30.8% and bisoprolol (from 2.4% to 20.3%, in group of angiotensin converting enzyme inhibitors – enalapril (from 3.6% to 27%, lisinopril (from 4.4% to 23.9% and perindopril (from 0.9% to 7.8%, among calcium channel blockers – amlodipine (from 5.6% to 11.3%, in group of diuretics – indapamide (from 2.5% to 13% and spironolactone (from 3% to 12.5%, and in group of angiotensin II antagonists – losartan (from 0.4% to 15.6%. Angiotensin converting enzyme inhibitors were the most used therapeutic class of antihypertensive drugs in Chukotka Autonomous Okrug, the Magadan region and Kamchatka Krai. At the same time, β-blockers accounted for more than a half of state and municipal procurements in the Sakha Republic (Yakutia.Conclusion. It is necessary to study regional aspects and approaches to therapy to assess the extent and specificity of the implementation of research results, standards and recommendations in real clinical practice.

Assessment of tobramycin RIA for drug monitoring and dosage regimen. Comparison with other assay technics

International Nuclear Information System (INIS)

Takahashi, S.; Shinozaki, K.; Tsujino, D.; Ohhara, H.; Tanaka, Y.; Arai, S.; Someya, K.; Sasaki, Y.

1983-01-01

Because of wide range of inter-individual difference of pharmacokinetic parameter, importance of monitoring blood concentration of aminoglycoside antibiotics in each patient has been recognized. With the purpose to use for monitoring of serum tobramycin (TOB) levels and for adequate dosage regimen RIA of TOB was evaluated in comparison with other assay technics. Gamma Coat TOB RIA kits (Clinical Assay-Travenol Japan) were used for RIA of TOB. The TOB concentrations in the same samples were also measured by two kinds of enzyme immunoassay (EIA) (EMIT EIA and SLFIA EIA), High Performance Liquid Chromatography (HPLC) and bioassay (BA). RIA of TOB is a useful assay method with high sensitivity and reasonably good precision to be used for drug monitoring and adequate dosage regimen. Modification of the method for rapid assay of a small number of samples will increase the clinical usefulness in individualized drug monitoring

Laboratory monitoring of patients treated with antihypertensive drugs and newly exposed to non steroidal anti-inflammatory drugs: a cohort study.

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Jean-Pascal Fournier

Full Text Available BACKGROUND: Drug-Drug Interactions between Non Steroidal Anti-Inflammatory Drugs (NSAIDs and Angiotensin Converting Enzyme Inhibitors (ACEIs, Angiotensin Receptor Blocker (ARBs or diuretics can lead to renal failure and hyperkalemia. Thus, monitoring of serum creatinine and potassium is recommended when a first dispensing of NSAID occur in patients treated with these drugs. METHODS: We conducted a pharmacoepidemiological retrospective cohort study using data from the French Health Insurance Reimbursement Database to evaluate the proportion of serum creatinine and potassium laboratory monitoring in patients treated with ACEI, ARB or diuretic and receiving a first dispensing of NSAID. We described the first dispensing of NSAID among 3,500 patients of a 4-year cohort (6,633 patients treated with antihypertensive drugs and analyzed serum creatinine and potassium laboratory monitoring within the 3 weeks after the first NSAID dispensing. RESULTS: General Practitioners were the most frequent prescribers of NSAIDs (85.5%, 95% CI: 84.3-86.6. The more commonly prescribed NSAIDs were ibuprofen (20%, ketoprofen (15%, diclofenac (15% and piroxicam (12%. Serum creatinine and potassium monitoring was 10.7% (95% CI: 9.5-11.8 in patients treated by ACEIs, ARBs or diuretics. Overall, monitoring was more frequently performed to women aged over 60, treated with digoxin or glucose lowering drugs, but not to patients treated with ACEIs, ARBs or diuretics. Monitoring was more frequent when NSAIDs' prescribers were cardiologists or anesthesiologists. CONCLUSION: Monitoring of serum creatinine and potassium of patients treated with ACEIs, ARBs or diuretics and receiving a first NSAID dispensing is insufficiently performed and needs to be reinforced through specific interventions.

INFLUENCE OF CHRONOTHERAPY WITH DIFFERENT ANTIHYPERTENSIVE DRUGS ON CIRCADIAN BLOOD PRESSURE PATTERN

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V. M. Gorbunov

2016-01-01

Full Text Available Aim. To determine the value of different blood pressure (BP measurement methods for arterial hypertension (HT chronotherapy efficacy assessment. Material and methods. Two similar open, randomized, cross-over studies (morning vs evening intake were carried out. Duration of the initial wash-out period was 2 weeks; duration of both treatment courses — 3 weeks; the interval between courses — 1 week. Only patients with stable HT (mean day-time BP>135/85 mm Hg were included. Ambulatory BP monitoring (ABPM was carried out prior to treatment and at the end of both treatment courses. The patients performed home BP monitoring (HBPM throughout the study. Pharmacokinetics of verapamil (n=14, mean daily dose — 240.0±16.3 mg was studied to assess compliance with verapamil therapy. In ramipril trial (n=30 its mean daily dose was 8.9±0.7 mg. The following main ABPM variables were analyzed: ABPM means and variability, maximal and minimal values, nocturnal BP fall, parameters of Fourier transformation and smoothness index. The morning and evening BP means and morning BP surge (morning – evening BP were assessed by HBPM. Student’s t-value and Mahalanobis distance were used to evaluate individual value of each variable (“morning” vs “evening” effect. This analysis was first done separately for each trial. After that, combined data were analyzed. Results. Overall antihypertensive effect was more intense with morning ramipril (p<0.05 intake and evening verapamil intake. The t-values ranged 2.2-2.3 for nocturnal BP fall; 2.0-2.1 for night-time BP variability; 3.8-4.3 for morning BP surge. The t-values of office and 24-hour BP were low (0.2-1.7. Conclusion. Morning BP surge based on HBPM is a good instrument for chronotherapy effect assessment. Evening administration of antihypertensive drugs causes nocturnal BP fall shift towards “dipper” status.

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.

A Faropenem, Linezolid, and Moxifloxacin Regimen for Both Drug-Susceptible and Multidrug-Resistant Tuberculosis in Children: FLAME Path on the Milky Way.

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Deshpande, Devyani; Srivastava, Shashikant; Nuermberger, Eric; Pasipanodya, Jotam G; Swaminathan, Soumya; Gumbo, Tawanda

2016-11-01

 The regimen of linezolid and moxifloxacin was found to be efficacious in the hollow fiber system model of pediatric intracellular tuberculosis. However, its kill rate was slower than the standard 3-drug regimen of isoniazid, rifampin, and pyrazinamide. We wanted to examine the effect of adding a third oral agent, faropenem, to this dual combination.  We performed a series of studies in the hollow fiber system model of intracellular Mycobacterium tuberculosis, by mimicking pediatric pharmacokinetics of each antibiotic. First, we varied the percentage of time that faropenem persisted above minimum inhibitory concentration (T MIC ) on the moxifloxacin-linezolid regimen. After choosing the best faropenem exposure, we performed experiments in which we varied the moxifloxacin and linezolid doses in the triple regimen. Finally, we performed longer-duration therapy validation experiments. Bacterial burden was quantified using both colony-forming units per milliliter (CFU/mL) and time to positivity (TTP). Kill slopes were modeled using exponential regression.  TTP was a more sensitive measure of bacterial burden than CFU/mL. A faropenem T MIC > 62% was associated with steepest microbial kill slope. Regimens of standard linezolid and moxifloxacin plus faropenem T MIC > 60%, as well as higher-dose moxifloxacin, achieved slopes equivalent to those of the standard regimen based by both TTP and CFU/mL over 28 days of treatment.  We have developed an oral faropenem-linezolid-moxifloxacin (FLAME) regimen that is free of first-line drugs. The regimen could be effective against both multidrug-resistant and drug-susceptible tuberculosis in children. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

HIV drug resistance in infants increases with changing prevention of mother-to-child transmission regimens.

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Poppe, Lisa K; Chunda-Liyoka, Catherine; Kwon, Eun H; Gondwe, Clement; West, John T; Kankasa, Chipepo; Ndongmo, Clement B; Wood, Charles

2017-08-24

The objectives of this study were to determine HIV drug resistance (HIVDR) prevalence in Zambian infants upon diagnosis, and to determine how changing prevention of mother-to-child transmission (PMTCT) drug regimens affect drug resistance. Dried blood spot (DBS) samples from infants in the Lusaka District of Zambia, obtained during routine diagnostic screening, were collected during four different years representing three different PMTCT drug treatment regimens. DNA extracted from dried blood spot samples was used to sequence a 1493 bp region of the reverse transcriptase gene. Sequences were analyzed via the Stanford HIVDRdatabase (http://hivdb.standford.edu) to screen for resistance mutations. HIVDR in infants increased from 21.5 in 2007/2009 to 40.2% in 2014. Nonnucleoside reverse transcriptase inhibitor resistance increased steadily over the sampling period, whereas nucleoside reverse transcriptase inhibitor resistance and dual class resistance both increased more than threefold in 2014. Analysis of drug resistance scores in each group revealed increasing strength of resistance over time. In 2014, children with reported PMTCT exposure, defined as infant prophylaxis and/or maternal treatment, showed a higher prevalence and strength of resistance compared to those with no reported exposure. HIVDR is on the rise in Zambia and presents a serious problem for the successful lifelong treatment of HIV-infected children. PMTCT affects both the prevalence and strength of resistance and further research is needed to determine how to mitigate its role leading to resistance.

Perceived efficacy of analgesic drug regimens used for koalas (Phascolarctos cinereus) in Australia.

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de Kauwe, Tyron; Kimble, Benjamin; Govendir, Merran

2014-06-01

Recent publications report that some therapeutic drugs used in koalas (Phascolarctos cinereus) have poor oral absorption and are rapidly eliminated. Therefore, information on both the analgesic drug dosage regimens used to treat koalas in Australia and koala caretakers' perceptions of the efficacy of these drugs to control pain was collected for the purpose of identifying the most popular analgesics to prioritize future analgesic pharmacokinetic studies for this species. A one-page, double-sided questionnaire was distributed both electronically and by mail to Australian koala care facilities such as zoos and wildlife hospitals. Information was received from 13 respondents. Nonsteroidal anti-inflammatory drugs (NSAIDs) were the most frequently used analgesics, followed by full micro- and partial opioid receptor agonists and acetaminophen with or without codeine. The full micro-opioid receptor agonists and acetaminophen with or without codeine were most consistently considered efficacious, with wider variation in perceived efficacy of the NSAIDs. Analgesic drug combinations were generally thought efficacious.

Antithyroid drug regimens before and after 131I-therapy for hyperthyroidism: evidence-based?

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Mijnhout, G S; Franken, A A M

2008-06-01

In view of the new national guideline on thyroid dysfunction, the evidence base for current practice as well as the new guideline is assessed with regard to the use of antithyroid drugs (ATDs) before and after radioiodine (131I) therapy. In December 2006, we surveyed 16 hospitals by telephone about different aspects of their antithyroid drug regimen: all eight academic centres and eight nonacademic teaching hospitals. The literature was searched for an evidence-based answer to each question in the inquiry. 13 of 16 hospitals (81%) use antithyroid drugs for pretreatment before 131I. ATDs are discontinued on average four days before 131I or diagnostic scan. However, 27% stop only three days beforehand, which may diminish the effect of 131I. Propylthiouracil (PTU) is also withdrawn four days before 131I, although the literature shows that PTU diminishes the effect of 131I even if it is stopped 15 days beforehand. Resumption of ATDs after 131I to prevent thyrotoxicosis is common practice (81%). One hospital (6%) never restarts ATDs, two (13%) only by indication. Adjunctive treatment consists of combination therapy in 93%, is usually resumed within two days after 131I therapy, and then continued for two to six months. Routine adjunctive treatment is not evidence-based and may be limited to a high-risk subset, especially elderly patients (>70 years) and patients with cardiac comorbidity. Resumption of ATDs within five to seven days after 131I may diminish the effect of 131I. Antithyroid drug regimens in the Netherlands are heterogeneous. The evidence base of current practice and the new guideline are discussed.

Investigation of the Relationship of Some Antihypertensive Drugs with Oxidant/Antioxidant Parameters and DNA Damage on Rat Uterus Tissue

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Mustafa Talip Sener

2011-01-01

Full Text Available Background: In this study, we investigated the effects of treatment with chronic antihypertensivedrugs (clonidine, methyldopa, amlodipine, ramipril and rilmenidine on oxidant-antioxidantparameters and toxic effects on DNA in rat uterus tissue. In addition, uterus tissues were examinedhistopathologically.Materials and Methods: A total of 36 albino Wistar rats were divided into the following six groups:0.075 mg/kg clonidine group; 100 mg/kg methyldopa group; 2 mg/kg amlodipine group; 2.5 mg/kgramipril group; 0.5 mg/kg rilmenidine group; and the healthy group. Rats underwent chronic drugadministration for 30 days and at the end, biochemical and histopathological examinations wereperformed. All data were subjected to one-way ANOVA test.Results: We divided these drugs into the following three groups according to their effects on ratuteri: (I mild negative effects (clonidine, (II moderate negative effects (rilmenidine, methyldopaand (III drugs which had severe negative effects (amlodipine, ramipril.Conclusion: These data may help with selection of antihypertensive drugs, in order to determinewhich drugs have the lowest toxicity in pregnant and non-pregnant (pre-pregnancy women.

Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease

DEFF Research Database (Denmark)

Bis, Joshua C; Sitlani, Colleen; Irvin, Ryan

2015-01-01

BACKGROUND: Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medica...

COMBINED ANTIHYPERTENSIVE THERAPY IN REAL CLINICAL PRACTICE. FOCUS ON FIXED COMBINATIONS OF ANTIHYPERTENSIVE DRUGS (According to the Data of Outpatient Registries RECVASA and PROFILE

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S. Yu. Martsevich

2017-01-01

Full Text Available On Behalf of the Working Groups of the Registries PROFILE and REСVASA. Working Group of the PROFILE Registry: Akimova A.V., Voronina V.P., Dmitrieva N.A., Zakharova A.V., Zakharova N.A., Zagrebelnyy A.V., Kutishenko N.P., Lerman O.V., Lukina Yu.V., Tolpygina S.N., Martsevich S.Y.Working Group of the RECVASA Registry: Vorobyev A.N., Zagrebelnyy A.V., Kozminsky A.N., Lukina Yu.V., Loukianov M.M., Moseichuk K.A., Nikulina N.N., Pereverzeva K.G., Pravkina E.A., Boytsov S.A., Martsevich S.Yu., Yakushin S.S.Aim. To assess the frequency of prescription of different combinations of the main groups of antihypertensive drugs (AHD and their fixed combinations to patients with arterial hypertension by physicians according to two outpatient registries.Material and methods. Hypertension was diagnosed in 3648 (98.9% patients of the RECVASA registry and in 1230 patients of the PROFILE registry (80.3%. Data on doctor’s prescriptions reflected in the outpatient charts of patients of the both registries were analyzed. The following information of the prescribed antihypertensive therapy was studied in details: AHD, including fixed and free combinations, original and generic AHD. Data on the achievement/non-achievement of target blood pressure (BP level in patients with hypertension were also analyzed.Results. Women were predominated among hypertensive patients of the RECVASA registry, (71.9%. The ratio of men and women was close to 1:1 in the PROFILE registry. Patients of the registry RECVASA were older: the average age was 66.2±12.8 years compared to 63.7±11.4 years in patients of the PROFILE registry, respectively. The majority of patients in the RECVASA registry (61.4% had hypertension of the 3rd degree, patients of the PROFILE registry revealed mostly hypertension of the 2 degree (53.3%. Fixed combinations were prescribed to 14% of patients in the registry of RECVASA and to 16% of patients in the PROFILE registry. Doctors of the PROFILE registry often

Safety and Antihypertensive Effect of Selara® (Eplerenone: Results from a Postmarketing Surveillance in Japan

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Shoko Takahashi

2016-01-01

Full Text Available Prospective postmarketing surveillance of Selara (eplerenone, a selective mineralocorticoid receptor antagonist, was performed to confirm its safety and efficacy for hypertension treatment in Japan. The change in blood pressure after initiation of eplerenone treatment was also examined. Patients with essential hypertension who were eplerenone-naïve were recruited regardless of the use of other antihypertensive drugs. For examination of changes in blood pressure, patients were excluded if eplerenone was contraindicated or used off-label. Patients received 50–100 mg of eplerenone once daily and were observed for 12 weeks. No treatments including antihypertensive drugs were restricted during the surveillance period. Across Japan, 3,166 patients were included for safety analysis. The incidence of adverse drug reactions was 2.4%. The major adverse drug reactions observed were hyperkalemia (0.6%, dizziness, renal impairment, and increased serum potassium (0.2% each. The mean systolic blood pressure decreased from 152.1±19.0 mmHg to 134.8±15.2 mmHg at week 12, and the mean diastolic blood pressure decreased from 85.8±13.7 mmHg to 77.7±11.4 mmHg. There were no significant new findings regarding the type or incidence of adverse reactions, and eplerenone had a clinically significant antihypertensive effect, leading to favorable blood pressure control.

Aggressive regimens for multidrug-resistant tuberculosis decrease all-cause mortality.

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Carole D Mitnick

Full Text Available A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen.This study assessed the impact of an aggressive regimen-one containing at least five likely effective drugs, including a fluoroquinolone and injectable-on treatment outcomes in a large MDR-TB patient cohort.This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death.In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7 drugs. Cure or completion was achieved in 66.1% (442 of patients; death occurred in 20.8% (139. Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89, compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93.The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB.

Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS)

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Bath, Philip M W; Woodhouse, Lisa; Scutt, Polly

2015-01-01

BACKGROUND: High blood pressure is associated with poor outcome after stroke. Whether blood pressure should be lowered early after stroke, and whether to continue or temporarily withdraw existing antihypertensive drugs, is not known. We assessed outcomes after stroke in patients given drugs......·91-1·13; p=0·83), and with continue versus stop antihypertensive drugs OR was 1·05 (0·90-1·22; p=0·55). INTERPRETATION: In patients with acute stroke and high blood pressure, transdermal glyceryl trinitrate lowered blood pressure and had acceptable safety but did not improve functional outcome. We show...

Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric Acute Lymphocytic Leukemia (ALL): Review from an International Consensus Conference

NARCIS (Netherlands)

T.M. Horton (Terzah); R. Sposto (Richard); P. Brown (Patrick); C.P. Reynolds (Patrick); S.P. Hunger (Stephen); N.J. Winick (Naomi); E.A. Raetz (Elizabeth); W.L. Carroll (William); R.J. Arceci (Robert); M.J. Borowitz (Michael); P.S. Gaynon (Paul); L. Gore (Lia); S. Jeha (Sima); B.J. Maurer (Barry); S.E. Siegel (Stuart); A. Biondi (Andrea); P. Kearns (Pamela); A. Narendran (Aru); L.B. Silverman (Lewis); M.A. Smith (Malcolm); C.M. Zwaan (Christian Michel); J.A. Whitlock (James)

2010-01-01

textabstractOne of the challenges of incorporating molecularly targeted drugs into multi-agent chemotherapy (backbone) regimens is defining dose-limiting toxicities (DLTs) of the targeted agent against the background of toxicities of the backbone regimen. An international panel of 22 pediatric acute

Tailored antihypertensive drug therapy prescribed to older women attenuates circulating levels of interleukin-6 and tumor necrosis factor-α

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Toledo JO

2015-01-01

Full Text Available Juliana O Toledo,1 Clayton F Moraes,2,3 Vinícius C Souza,2 Audrey C Tonet-Furioso,2 Luís CC Afonso,4 Cláudio Córdova,3 Otávio T Nóbrega1,2 1Graduate Program in Health Sciences, 2Graduate Program in Medical Sciences, University of Brasília, Brasília, 3Graduate Program in Gerontology, Catholic University of Brasília, Brasília, 4Research Center in Biological Sciences, Federal University of Ouro Preto, Ouro Preto, Brazil Objective: To test the hypothesis that antihypertensive drug therapy produces anti-inflammatory effects in clinical practice, this study investigated circulating levels of selected proinflammatory mediators (interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α], and interferon-γ [INF-γ] in response to multivariate drug directions for blood pressure (BP control.Methods: Prospective study involving 110 hypertensive, community-dwelling older women with different metabolic disorders. A short-term BP-lowering drug therapy was conducted according to current Brazilian guidelines on hypertension, and basal cytokine levels were measured before and after intervention.Results: Interventions were found to represent current hypertension-management practices in Brazil and corresponded to a significant reduction in systolic and diastolic BP levels in a whole-group analysis, as well as when users and nonusers of the most common therapeutic classes were considered separately. Considering all patients, mean IL-6 and TNF-α levels showed a significant decrease in circulating concentrations (P<0.01 at the endpoint compared with baseline, whereas the mean INF-γ level was not significantly different from baseline values. In separate analyses, only users of antagonists of the renin–angiotensin system and users of diuretics exhibited the same significant treatment-induced reduction in serum IL-6 and TNF-α observed in the whole group.Conclusion: Our data demonstrates that a clinically guided antihypertensive treatment is effective in

New-onset diabetes and antihypertensive treatment

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Rychlik, Reinhard

2010-03-01

Full Text Available Introduction: Chronic diseases substantially contribute to the continuous increase in health care expenditures, including type-2 diabetes mellitus as one of the most expensive chronic diseases. Arterial hypertension presents a risk factor for the development of type-2 diabetes mellitus. Numerous analyses have demonstrated that antihypertensive therapies promote the development of type-2-diabetes mellitus. Studies indicate, that the application of angiotensin converting enzyme (ACE inhibitors and angiotensin-receptor-blockers (ARB lead to less new-onset diabetes compared to beta-blockers, diuretics and placebo. Given that beta-blockers and diuretics impair the glucose metabolism, the metabolic effects of different antihypertensive drugs should be regarded; otherwise not only the disease itself, but also antihypertensive therapies may promote the development of new-onset diabetes. Even though, the cost of ACE inhibitors and ARB are higher, the use in patients with metabolic disorders could be cost-effective in the long-term if new-onset diabetes is avoided. Objectives: To evaluate which class of antihypertensive agents promote the development or the manifestation of type-2 diabetes mellitus. How high is the incidence of new-onset diabetes during antihypertensive therapy and how is treatment-induced type-2 diabetes mellitus evaluated clinically? Which agents are therefore cost-effective in the long term? Which ethical, social or legal aspects should be regarded?MethodsA systematic literature review was conducted including clinical trials with at least ten participants which reported new-onset diabetes in the course of antihypertensive treatment. The trials had to be published after 1966 (after 2003 for economic publications in English or German. Results: A total of 34 clinical publications meet the inclusion criteria. Of these, eight publications focus on the development of diabetes mellitus under treatment with diuretic and/or beta-blockers, six

Trends in Prescription and Determinants of Persistence to Antihypertensive Therapy : The PAPEETE Study.

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Costa, Francesco Vittorio; Degli Esposti, Luca; Cerra, Carlo; Veronesi, Chiara; Buda, Stefano

2009-12-01

To assess trends in prescriptions, determinants and timing of treatment discontinuation and/or changes in antihypertensive drug therapy in a cohort of hypertensive patients living in Pavia, a city in the north of Italy. The cohort included 61 493 patients aged ≥18 years who received their first antihypertensive drug prescription (monotherapy, fixed or extemporaneous combination) during the period 2003-6. Patients were classified as 'persistent' if 12 months after the beginning of treatment they were still taking a regular therapy (same drug = 'same therapy users', added one or more drugs = 'add-on therapy users', different drug = 'switchers'). Otherwise, they were classified as 'non-persistent' (stopping therapy after the first prescription = 'occasional users'; stopping treatment early = 'stoppers'; taking medicines in an erratic fashion = 'intermittent users'). ACE inhibitors were the most frequently prescribed drugs (22.8%), followed by β-adrenoceptor antagonists (β-blockers) [14.3%], diuretics (13.9%), Ca(2+) antagonists (11.4%) and angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) [9.3%]. After 12 months, persistent patients were only 11.2% (same therapy users 6.7%, switchers 3.2%, add-on therapy users 1.3%). Non-persistent patients were 88.8% (35.3% occasional users, 20.6% stoppers, 32.8% intermittent users). Patient-related predictors of persistence were older age, male sex, concomitant treatment with antidiabetic and hypolipidaemic drugs and previous hospitalizations for cardiovascular events. Highest level of persistence was seen in patients starting with ARBs (18.8%), followed by ACE inhibitors (11.4%), β-blockers (11.0%), Ca(2+) antagonists (10.8%) and diuretics (3.0%). Among ARBs, considering separately monotherapy and fixed-combination therapy, highest level of persistence was observed in patients starting with candesartan, irbesartan, valsartan and telmisartan given in monotherapy, and with valsartan and

Prescription Pattern of Antihypertensive Agents in T2DM Patients Visiting Tertiary Care Centre in North India

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Ethiraj Dhanaraj

2012-01-01

Full Text Available Background. Hypertension management is of a paramount importance in diabetic patients for cardiovascular risk reduction. Aim. To evaluate prescribing pattern of antihypertensive in T2DM (type 2 diabetes patients and compare with existing recent guidelines. Methods. A cross-sectional study involving evaluation of all T2DM patients referred to endocrinology unit at tertiary care centre for hypertension, comorbid complications, and recording prescription. Utilization of 5 different antihypertensive drug classes was compared for all patients receiving 1, 2, 3, 4, or more drugs. Logistical regression was used to assess likelihood of prescription of drugs and/or therapy for specific conditions mentioned in the guidelines. Results. Out of 1358, T2DM enrolled patients 1186 (87% had hypertension (males 52%, females 48%. The median duration (IQ of hypertension diabetics was 4 (1–10 years. A total of 25% patients had controlled BP and 75% with uncontrolled blood pressure (13% isolated systolic hypertension, 6% isolated diastolic hypertension, and 55% both elevated. Overall, ACE inhibitors (ACEIs were prescribed the highest (59% followed by angiotensin receptor blockers (ARBs (52%, calcium channel blockers (CCBs (29%, diuretics (27%, and beta-blockers (14%. Overall, 55% of T2DM patients were on polytherapy, 41% on monotherapy, and 4% had no antihypertensive treatment. Polytherapy was more predominant with age, duration of diabetes, duration of hypertension, and comorbid complications. Conclusion. Although prescribing pattern of antihypertensive showed adherence to existing evidence-based guidelines, higher proportion of uncontrolled hypertensive patients was found.

Antihypertensive effects of astaxanthin

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Hiroshi Yoshida

2008-10-01

Full Text Available Hidekatsu Yanai1,2, Kumie Ito1,2, Hiroshi Yoshida2,3, Norio Tada1,21Department of Internal Medicine; 2Institute of Clinical Medicine and Research; 3Department of Laboratory Medicine, The Jikei University School of Medicine, Chiba, JapanAbstract: Astaxanthin is a biological antioxidant naturally found in a wide variety of aquatic living organisms, and has shown various pharmacological activities, such as anti-inflammatory and antidiabetic activities. A recent study reported that the administration of astaxanthin induced a significant reduction in blood pressure and delayed the incidence of stroke in stroke-prone spontaneously hypertensive rats, suggesting that astaxanthin also has antihypertensive effect. In a study using aortic rings of spontaneously hypertensive rats, astaxanthin induced a significant reduction of the contractile responses of the aorta to α-adrenergic receptor agonist and angiotensin II, which may contribute to the antihypertensive effect of astaxanthin. In a histopathological study, astaxanthin decreased coronary artery wall thickness compared with the control, indicating the possibility that astaxanthin ameliorates hypertension-induced vascular remodeling. Astaxanthin has anti-inflammatory, antidiabetic, antihypertensive, and antioxidative activities; therefore, we should perform further studies to elucidate an antiatherogenic effect of astaxanthin.Keywords: astaxanthin, antioxidant, antihypertensive effect, atherosclerosis

APF530 (granisetron injection extended-release) in a three-drug regimen for delayed CINV in highly emetogenic chemotherapy.

Science.gov (United States)

Schnadig, Ian D; Agajanian, Richy; Dakhil, Christopher; Gabrail, Nashat Y; Smith, Robert E; Taylor, Charles; Wilks, Sharon T; Schwartzberg, Lee S; Cooper, William; Mosier, Michael C; Payne, J Yvette; Klepper, Michael J; Vacirca, Jeffrey L

2016-06-01

APF530, extended-release granisetron, provides sustained release for ≥5 days for acute- and delayed-phase chemotherapy-induced nausea and vomiting (CINV). We compared efficacy and safety of APF530 versus ondansetron for delayed CINV after highly emetogenic chemotherapy (HEC), following a guideline-recommended three-drug regimen. HEC patients received APF530 500 mg subcutaneously or ondansetron 0.15 mg/kg intravenously, with dexamethasone and fosaprepitant. Primary end point was delayed-phase complete response (no emesis or rescue medication). A higher percentage of APF530 versus ondansetron patients had delayed-phase complete response (p = 0.014). APF530 was generally well tolerated; treatment-emergent adverse event incidence was similar across arms, mostly mild-to-moderate injection-site reactions. APF530 versus the standard three-drug regimen provided superior control of delayed-phase CINV following HEC. ClinicalTrials.gov : NCT02106494.

Toward a noncytotoxic glioblastoma therapy: blocking MCP-1 with the MTZ Regimen

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Salacz ME

2016-04-01

Full Text Available Michael E Salacz,1,2 Richard E Kast,3 Najmaldin Saki,4 Ansgar Brüning,5 Georg Karpel-Massler,6 Marc-Eric Halatsch6 1Department of Internal Medicine, 2Department of Neurosurgery, University of Kansas, Kansas City, KS, USA; 3IIAIGC Study Center, Burlington, VT, USA; 4Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 5Molecular Biology Laboratory, University Hospital Munich, Munich, Germany; 6Department of Neurosurgery, University of Ulm, Ulm, Germany Abstract: To improve the prognosis of glioblastoma, we developed an adjuvant treatment directed to a neglected aspect of glioblastoma growth, the contribution of nonmalignant monocyte lineage cells (MLCs (monocyte, macrophage, microglia, dendritic cells that infiltrated a main tumor mass. These nonmalignant cells contribute to glioblastoma growth and tumor homeostasis. MLCs comprise of approximately 10%–30% of glioblastoma by volume. After integration into the tumor mass, these become polarized toward an M2 immunosuppressive, pro-angiogenic phenotype that promotes continued tumor growth. Glioblastoma cells initiate and promote this process by synthesizing 13 kDa MCP-1 that attracts circulating monocytes to the tumor. Infiltrating monocytes, after polarizing toward an M2 phenotype, synthesize more MCP-1, forming an amplification loop. Three noncytotoxic drugs, an antibiotic – minocycline, an antihypertensive drug – telmisartan, and a bisphosphonate – zoledronic acid, have ancillary attributes of MCP-1 synthesis inhibition and could be re-purposed, singly or in combination, to inhibit or reverse MLC-mediated immunosuppression, angiogenesis, and other growth-enhancing aspects. Minocycline, telmisartan, and zoledronic acid – the MTZ Regimen – have low-toxicity profiles and could be added to standard radiotherapy and temozolomide. Re-purposing older drugs has advantages of established safety and low

Drug-Drug Interactions Between the Anti-Hepatitis C Virus 3D Regimen of Ombitasvir, Paritaprevir/Ritonavir, and Dasabuvir and Eight Commonly Used Medications in Healthy Volunteers.

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Polepally, Akshanth R; King, Jennifer R; Ding, Bifeng; Shuster, Diana L; Dumas, Emily O; Khatri, Amit; Chiu, Yi-Lin; Podsadecki, Thomas J; Menon, Rajeev M

2016-08-01

The three direct-acting antiviral regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D regimen) is approved for treatment of hepatitis C virus (HCV) genotype 1 infection. Drug-drug interaction (DDI) studies of the 3D regimen and commonly used medications were conducted in healthy volunteers to provide information on coadministering these medications with or without dose adjustments. Three phase I studies evaluated DDIs between the 3D regimen (ombitasvir/paritaprevir/ritonavir 25/150/100 mg once daily + dasabuvir 250 mg twice daily) and hydrocodone bitartrate/acetaminophen (5/300 mg), metformin hydrochloride (500 mg), diazepam (2 mg), cyclobenzaprine hydrochloride (5 mg), carisoprodol (250 mg), or sulfamethoxazole/trimethoprim (SMZ/TMP) (800/160 mg twice daily), all administered orally. DDI magnitude was determined using geometric mean ratios and 90 % confidence intervals for the maximum plasma concentration (C max) and area under the plasma concentration-time curve (AUC). Changes in exposures (C max and AUC geometric mean ratios) of acetaminophen, metformin, sulfamethoxazole, trimethoprim, and diazepam were ≤25 % upon coadministration with the 3D regimen. The C max and AUC of nordiazepam, an active metabolite of diazepam, increased by 10 % and decreased by 44 %, respectively. Exposures of cyclobenzaprine and carisoprodol decreased by ≤40 and ≤46 %, respectively, whereas exposures of hydrocodone increased up to 90 %. Ombitasvir, paritaprevir, ritonavir, and dasabuvir exposures changed by ≤25 %, except for a 37 % decrease in paritaprevir C max with metformin and a 33 % increase in dasabuvir AUC with SMZ/TMP. Acetaminophen, metformin, sulfamethoxazole, and trimethoprim can be coadministered with the 3D regimen without dose adjustment. Higher doses may be needed for diazepam, cyclobenzaprine, and carisoprodol based on clinical monitoring. A 50 % lower dose and/or clinical monitoring should be considered for hydrocodone. No dose

Adherence to Antihypertensive Treatment and the Blood Pressure-Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial.

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Azizi, Michel; Pereira, Helena; Hamdidouche, Idir; Gosse, Philippe; Monge, Matthieu; Bobrie, Guillaume; Delsart, Pascal; Mounier-Véhier, Claire; Courand, Pierre-Yves; Lantelme, Pierre; Denolle, Thierry; Dourmap-Collas, Caroline; Girerd, Xavier; Michel Halimi, Jean; Zannad, Faiez; Ormezzano, Olivier; Vaïsse, Bernard; Herpin, Daniel; Ribstein, Jean; Chamontin, Bernard; Mourad, Jean-Jacques; Ferrari, Emile; Plouin, Pierre-François; Jullien, Vincent; Sapoval, Marc; Chatellier, Gilles

2016-09-20

The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure-lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report the influence of adherence to antihypertensive treatment on blood pressure control. One hundred six patients with hypertension resistant to 4 weeks of treatment with indapamide 1.5 mg/d, ramipril 10 mg/d (or irbesartan 300 mg/d), and amlodipine 10 mg/d were randomly assigned to renal denervation plus standardized stepped-care antihypertensive treatment, or the same antihypertensive treatment alone. For standardized stepped-care antihypertensive treatment, spironolactone 25 mg/d, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d were sequentially added at monthly visits if home blood pressure was ≥135/85 mm Hg after randomization. We assessed adherence to antihypertensive treatment at 6 months by drug screening in urine/plasma samples from 85 patients. The numbers of fully adherent (20/40 versus 21/45), partially nonadherent (13/40 versus 20/45), or completely nonadherent patients (7/40 versus 4/45) to antihypertensive treatment were not different in the renal denervation and the control groups, respectively (P=0.3605). The difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the 2 groups was -6.7 mm Hg (P=0.0461) in fully adherent and -7.8 mm Hg (P=0.0996) in nonadherent (partially nonadherent plus completely nonadherent) patients. The between-patient variability of daytime ambulatory systolic blood pressure was greater for nonadherent than for fully adherent patients. In the DENERHTN trial, the prevalence of nonadherence to antihypertensive drugs at 6 months was high (≈50%) but not different in the renal denervation and control groups. Regardless of adherence to treatment, renal denervation plus standardized stepped-care antihypertensive treatment resulted in

Importance of confirming data on the in vivo efficacy of novel antibacterial drug regimens against various strains of Mycobacterium tuberculosis.

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De Groote, Mary A; Gruppo, Veronica; Woolhiser, Lisa K; Orme, Ian M; Gilliland, Janet C; Lenaerts, Anne J

2012-02-01

In preclinical testing of antituberculosis drugs, laboratory-adapted strains of Mycobacterium tuberculosis are usually used both for in vitro and in vivo studies. However, it is unknown whether the heterogeneity of M. tuberculosis stocks used by various laboratories can result in different outcomes in tests of antituberculosis drug regimens in animal infection models. In head-to-head studies, we investigated whether bactericidal efficacy results in BALB/c mice infected by inhalation with the laboratory-adapted strains H37Rv and Erdman differ from each other and from those obtained with clinical tuberculosis strains. Treatment of mice consisted of dual and triple drug combinations of isoniazid (H), rifampin (R), and pyrazinamide (Z). The results showed that not all strains gave the same in vivo efficacy results for the drug combinations tested. Moreover, the ranking of HRZ and RZ efficacy results was not the same for the two H37Rv strains evaluated. The magnitude of this strain difference also varied between experiments, emphasizing the risk of drawing firm conclusions for human trials based on single animal studies. The results also confirmed that the antagonism seen within the standard HRZ regimen by some investigators appears to be an M. tuberculosis strain-specific phenomenon. In conclusion, the specific identity of M. tuberculosis strain used was found to be an important variable that can change the apparent outcome of in vivo efficacy studies in mice. We highly recommend confirmation of efficacy results in late preclinical testing against a different M. tuberculosis strain than the one used in the initial mouse efficacy study, thereby increasing confidence to advance potent drug regimens to clinical trials.

Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe

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Hofstra, L Marije; Sauvageot, Nicolas; Albert, Jan

2016-01-01

BACKGROUND:  Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management......, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. METHODS:  Demographic, clinical, and virological data from 4140 antiretroviral-naive human...... immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002...

Viro-immunological response of drug-naive HIV-1-infected patients starting a first-line regimen with viraemia >500,000 copies/ml in clinical practice.

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Santoro, Maria Mercedes; Di Carlo, Domenico; Armenia, Daniele; Zaccarelli, Mauro; Pinnetti, Carmela; Colafigli, Manuela; Prati, Francesca; Boschi, Andrea; Antoni, Anna Maria Degli; Lagi, Filippo; Sighinolfi, Laura; Gervasoni, Cristina; Andreoni, Massimo; Antinori, Andrea; Mussini, Cristina; Perno, Carlo Federico; Borghi, Vanni; Sterrantino, Gaetana

2017-09-22

Virological success (VS) and immunological reconstitution (IR) of antiretroviral-naive HIV-1-infected patients with pre-therapy viral load (VL) >500,000 copies/ml was assessed after 12 months of treatment according to initial drug-class regimens. An observational multicentre retrospective study was performed. VS was defined as the first VL 500,000 copies/ml who start a first-line regimen containing PI+INI or NNRTI yield a better VS compared to those receiving a PI-based regimen.

A Comparison of the Effectiveness of Three Drug Regimens on Cognitive Performance of Patients with Parkinson's disease

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Emsaki, Golit; Asgari, Karim; Molavi, Hossein; Chitsaz, Ahmad

2013-01-01

In the present study, the effectiveness of 3 drug regimen on cognitive performance of PD patients was compared. 12 patients who had been using pramipexole, levodopa and amantadine for at least 1 month entered the study and compared with those 12 who had been using trihexiphenidyle, levodopa and amantadine. There was also a control group…

Mechanisms of remodelling of small arteries, antihypertensive therapy and the immune system in hypertension.

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Schiffrin, Ernesto L

2015-12-04

This review summarizes my lecture for the 2015 Distinguished Scientist Award from the Canadian Society of Clinical Investigation, and is based mainly on studies in my laboratory on the mechanisms of remodelling of small arteries in experimental animal and human hypertension and on treatments that lower blood pressure and improve structure and function of resistance vessels. Small resistance arteries undergo either inward eutrophic or hypertrophic remodelling, which raises blood pressure and impairs tissue perfusion. These vascular changes are corrected by some antihypertensive drugs, which may lead to improved outcomes. Vasoconstriction, growth, oxidative stress and inflammation are some of the mechanisms, within the vascular wall, that can be beneficially affected by antihypertensive agents. These antihypertensive-sensitive mechanisms are reviewed in this review, together with the inflammatory and immune mechanisms that may participate in hypertension and associated cardiovascular injury. Molecular studies, based on this research, will hopefully identify novel diagnostic and therapeutic targets, which will improve our ability to prevent and treat hypertension and cardiovascular disease.

L-type Ca²⁺ channel blockade with antihypertensive medication disrupts VTA synaptic plasticity and drug-associated contextual memory.

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Degoulet, M; Stelly, C E; Ahn, K-C; Morikawa, H

2016-03-01

Drug addiction is driven, in part, by powerful and enduring memories of sensory cues associated with drug intake. As such, relapse to drug use during abstinence is frequently triggered by an encounter with drug-associated cues, including the drug itself. L-type Ca(2+) channels (LTCCs) are known to regulate different forms of synaptic plasticity, the major neural substrate for learning and memory, in various brain areas. Long-term potentiation (LTP) of NMDA receptor (NMDAR)-mediated glutamatergic transmission in the ventral tegmental area (VTA) may contribute to the increased motivational valence of drug-associated cues triggering relapse. In this study, using rat brain slices, we found that isradipine, a general LTCC antagonist used as antihypertensive medication, not only blocks the induction of NMDAR LTP but also promotes the reversal of previously induced LTP in the VTA. In behaving rats, isradipine injected into the VTA suppressed the acquisition of cocaine-paired contextual cue memory assessed using a conditioned place preference (CPP) paradigm. Furthermore, administration of isradipine or a CaV1.3 subtype-selective LTCC antagonist (systemic or intra-VTA) before a single extinction or reinstatement session, while having no immediate effect at the time of administration, abolished previously acquired cocaine and alcohol (ethanol) CPP on subsequent days. Notably, CPP thus extinguished cannot be reinstated by drug re-exposure, even after 2 weeks of withdrawal. These results suggest that LTCC blockade during exposure to drug-associated cues may cause unlearning of the increased valence of those cues, presumably via reversal of glutamatergic synaptic plasticity in the VTA.

Antihypertensive treatment

DEFF Research Database (Denmark)

Christensen, Cramer; Mogensen, C E

1987-01-01

This study was undertaken to clarify whether antihypertensive treatment has any effect on the rate of progression of kidney disease in patients with incipient diabetic nephropathy. Six insulin-dependent diabetic men with incipient nephropathy (urinary albumin excretion above 15 micrograms....../min and total protein excretion below 0.5 g/24 h) were first given metoprolol (200 mg daily) with the subsequent addition of hydroflumethiazide. At the start of antihypertensive treatment, mean patient age was 32 +/- 4.2 years (SD) and mean duration of diabetes was 18 +/- 1.2 years. The patients were followed...... with repeated measurements of urinary albumin excretion for a mean of 5.4 +/- 3.1 years prior to, and for 4.7 +/- 1.3 years (SD) during treatment. Mean arterial blood pressure declined significantly during treatment, e.g., the values at 6 months before initiation of treatment being compared with values during...

Antihypertensive treatment and stroke prevention: are angiotensin receptor blockers superior to other antihypertensive agents?

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Armario, Pedro; de la Sierra, Alejandro

2009-06-01

Stroke remains a common vascular event with high mortality and morbidity. After heart disease, stroke is the second leading cause of death worldwide in adult persons. Silent or subclinical stroke is likely to occur with even greater frequency than clinical stroke and increases the risk of subsequent cerebrovascular events. Hypertension is by far the single most important controllable risk factor for stroke. The relationship between blood pressure (BP) and stroke mortality is strong, linear, and continuous in subjects with levels of BP higher than 115/75 mm Hg. Blood pressure reduction by antihypertensive treatment is clearly efficacious in the prevention of stroke (both primary and secondary). Although meta-analyses suggest that BP reduction, per se, is the most important determinant for stroke risk reduction, the question is if specific classes of antihypertensive drugs offer special protection against stroke is still controversial. Some studies have suggested that angiotensin receptors blockers (ARBs) appear to offer additional protection against stroke. This has been hypothesized in studies in hypertensives, such as LIFE and SCOPE, and especially in the only comparative trial focused on secondary stroke prevention. In the MOSES trial, the comparison of eprosartan versus nitrendipine in patients with a previous stroke resulted, despite a similar BP reduction, in a significant reduction in the primary composite endpoint of total mortality plus cardiovascular and cerebrovascular events, including recurrent events. These results may suggest a blood pressure-independent effect of ARBs, which can be mediated through several mechanisms, including their ability to counteract other markers of target organ damage, but also through a direct neuroprotective effect.

Quality of life before and during antihypertensive treatment : A comparative study of celiprolol and atenolol

NARCIS (Netherlands)

Cleophas, TJM; vanderMey, N; vanderMeulen, J; Niemeyer, MG

Background: The well-being of hypertensive patients may be adversely affected by the disease itself, its complications, and other concomitant processes such as anxiety, sedation, and side effects of the prescribed drugs. Some recently developed antihypertensive agents have been suggested to be

The regional localization of a new potent centrally acting antihypertensive agent R 28935 and its less active threo isomer R 29814 in the cat brain

NARCIS (Netherlands)

Loonen, A.J.M.; Soudijn, W.; Van Rooy, H.H.; Van Wijngaarden, I.

1977-01-01

Systemic administration of the centrally acting antihypertensive agent R 28935 to cats resulted in a long lasting decrease of mean arterial pressure (±30%) whereas the same dose of the threo-isomer R 29814 was ineffective. The antihypertensive activity was due to the unaltered drug. In spite of an

Rifampicin and anti-hypertensive drugs in chronic kidney disease: Pharmacokinetic interactions and their clinical impact

Directory of Open Access Journals (Sweden)

A Agrawal

2016-01-01

Full Text Available Patients on dialysis have an increased incidence of tuberculosis (TB. Rifampicin, a first-line antitubercular therapy (ATT drug, is a potent inducer of hepatic cytochrome P450 (CYP. There is potential for pharmacokinetic interaction between rifampicin and anti-hypertensives that are CYP substrates: amlodipine and metoprolol. Therefore, hypertensive patients receiving rifampicin-based ATT are at risk for worsening of hypertension. However, this hypothesis has not yet been systematically studied. In this prospective study, hypertensive CKD 5D patients with TB were followed after rifampicin initiation. Blood pressure (BP was ≤140/90 mmHg with stable anti-HT requirement at inclusion. Serum amlodipine, metoprolol, and prazosin levels were estimated by high-performance liquid chromatography at baseline and 3, 7, 10, and 14 days after rifampicin initiation. BP and anti-HT requirement were monitored for 2 weeks or until stabilization. All 24 patients in the study had worsening of hypertension after rifampicin and 83.3% required increase in drugs to maintain BP 50% in all patients and became undetectable in 50-75%. Drug requirement increased from 4.5 ± 3.6 to 8.5 ± 6.4 units (P < 0.0001. Mean time to first increase in dose was 6.5 ± 3.6 days. Eleven (46% patients experienced a hypertensive crisis at 9.1 ± 3.8 days. Three of them had a hypertensive emergency with acute pulmonary edema. In two patients, rifampicin had to be discontinued to achieve BP control. In conclusion, rifampicin caused a significant decrease in blood levels of commonly used anti hypertensives. This decrease in levels correlated well with worsening of hypertension. Thus, we suggest very close BP monitoring in CKD patients after rifampicin initiation.

Follow-up of Antihypertensive Therapy Improves Blood Pressure Control: Results of HYT (HYperTension survey) Follow-up.

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Fici, F; Seravalle, G; Koylan, N; Nalbantgil, I; Cagla, N; Korkut, Y; Quarti-Trevano, F; Makel, W; Grassi, G

2017-09-01

Although improved during the past few years, blood pressure control remains sub optimal. The impact of follow-up assessment on blood pressure control was evaluated in a group of patients of the HYT (HYperTension survey), treated with a combination of different dihydropyridine calcium-channel blockers (CCBs regimen) and inhibitors of renin-angiotensin-aldosterone system (RAAS) and with uncontrolled blood pressure. This was obtained assessing (a) the rate of blood pressure control at 3 and 6 months of follow-up in the whole group of patients, (b) the rate of blood pressure control and the average blood pressure values in subjects treated with different DHP-CCBs regimen. From the 4993 patients with uncontrolled blood pressure, (BP ≥ 140/90 or ≥140/85 in patients with diabetes), 3729 (mean age 61.2 ± 11.5 years), maintained CCBs regimen combined wih RAAS blockers and were evaluated at 3 and 6 months follow-up. At each visit BP (semiautomatic device, Omron-M6, 3 measurements), heart rate, adverse events and treatment persistence were collected. At 1st and 2nd follow-up the rate of controlled BP was 63.5 and 72.8% respectively (p blood pressure control; (b) there is no significant difference in the antihypertensive effect between different CCBs regimen; (c) lipophilic CCBs induce less ankle edema.

Colchicine in Pericardial Disease: from the Underlying Biology and Clinical Benefits to the Drug-Drug Interactions in Cardiovascular Medicine.

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Schenone, Aldo L; Menon, Venu

2018-06-14

This is an in-depth review on the mechanism of action, clinical utility, and drug-drug interactions of colchicine in the management of pericardial disease. Recent evidence about therapeutic targets on pericarditis has demonstrated that NALP3 inflammasome blockade is the cornerstone in the clinical benefits of colchicine. Such benefits extend from acute and recurrent pericarditis to transient constriction and post-pericardiotomy syndrome. Despite the increased utilization of colchicine in cardiovascular medicine, safety concerns remains unsolved regarding the long-term use of colchicine in the cardiac patient. Moreover, recent evidence has demonstrated that numerous cardiovascular medications, ranging from antihypertensive medication to antiarrhythmics, are known to interact with the CYP3A4 and/or P-gp system increasing the toxicity potential of colchicine. The use of adjunctive colchicine in the management of inflammatory pericardial diseases is standard of care in current practice. It is advised that a careful medication reconciliation with emphasis on pharmacokinetic is completed before prescribing colchicine in order to avoid harmful interaction by finding an alternative regimen or adjusting colchicine dosing.

Utilization Study of Antihypertensives in a South Indian Tertiary Care Teaching Hospital and Adherence to Standard Treatment Guidelines.

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Datta, Supratim

2016-12-01

Hypertension represents a major health problem primarily because of its role in contributing to the initiation and progression of major cardiovascular diseases. Concerns pertaining to hypertension and its sequelae can be substantially addressed and consequent burden of disease reduced by early detection and appropriate therapy of elevated blood pressure. This cross-sectional observational study aims at analyzing the utilization pattern of antihypertensives used for the treatment of hypertension at a tertiary care hospital in perspective of standard treatment guidelines. Prescriptions were screened for antihypertensives at the medicine outpatient department of a tertiary care teaching hospital. Medical records of the patients were scrutinized after which 286 prescriptions of patients suffering from hypertension were included. The collected data were sorted and analyzed on the basis of demographic characteristics and comorbidities. The calcium channel blockers were the most frequently used antihypertensive class of drugs (72.3%). Amlodipine (55.6%) was the single most frequently prescribed antihypertensive agent. The utilization of thiazide diuretics was 9%. Adherence to the National List of Essential Medicines (NLEMs) was 65%. The combination therapy was used more frequently (51.5%) than monotherapy (48.8%). The use of angiotensin-converting enzyme inhibitors/angiotensin 2 receptor blockers (ACE-I/ARB) was 41.4% in diabetes. The treatment pattern, in general, conformed to standard treatment guidelines. Few areas, however, need to be addressed such as the underutilization of thiazide diuretics, need for more awareness of drugs from the NLEMs and enhanced use of ACE-I/ARB in diabetic hypertensives.

Male Infertility during Antihypertensive Therapy: Are We Addressing Correctly The Problem?

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Laganà, Antonio Simone; Vitale, Salvatore Giovanni; Iaconianni, Paola; Gatti, Simona; Padula, Francesco

2016-01-01

Male fertility significantly decreased in the last 50 years, as showed in several studies reporting a reduction of sperm counts per ml in the seminal fluid. Several "acute" pharmacological treatments, as antibiotics, could cause subclinical and temporary reduction of male fertility; conversely, long-term medical treatment may severely affect male fertility, although this effect could be considered transient in most of the cases. Thus, nowadays, several long-term pharmacological treatments may represent a clinical challenge. The association between several kind of antihypertensive drugs and reduction of male fertility has been showed in the mouse model, although the modification(s) which may alter this fine-regulated machinery are still far to be elucidated. Furthermore, well-designed observational studies and randomized controlled trials are needed to accurately define this association in human model, meaning a narrative overview synthesizing the findings of literature retrieved from searches of computerized databases. We strongly solicit future human studies (both observational and randomized clinical trials) on large cohorts with adequate statistical power which may clarify this possible association and the effects (reversible or permanent) of each drug. Furthermore, we suggest a close collaboration between general practitioners, cardiologists, and andrologists in order to choose the most appropriate antihypertensive therapy considering also patient's reproductive desire and possible risk for his fertility.

Does fermented milk possess antihypertensive effect in humans?

DEFF Research Database (Denmark)

Usinger, Lotte; Ibsen, Hans; Jensen, Lars T

2009-01-01

The putative antihypertensive effect of milk after fermentation by lactic bacteria has attracted attention over the past 20 years. Research on fermented milk and hypertension has mainly focused on the content of peptides with in-vitro angiotensin converting enzyme-inhibitor effect. However......, fermented milk products contain several proteins, peptides and minerals, all with possible different antihypertensive modes of actions. The burden of cardiovascular events in industrialized countries caused by hypertension is considerable. Diet modifications are one way to lower blood pressure......, and fermented milk could be a feasible way. In this review, interventional human studies of the possible antihypertensive effect of fermented milk are evaluated. The results are diverging, and the antihypertensive effect is still debatable. Additionally, present knowledge of bioavailability and in-vivo actions...

Targeting nocturnal hypertension in type 2 diabetes mellitus.

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Rossen, Niklas Blach; Knudsen, Søren Tang; Fleischer, Jesper; Hvas, Anne-Mette; Ebbehøj, Eva; Poulsen, Per Løgstrup; Hansen, Klavs Würgler

2014-11-01

Several studies in different populations have suggested that nighttime blood pressure (BP) is a stronger predictor of cardiovascular events than daytime BP. Consequently, treatment strategies to target nighttime BP have come into focus. The aim of the present study was to investigate the effect of change of administration time of antihypertensive drugs. We included 41 patients with type 2 diabetes mellitus and nocturnal hypertension (nighttime systolic BP >120 mm Hg) in an open-label, crossover study. Patients were randomized to 8 weeks of either morning or bedtime administration of all of the individual's once-daily antihypertensive drugs, followed by 8 weeks of switched dosing regimen. Bedtime administration of antihypertensive drugs resulted in a significant reduction in nighttime (7.5 mm Hg; Pdiabetes mellitus and nocturnal hypertension, administration of once-daily antihypertensive drugs at bedtime may be favorable. The increased nocturnal natriuresis may reflect increased effect of bedtime-administered thiazides and renin-angiotensin system inhibitors, suggesting a potential mechanism of the observed effects on BP with chronotherapeutic intervention. © 2014 American Heart Association, Inc.

Drugs and lactation

International Nuclear Information System (INIS)

Kelssering, G.; Aguiar, L.F.; Ribeiro, R.M.; Souza, A.Z. de

1988-01-01

Different kinds of drugs who can be transferred through the mother's milk to the lactant and its effects are showed in this work. A list of them as below: cardiotonics, diuretics, anti-hypertensives, beta-blockings, anti-arrythmics, drugs with gastrintestinal tract action, hormones, antibiotics and chemotherapeutics, citostatic drugs, central nervous system action drugs and anticoagulants drugs. (L.M.J.) [pt

Leveraging protein binding and the EPR effect in legacy chemotherapy regimens

Directory of Open Access Journals (Sweden)

Shireesh Apte

2016-12-01

Full Text Available Legacy chemotherapy regimens have the potential to be significantly more effective and less toxic if the dosage is titrated so that the mole ratio of drugs to circulating albumin is less than or equal to 1 and the order of administration of the drugs within each course of the regimen follows the sequence most hydrophobic (usually the least dose to least hydrophobic (usually the largest dose

What role does African ancestry play in how hypertensive patients respond to certain antihypertensive drug therapy?

NARCIS (Netherlands)

Seedat, Yackoob K.; Brewster, Lizzy M.

2014-01-01

This article is a summary of the response of the four commonly used antihypertensive agents in African ancestry patients. They are thiazide like diuretics or indapamide, calcium channel blockers (CCB), angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers, and β-adrenergic

Different antihypertensive effect of beta-blocking drugs in low and normal-high renin hypertension.

Science.gov (United States)

Kralberg, B E; Tolagen, K

1976-05-31

The treatment response to beta-adrenoceptor blocking drugs was compared in two groups of patients with primary (essential) hypertension and different renin levels. Each group consisted of 25 patients and was equally distributed regarding age, severity and stage of hypertension. In the first group (group 1), the mean upright plasma renin activity was 0.8 ng ml-1h-1 (range 0.3 to 1.5) and the patients were considered to have low renin hypertension. In the other group (group 2) the patients had a mean plasma renin activity of 2.1 ng ml-1h-1 (range 1.1 to 5.1) and were considered to have normal to high renin hypertension. In both groups the patients were initially treated with beta-blocking drugs; in group 1 with a beta-blocker corresponding to an average dose of 311 mg propranolol a day for at least eight weeks and in group 2 with propranolol 320 mg a day in a fixed dose for eight weeks. The hypotensive response differed significantly between the two groups (p less than 0.001). In group 1 the pretreatment blood pressure was 197/117 mm Hg supine and 198/120 mm Hg standing. During treatment blood pressure decreased only 5/3 mm Hg supine and 9/5 mm Hg standing. The pretreatment blood pressure in group 2 was 187/114 mm Hg supine and 186/117 mm Hg standing. Beta-blocking therapy reduced blood pressure 36/23 and 34/18 mm Hg, respectively (both p less than 0.001). Pulse rates fell significantly in the two groups, both in the lying and standing positions. In 17 patients with low renin hypertension (group 1), a volume-depleting drug was added (spironolactone, 14 patients; thiazides, 3 patients) and this achieved a marked fall in blood pressure levels of 38/16 mm Hg supine and 37/19 mm Hg standing (both p less than 0.001). These results suggest the following: (1) Most patients with normal to high plasma renin activity respond well to moderate doses of propranolol. (2) Propranolol given in the same doses is almost without antihypertensive effect in patients with low renin

Pharmacokinetics of Pyrazinamide and Optimal Dosing Regimens for Drug-Sensitive and -Resistant Tuberculosis.

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Chirehwa, Maxwell T; McIlleron, Helen; Rustomjee, Roxana; Mthiyane, Thuli; Onyebujoh, Philip; Smith, Peter; Denti, Paolo

2017-08-01

Pyrazinamide is used in the treatment of tuberculosis (TB) because its sterilizing effect against tubercle bacilli allows the shortening of treatment. It is part of standard treatment for drug-susceptible and drug-resistant TB, and it is being considered as a companion drug in novel regimens. The aim of this analysis was to characterize factors contributing to the variability in exposure and to evaluate drug exposures using alternative doses, thus providing evidence to support revised dosing recommendations for drug-susceptible and multidrug-resistant tuberculosis (MDR-TB). Pyrazinamide pharmacokinetic (PK) data from 61 HIV/TB-coinfected patients in South Africa were used in the analysis. The patients were administered weight-adjusted doses of pyrazinamide, rifampin, isoniazid, and ethambutol in fixed-dose combination tablets according to WHO guidelines and underwent intensive PK sampling on days 1, 8, 15, and 29. The data were interpreted using nonlinear mixed-effects modeling. PK profiles were best described using a one-compartment model with first-order elimination. Allometric scaling was applied to disposition parameters using fat-free mass. Clearance increased by 14% from the 1st day to the 29th day of treatment. More than 50% of patients with weight less than 55 kg achieved lower pyrazinamide exposures at steady state than the targeted area under the concentration-time curve from 0 to 24 h of 363 mg · h/liter. Among patients with drug-susceptible TB, adding 400 mg to the dose for those weighing 30 to 54 kg improved exposure. Average pyrazinamide exposure in different weight bands among patients with MDR-TB could be matched by administering 1,500 mg, 1,750 mg, and 2,000 mg to patients in the 33- to 50-kg, 51- to 70-kg, and greater than 70-kg weight bands, respectively. Copyright © 2017 American Society for Microbiology.

Male infertility during antihypertensive therapy: are we addressing correctly the problem?

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Antonio Simone Laganà

2016-09-01

Full Text Available Male fertility significantly decreased in the last 50 years, as showed in several studies reporting a reduction of sperm counts per ml in the seminal fluid. Several “acute” pharmacological treatments, as antibiotics, could cause subclinical and temporary reduction of male fertility; conversely, long-term medical treatment may severely affect male fertility, although this effect could be considered transient in most of the cases. Thus, nowadays, several long-term pharmacological treatments may represent a clinical challenge. The association between several kind of antihypertensive drugs and reduction of male fertility has been showed in the mouse model, although the modification(s which may alter this fine-regulated machinery are still far to be elucidated. Furthermore, well-designed observational studies and randomized controlled trials are needed to accurately define this association in human model, meaning a narrative overview synthesizing the findings of literature retrieved from searches of computerized databases. We strongly solicit future human studies (both observational and randomized clinical trials on large cohorts with adequate statistical power which may clarify this possible association and the effects (reversible or permanent of each drug. Furthermore, we suggest a close collaboration between general practitioners, cardiologists, and andrologists in order to choose the most appropriate antihypertensive therapy considering also patient’s reproductive desire and possible risk for his fertility.

Antihypertensive use, prescription patterns, and cost of medications ...

African Journals Online (AJOL)

Antihypertensive use, prescription patterns, and cost of medications in a Teaching Hospital in Lagos, Nigeria. ... Conclusions: Antihypertensive prescription pattern was in accordance with the seventh report of Joint National Committee on Prevention, Detection, Evaluation, and Treatment of high blood pressure.

Antihypertensive potential of bioactive hydrolysate from edible bird's nest

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Ramachandran, Ravisangkar; Babji, Abdul Salam; Sani, Norrakiah Abdullah

2018-04-01

The aim of this study is to determine and compare the proximate composition, the degree of hydrolysis (DH) and the antihypertensive activity of edible bird's nest (EBN) hydrolysates of two different drying methods. Four types of enzymes (alcalase, bromelain, pancreatin and papain) were used in this study and with different hydrolysis time (30, 60, 90, 120, 180 and 240 min). The highest DH for alcalase (79.48 - 84.09%), pancreatine (77.10 - 80.45%) and papain (82.33%) for EBN hydrolysates was produced with alcalase treatment at 60 - 90 min, pancreatine treatment at 30 - 90 min and papain treatment at 90 min. Bromelain generated hydrolysates showed low DH. EBN hydrolysed using alcalase, pancreatin and papain have significantly higher protein content compared to raw EBN and the moisture content of all hydrolysates treatments was significantly lower compared to raw EBN. For antihypertensive assay, freeze dried EBN hydrolysates have higher antihypertensive activity compared to spray dried hydrolysates. The highest antihypertensive activity for freeze dried samples was produced by alcalase, bromelain and pancreatin and in the range of 80.22 - 86.97%. Meanwhile, papain proved to be less effective in producing hydrolysate with antihypertensive ability. In conclusion, EBN hydrolysate prepared by alcalase, bromelain and pancreatin could be classified as a functional food as it showed significant antihypertensive activity.

Molecular Targets of Antihypertensive Peptides: Understanding the Mechanisms of Action Based on the Pathophysiology of Hypertension

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Kaustav Majumder

2014-12-01

Full Text Available There is growing interest in using functional foods or nutraceuticals for the prevention and treatment of hypertension or high blood pressure. Although numerous preventive and therapeutic pharmacological interventions are available on the market, unfortunately, many patients still suffer from poorly controlled hypertension. Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE, are often associated with significant adverse effects. Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention. Some of these peptides have exhibited potent in vivo antihypertensive activity in both animal models and human clinical trials. This review provides an overview about the complex pathophysiology of hypertension and demonstrates the potential roles of food derived bioactive peptides as viable interventions targeting specific pathways involved in this disease process. This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides.

Discovery of Anti-Hypertensive Oligopeptides from Adlay Based on In Silico Proteolysis and Virtual Screening

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Liansheng Qiao

2016-12-01

Full Text Available Adlay (Coix larchryma-jobi L. was the commonly used Traditional Chinese Medicine (TCM with high content of seed storage protein. The hydrolyzed bioactive oligopeptides of adlay have been proven to be anti-hypertensive effective components. However, the structures and anti-hypertensive mechanism of bioactive oligopeptides from adlay were not clear. To discover the definite anti-hypertensive oligopeptides from adlay, in silico proteolysis and virtual screening were implemented to obtain potential oligopeptides, which were further identified by biochemistry assay and molecular dynamics simulation. In this paper, ten sequences of adlay prolamins were collected and in silico hydrolyzed to construct the oligopeptide library with 134 oligopeptides. This library was reverse screened by anti-hypertensive pharmacophore database, which was constructed by our research team and contained ten anti-hypertensive targets. Angiotensin-I converting enzyme (ACE was identified as the main potential target for the anti-hypertensive activity of adlay oligopeptides. Three crystal structures of ACE were utilized for docking studies and 19 oligopeptides were finally identified with potential ACE inhibitory activity. According to mapping features and evaluation indexes of pharmacophore and docking, three oligopeptides were selected for biochemistry assay. An oligopeptide sequence, NPATY (IC50 = 61.88 ± 2.77 µM, was identified as the ACE inhibitor by reverse-phase high performance liquid chromatography (RP-HPLC assay. Molecular dynamics simulation of NPATY was further utilized to analyze interactive bonds and key residues. ALA354 was identified as a key residue of ACE inhibitors. Hydrophobic effect of VAL518 and electrostatic effects of HIS383, HIS387, HIS513 and Zn2+ were also regarded as playing a key role in inhibiting ACE activities. This study provides a research strategy to explore the pharmacological mechanism of Traditional Chinese Medicine (TCM proteins based on

Possible impact of the standardized Category IV regimen on multidrug-resistant tuberculosis patients in Mumbai.

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Udwadia, Zarir F; Mullerpattan, Jai Bharat; Shah, Kushal D; Rodrigues, Camilla S

2016-01-01

Treatment of multidrug-resistant tuberculosis (MDR-TB) in the Programmatic Management of Drug-resistant TB program involves a standard regimen with a 6-month intensive phase and an 18-month continuation phase. However, the local drug resistance patterns in high MDR regions such as Mumbai may not be adequately reflected in the design of the regimen for that particular area. The study was carried out at a private Tertiary Level Hospital in Mumbai in a mycobacteriology laboratory equipped to perform the second-line drug susceptibility testing (DST). We attempted to analyze the impact of prescribing the standardized Category IV regimen to all patients receiving a DST at our mycobacteriology laboratory. All samples confirmed to be MDR-TB and tested for the second-line drugs at Hinduja Hospital's Mycobacteriology Laboratory in the year 2012 were analyzed. A total of 1539 samples were analyzed. Of these, 464 (30.14%) were MDR-TB, 867 (56.33%) were MDR with fluoroquinolone resistance, and 198 (12.8%) were extensively drug-resistant TB. The average number of susceptible drugs per sample was 3.07 ± 1.29 (assuming 100% cycloserine susceptibility). Taking 4 effective drugs to be the cut or an effective regimen, the number of patients receiving 4 or more effective drugs from the standardized directly observed treatment, short-course plus regimen would be 516 (33.5%) while 66.5% of cases would receive 3 or less effective drugs. Our study shows that a high proportion of patients will have resistance to a number of the first- and second-line drugs. Local epidemiology must be factored in to avoid amplification of resistance.

Home blood pressure-guided antihypertensive therapy in chronic kidney disease: more data are needed.

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Georgianos, Panagiotis I; Champidou, Eleni; Liakopoulos, Vassilios; Balaskas, Elias V; Zebekakis, Pantelis E

2018-04-01

In the era of newly introduced hypertension guidelines recommending lower blood pressure (BP) targets for drug-treated hypertensives, the necessity for optimized management of hypertension becomes even more urgent. The concept of home BP-guided antihypertensive therapy is for long suggested as a simple and feasible approach to improve BP control rates and optimize the management of hypertension. Home BP-guided antihypertensive therapy is particularly applicable to hypertensives with chronic kidney disease (CKD) for several reasons including the following: (1) difficult-to-control BP and high BP variability in the CKD setting; (2) poor accuracy of office BP in determining hypertension control status and detecting "white-coat" and "masked" hypertension; (3) poor value of routine office BP recordings in predicting the longitudinal progression of target-organ damage; and (4) superiority of home BP over office BP recordings in prognosticating the risk of incident end-stage renal disease or death. The concept of home BP-guided antihypertensive therapy is even more relevant for those on hemodialysis, given the high intradialytic and interdialytic BP variability and poor value of conventional peridialytic BP recordings in estimating the actual BP load recorded outside of dialysis with the use of home or ambulatory BP monitoring. Randomized trials comparing home BP-guided antihypertensive therapy versus usual care are warranted to prove the feasibility and effectiveness of this therapeutic approach and convince clinicians for using home BP monitoring as the standard of care when managing hypertension, particularly in people with CKD or end-stage renal disease. Copyright © 2018 American Heart Association. Published by Elsevier Inc. All rights reserved.

Antihypertensive medication classes used among medicare beneficiaries initiating treatment in 2007-2010.

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Kent, Shia T; Shimbo, Daichi; Huang, Lei; Diaz, Keith M; Kilgore, Meredith L; Oparil, Suzanne; Muntner, Paul

2014-01-01

After the 2003 publication of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines, there was a 5-10% increase in patients initiating antihypertensive medication with a thiazide-type diuretic, but most patients still did not initiate treatment with this class. There are few contemporary published data on antihypertensive medication classes filled by patients initiating treatment. We used the 5% random Medicare sample to study the initiation of antihypertensive medication between 2007 and 2010. Initiation was defined by the first antihypertensive medication fill preceded by 365 days with no antihypertensive medication fills. We restricted our analysis to beneficiaries ≥ 65 years who had two or more outpatient visits with a hypertension diagnosis and full Medicare fee-for-service coverage for the 365 days prior to initiation of antihypertensive medication. Between 2007 and 2010, 32,142 beneficiaries in the 5% Medicare sample initiated antihypertensive medication. Initiation with a thiazide-type diuretic decreased from 19.2% in 2007 to 17.9% in 2010. No other changes in medication classes initiated occurred over this period. Among those initiating antihypertensive medication in 2010, 31.3% filled angiotensin-converting enzyme inhibitors (ACE-Is), 26.9% filled beta blockers, 17.2% filled calcium channel blockers, and 14.4% filled angiotensin receptor blockers (ARBs). Initiation with >1 antihypertensive medication class decreased from 25.6% in 2007 to 24.1% in 2010. Patients initiated >1 antihypertensive medication class most commonly with a thiazide-type diuretic and either an ACE-I or ARB. These results suggest that JNC 7 had a limited long-term impact on the choice of antihypertensive medication class and provide baseline data prior to the publication of the 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults from the Panel Members Appointed to

How much elderly people of Isfahan are adherent to their drug therapy regimens?

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Abazari, Parvaneh; Jafari, Tayebe Arab; Sabzghabaee, Ali Mohammad

2017-01-01

The need for a correct follow-up for medical advices of health givers is the cornerstone for avoiding drug-related complications in especial period of elderly people life. There isn't any data about drug therapy regimens adherence of elderly people of Isfahan. In this study, we aimed to cover this deficit. In this cross-sectional study which was carried out in Isfahan (Iran) in 2013 senior citizens (aged 65 or more) who were taking at least one medication and had no record of residency in nursing homes were included. We used Morisky medication adherence scale (after validation and reliability assessment for using this questionnaire in Persian language) to evaluate the level of adherence in the study population. A total of 200 elderly participants were fully studied ( n = 200, 61% females), and 52% of them had poor medication adherence. 77.5% of participants were suffered from at least four medical illnesses, and 18.5% of them were taking more than eight medications per day. We have not found any significant statistical relationship between vision or hearing loss disorders and the medication adherence of the participants). There was a significant positive relationship between the level of education and medication adherence ( P = 0.001), ( χ 2 = 0.29). Low Medication adherence is a common and important drug issue in the elderly in Isfahan. This issue can lead to medical complications and huge cost if it is not addressed appropriately.

Metoprolol succinate extended release/hydrochlorothiazide combination tablets

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James W Hainer

2007-07-01

Full Text Available James W Hainer, Jennifer SuggAstraZeneca LP, Wilmington, DE, USAAbstract: Lowering elevated blood pressure (BP with drug therapy reduces the risk for catastrophic fatal and nonfatal cardiovascular events such as stroke and myocardial infarction. Given the heterogeneity of hypertension as a disease, the marked variability in an individual patient’s BP response, and low response rates with monotherapy, expert groups such as the Joint National Committee (JNC emphasize the value of combination antihypertensive regimens, noting that combinations, usually of different classes, have additive antihypertensive effects. Metoprolol succinate extended-release tablet is a beta-1 (cardio-selective adrenoceptor-blocking agent formulated to provide controlled and predictable release of metoprolol. Hydrochlorothiazide (HCT is a well-established diuretic and antihypertensive agent, which promotes natruresis by acting on the distal renal tubule. The pharmacokinetics, efficacy, and safety/tolerability of the antihypertensive combination tablet, metoprolol extended release hydrochlorothiazide, essentially reflect the well-described independent characteristics of each of the component agents. Not only is the combination product more effective than monotherapy with the individual components but the combination product allows a low-dose multidrug regimen as an alternative to high-dose monotherapy, thereby, minimizing the likelihood of dose-related side-effects.Keywords: antihypertensive, blood pressure, cardiovascular disease, combination product

Drug adherence in treatment resistant and in controlled hypertension-Results from the Swedish Primary Care Cardiovascular Database (SPCCD).

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Holmqvist, Lina; Boström, Kristina Bengtsson; Kahan, Thomas; Schiöler, Linus; Qvarnström, Miriam; Wettermark, Björn; Hjerpe, Per; Hasselström, Jan; Manhem, Karin

2018-03-01

To assess drug adherence in patients treated with ≥3 antihypertensive drug classes, with both controlled and uncontrolled blood pressure and describe associated factors for nonadherence. Patients with hypertension, without cardiovascular comorbidity, aged >30 years treated with ≥3 antihypertensive drug classes were followed for 2 years. Both patients with treatment resistant hypertension (TRH) and patients with controlled hypertension were included. Clinical data were derived from a primary care database. Pharmacy refill data from the Swedish Prescribed drug registry was used to calculate proportion of days covered (PDC). Patients with a PDC level ≥ 80% were included. We found 5846 patients treated ≥3 antihypertensive drug classes, 3508 with TRH (blood pressure ≥ 140/90), and 2338 with controlled blood pressure (drug therapy had similar decline in adherence over time regardless of initial blood pressure control. Diabetes was associated with better adherence, which may imply that the structured caregiving of these patients enhances antihypertensive drug treatment. Copyright © 2018 John Wiley & Sons, Ltd.

The Cost-Effectiveness of Low-Cost Essential Antihypertensive Medicines for Hypertension Control in China: A Modelling Study.

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Dongfeng Gu

2015-08-01

Full Text Available Hypertension is China's leading cardiovascular disease risk factor. Improved hypertension control in China would result in result in enormous health gains in the world's largest population. A computer simulation model projected the cost-effectiveness of hypertension treatment in Chinese adults, assuming a range of essential medicines list drug costs.The Cardiovascular Disease Policy Model-China, a Markov-style computer simulation model, simulated hypertension screening, essential medicines program implementation, hypertension control program administration, drug treatment and monitoring costs, disease-related costs, and quality-adjusted life years (QALYs gained by preventing cardiovascular disease or lost because of drug side effects in untreated hypertensive adults aged 35-84 y over 2015-2025. Cost-effectiveness was assessed in cardiovascular disease patients (secondary prevention and for two blood pressure ranges in primary prevention (stage one, 140-159/90-99 mm Hg; stage two, ≥160/≥100 mm Hg. Treatment of isolated systolic hypertension and combined systolic and diastolic hypertension were modeled as a reduction in systolic blood pressure; treatment of isolated diastolic hypertension was modeled as a reduction in diastolic blood pressure. One-way and probabilistic sensitivity analyses explored ranges of antihypertensive drug effectiveness and costs, monitoring frequency, medication adherence, side effect severity, background hypertension prevalence, antihypertensive medication treatment, case fatality, incidence and prevalence, and cardiovascular disease treatment costs. Median antihypertensive costs from Shanghai and Yunnan province were entered into the model in order to estimate the effects of very low and high drug prices. Incremental cost-effectiveness ratios less than the per capita gross domestic product of China (11,900 international dollars [Int$] in 2015 were considered cost-effective. Treating hypertensive adults with prior

Antihypertensive medication classes used among medicare beneficiaries initiating treatment in 2007-2010.

Directory of Open Access Journals (Sweden)

Shia T Kent

Full Text Available After the 2003 publication of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7 guidelines, there was a 5-10% increase in patients initiating antihypertensive medication with a thiazide-type diuretic, but most patients still did not initiate treatment with this class. There are few contemporary published data on antihypertensive medication classes filled by patients initiating treatment.We used the 5% random Medicare sample to study the initiation of antihypertensive medication between 2007 and 2010. Initiation was defined by the first antihypertensive medication fill preceded by 365 days with no antihypertensive medication fills. We restricted our analysis to beneficiaries ≥ 65 years who had two or more outpatient visits with a hypertension diagnosis and full Medicare fee-for-service coverage for the 365 days prior to initiation of antihypertensive medication. Between 2007 and 2010, 32,142 beneficiaries in the 5% Medicare sample initiated antihypertensive medication. Initiation with a thiazide-type diuretic decreased from 19.2% in 2007 to 17.9% in 2010. No other changes in medication classes initiated occurred over this period. Among those initiating antihypertensive medication in 2010, 31.3% filled angiotensin-converting enzyme inhibitors (ACE-Is, 26.9% filled beta blockers, 17.2% filled calcium channel blockers, and 14.4% filled angiotensin receptor blockers (ARBs. Initiation with >1 antihypertensive medication class decreased from 25.6% in 2007 to 24.1% in 2010. Patients initiated >1 antihypertensive medication class most commonly with a thiazide-type diuretic and either an ACE-I or ARB.These results suggest that JNC 7 had a limited long-term impact on the choice of antihypertensive medication class and provide baseline data prior to the publication of the 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults from the Panel

Cost-utility analysis of antihypertensive medications in Nigeria: a decision analysis

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Ekwunife Obinna Ikechukwu

2013-01-01

Full Text Available Abstract Background Many drugs are available for control of hypertension and its sequels in Nigeria but some are not affordable for majority of the populace. This serious pharmacoeconomic question has to be answered by the nation’s health economists. The objective of this study was to evaluate the cost-effectiveness of drugs from 4 classes of antihypertensive medications commonly used in Nigeria in management of hypertension without compelling indication to use a particular antihypertensive drug. Methods The study employed decision analytic modeling. Interventions were obtained from a meta-analysis. The Markov process model calculated clinical outcomes and costs during a life cycle of 30 years of 1000 hypertensive patients stratified by 3 cardiovascular risk groups, under the alternative intervention scenarios. Quality adjusted life year (QALY was used to quantify clinical outcome. The average cost of treatment for the 1000 patient was tracked over the Markov cycle model of the alternative interventions and results were presented in 2010 US Dollars. Probabilistic cost-effectiveness analysis was performed using Monte Carlo simulation, and results presented as cost-effectiveness acceptability frontiers. Expected value of perfect information (EVPI and expected value of parameter perfect information (EVPPI analyses were also conducted for the hypothetical population. Results Thiazide diuretic was the most cost-effective option across the 3 cardiovascular risk groups. Calcium channel blocker was the second best for Moderate risk and high risk with a willingness to pay of at least 2000$/QALY. The result was robust since it was insensitive to the parameters alteration. Conclusions The result of this study showed that thiazide diuretic followed by calcium channel blocker could be a feasible strategy in order to ensure that patients in Nigeria with hypertension are better controlled.

Trends in prescribing and persistence with antihypertensive therapy: results of the study PAPEETE (Population-based Analysis of Persistence and Economics of treatment with telmisartan study

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Francesco Vittorio Costa

2009-12-01

Full Text Available This paper summarizes the results of the PAPEETE study (Population-based Analysis of PErsistence with treatment and Economics of TElmisartan that assessed trends in prescriptions, determinants and timing of treatment discontinuation and/or changes in antihypertensive drug therapy in a cohort of hypertensive patients living in Pavia. In the study were included all new users 18 years old or over receiving a first prescription for diuretics, beta-blockers, calcium channel-blockers, ACE inhibitors (ACEi or angiotensin receptor blockers (ARBs between 1 January 2003 and 31 December 2006. The follow-up period for each patient was 12 months starting from enrolment date. Based in the presence of continuous therapy, patients were defined as persistent and non-persistent users. A total of 61,493 patients was included in the study of whom 11.2% were persistent. Persistence with the treatment seems to be associated with patient-related factors and with the class of anti-hypertensive drug initially prescribed with the lowest persistence to antihypertensive treatment with diuretics (3.0% and the highest with ARBs (18.8%.

Interventional procedures and future drug therapy for hypertension

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Lobo, Melvin D.; Sobotka, Paul A.; Pathak, Atul

2017-01-01

Hypertension management poses a major challenge to clinicians globally once non-drug (lifestyle) measures have failed to control blood pressure (BP). Although drug treatment strategies to lower BP are well described, poor control rates of hypertension, even in the first world, suggest that more needs to be done to surmount the problem. A major issue is non-adherence to antihypertensive drugs, which is caused in part by drug intolerance due to side effects. More effective antihypertensive drugs are therefore required which have excellent tolerability and safety profiles in addition to being efficacious. For those patients who either do not tolerate or wish to take medication for hypertension or in whom BP control is not attained despite multiple antihypertensives, a novel class of interventional procedures to manage hypertension has emerged. While most of these target various aspects of the sympathetic nervous system regulation of BP, an additional procedure is now available, which addresses mechanical aspects of the circulation. Most of these new devices are supported by early and encouraging evidence for both safety and efficacy, although it is clear that more rigorous randomized controlled trial data will be essential before any of the technologies can be adopted as a standard of care. PMID:27406184

Economic evaluation of a shortened standardised treatment regimen of antituberculosis drugs for patients with multidrug-resistant tuberculosis (STREAM): study protocol.

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Gama, Elvis; Madan, Jason; Langley, Ivor; Girma, Mamo; Evans, Denise; Rosen, Sydney; Squire, S Bertel

2016-10-17

Multidrug-resistant tuberculosis (MDR-TB) poses a serious financial challenge to health systems and patients. The current treatment for patients with MDR-TB takes up to 24 months to complete. Evidence for a shorter regimen which differs from the standard WHO recommended MDR-TB regimen and typically lasts between 9 and 12 months has been reported from Bangladesh. This evaluation aims to assess the economic impact of a shortened regimen on patients and health systems. This evaluation is innovative as it combines patient and health system costs, as well as operational modelling in assessing the impact. An economic evaluation nested in a clinical trial with 2 arms will be performed at 4 facilities. The primary outcome measure is incremental cost to the health system of the study regimen compared with the control regimen. Secondary outcome measures are mean incremental costs incurred by patients by treatment outcome; patient costs by category (direct medical costs, transport, food and accommodation costs, and cost of guardians/accompanying persons and lost time); health systems cost by category and drugs; and costs related to serious adverse events. The study has been evaluated and approved by the Ethics Advisory Group of the International Union Against Tuberculosis and Lung Disease; South African Medical Research Ethics Committee; Wits Health Consortium Protocol Review Committee; University of the Witwatersrand Human Research Ethics Committee; University of Kwazulu-Natal Biomedical Research Ethics Committee; St Peter TB Specialized Hospital Ethical Review Committee; AHRI-ALERT Ethical Review Committee, and all participants will provide written informed consent. The results of the economic evaluation will be published in a peer-reviewed journal. ISRCTN78372190. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Preclinical optimization of a broad-spectrum anti-bladder cancer tri-drug regimen via the Feedback System Control (FSC) platform

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Liu, Qi; Zhang, Cheng; Ding, Xianting; Deng, Hui; Zhang, Daming; Cui, Wei; Xu, Hongwei; Wang, Yingwei; Xu, Wanhai; Lv, Lei; Zhang, Hongyu; He, Yinghua; Wu, Qiong; Szyf, Moshe; Ho, Chih-Ming; Zhu, Jingde

2015-06-01

Therapeutic outcomes of combination chemotherapy have not significantly advanced during the past decades. This has been attributed to the formidable challenges of optimizing drug combinations. Testing a matrix of all possible combinations of doses and agents in a single cell line is unfeasible due to the virtually infinite number of possibilities. We utilized the Feedback System Control (FSC) platform, a phenotype oriented approach to test 100 options among 15,625 possible combinations in four rounds of assaying to identify an optimal tri-drug combination in eight distinct chemoresistant bladder cancer cell lines. This combination killed between 82.86% and 99.52% of BCa cells, but only 47.47% of the immortalized benign bladder epithelial cells. Preclinical in vivo verification revealed its markedly enhanced anti-tumor efficacy as compared to its bi- or mono-drug components in cell line-derived tumor xenografts. The collective response of these pathways to component drugs was both cell type- and drug type specific. However, the entire spectrum of pathways triggered by the tri-drug regimen was similar in all four cancer cell lines, explaining its broad spectrum killing of BCa lines, which did not occur with its component drugs. Our findings here suggest that the FSC platform holdspromise for optimization of anti-cancer combination chemotherapy.

[C-reactive protein changes with antihypertensive and statin treatment].

Science.gov (United States)

Rodilla, Enrique; Gómez-Belda, Ana; Costa, José A; Aragó, Miriam; Miralles, Amparo; González, Carmen; Pascual, José M

2005-10-29

The aim of this study was to evaluate the modifications of high sensitivity C-reactive protein (CRP) with antihypertensive and statin treatment in a hypertensive population with a wide range of coronary risks (CR). Retrospective follow-up study in 665 hypertensive patients: 556 (52% male) without dyslipidemia and CR (Framingham at 10 years) of 8.3 (7.6) as a control group (C) and 109 (61% male) with dyslipidemia and CR of 13.1 (8.8) who were treated with statins (T). Statins treatment was established according to NCEP-ATP-III. In both groups, the antihypertensive treatment was optimized in order to achieve blood pressure (BP) control (< 140/90 mmHg). A lipid profile and high sensitivity CRP (analyzed by nephelometry) was performed at the beginning and at the end of follow up [14.3 (3.6) months]. CRP levels were reduced in the T group -0.17 (0.2) mg/L vs. 0.14 (0.09) mg/L (p = 0.003, Mann-Whitney) in C. The lessening of CRP was not related to the reduction of lipids levels: total cholesterol (r = 0.06; p = 0.49), LDL-C (r = 0.11; p = 0.24), triglycerides (r = -0.02; p = 0.81) (Spearman), or to the reduction of systolic BP (r = -0.07; p = 0.44) and diastolic BP (r = -0.121; p = 0.21). The T group was treated with more antihypertensive drugs than C (2.2 [2.3] vs. 2.5 [1.2]; p = 0.02). Patients treated with ECA inhibitors or angiotensin II antagonist showed a tendency to decreasing the CRP levels more (p = 0.08). In hypertensive populations, statins induce a reduction of CRP levels. The reduction is not related to the lowering of lipids levels or BP values. The effect of statins on the reduction of CRP in hypertensive patients is not related to the lowering of lipids or BP.

Invited review: Fermented milk as antihypertensive functional food.

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Beltrán-Barrientos, L M; Hernández-Mendoza, A; Torres-Llanez, M J; González-Córdova, A F; Vallejo-Córdoba, B

2016-06-01

Over the past decade, interest has risen in fermented dairy foods that promote health and could prevent diseases such as hypertension. This biological effect has mainly been attributed to bioactive peptides encrypted within dairy proteins that can be released during fermentation with specific lactic acid bacteria or during gastrointestinal digestion. The most studied bioactive peptides derived from dairy proteins are antihypertensive peptides; however, a need exists to review the different studies dealing with the evaluation of antihypertensive fermented milk before a health claim may be associated with the product. Thus, the objective of this overview was to present available information related to the evaluation of fermented milk containing antihypertensive peptides by in vitro and in vivo studies, which are required before a fermented functional dairy product may be introduced to the market. Although commercial fermented milks with antihypertensive effects exist, these are scarce and most are based on Lactobacillus helveticus. Thus, a great opportunity is available for the development of functional dairy products with new lactic acid bacteria that support heart health through blood pressure- and heart rate-lowering effects. Hence, the consumer may be willing to pay a premium for foods with important functional benefits. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Pharmacokinetic modeling of an induction regimen for in vivo combined testing of novel drugs against pediatric acute lymphoblastic leukemia xenografts.

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Barbara Szymanska

Full Text Available Current regimens for induction therapy of pediatric acute lymphoblastic leukemia (ALL, or for re-induction post relapse, use a combination of vincristine (VCR, a glucocorticoid, and L-asparaginase (ASP with or without an anthracycline. With cure rates now approximately 80%, robust pre-clinical models are necessary to prioritize active new drugs for clinical trials in relapsed/refractory patients, and the ability of these models to predict synergy/antagonism with established therapy is an essential attribute. In this study, we report optimization of an induction-type regimen by combining VCR, dexamethasone (DEX and ASP (VXL against ALL xenograft models established from patient biopsies in immune-deficient mice. We demonstrate that the VXL combination was synergistic in vitro against leukemia cell lines as well as in vivo against ALL xenografts. In vivo, VXL treatment caused delays in progression of individual xenografts ranging from 22 to >146 days. The median progression delay of xenografts derived from long-term surviving patients was 2-fold greater than that of xenografts derived from patients who died of their disease. Pharmacokinetic analysis revealed that systemic DEX exposure in mice increased 2-fold when administered in combination with VCR and ASP, consistent with clinical findings, which may contribute to the observed synergy between the 3 drugs. Finally, as proof-of-principle we tested the in vivo efficacy of combining VXL with either the Bcl-2/Bcl-xL/Bcl-w inhibitor, ABT-737, or arsenic trioxide to provide evidence of a robust in vivo platform to prioritize new drugs for clinical trials in children with relapsed/refractory ALL.

Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

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A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

Angiotensin converting enzyme inhibition in clinical practice. A re-examination of stepped-care: a retrospective and a prospective.

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Zanchetti, A

1985-01-01

Diuretics have so far enjoyed a prominent position in all stepped-care programs, as the preferred first choice drug in most American schemes or as an alternative first choice drug with respect to beta-blockers in the WHO scheme. Among various reasons for this prominence has been that antihypertensive drugs available until recently all gradually led to sodium and water retention, and therefore required to be combined with a diuretic. This is no longer true: several antihypertensive agents are available now that do not require combination with diuretics, these new agents including not only beta-blockers but also angiotensin-converting enzyme (ACE) inhibitors and calcium entry blockers. Furthermore, some concern about the metabolic effects of diuretics has recently been raised, especially because of the failure to prevent coronary heart disease by the current diuretic-based antihypertensive regimens. Without denying the importance that diuretics have had in the past in making antihypertensive therapy successful and their continuing essential role in treating severe hypertension, it is likely, in my opinion, that in future years diuretics are going to be more often used as agents of second choice, mostly in combination with beta-blockers, ACE inhibitors, and, perhaps, some of the calcium blockers. In conclusion, although opinions of various experts about the sequence of choices between antihypertensive drugs may obviously differ, there is no doubt that the addition of new classes of effective agents, such as the ACE inhibitors and the calcium entry blockers, is making antihypertensive therapy more flexible and more easily suitable to the needs of individual patients.

Compliance to antihypertensive therapy

International Nuclear Information System (INIS)

Almas, A.; Hameed, A.; Ahmed, B.; Islam, M.

2006-01-01

Objective: To determine compliance, factors affecting compliance to antihypertensive therapy and to compare compliant and non-compliant groups, in a tertiary care setting. Study Design: Analytical (cross-sectional) study. Place and Duration of Study: The outpatient clinics at the Aga Khan University from May 2004 to February 2005. Patients and Methods: Two hundred patients presenting to the outpatients clinic were included. All patients 18 years and above, who had stage 1 and 2 hypertension, had one clinic visit to a medicine clinic, 6 months prior to presentation and started on antihypertensive medicines, were included. Results: Sixty-six percent were males and 33.5 % were females. Mean age was 58.1 ( +- 12) years and mean duration of hypertension was 7.2 (+- 6.7) years. Fifty-seven percent were compliant and 43% were noncompliant. In the noncompliant group, 53.4 % had mild noncompliance, 24.4 % had severe non-compliance, while 22% had moderate noncompliance. Factors of noncompliance were 56.8% missed doses due to forgetfulness, 12.7% deliberately missed their doses, 11.6% could not take the medicine due to side effects, 10.4% did not take the dose due to increased number of tablets, 4.6% were not properly counseled by the physician and 3.48% did not take medicines due to cost issues. The mean systolic blood pressure was 126 +- 19.2 mmHg in the compliant group while it was 133 +- 16.5 mmHg in the noncompliant group (p-value 0.004). The mean diastolic blood pressure in the compliant group was 76 +- 11.9 mmHg, while in the noncompliant group it was 81.9 +- 10.9 mmHg (p-value 0.001). Conclusion: Compliance to antihypertensive therapy in a tertiary care center is significantly good. Forgetfulness was the major reason for noncompliance. The mean blood pressure control was better in the compliant group. (author)

Antihypertensive Medications Adherence Among Nigerian ...

African Journals Online (AJOL)

Hospital, Ogbomosho, 2Goshen Heart Clinic, Osogbo, 3Department of Economics, Osun State University, Osogbo, Nigeria ... significant impact of antihypertensive medication adherence.[13]. The level of information provided to patients may also impact ..... Muntner P. New medication adherence scale versus pharmacy.

Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy

DEFF Research Database (Denmark)

Parving, H H; Smidt, U M; Hommel, E

1993-01-01

The effect of long-term, aggressive, antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in 11 insulin-dependent diabetic patients (mean age, 30 years). Renal function was assessed every 4 months by measurement of glomerular filtration rate (GFR) (single...... infarction (GFR, 46 mL/min/1.73 m2). Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy....

Revisiting Dosing Regimen Using Pharmacokinetic/Pharmacodynamic Mathematical Modeling: Densification and Intensification of Combination Cancer Therapy.

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Meille, Christophe; Barbolosi, Dominique; Ciccolini, Joseph; Freyer, Gilles; Iliadis, Athanassios

2016-08-01

Controlling effects of drugs administered in combination is particularly challenging with a densified regimen because of life-threatening hematological toxicities. We have developed a mathematical model to optimize drug dosing regimens and to redesign the dose intensification-dose escalation process, using densified cycles of combined anticancer drugs. A generic mathematical model was developed to describe the main components of the real process, including pharmacokinetics, safety and efficacy pharmacodynamics, and non-hematological toxicity risk. This model allowed for computing the distribution of the total drug amount of each drug in combination, for each escalation dose level, in order to minimize the average tumor mass for each cycle. This was achieved while complying with absolute neutrophil count clinical constraints and without exceeding a fixed risk of non-hematological dose-limiting toxicity. The innovative part of this work was the development of densifying and intensifying designs in a unified procedure. This model enabled us to determine the appropriate regimen in a pilot phase I/II study in metastatic breast patients for a 2-week-cycle treatment of docetaxel plus epirubicin doublet, and to propose a new dose-ranging process. In addition to the present application, this method can be further used to achieve optimization of any combination therapy, thus improving the efficacy versus toxicity balance of such a regimen.

Can Walmart make us healthier? Prescription drug prices and health care utilization.

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Borrescio-Higa, Florencia

2015-12-01

This paper analyzes how prices in the retail pharmaceutical market affect health care utilization. Specifically, I study the impact of Walmart's $4 Prescription Drug Program on utilization of antihypertensive drugs and on hospitalizations for conditions amenable to drug therapy. Identification relies on the change in the availability of cheap drugs introduced by Walmart's program, exploiting variation in the distance to the nearest Walmart across ZIP codes in a difference-in-differences framework. I find that living close to a source of cheap drugs increases utilization of antihypertensive medications by 7 percent and decreases the probability of an avoidable hospitalization by 6.2 percent. Copyright © 2015 Elsevier B.V. All rights reserved.

Marketing research on the angiotensin-converting enzyme inhibitors antihypertensive medicines.

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Boboia, Anamaria; Grigorescu, Marius Rareş; Turcu-Ştiolică, Adina

2017-01-01

The research aimed at investigating sales trends of angiotensin-converting enzyme inhibitors antihypertensive medicines, both in terms of quantity and value, in ten community pharmacies, for a period of three years. The research on the antihypertensive medicines consumption is important for highlighting the ever increasing impact of hypertension among the population. The methods used in this research were the following: marketing research, method of sampling, descriptive methods, retrospective analysis, method of comparison. The results showed that the drugs containing the active substances of the angiotensin converting enzyme inhibitors class had had significant increases in quantitative and value sales, bringing substantial revenues to pharmacies. From the quantitative perspective, the best-selling products were those containing Enalaprilum, while in terms of value, the best-selling medicines were those containing Perindoprilum. We evidenced that spectacular sales were also achieved for products that have Lisinoprilum, respectively Captoprilum, as active substances. The largest quantities were marketed for the Captopril Terapia® product and the highest earnings were recorded for the Prestarium® medicine. This paper approaches an interesting and topical issue, which can be helpful to professionals (pharmacists, doctors) and other categories, such as economists, statisticians, representatives of companies manufacturing medicines, as well as to hypertensive patients, as it could be used to warn population regarding the incidence of cardiovascular diseases, and, at the same time, trace sales trends in order to accomplish profitable business plans.

Differences in Lipid Measurements by Antiretroviral Regimen Exposure in Cohorts from Asia and Australia

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Amit C. Achhra

2012-01-01

Full Text Available We explored the mean differences in routinely measured lipids (total cholesterol, triglycerides, and high-density lipoprotein cholesterol according to exposure to different combination antiretroviral regimens in Asian (n=2051 and Australian (predominantly Caucasian, n=794 cohorts. The regimen was defined as at least 3 antiretroviral drugs with at least 2 nucleoside-reverse transcriptases (NRTIs and either of at least one protease inhibitor (PI or non-nucleoside-reverse transcriptases (NNRTIs. We categorised cART regimens as: NRTIs as tenofovir based or not; NNRTIs as nevirapine or efavirenz (but not both; and PI as atazanavir based or not. We found that the impact of various antiretroviral regimens on lipids in Asian and Australian cohorts was only different by cohort for total cholesterol (P for interaction between regimen and cohort: 0.05. The differences in total cholesterol were however small and unlikely to be of clinical significance. Overall, tenofovir with nevirapine or atazanavir was associated with the most favorable lipids, while the PI regimens without tenofovir and atazanavir were associated with least favorable lipids. We conclude that the impact of various ART regimens on lipids is largely similar in Asian and Australian cohorts and that the newer drugs such as tenofovir and atazanavir are likely to provide similar benefit in terms of lipid profiles in both populations.

Comparison of a four-drug fixed-dose combination regimen with a single tablet regimen in smear-positive pulmonary tuberculosis.

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Bartacek, A; Schütt, D; Panosch, B; Borek, M

2009-06-01

To compare the efficacy, safety and acceptability of two short-course regimens of isoniazid, rifampicin, pyrazinamide and ethambutol (HRZE) given either as fixed-dose combination (4-FDC) tablets or as single tablets (ST) in patients with newly diagnosed pulmonary tuberculosis (PTB). This randomised, open, multicentre, multinational study was conducted in 26 centres and included 1159 patients with smear-positive PTB. 4-FDC daily for 2 months then H+R for 4 months, or single preparations of H, R, Z and E for 2 months followed by H and R for 4 months were administered daily. Sputum smear conversion rates at 2, 4 and 6 months (end of treatment [EOT], primary endpoint) and at 9 and 12 months (follow-up) were measured, together with adverse events and the acceptability of the formulations. Smear conversion rates for 4-FDC and ST at EOT were 80.4% (468/582 patients) vs. 82.7% (477/577) in the intent-to-treat (ITT) population, and 98.1% (404/412) vs. 98.6% (416/422) in the per-protocol (PP) subgroup. Non-inferiority of 4-FDC was demonstrated at month 2, EOT and follow-up in both the ITT and the PP populations. Overall numbers of adverse events were not significantly different between the groups. The efficacy of the 4-FDC regimen was non-inferior to that of the ST regimens, but patient acceptability significantly improved with 4-FDC.

DRUG UTILISATION STUDY IN THE TREATMENT OF HYPERTENSION IN A TERTIARY CARE HOSPITAL

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Amol Chandrakant Deshmukh

2017-11-01

Full Text Available BACKGROUND Hypertension, a common clinical problem is considered as an ‘iceberg disease’ because its unknown morbidity far exceeds the known morbidity. In terms of attributable deaths, it is one of the leading behavioural and physiological risk factors amounting to 13% of global deaths. Drug selection is based on efficacy in lowering BP (blood pressure and in reducing Cardiovascular (CV endpoints like stroke, myocardial infarction and heart failure. This study was carried out to evaluate the pattern, extent, rationality and frequency of the use of antihypertensive drugs in the treatment of hypertension. The aim of the study is to analyse drug utilisation in the treatment of hypertension in a tertiary care hospital. MATERIALS AND METHODS This study was conducted during January 2014 to December 2015 in Medicine OPD (Outpatient Department in a tertiary care hospital. The sample size was selected as per the WHO recommendations on conducting Drug Utilisation Studies (DUS. Statistical Analysis- The collected data was numerically coded and entered in Microsoft Excel 2007 and analysed by SPSS version 16. Settings and Design- Prospective, cross-sectional, observational study. RESULTS Out of 612 patients, 262 (42.81% were in the age group of 60 and above. Considering gender distribution, 328 (53.59% were males and 284 (46.41% were females. Of these, 274 (44.78% were prescribed monotherapy, 256 (41.83% were prescribed two-drug therapy, 72 (11.76% were prescribed three-drug therapy and 10 (1.63% were prescribed four-drug therapy. Among 274 (44.78% patients prescribed with monotherapy, 112 (40.87% were prescribed with CCB (calcium channel blocker, 76 (27.73% were given BB (B-blocker, 45 (16.42% were prescribed ACEI (angiotensin converting enzyme inhibitor, 35 (12.77% were prescribed with ARB (angiotensin receptor blocker and 6 (2.18% were prescribed with Diuretics (D. Of the total antihypertensive drugs prescribed, 68.30% were prescribed by generic name

Placebo substitution for tnethyldopa in geriatric hypertensive patients

African Journals Online (AJOL)

and the benefit of treatment is still disputed.6 The aim of this study was to substitute a matching placebo for methyldopa in order to evaluate the effect of removal of a drug from the antihypertensive regimen of elderly patients without concomitantly inducing a sense of in- security. Sex (female/male) 16/2. Mean age (yrs). 75,7.

[Clinical observation on controlling antihypertension with the general anesthesia of TEAS and anesthetics in endoscopic endonasal surgery].

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Zhao, Wensheng; Zhao Xian; Li, Jinjin; Fang, Jianqiao

2015-12-01

To study whether the dose of controlling antihypertensive drug is reduced by transcutaneous electrical acupoint stimulation (TEAS) and the anesthetics, as well as the control of blood pressure (BP) and heart rate (HR) in endoscopic endonasal surgery with general anesthesia. Sixty patients for selective endoscopic endonasal surgery with general anesthetics and controlling antihypertension involved were selected and randomized into a TEAS group, a sham-TEAS group, 30 cases in each one. The electric pads were attached to bilateral Hegu (LI 4), Zusanli (ST 36), Sanyinjiao (SP 6) and Quchi (LI 11), stimulated with Hans-200 apparatus, 3 to 5 mA, 2 Hz/100 Hz in the TEAS group based on the patients' response to comfort. No electric stimulation was applied to the sham-TEAS group. The general anesthesia started after 30 min intervention and lasted till the end of surgery. The BP and HR were observed and recorded at the end of monitoring in operation room, 10 min after tranquilization (T0), 30 min after intervention (Tj, after induction~of general anestiesa (T2), 30 min after surgery start (T3), 60 min after surgery start (T4) and 30 min after extubation (T5). The doses of vecuronium bromide, propofol and nitroglycerin were recorded statistically in surgery, as well as the operative bleeding volume, the operative time, the resuscitation time and the visual analogue scale (VAS) score after resuscitation. Compared with that at T0, the mean arterial pressure (MAP) at T2, T3, T4 and T5 in the TEAS group and at T3 and T4 in the sham-TEAS group was all reduced, indicating the significant difference (all P 0.05). HR was different at T2 to Ts in the sham-TEAS group statistically (all P 0.05). The general anesthesia with TEAS and anesthetics involved for controlling antihypertension contributes to the control of BP and HR in the patients in endoscopic endonasal surgery. The impacts are not obvious on the doses of antihypertensive drug, the general anesthetics, the operative bleeding

PROPOSAL OF ANTI-TUBERCULOSIS REGIMENS BASED ON SUSCEPTIBILITY TO ISONIAZID AND RIFAMPICIN

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Mendoza-Ticona, Alberto; Moore, David AJ; Alarcón, Valentina; Samalvides, Frine; Seas, Carlos

2014-01-01

Objective To elaborate optimal anti-tuberculosis regimens following drug susceptibility testing (DST) to isoniazid (H) and rifampicin (R). Design 12 311 M. tuberculosis strains (National Health Institute of Peru 2007-2009) were classified in four groups according H and R resistance. In each group the sensitivity to ethambutol (E), pirazinamide (Z), streptomycin (S), kanamycin (Km), capreomycin (Cm), ciprofloxacin (Cfx), ethionamide (Eto), cicloserine (Cs) and p-amino salicilic acid (PAS) was determined. Based on resistance profiles, domestic costs, and following WHO guidelines, we elaborated and selected optimal putative regimens for each group. The potential efficacy (PE) variable was defined as the proportion of strains sensitive to at least three or four drugs for each regimen evaluated. Results Selected regimes with the lowest cost, and highest PE of containing 3 and 4 effective drugs for TB sensitive to H and R were: HRZ (99,5%) and HREZ (99,1%), respectively; RZECfx (PE=98,9%) and RZECfxKm (PE=97,7%) for TB resistant to H; HZECfx (96,8%) and HZECfxKm (95,4%) for TB resistant to R; and EZCfxKmEtoCs (82.9%) for MDR-TB. Conclusion Based on resistance to H and R it was possible to select anti-tuberculosis regimens with high probability of success. This proposal is a feasible alternative to tackle tuberculosis in Peru where the access to rapid DST to H and R is improving progressively. PMID:23949502

Drugs for preventing malaria in pregnant women in endemic areas: any drug regimen versus placebo or no treatment

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Radeva-Petrova, Denitsa; Kayentao, Kassoum; ter Kuile, Feiko O; Sinclair, David; Garner, Paul

2014-01-01

Background Pregnancy increases the risk of malaria and this is associated with poor health outcomes for both the mother and the infant, especially during the first or second pregnancy. To reduce these effects, the World Health Organization recommends that pregnant women living in malaria endemic areas sleep under insecticide-treated bednets, are treated for malaria illness and anaemia, and receive chemoprevention with an effective antimalarial drug during the second and third trimesters. Objectives To assess the effects of malaria chemoprevention given to pregnant women living in malaria endemic areas on substantive maternal and infant health outcomes. We also summarised the effects of intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) alone, and preventive regimens for Plasmodium vivax. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and reference lists up to 1 June 2014. Selection criteria Randomized controlled trials (RCTs) and quasi-RCTs of any antimalarial drug regimen for preventing malaria in pregnant women living in malaria-endemic areas compared to placebo or no intervention. In the mother, we sought outcomes that included mortality, severe anaemia, and severe malaria; anaemia, haemoglobin values, and malaria episodes; indicators of malaria infection, and adverse events. In the baby, we sought foetal loss, perinatal, neonatal and infant mortality; preterm birth and birthweight measures; and indicators of malaria infection. We included regimens that were known to be effective against the malaria parasite at the time but may no longer be used because of parasite drug resistance. Data collection and analysis Two review authors applied inclusion criteria, assessed risk of bias and extracted data. Dichotomous outcomes were compared using risk ratios (RR), and continuous outcomes using mean differences (MD); both are presented with 95% confidence intervals (CI). We

ANTIHYPERTENSIVE EFFICACY OF VERAPAMIL PLUS INDAPAMIDE IN PATIENTS WITH METABOLIC SYNDROME

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E. M. Idrisova

2008-01-01

Full Text Available Aim. To study effect of combination of verapamil retard (Isoptinum SR with indapamide retard (Arifon retard on blood pressure (BP level as well as lipid profile, glucose and electrolytes serum level in patients with metabolic syndrome (MS.Material and methods. 20 women of 35-65 y.o. with MS were examined. The combination of verapamil retard and indapamide retard were prescribed to patients during 24 weeks. Ambulatory BP monitoring (ABPM, lipide profile tests, electrolytes and glucose serum level tests were performed in all patients initially and after treatment.Results. Target systolic BP (SBP was achieved in 90% of patients. Target diastolic BP (DBP was achieved in 75% of patients. Drug combination effectively reduced SBP, DBP and pulse BP levels and improved other BP indices. This drug combination did not affect BP profile as well as glucose and electrolytes serum level, lipid profile.Conclusion. High antihypertensive efficacy and metabolic neutrality of verapamil retard and indapamide retard allows to use this combination in patients with MS.

A cohort study of possible risk factors for over-reporting of antihypertensive adherence

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Lee Mei-Ling Ting

2001-12-01

Full Text Available Abstract Background The identification of poor medicinal adherence is difficult because direct observation of medication use is usually impractical. Up to 50% of individuals on chronic therapies may not be taking their medication as prescribed. This study is one of the first to explore possible risk factors for over-reporting of antihypertensive adherence using electronic medication monitoring. Methods The adherence of 286 individuals on single-drug antihypertensive therapy in a large managed care organization was electronically monitored for approximately three months. Questionnaires on socioeconomic background, adherence to therapy, health beliefs, and social support before and after adherence monitoring were completed. Over-reporting of antihypertensive adherence was assessed by comparing the self-reported frequency of noncompliance with that determined from electronic dosing records. Risk factors for over-reporting were identified by contingency table analysis and step-wise logistic regression. Results Although only 21% of participants acknowledged missing doses on one or more days per week, electronic monitoring documented nonadherence at this or a higher level in 42% of participants. The following variables were associated with over-reporting: >1 versus 1 daily dose (OR = 2.58; 95% CI = 1.50–4.41; p = .0006, lower perceived health risk from nonadherence (OR = 1.35; 95% CI = 1.10–1.64; p = .0035, and annual household income of $30,000 (OR = 2.64; 95% CI = 1.13–6.18; p = .025. Conclusions Over-reporting of adherence may be affected by factors related to dosing frequency, health beliefs and socioeconomic status. This topic deserves further investigation in other patient populations to elucidate possible underlying behavioral explanations.

High rates of regimen change due to drug toxicity among a cohort of South Indian adults with HIV infection initiated on generic, first-line antiretroviral treatment.

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Sivadasan, Ajith; Abraham, O C; Rupali, Priscilla; Pulimood, Susanne A; Rajan, Joyce; Rajkumar, S; Zachariah, Anand; Kannangai, Rajesh; Kandathil, Abraham Joseph; Sridharan, G; Mathai, Dilip

2009-05-01

To determine the rates, reasons and predictors of treatment change of the initial antiretroviral treatment (ART) regimen in HIV-infected south Indian adults. In this prospective cohort study, ART-naive adults initiated on generic, fixed dose combination ART as per the National AIDS Control Organization guidelines were followed up at an academic medical center. Treatment change was defined as any event which necessitated a change in or discontinuation of the initial ART regimen. Two hundred and thirty persons with HIV infection (males 74.8% and median age 37 years) were followed up for median duration of 48 weeks. The majority (98.7%) had acquired HIV infection through the heterosexual route. Most (70.4%) had advanced IV infection (WHO clinical stage 3 or 4) and 78% had CD4+ T-lymphocyte counts below 200 cells/microL. The initial ART regimens used were: Lamivudine (3TC) with Stavudine (d4T) (in 76%) or Azidothymidine (AZT) and Nevirapine (NVP) (in 86%) or Efavirenz (EFV). The cumulative incidence of treatment change was 39.6% (91 patients). Drug toxicity (WHO grade 3 or 4) was the reason for treatment change among 62 (27%) (incidence rate 35.9/100 person-years). The most common toxicities were attributable to the thymidine analogue nucleoside reverse transcriptase inhibitors (NRTIs), d4T and AZT [lactic acidosis (8.7%), anemia (7%) and peripheral neuropathy (5.2%)]. The other toxicities were rash (3.9%) and hepatitis (1.3%) due to NVP. The mortality (4.6/100 person-years) and disease progression rates (4.1/100 person-years) were low. The ART regimens used in this study were effective in decreasing disease progression and death. However, they were associated with high rates of drug toxicities, particularly those attributable to thymidine analogue NRTI. As efforts are made to improve access to ART, treatment regimens chosen should not only be potent, but also safe.

High blood pressure, antihypertensive medication and lung function in a general adult population

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2011-01-01

Background Several studies showed that blood pressure and lung function are associated. Additionally, a potential effect of antihypertensive medication, especially beta-blockers, on lung function has been discussed. However, side effects of beta-blockers have been investigated mainly in patients with already reduced lung function. Thus, aim of this analysis is to determine whether hypertension and antihypertensive medication have an adverse effect on lung function in a general adult population. Methods Within the population-based KORA F4 study 1319 adults aged 40-65 years performed lung function tests and blood pressure measurements. Additionally, information on anthropometric measurements, medical history and use of antihypertensive medication was available. Multivariable regression models were applied to study the association between blood pressure, antihypertensive medication and lung function. Results High blood pressure as well as antihypertensive medication were associated with lower forced expiratory volume in one second (p = 0.02 respectively p = 0.05; R2: 0.65) and forced vital capacity values (p = 0.01 respectively p = 0.05, R2: 0.73). Furthermore, a detailed analysis of antihypertensive medication pointed out that only the use of beta-blockers was associated with reduced lung function, whereas other antihypertensive medication had no effect on lung function. The adverse effect of beta-blockers was significant for forced vital capacity (p = 0.04; R2: 0.65), while the association with forced expiratory volume in one second showed a trend toward significance (p = 0.07; R2: 0.73). In the same model high blood pressure was associated with reduced forced vital capacity (p = 0.01) and forced expiratory volume in one second (p = 0.03) values, too. Conclusion Our analysis indicates that both high blood pressure and the use of beta-blockers, but not the use of other antihypertensive medication, are associated with reduced lung function in a general adult

Marketing research on the angiotensin-converting enzyme inhibitors antihypertensive medicines

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BOBOIA, ANAMARIA; GRIGORESCU, MARIUS RAREŞ; TURCU - ŞTIOLICĂ, ADINA

2017-01-01

Background and aims The research aimed at investigating sales trends of angiotensin-converting enzyme inhibitors antihypertensive medicines, both in terms of quantity and value, in ten community pharmacies, for a period of three years. The research on the antihypertensive medicines consumption is important for highlighting the ever increasing impact of hypertension among the population. Methods The methods used in this research were the following: marketing research, method of sampling, descriptive methods, retrospective analysis, method of comparison. Results The results showed that the drugs containing the active substances of the angiotensin converting enzyme inhibitors class had had significant increases in quantitative and value sales, bringing substantial revenues to pharmacies. From the quantitative perspective, the best-selling products were those containing Enalaprilum, while in terms of value, the best-selling medicines were those containing Perindoprilum. We evidenced that spectacular sales were also achieved for products that have Lisinoprilum, respectively Captoprilum, as active substances. The largest quantities were marketed for the Captopril Terapia® product and the highest earnings were recorded for the Prestarium® medicine. Conclusion This paper approaches an interesting and topical issue, which can be helpful to professionals (pharmacists, doctors) and other categories, such as economists, statisticians, representatives of companies manufacturing medicines, as well as to hypertensive patients, as it could be used to warn population regarding the incidence of cardiovascular diseases, and, at the same time, trace sales trends in order to accomplish profitable business plans. PMID:28246502

Regression of left ventricular hypertrophy and microalbuminuria changes during antihypertensive treatment.

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Rodilla, Enrique; Pascual, Jose Maria; Costa, Jose Antonio; Martin, Joaquin; Gonzalez, Carmen; Redon, Josep

2013-08-01

The objective of the present study was to assess the regression of left ventricular hypertrophy (LVH) during antihypertensive treatment, and its relationship with the changes in microalbuminuria. One hundred and sixty-eight previously untreated patients with echocardiographic LVH, 46 (27%) with microalbuminuria, were followed during a median period of 13 months (range 6-23 months) and treated with lifestyle changes and antihypertensive drugs. Twenty-four-hour ambulatory blood pressure monitoring, echocardiography and urinary albumin excretion were assessed at the beginning and at the end of the study period. Left ventricular mass index (LVMI) was reduced from 137 [interquartile interval (IQI), 129-154] to 121 (IQI, 104-137) g/m (P 50%) had the same odds of achieving regression of LVH as patients with normoalbuminuria (ORm 1.1; 95% CI 0.38-3.25; P = 0.85). However, those with microalbuminuria at baseline, who did not regress, had less probability of achieving LVH regression than the normoalbuminuric patients (OR 0.26; 95% CI 0.07-0.90; P = 0.03) even when adjusted for age, sex, initial LVMI, GFR, blood pressure and angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) treatment during the follow-up. Patients who do not have a significant reduction in microalbuminuria have less chance of achieving LVH regression, independent of blood pressure reduction.

TO COMPARE THE SAFETY AND EFFICACY OF THREE DIFFERENT, PROTON PUMP INHIBITORS OMEPRAZOLE, ESO M EPRAZOLE AND RABEPRAZOLE IN A TRIPLE DRUG REGIMEN IN PATIENTS WITH PEPTIC ULCER DISEASE IN THE ERADICATION OF H. PYLORI INFECTION

Directory of Open Access Journals (Sweden)

Margaret Viola

2015-03-01

Full Text Available Peptic ulcer disease continues to be issue especially due to its high prevalence in the developing world. Helicobacter pylori ( H. pylori infection associated duodenal ulcers should undergo eradication therapy. There are many regimens offered for H. pylori eradication which include triple , quadruple , or sequential therapy regimens. In our study we planned to see whether these differences in pharmacokinetic properties show any difference in t he efficacy and safety parameters between treatment with omeprazole rabeprazole and esomeprazole in the triple drug regimen for eradication of H.pylori infection in peptic ulcer patients in our hospital Osmania General Hospital / Osmania Medical College , Hyderabad. MATERIALS AND METHODS: A total number of 45 patients were enrolled in the study. Patients with either sex suffering from peptic ulcer defined as ulcer crater of >2.5mm in size by endoscopy. Study Design : It was a randomized double blind , paralle l and comparative study. CONCLUSION: Two weeks after triple drug treatment , H.pylori was negative in 66.7% , 73% and 80% and Rapid urease test was negative in 53% , 60% and 66% in group A , B and C respectively. Endoscopy findings showed significant reduction in size and healing of ulcers in group A , B and C. There was improvement in signs and symptoms by 53 to 80% , after 2 weeks. Hence after therapy with triple drug regimen H.pylori eradication was 66 - 80% and healing of ulcers was 83 – 100% which was higher in Rabeprazole group. At 6 weeks , there was complete relief of signs and symptoms. At the follow up of 10 weeks there was no ulcer recurrence. No adverse effects were noted in all the groups. In conclusion , Triple drug regimen had shown to eradicate H.pylori infection in the treatment of Peptic ulcer. There was healing of ulcers in all the groups which was highly significant. There was no recurrence of peptic ulcer with these regimens in all the groups. However Rabeprazole group patients

Drug interactions in primary health care in the George subdistrict ...

African Journals Online (AJOL)

2012-02-15

Feb 15, 2012 ... Drug-drug interactions are a recognised cause of morbidity and mortality ..... or fatal if the interaction increases toxicity or reduces the intended effect of the ... antihypertensive effect of angiotensin-converting enzyme inhibitors ...

[Abpm and duration of the antihypertensive effect: a study with a new formulation of sustained release losartan (CRONOS)].

Science.gov (United States)

Bendersky, Mario; Juncos, Luis; Waisman, Gabriel Dario; Piskorz, Daniel; Lopez-Santi, Ricardo; Montaña, Oscar; Caruso, Gustavo; Kotetzky, Martin; Penna, Maria; Gomez, Roberto

2012-01-01

Antihypertensive drugs action should last at least 24 h in order to enhance adherence, with positive impact on CV morbimortality. ABPM allow us to evaluate duration of action of drugs, against placebo, using Trough:Peak Ratio, antihypertensive effect in the last 4 h interdosis, and calculating the rate of BP morning surge. Losartán is an Antagonist At1 with good antihypertensive efficacy and renal, cardiac and cerebrovascular protection. Some studies shows less than 24 hs of action, that suggest twice a day dosing. The merge of a new formulation, Losartan Cronos, a bilayer tablet containing 50 mg of Losartan immediate release (IR) and 50 mg extended release (ER) would allow 24 h coverage, maintaining the previous advantages. To assess antihypertensive duration of action of Losartán Cronos in patients with essential hypertension throughout a 24-h dosing interval, using ABPM and response rates, AASI and Smoothness Index. 97 essential hypertensives, where included and received a single morning dose of Losartán Cronos (50 mg of regular release and 50 mg of controlled and retarded release) during 8 weeks. Performed valid ABPM post placebo and post active treatment. Results Mean age 58 (26-86), 60% women. 63% treatment naïve. The mean reduction in BP from baseline to week 8 (end of treatment) was statistically significant for all times analyzed (24 hours, daytime, night-time, and last 4 hours monitoring). There were no significant changes in 24h heart rate. BP morning surge (mmHg/hour) decreased from 4.53 to 3,68 (p=0.03).T:P Ratio was 0.91 for SBP and 1.14 for DBP. Smoothness Index: SBP 2.86 (95% CI 1.84-3.7) - DBP 3.17 (95% CI 2.03-3.9) 19 patients had adverse events, no-one cough, all mild, without discontinuations. Conclusion Losartán Cronos demonstrated efficacy and safety, decreases BP without significant effects in heart rate, it reduces the pulse pressure, and its effect lasts for 24 hs, assessed by T:P ratio, last 4 hours effects, decreasing morning surge

Randomized controlled study of a novel triple nitazoxanide (NTZ)-containing therapeutic regimen versus the traditional regimen for eradication of Helicobacter pylori infection.

Science.gov (United States)

Shehata, Mona Ah; Talaat, Raghda; Soliman, Samah; Elmesseri, Huda; Soliman, Shaimaa; Abd-Elsalam, Sherief

2017-10-01

Helicobacter pylori infection has become more and more resistant to conventional first-line treatment regimens. So, there is a considerable interest in evaluating new antibiotic combinations and regimens. Nitazoxanide is an anti-infective drug with demonstrated activity against protozoa and anaerobic bacteria including H. pylori. This work is designed to evaluate the efficacy and safety of a unique triple nitazoxanide-containing regimen as a treatment regimen in Egyptian patients with H. pylori infection. Two hundred and 24 patients with upper gastrointestinal tract (GIT) dyspeptic symptoms in whom H. pylori -induced GIT disease was confirmed were included in the study. They have been randomized to receive either nitazoxanide 500 mg b.i.d., clarithromycin 500 mg b.i.d., and omeprazole 40 mg twice daily for 14 days or metronidazole 500 mg b.i.d., clarithromycin 500 mg b.i.d., and omeprazole 40  mg twice daily for 14 days. Laboratory evaluation for H. pylori antigen within the stool was performed 6 weeks after cessation of H. pylori treatment regimens to assess the response. The response to treatment was significantly higher in group 1 of nitazoxanide treatment regimen than group 2 of traditional treatment regimen. One hundred and six cases (94.6%) of 112 patients who completed the study in group 1 showed complete cure, while only 63 cases (60.6%) of 104 patients who completed the study in group 2 showed the same response according to per-protocol (PP) analysis (Ppylori. (ClinicalTrials.gov Identifier: NCT02422706). © 2017 John Wiley & Sons Ltd.

Terbinafine-induced lichenoid drug eruption.

Science.gov (United States)

Zheng, Yue; Zhang, Jie; Chen, Haiyan; Lai, Wei; Maibach, Howard I

2017-03-01

Drug-induced lichen planus has been induced by antibiotics, anticonvulsants, antidiabetics, antimalarials, antitubercular drugs, antihypertensives, psychiatric drugs, chemotherapeutic agents, diuretic, heavy metals, NSAIDs, etc. Terbinafine, an antifungal agent, is widely used for dermatophyte infections and onychomycosis. Cutaneous adverse effects of terbinafine are rarely reported. Here, we report a case of terbinafine-induced lichenoid drug eruption in a 22-year-old who presented with generalized lichenoid eruption 2 weeks after terbinafine initiation of. The body and lip cleared completely after 8 weeks of drug withdrawal; nail change cleared after 12 weeks.

Low blood pressure and antihypertensive treatment are independently associated with physical and mental health status in patients with arterial disease: the SMART study.

Science.gov (United States)

Muller, M; Jochemsen, H M; Visseren, F L J; Grool, A M; Launer, L J; van der Graaf, Y; Geerlings, M I

2013-09-01

To investigate the independent effects of antihypertensive treatment and blood pressure (BP) levels on physical and mental health status in patients with arterial disease. Cross-sectional analyses were conducted within the single-centre Secondary Manifestations of ARTerial disease (SMART) study, in a hospital care setting. A total of 5877 patients (mean age 57 years) with symptomatic and asymptomatic arterial disease underwent standardized vascular screening. The primary outcome was self-rated physical and mental health assessed using the 36-item short-form health survey. In the total population, antihypertensive drug use and increased intensity of antihypertensive treatment were associated with poorer health status independent of important confounders including BP levels; adjusted mean differences [95% confidence interval (CI)] in physical and mental health between n = 0 and n ≥ 3 antihypertensives were -1.2 (-2.1; -0.3) and -3.5 (-4.4; -2.6), respectively. Furthermore, both lower systolic and lower diastolic BP levels were related to poorer physical and mental health status independent of antihypertensive treatment. Mean differences (95% CI) in physical and mental health status per SD decrease in systolic BP were -0.56 (-0.84; -0.27) and -0.32 (-0.61; -0.03) and per SD decrease in diastolic BP were -0.50 (-0.78; -0.23) and -0.08 (-0.36; 0.20), respectively. The association between low BP and poor health status was particularly present in patients with coronary artery disease. In a population of patients with asymptomatic and symptomatic arterial disease, antihypertensive treatment and lower BP levels are independently associated with poorer self-rated physical and mental health. These findings suggest that different underlying mechanisms may explain these independent associations. © 2013 The Association for the Publication of the Journal of Internal Medicine.

Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric acute lymphocytic leukemia (ALL): review from an international consensus conference.

Science.gov (United States)

Horton, Terzah M; Sposto, Richard; Brown, Patrick; Reynolds, C Patrick; Hunger, Stephen P; Winick, Naomi J; Raetz, Elizabeth A; Carroll, William L; Arceci, Robert J; Borowitz, Michael J; Gaynon, Paul S; Gore, Lia; Jeha, Sima; Maurer, Barry J; Siegel, Stuart E; Biondi, Andrea; Kearns, Pamela R; Narendran, Aru; Silverman, Lewis B; Smith, Malcolm A; Zwaan, C Michel; Whitlock, James A

2010-07-01

One of the challenges of incorporating molecularly targeted drugs into multi-agent chemotherapy (backbone) regimens is defining dose-limiting toxicities (DLTs) of the targeted agent against the background of toxicities of the backbone regimen. An international panel of 22 pediatric acute lymphocytic leukemia (ALL) experts addressed this issue (www.ALLNA.org). Two major questions surrounding DLT assessment were explored: (1) how toxicities can be best defined, assessed, and attributed; and (2) how effective dosing of new agents incorporated into multi-agent ALL clinical trials can be safely established in the face of disease- and therapy-related systemic toxicities. The consensus DLT definition incorporates tolerance of resolving Grade 3 and some resolving Grade 4 toxicities with stringent safety monitoring. This functional DLT definition is being tested in two Children's Oncology Group (COG) ALL clinical trials. Copyright 2010 Wiley-Liss, Inc.

EFFECT OF ANTIHYPERTENSIVE THERAPY BASED ON NEW METHOD OF INDIVIDUAL CHOICE OF DRUGS ON LEFT VENTRICULAR HYPERTROPHY IN ELDERLY PATIENTS

Directory of Open Access Journals (Sweden)

K. I. Pshenichkin

2015-12-01

Full Text Available Aim. To study the effects of antihypertensive therapy based on consideration of individual heart rhythm variability (HRV on left ventricular hypertrophy (LVH in hypertensive elderly patients.Material and methods. 60 hypertensive elderly patients with LVH were included in the study. They were split in two groups (30 people in each one. Patients of the group-I had common antihypertensive therapy. Patients of group-II received medications prescribed with consideration of individual heart rate variability. Holter monitoring with analysis of HRV, 24-hour blood pressure monitoring and ultrasonography were conducted initially and 18 months after treatment beginning.Results. BP control was reached in the majority of patients of both groups. The patients of group-II in comparison with patients of group-I had reduction of low- high frequency power ratio (LF/HF and higher rate of LVH reduction. Relationship between LVH dynamics and ratio LF/HF was found.Conclusion. Arterial hypertension therapy considering individual HRV contributes in LVH reduction in elderly patients.

Effect of Clonidine (an Antihypertensive Drug Treatment on Oxidative Stress Markers in the Heart of Spontaneously Hypertensive Rats

Directory of Open Access Journals (Sweden)

Nik Syamimi Nik Yusoff

2013-01-01

Full Text Available Hypertension is a risk factor for several cardiovascular diseases and oxidative stress suggested to be involved in the pathophysiology. Antihypertensive drug Clonidine action in ameliorating oxidative stress was not well studied. Therefore, this study investigate the effect of Clonidine on oxidative stress markers and nitric oxide (NO in SHR and nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME administered SHR. Male rats were divided into four groups [SHR, SHR+Clonidine (SHR-C, SHR+L-NAME, SHR+Clonidine+L-NAME(SHRC+L-NAME]. Rats (SHRC were administered with Clonidine (0.5 mg kg−1 day−1 from 4 weeks to 28 weeks in drinking water and L-NAME (25 mg kg−1 day−1 from 16 weeks to 28 weeks to SHRC+L-NAME. Systolic blood pressure (SBP was measured. At the end of 28 weeks, all rats were sacrificed and in their heart homogenate, oxidative stress parameters and NO was assessed. Clonidine treatment significantly enhanced the total antioxidant status (TAS (P<0.001 and reduced the thibarbituric acid reactive substances (TBARS (P<0.001 and protein carbonyl content (PCO (P<0.05. These data suggest that oxidative stress is involved in the hypertensive organ damage and Clonidine not only lowers the SBP but also ameliorated the oxidative stress in the heart of SHR and SHR+L-NAME.

Marketing research on the angiotensin-converting enzyme inhibitors antihypertensive medicines

OpenAIRE

BOBOIA, ANAMARIA; GRIGORESCU, MARIUS RARE?; TURCU - ?TIOLIC?, ADINA

2017-01-01

Background and aims The research aimed at investigating sales trends of angiotensin-converting enzyme inhibitors antihypertensive medicines, both in terms of quantity and value, in ten community pharmacies, for a period of three years. The research on the antihypertensive medicines consumption is important for highlighting the ever increasing impact of hypertension among the population. Methods The methods used in this research were the following: marketing research, method of sampling, descr...

PHARMACOECONOMIC ANALYSIS OF ANTIHYPERTENSIVE DRUG COMBINATIONS USE

Directory of Open Access Journals (Sweden)

E. I. Tarlovskaya

2015-09-01

Full Text Available Aim. To pursue pharmacoeconomic analysis of two drug combinations of ACE inhibitor (enalapril and diuretic.Material and methods. Patients with arterial hypertension degree 2 and diabetes mellitus type 2 without ischemic heart disease (n=56 were included into the study. Blood pressure (BP dynamics and cost/effectiveness ratio were evaluated.Results. In group A (fixed combination of original enalapril/hydrochlorothiazide 61% of patients achieved target BP level with initial dose, and the rest 39% of patients – with double dose. In group B (non-fixed combination of generic enalapril/indapamide 60% of patients achieved the target BP with initial dose of drugs, 33% - with double dose of ACE inhibitor, and 7% - with additional amlodipine administration. In patients of group A systolic BP (SBP reduction was 45.82±1.23 mm Hg by the 12th week vs. 40.0±0.81 mm Hg in patients of group B; diastolic BP (DBP reduction was 22.47±1.05 mm Hg and 18.76±0.70 mm Hg, respectively, by the 12th week of treatment. In the first month of treatment costs of target BP achievement was 298.62 rubles per patient in group A, and 299.50 rubles – in group B; by the 12th week of treatment – 629.45 and 631.22 rubles, respectively. Costs of SBP and DBP reduction by 1 mm Hg during 12 weeks of therapy were 13 and 27 rubles per patient, respectively, in group A, and 16 and 34 rubles per patient, respectively, in group B.Conclusion. The original fixed combination (enalapril+hydrochlorothiazide proved to be more clinically effective and more cost effective in the treatment of hypertensive patients in comparison with the non-fixed combination of generic drugs (enalapril+indapamide.

The right choice of antihypertensives protects primary human hepatocytes from ethanol- and recombinant human TGF-β1-induced cellular damage

Directory of Open Access Journals (Sweden)

Ehnert S

2013-03-01

damage, except for furosemide, which had no effect. As a common mechanism, all antihypertensives increased heme-oxygenase-1 (HO-1 expression, and inhibition of HO-1 activity reversed the protective effect of the drugs. Interestingly, Smad3/4 signaling was reduced by all compounds except furosemide, which even enhanced this profibrotic signaling. This effect was mediated by expressional changes of Smad3 and/or Smad4.Conclusions: Our results suggest that antihypertensives may both positively and negatively influence chronic liver disease progression. Therefore, we propose that in future patients with ALD and high blood pressure, they could benefit from an adjusted antihypertensive therapy with additional antifibrotic effects.Keywords: primary human hepatocytes, alcoholic liver disease, ethanol, TGF-β1, antihypertensives

Once-daily dose regimen of ribavirin is interchangeable with a twice-daily dose regimen: randomized open clinical trial

Directory of Open Access Journals (Sweden)

Balk JM

2015-08-01

.05. No significant differences in the hematological profile were observed (P>0.05. Conclusion: The standard twice-daily RBV regimen is interchangeable with the once-daily regimen. The once-daily regimen will improve compliance and opens the opportunity to combine RBV with other drugs dosed once a day, in a single pill. Keywords: hepatitis C, dose regimen, ribavirin, pegylated interferon

Triple Drug Combination of Zidovudine, Efavirenz and Lamivudine Loaded Lactoferrin Nanoparticles: an Effective Nano First-Line Regimen for HIV Therapy.

Science.gov (United States)

Kumar, Prashant; Lakshmi, Yeruva Samrajya; Kondapi, Anand K

2017-02-01

To enhance efficacy, bioavailability and reduce toxicity of first-line highly active anti-retroviral regimen, zidovudine + efavirenz + lamivudine loaded lactoferrin nanoparticles were prepared (FLART-NP) and characterized for physicochemical properties, bioactivity and pharmacokinetic profile. Nanoparticles were prepared using sol-oil protocol and characterized using different sources such as FE-SEM, AFM, NanoSight, and FT-IR. In-vitro and in-vivo studies have been done to access the encapsulation-efficiency, cellular localization, release kinetics, safety analysis, biodistribution and pharmacokinetics. FLART-NP with a mean diameter of 67 nm (FE-SEM) and an encapsulation efficiency of >58% for each drug were prepared. In-vitro studies suggest that FLART-NP deliver the maximum of its payload at pH5 with a minimum burst release throughout the study period with negligible toxicity to the erythrocytes plus improved in-vitro anti-HIV activity. FLART-NP has improved the in-vivo pharmacokinetics (PK) profiles over the free drugs; an average of >4fold increase in AUC and AUMC, 30% increase in the C max , >2fold in the half-life of each drug. Biodistribution data suggest that FLART-NP has improved the bioavailability of all drugs with less tissue-related inflammation as suggested with histopathological evaluation CONCLUSIONS: The triple-drug loaded nanoparticles have various advantages against soluble (free) drug combination in terms of enhanced bioavailability, improved PK profile and diminished drug-associated toxicity.

Medication reconciliation in acute care: ensuring an accurate drug regimen on admission and discharge.

Science.gov (United States)

Rodehaver, Claire; Fearing, Deb

2005-07-01

Several factors contribute to the potential for patient confusion regarding his or her medication regimen, including multiple names for a single drug and formulary variations when the patient receives medications from more than one pharmacy. A 68-year-old woman was discharged from the hospital on a HMG-CoA reductase inhibitor (statin) and resumed her home statin. Eleven days later she returned to the hospital with a diagnosis of severe rhabdomyolysis due to statin overdose. IMPLEMENTING SOLUTIONS: Miami Valley Hospital, Dayton, Ohio, implemented a reconciliation process and order form at admission and discharge to reduce the likelihood that this miscommunication would recur. Initial efforts were trialed on a 44-bed orthopedic unit, with spread of the initiative to the cardiac units and finally to the remaining 22 nursing units. The team successfully implemented initiation of the order sheet, yet audits indicated the need for improvement in reconciling the medications within 24 hours of admission and in reconciling the home medications at the point of discharge. Successful implementation of the order sheet to drive reconciliation takes communication, perseverance, and a multidisciplinary team approach.

Polypharmacy: correlations with sex, age and drug regimen

DEFF Research Database (Denmark)

Bjerrum, L; Søgaard, J; Hallas, J

1998-01-01

by inhabitants in the county of Funen (n = 466567). The number of individuals concurrently using two to four drugs (minor PP) and five or more drugs (major PP) was calculated on a random day in 1994. Drugs were classified according to the Anatomical Therapeutical Chemical (ATC) classification index. The main...... therapeutic class (second level of the ATC code) was used as an indicator for the type of health problem. A stepwise backwards logistic regression was used to identify predictors of major PP. Odds ratios were calculated for different drug classes, and the age and sex of all drug users. RESULTS: On a random...... day, 8.3% of the population were exposed to minor PP and 1.2% to major PP. The prevalence of PP increased with age, and from the age of 70 years, two thirds of all drug users were PP users. Drug use was 50% more prevalent among women than men, but over the age of 70, the sexes did not differ...

Effect of antihypertensive therapy on aortic distensibility in patients with hypertension. Comparison with nicardipine and trichlormethiazide

Energy Technology Data Exchange (ETDEWEB)

Honda, Toshio [Ehime Prefectural Iyomishima Hospital (Japan)

1995-03-01

To evaluate the aortic wall distensibility (AD) in patients with hypertension, AD was measured using cine magnetic resonance imaging in 37 hypertensive patients (HT) and 40 normal control subjects (NC). In addition, to evaluate the effect of antihypertensive drugs on AD, AD was measured before and after following antihypertensive treatments in 23 HT. Thirteen HT and 10 HT were treated for 12 weeks by 80 mg per day of nicardipine (group N) and 2-4 mg per day of trichlormethiazide (group T), respectively. Cine magnetic resonance imaging was performed at ascending (ASC) and descending (DESC) aortic levels. Aortic area was measured at the maximum and minimum frames. AD was calculated from the following formula: (Max. area - Min. area)/(Min. area x pulse pressure). AD was lower in HT than in NC both at ASC (p<0.01) and DESC (p<0.01). There was negative correlationship between age and AD in both HT and NC. After treatment of N and T, AD in all patients increased significantly. AD in ASC changed from 1.38{+-}0.99 to 5.29{+-}2.78 in HT treated by N, from 1.15{+-}0.70 to 2.48{+-}1.08 in HT treated by T, respectively. AD in DESC changed from 1.56{+-}0.87 to 5.53{+-}2.57 in HT treated by N, from 1.28{+-}0.59 to 2.67{+-}0.75 in HT treated by T, respectively. There were no significant differences in ADs of both ASC and DESC before treatment between HT treated by N and T. However, there were significant differences in ADs of both ASC and DESC after treatment between HT treated by N and T. There were no significant differences in systolic, diastolic and pulse pressures both before and after treatment between group N and group T. In conclusion, it is suspected that hypertension is the strong factor which promotes the aortic sclerosis. In addition, antihypertensive drugs have a beneficial effect on aortic distensibility, and its effect of nicardipine is stronger than that of trichlormethiazide. (author) 57 refs.

The antihypertensive effect of fermented milk in individuals with prehypertension or borderline hypertension

DEFF Research Database (Denmark)

Usinger, Lotte; Jensen, L T; Flambard, B

2010-01-01

 Hg have been reported in spontaneously hypertensive rats fed FM. Results from human studies of the antihypertensive effect are inconsistent. However, many studies suffer from methodological weaknesses, as insufficient blinding and the use of office BP measurements. We conducted a randomised, double......, which could be compatible with a minor antihypertensive effect. Heart rate and lipids remained unchanged between groups. Hence, our study does not support earlier studies measuring office BP-measurements, reporting antihypertensive effect of FM. Based on straight performed 24-h ambulatory BP...

Photostabilization studies of antihypertensive 1,4-dihydropyridines using polymeric containers.

Science.gov (United States)

De Luca, Michele; Ioele, Giuseppina; Spatari, Claudia; Ragno, Gaetano

2016-05-30

1,4-dihydropyridine antihypertensives (DHPs) are almost all dispensed in solid pharmaceutical formulations for their easy lability when exposed to light. This paper reports a study on the photoprotective effect of containers in different glassy or polymeric matrices with regard to four known DHPs when in solutions. The samples were subjected to forced degradation by means of a Xenon lamp, in accordance with the international rules on drug stability evaluation. The simultaneous determination of the drugs and their photoproducts was carried out by applying the multivariate curve resolution (MCR) methodology to the spectral data recorded along the irradiation test. This technique was able to determine the kinetic parameters and resolve the spectra of the photoproducts. The time required to reduce by 10% the concentration of the drug (t0.1) was adopted as a criterion to compare the protective ability of the containers. A significant photoprotection for all drugs tested was obtained by the use of polyethylene terephthalate (PET) containers. The best result was achieved for the felodipine solution in blue PET transparent bottle of 0.6mm thickness, reaching an almost complete stabilization up to six hours under stressing irradiation. In contrast, the glass containers, whether or not coloured, did not provide a satisfactory photoprotection of the drugs, showing in any case t0.1 values under 24min. These results can be a good opportunity to design new photoprotective pharmaceutical packaging for DHPs in liquid dosage form. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Directory of Open Access Journals (Sweden)

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.

Original Research Prescription pattern of antihypertensive ...

African Journals Online (AJOL)

2017 The College of Medicine and the Medical Association of Malawi. This work is licensed ... This study assessed the prescription pattern of antihypertensive medications and BP .... Data were analysed using the Statistical Package for Social. Sciences ... chi-square test was used to determine the significance of observed ...

Relationship between patients' beliefs about their antihypertensives ...

African Journals Online (AJOL)

... patients' beliefs about their antihypertensives and adherence in a secondary hospital in ... The study was a cross-sectional study on hypertensive patients in General ... were effective in protecting them from the effects of high blood pressure.

Low body weight and type of protease inhibitor predict discontinuation and treatment-limiting adverse drug reactions among HIV-infected patients starting a protease inhibitor regimen: consistent results from a randomized trial and an observational cohort

DEFF Research Database (Denmark)

Kirk, O; Gerstoft, J; Pedersen, C

2001-01-01

OBJECTIVES: To assess predictors for discontinuation and treatment-limiting adverse drug reactions (TLADR) among patients starting their first protease inhibitor (PI). METHODS: Data on patients starting a PI regimen (indinavir, ritonavir, ritonavir/saquinavir and saquinavir hard gel) in a randomi......OBJECTIVES: To assess predictors for discontinuation and treatment-limiting adverse drug reactions (TLADR) among patients starting their first protease inhibitor (PI). METHODS: Data on patients starting a PI regimen (indinavir, ritonavir, ritonavir/saquinavir and saquinavir hard gel....... Low body weight and initiation of ritonavir relative to other PIs were associated with an increased risk of TLADRs. Very consistent results were found in a randomized trial and an observational cohort....

Solidified self-nanoemulsifying formulation for oral delivery of combinatorial therapeutic regimen

DEFF Research Database (Denmark)

Jain, Amit K; Thanki, Kaushik; Jain, Sanyog

2014-01-01

PURPOSE: The present work reports rationalized development and characterization of solidified self-nanoemulsifying drug delivery system for oral delivery of combinatorial (tamoxifen and quercetin) therapeutic regimen. METHODS: Suitable oil for the preparation of liquid SNEDDS was selected based...

Repurposing and Rescuing of Mibefradil, an Antihypertensive, for Cancer: A Case Study.

Science.gov (United States)

Krouse, Andrew J; Gray, Lloyd; Macdonald, Timothy; McCray, John

2015-12-01

The expanding "valley of death" in drug development is leaving potentially life-saving new chemical entities and molecular targets fallow. This situation is forcing early-stage companies to think creatively about moving their technologies forward, especially as institutional investors show more interest in later stages of development. Drug repurposing, a strategy to examine existing drugs for therapeutic value against different diseases, is an emerging method to bring an off-market drug back onto the market. Tau Therapeutics LLC identified the role of T-type calcium channel blockers (Cav3) in cancer proliferation, but the company was unable to attract funding while having both a nonvalidated drug target and new chemical entities. To change the risk profile of the company, Tau set out to repurpose the known Cav3 drug mibefradil as a proof of concept for the treatment of cancer. Mibefradil was launched for hypertension in the 1990s but withdrawn because of drug-drug interactions. A new sequential combination treatment, termed Interlaced Therapy™, uses short-term administration of mibefradil to enhance the overall therapeutic potential of conventional anticancer agents. Mibefradil is currently in a phase Ib clinical trial with the National Cancer Institute (NCI) Adult Brain Tumor Consortium. Mibefradil has been repurposed from an abandoned antihypertensive to a targeted solid tumor treatment, and it has been rescued from drug-drug interactions by using short-term dose exposure. Tau is using the early success of mibefradil as a proof of concept to build a platform technology of Cav3 blockers for broad antitumor applications in combination with new targeted cancer therapies, well-established chemotherapies, and radiation.

A cross-sectional study of tuberculosis drug resistance among previously treated patients in a tertiary hospital in Accra, Ghana: public health implications of standardized regimens.

Science.gov (United States)

Forson, Audrey; Kwara, Awewura; Kudzawu, Samuel; Omari, Michael; Otu, Jacob; Gehre, Florian; de Jong, Bouke; Antonio, Martin

2018-04-02

Mycobacterium tuberculosis drug resistance is a major challenge to the use of standardized regimens for tuberculosis (TB) therapy, especially among previously treated patients. We aimed to investigate the frequency and pattern of drug resistance among previously treated patients with smear-positive pulmonary tuberculosis at the Korle-Bu Teaching Hospital Chest Clinic, Accra. This was a cross-sectional survey of mycobacterial isolates from previously treated patients referred to the Chest Clinic Laboratory between October 2010 and October 2013. The Bactec MGIT 960 system for mycobactrerial culture and drug sensitivity testing (DST) was used for sputum culture of AFB smear-positive patients with relapse, treatment failure, failure of smear conversion, or default. Descriptive statistics were used to summarize patient characteristics, and frequency and patterns of drug resistance. A total of 112 isolates were studied out of 155 from previously treated patients. Twenty contaminated (12.9%) and 23 non-viable isolates (14.8%) were excluded. Of the 112 studied isolates, 53 (47.3%) were pan-sensitive to all first-line drugs tested Any resistance (mono and poly resistance) to isoniazid was found in 44 isolates (39.3%) and any resistance to streptomycin in 43 (38.4%). Thirty-one (27.7%) were MDR-TB. Eleven (35.5%) out of 31 MDR-TB isolates were pre-XDR. MDR-TB isolates were more likely than non-MDR isolates to have streptomycin and ethambutol resistance. The main findings of this study were the high prevalence of MDR-TB and streptomycin resistance among previously treated TB patients, as well as a high prevalence of pre-XDR-TB among the MDR-TB patients, which suggest that first-line and second-line DST is essential to aid the design of effective regimens for these groups of patients in Ghana.

Towards personalized antihypertensive therapy: innovate or denervate?

NARCIS (Netherlands)

Eeftinck Schattenkerk, D.W.

2017-01-01

In this thesis we employed novel techniques to gain a better understanding of hypertensive disorders and improve antihypertensive treatment strategies. We discuss novel aspects in phenotyping and treatment modalities. Assessment of central hemodynamics may improve hypertensive phenotyping beyond

MedMinify: An Advice-giving System for Simplifying the Schedules of Daily Home Medication Regimens Used to Treat Chronic Conditions.

Science.gov (United States)

Flynn, Allen J; Klasnja, Predrag; Friedman, Charles P

2014-01-01

For those with high blood pressure, diabetes, or high cholesterol, adherence to a home medication regimen is important for health. Reductions in the number of daily medication-taking events or daily pill burden improve adherence. A novel advice-giving computer application was developed using the SMART platform to generate advice on how to potentially simplify home medication regimens. MedMinify generated advice for 41.3% of 1,500 home medication regimens for adults age 60 years and older with chronic medical conditions. If the advice given by MedMinify were implemented, 320 regimen changes would have reduced daily medication-taking events while an additional 295 changes would have decreased the daily pill burden. The application identified four serious drug-drug interactions and so advised against taking two pairs of medications simultaneously. MedMinify can give advice to change home medication regimens that could result in simpler home medication-taking schedules.

A rational quantitative approach to determine the best dosing regimen for a target therapeutic effect: a unified formalism for antibiotic evaluation.

Science.gov (United States)

Li, Jun; Nekka, Fahima

2013-02-21

The determination of an optimal dosing regimen is a critical step to enhance the drug efficacy and avoid toxicity. Rational dosing recommendations based on mathematical considerations are increasingly being adopted in the process of drug development and use. In this paper, we propose a quantitative approach to evaluate the efficacy of antibiotic agents. By integrating both pharmacokinetic (PK) and pharmacodynamic (PD) information, this approach gives rise to a unified formalism able to measure the cause-effect of dosing regimens. This new pharmaco-metric allows to cover a whole range of antibiotics, including the two well known concentration and time dependent classes, through the introduction of the Hill-dependency concept. As a direct fallout, our formalism opens a new path toward the bioequivalence evaluation in terms of PK and PD, which associates the in vivo drug concentration and the in vitro drug effect. Using this new approach, we succeeded to reveal unexpected, but relevant behaviors of drug performance when different drug regimens and drug classes are considered. Of particular notice, we found that the doses required to reach the same therapeutic effect, when scheduled differently, exhibit completely different tendencies for concentration and time dependent drugs. Moreover, we theoretically confirmed the previous experimental results of the superiority of the once daily regimen of aminoglycosides. The proposed methodology is appealing for its computational features and can easily be applicable to design fair clinical protocols or rationalize prescription decisions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Antihypertensive Drug and Inner Ear Perfusion: An Otologist’s Point of View

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Antonio Pirodda

2009-09-01

Full Text Available A number of labyrinthine disorders with sensorineural hearing loss, vertigo, and tinnitus are known to occur to young people without vascular risk factors, thus being classified as “idiopathic” in the absence of satisfactory explanations; in the last decade, this phenomenon has found a reliable explanation by the adverse effect of a sharp decrease of blood pressure values followed by an abnormal vasomotor regulation. This model may not only be applied to healthy subjects, but even had some confirmation in conditions possibly affecting hemodynamic changes, such as heart failure or treated hypertension. In particular, the results of a recent study on the impact of different antihypertensive therapies, which was analyzed by monitoring the onset or enhancement of tinnitus as a symptom of inner ear sufferance, unequivocally demonstrated an increased prevalence of tinnitus in subjects submitted to more “aggressive” treatments. This seems in agreement with recent observations about the model of fluid homeostasis of the inner ear, and suggests, when possible, to resort to treatments with modulatory effects in order to maintain a steady perfusion to the labyrinth thus protecting its function.

Lactotripeptides and antihypertensive effects: A critical review

NARCIS (Netherlands)

Boelsma, E.; Kloek, J.

2009-01-01

Hypertension or high blood pressure is a significant health problem worldwide. Typically, lifestyle changes, including adopting a healthy diet, are recommended for people with an elevated blood pressure. Lactotripeptides are bioactive milk peptides with potential antihypertensive properties in man.

Cost-effectiveness analysis of lopinavir/ritonavir and atazanavir+ritonavir regimens in the CASTLE study.

Science.gov (United States)

Simpson, Kit N; Rajagopalan, Rukmini; Dietz, Birgitta

2009-02-01

The purpose of the study was to conduct a cost-effectiveness analysis and budget impact analysis comparing lopinavir with ritonavir (LPV/r) and atazanavir plus ritonavir (ATV+RTV) for antiretroviral-naïve patients with a baseline CD4+ T-cell distribution and total cholesterol (TC) profile as reported in the CASTLE study. This decision analysis study used a previously published Markov model of HIV disease, incorporating coronary heart disease (CHD) events to compare the short- and long-term budget impacts and CHD consequences expected for the two regimens. Patients were assumed to have a baseline CHD risk of 4.6% (based on demographic data) and it was also assumed that 50% of the population in the CASTLE study were smokers. The CHD risk differences (based on percent of patients with TC >240 mg/dL) in favor of ATV+RTV resulted in an average improvement in life expectancy of 0.031 quality-adjusted life years (QALYs) (11 days), and an incremental cost-effectiveness ratio of $1,409,734/QALY. Use of the LPV/r regimen saved $24,518 and $36,651 at 5 and 10 years, respectively, with lifetime cost savings estimated at $38,490. A sensitivity analysis using a cohort of all smokers on antihypertensive medication estimated an average improvement in life expectancy of 31 quality-adjusted days in favor of ATV+RTV, and a cost-effectiveness ratio of $520,861/QALY: a ratio that is still above the acceptable limit within the US. The use of an LPV/r-based regimen in antiretroviral-naïve patients with a baseline CHD risk similar to patients in the CASTLE study appears to be a more cost-effective use of resources compared with an ATV+RTV-based regimen. The very small added CHD risk predicted by LPV/r treatment is more than offset by the substantial short- and long-term cost savings expected with the use of LPV/r in antiretroviral-naïve individuals with average to moderately elevated CHD risk.

Kidney function after withdrawal of long-term antihypertensive treatment in diabetic nephropathy

DEFF Research Database (Denmark)

Hansen, H P; Nielsen, F S; Rossing, P

1997-01-01

) [median (range)] with diabetic nephropathy receiving antihypertensive treatment (angiotensin converting enzyme inhibition, N = 30) for 5 years (1 to 20 years). The following variables were measured the last day on antihypertensive treatment and one month after withdrawal of treatment; GFR (51Cr-EDTA), 24......-hour arterial blood pressure (24 hr MABP, Takeda TM2420) and albuminuria (ELISA); the mean 24-hour MABP rose from 102 +/- 11 to 111 +/- 10 (P ... +/- 25 to 70 +/- 26 ml.min-1.1.73 m-2, P = 0.21), after withdrawal of antihypertensive treatment. A significant correlation between the relative change in the 24 hour MABP measurement and the relative change in GFR (r = 0.44, P

Validated HPTLC methods for determination of some selected antihypertensive mixtures in their combined dosage forms

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Rasha A. Shaalan

2014-12-01

Full Text Available Simple and selective HPTLC methods were developed for the simultaneous determination of the antihypertensive drugs; carvedilol and hydrochlorothiazide in their binary mixture (Mixture I and amlodipine besylate, valsartan, and hydrochlorothiazide in their combined ternary formulation (Mixture II. Effective chromatographic separation was achieved on Fluka TLC plates 20 × 20 cm aluminum cards, 0.2 mm thickness through linear ascending development. For Mixture I, the mobile phase composed of chloroform–methanol in the ratio 8:2 v/v. Detection was performed at 254 nm for both carvedilol and hydrochlorothiazide. For Mixture II, the mobile phase was chloroform–methanol–ammonia in the volume ratio 8:2:0.1. Detection was performed at 254 nm for valsartan and hydrochlorothiazide, and at 365 nm for amlodipine. Quantification was based on spectrodensitometric analysis. Analytical performance of the proposed HPTLC procedures was statistically validated with respect to linearity, ranges, precision, accuracy, specificity, robustness, detection and quantification limits. The linearity ranges were 0.05–1.0 and 0.1–2.0 μg/spot for carvedilol and hydrochlorothiazide, respectively in Mixture I, 0.1–2.0, 0.1–2.0 and 0.2–4.0 μg/spot for amlodipine, hydrochlorothiazide and valsartan, respectively in Mixture II, with correlation coefficients >0.9992. The validated HPTLC methods were applied to the analysis of the cited antihypertensive drugs in their combined pharmaceutical tablets. The proposed methods confirmed peak identity and purity.

Acute and chronic antihypertensive effects of Cinnamomum zeylanicum stem bark methanol extract in L-NAME-induced hypertensive rats

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Nyadjeu Paulin

2013-01-01

Full Text Available Abstract Background Previous study showed that the aqueous extract of the stem bark of Cinnamomum zeylanicum possesses antihypertensive and vasodilatory properties. The present work investigates the acute and chronic antihypertensive effects of the methanol extract of Cinnamomum zeylanicum stem bark (MECZ in L-NAME-induced hypertensive rats. Methods The acute antihypertensive effects of MECZ (5, 10 and 20 mg/kg administered intravenously were evaluated in rats in which acute arterial hypertension has been induced by intravenous administration of L-NAME (20 mg/kg. For chronic antihypertensive effects, animals were treated with L-NAME (40 mg/kg/day plus the vehicle or L-NAME (40 mg/kg/day in combination with captopril (20 mg/kg/day or MECZ (300 mg/kg/day and compared with control group receiving only distilled water. All drugs were administered per os and at the end of the experiment that lasted for four consecutive weeks, blood pressure was measured by invasive method and blood samples were collected for the determination of the lipid profile. The heart and aorta were collected, weighed and used for both histological analysis and determination of NO tissue content. Results Acute intravenous administration of C. zeylanicum extract (5, 10 and 20 mg/kg to L-NAME-induced hypertensive rats provoked a long-lasting decrease in blood pressure. Mean arterial blood pressure decreased by 12.5%, 26.6% and 30.6% at the doses of 5, 10 and 20 mg/kg, respectively. In chronic administration, MECZ and captopril significantly prevented the increase in blood pressure and organs’ weights, as well as tissue histological damages and were able to reverse the depletion in NO tissue’s concentration. The MECZ also significantly lower the plasma level of triglycerides (38.1%, total cholesterol (32.1% and LDL-cholesterol (75.3% while increasing that of HDL-cholesterol (58.4% with a significant low atherogenic index (1.4 versus 5.3 for L-NAME group. Conclusion MECZ

Aggressive Regimens for Multidrug-Resistant Tuberculosis Reduce Recurrence

Science.gov (United States)

Franke, Molly F.; Appleton, Sasha C.; Mitnick, Carole D.; Furin, Jennifer J.; Bayona, Jaime; Chalco, Katiuska; Shin, Sonya; Murray, Megan; Becerra, Mercedes C.

2013-01-01

Background. Recurrent tuberculosis disease occurs within 2 years in as few as 1% and as many as 29% of individuals successfully treated for multidrug-resistant (MDR) tuberculosis. A better understanding of treatment-related factors associated with an elevated risk of recurrent tuberculosis after cure is urgently needed to optimize MDR tuberculosis therapy. Methods. We conducted a retrospective cohort study among adults successfully treated for MDR tuberculosis in Peru. We used multivariable Cox proportional hazards regression analysis to examine whether receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion from positive to negative was associated with a reduced rate of recurrent tuberculosis. Results. Among 402 patients, the median duration of follow-up was 40.5 months (interquartile range, 21.2–53.4). Receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion was associated with a lower risk of recurrent tuberculosis (hazard ratio, 0.40 [95% confidence interval, 0.17–0.96]; P = .04). A baseline diagnosis of diabetes mellitus also predicted recurrent tuberculosis (hazard ratio, 10.47 [95% confidence interval, 2.17–50.60]; P = .004). Conclusions. Individuals who received an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion experienced a lower rate of recurrence after cure. Efforts to ensure that an aggressive regimen is accessible to all patients with MDR tuberculosis, such as minimization of sequential ineffective regimens, expanded drug access, and development of new MDR tuberculosis compounds, are critical to reducing tuberculosis recurrence in this population. Patients with diabetes mellitus should be carefully managed during initial treatment and followed closely for recurrent disease. PMID:23223591

Effects of a lifestyle programme on ambulatory blood pressure and drug dosage in treated hypertensive patients: a randomized controlled trial.

Science.gov (United States)

Burke, Valerie; Beilin, Lawrie J; Cutt, Hayley E; Mansour, Jacqueline; Wilson, Amy; Mori, Trevor A

2005-06-01

To assess effects of multifactorial lifestyle modification on antihypertensive drug needs in treated hypertensive individuals. Randomized controlled trial. Research studies unit. Overweight hypertensive patients, receiving one or two antihypertensive drugs, were recruited by advertising, and allocated randomly to a usual care group (controls; n = 118) or a lifestyle modification group (programme group; n = 123). A 4-month programme of weight loss, a low-sodium 'Dietary Approaches to Stop Hypertension'-type diet with added fish, physical activity and moderation of alcohol intake. After 4 months, if mean 24-h ambulatory blood pressure (ABP) was less than 135/85 mmHg, antihypertensive drugs were withdrawn over 4 weeks and long-term home blood pressure monitoring was begun. Antihypertensive drug requirements, ABP, weight, waist girth at 4 months and 1-year follow-up. Ninety control group and 102 programme group participants completed the study. Mean 24-h ABP changed after 4 months by -1.0/-0.3 +/- 0.5/0.4 mmHg in controls and -4.1/-2.1 +/- 0.7/0.5 mmHg with the lifestyle programme (P lifestyle modification in patients with treated hypertension reduced blood pressure in the short-term. Decreased central obesity persisted 1 year later and could reduce overall cardiovascular risk.

Blood Pressure-Lowering Aspects of Lipid-Lowering and Anti-Diabetic Drugs

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Peter M. Nilsson

2010-12-01

Full Text Available Several studies have shown that blood pressure can be lowered by the use of drugs that are not traditional antihypertensive drugs. This might be of clinical importance when many risk patients are treated by combination drug therapy in order to prevent cardiovascular disease by way of improving the cardiovascular risk factor profile.

Micellar Enhanced Three-Dimensional Excitation-Emission Matrix Fluorescence for Rapid Determination of Antihypertensives in Human Plasma with Aid of Second-Order Calibration Methods

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Hai-Yan Fu

2015-01-01

Full Text Available A highly sensitive three-dimensional excitation-emission fluorescence method was proposed to determine antihypertensives including valsartan and amlodipine besylate in human plasma with the aid of second-order calibration methods based on parallel factor analysis (PARAFAC and alternating trilinear decomposition (ATLD algorithms. Antihypertensives with weak fluorescent can be transformed into a strong fluorescent property by changing microenvironment in samples using micellar enhanced surfactant. Both the adopted algorithms with second-order advantage can improve the resolution and directly attain antihypertensives concentration even in the presence of potential strong intrinsic fluorescence from human plasma. The satisfactory results can be achieved for valsartan and amlodipine besylate in complicated human plasma. Furthermore, some statistical parameters and figures of merit were evaluated to investigate the performance of the proposed method, and the accuracy and precision of the proposed method were also validated by the elliptical joint confidence region (EJCR test and repeatability analysis of intraday and interday assay. The proposed method could not only light a new avenue to directly determine valsartan or amlodipine besylate in human plasma, but also hold great potential to be extended as a promising alternative for more practical applications in the determination of weak fluorescent drugs.

A randomized trial evaluating a block-replacement regimen during radioiodine therapy

DEFF Research Database (Denmark)

Bonnema, Steen J; Grupe, Peter; Boel-Jørgensen, Henrik

2011-01-01

Eur J Clin Invest 2010 ABSTRACT: Background  Lack of consensus regarding the antithyroid drug regimen in relation to radioiodine ((131) I) therapy of hyperthyroidism prompted this randomized trial comparing two strategies. Design  Patients with Graves' disease (GD, n = 51) or toxic nodular goitre...

Preclinical Evaluations To Identify Optimal Linezolid Regimens for Tuberculosis Therapy

Science.gov (United States)

Drusano, George L.; Adams, Jonathan R.; Rodriquez, Jaime L.; Jambunathan, Kalyani; Baluya, Dodge L.; Brown, David L.; Kwara, Awewura; Mirsalis, Jon C.; Hafner, Richard; Louie, Arnold

2015-01-01

ABSTRACT Linezolid is an oxazolidinone with potent activity against Mycobacterium tuberculosis. Linezolid toxicity in patients correlates with the dose and duration of therapy. These toxicities are attributable to the inhibition of mitochondrial protein synthesis. Clinically relevant linezolid regimens were simulated in the in vitro hollow-fiber infection model (HFIM) system to identify the linezolid therapies that minimize toxicity, maximize antibacterial activity, and prevent drug resistance. Linezolid inhibited mitochondrial proteins in an exposure-dependent manner, with toxicity being driven by trough concentrations. Once-daily linezolid killed M. tuberculosis in an exposure-dependent manner. Further, 300 mg linezolid given every 12 hours generated more bacterial kill but more toxicity than 600 mg linezolid given once daily. None of the regimens prevented linezolid resistance. These findings show that with linezolid monotherapy, a clear tradeoff exists between antibacterial activity and toxicity. By identifying the pharmacokinetic parameters linked with toxicity and antibacterial activity, these data can provide guidance for clinical trials evaluating linezolid in multidrug antituberculosis regimens. PMID:26530386

Drug-induced gingival enlargement: Series of cases

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Isabella Manzur-Villalobos

2018-01-01

Full Text Available Introduction: Gingival enlargement (GA is a benign condition of the oral cavity that is characterized by the excessive growth of the gingiva in mass and volume. This lesion is not only caused by hereditary factors or poor oral hygiene, but also by the intake of medications, including antihypertensive, anticonvulsant and immunosuppressive drugs. Objective: To sensitize the prevention or early care in patients with pathologies that merit the use of antihypertensive and anticonvulsants in conjunction with the dentist, to treat or avoid the drug-induced gingival enlargement (DIGE. Materials and methods: A series of clinical cases of patients with gingival enlargement by various drugs are reported, including Phenytoin, Amlodipine and Nifedipine. Periodontal and gingivectomy hygienic phase measures were applied to obtain better effects. Results: Satisfactory results were obtained with a considerable decrease in DIGE. Conclusions: The integral management is important in conjunction with the treating physician to follow up the drug that can be generating gingival enlargement. It is necessary to employ an initial approach with strategies of periodontal hygiene, and in severe cases and, as last resort, the periodontal surgery with gingivectomy and gingivoplasty.

Neurocognitive Function in Children with Primary Hypertension after Initiation of Antihypertensive Therapy.

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Lande, Marc B; Batisky, Donald L; Kupferman, Juan C; Samuels, Joshua; Hooper, Stephen R; Falkner, Bonita; Waldstein, Shari R; Szilagyi, Peter G; Wang, Hongyue; Staskiewicz, Jennifer; Adams, Heather R

2018-04-01

To determine the change in neurocognitive test performance in children with primary hypertension after initiation of antihypertensive therapy. Subjects with hypertension and normotensive control subjects had neurocognitive testing at baseline and again after 1 year, during which time the subjects with hypertension received antihypertensive therapy. Subjects completed tests of general intelligence, attention, memory, executive function, and processing speed, and parents completed rating scales of executive function. Fifty-five subjects with hypertension and 66 normotensive control subjects underwent both baseline and 1-year assessments. Overall, the blood pressure (BP) of subjects with hypertension improved (24-hour systolic BP load: mean baseline vs 1 year, 58% vs 38%, P < .001). Primary multivariable analyses showed that the hypertension group improved in scores of subtests of the Rey Auditory Verbal Learning Test, Grooved Pegboard, and Delis-Kaplan Executive Function System Tower Test (P < .05). However, the control group also improved in the same measures with similar effects sizes. Secondary analyses by effectiveness of antihypertensive therapy showed that subjects with persistent ambulatory hypertension at 1 year (n = 17) did not improve in subtests of Rey Auditory Verbal Learning Test and had limited improvement in Grooved Pegboard. Overall, children with hypertension did not improve in neurocognitive test performance after 1 year of antihypertensive therapy, beyond that also seen in normotensive controls, suggesting improvements with age or practice effects because of repeated neurocognitive testing. However, the degree to which antihypertensive therapy improves BP may affect its impact upon neurocognitive function. Copyright © 2017 Elsevier Inc. All rights reserved.

Resistant and Refractory Hypertension: Antihypertensive Treatment Resistance vs Treatment Failure

Science.gov (United States)

Siddiqui, Mohammed; Dudenbostel, Tanja; Calhoun, David A.

2017-01-01

Resistant or difficult to treat hypertension is defined as high blood pressure that remains uncontrolled with 3 or more different antihypertensive medications, including a diuretic. Recent definitions also include controlled blood pressure with use of 4 or more medications as also being resistant to treatment. Recently, refractory hypertension, an extreme phenotype of antihypertensive treatment failure has been defined as hypertension uncontrolled with use of 5 or more antihypertensive agents, including a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Patients with resistant vs refractory hypertension share similar characteristics and comorbidities, including obesity, African American race, female sex, diabetes, coronary heart disease, chronic kidney disease, and obstructive sleep apnea. Patients with refractory vs resistant hypertension tend to be younger and are more likely to have been diagnosed with congestive heart failure. Refractory hypertension might also differ from resistant hypertension in terms of underlying cause. Preliminary evidence suggests that refractory hypertension is more likely to be neurogenic in etiology (ie, heightened sympathetic tone), vs a volume-dependent hypertension that is more characteristic of resistant hypertension in general. PMID:26514749

Antihypertensive Activity of Aqueous-Methanol Extract of Berberis ...

African Journals Online (AJOL)

HP

Median lethal dose (LD50) and sub-chronic toxicity of the extract were also determined ... possible mode(s) of action, side effects, toxicity ... medicinal uses. Berberis ... evaluate the possible antihypertensive effect of this plant. EXPERIMENTAL.

Factors predicting incremental administration of antihypertensive boluses during deep brain stimulator placement for Parkinson's disease.

Science.gov (United States)

Rajan, Shobana; Deogaonkar, Milind; Kaw, Roop; Nada, Eman Ms; Hernandez, Adrian V; Ebrahim, Zeyd; Avitsian, Rafi

2014-10-01

Hypertension is common in deep brain stimulator (DBS) placement predisposing to intracranial hemorrhage. This retrospective review evaluates factors predicting incremental antihypertensive use intraoperatively. Medical records of Parkinson's disease (PD) patients undergoing DBS procedure between 2008-2011 were reviewed after Institutional Review Board approval. Anesthesia medication, preoperative levodopa dose, age, preoperative use of antihypertensive medications, diabetes mellitus, anxiety, motor part of the Unified Parkinson's Disease Rating Scale score and PD duration were collected. Univariate and multivariate analysis was done between each patient characteristic and the number of antihypertensive boluses. From the 136 patients included 60 were hypertensive, of whom 32 were on angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), told to hold on the morning of surgery. Antihypertensive medications were given to 130 patients intraoperatively. Age (relative risk [RR] 1.01; 95% confidence interval [CI] 1.00-1.02; p=0.005), high Joint National Committee (JNC) class (p10 years (RR 1.2; 95%CI 1.1-1.3; p=0.001) were independent predictors for antihypertensive use. No difference was noted in the mean dose of levodopa (p=0.1) and levodopa equivalent dose (p=0.4) between the low (I/II) and high severity (III/IV) JNC groups. Addition of dexmedetomidine to propofol did not influence antihypertensive boluses required (p=0.38). Intraoperative hypertension during DBS surgery is associated with higher age group, hypertensive, diabetic patients and longer duration of PD. Withholding ACEI or ARB is an independent predictor of hypertension requiring more aggressive therapy. Levodopa withdrawal and choice of anesthetic agent is not associated with higher intraoperative antihypertensive medications. Copyright © 2014 Elsevier Ltd. All rights reserved.

PRESCRIBING OF ANTIHYPERTENSIVE AGENTS IN PUBLIC PRIMARY CARE CLINICS – IS IT IN ACCORDANCE WITH CURRENT EVIDENCE?

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SAJARI J

2010-01-01

Full Text Available Background: Large population surveys in Malaysia have consistently shown minimal improvement of blood pressure control rates over the last 10 years. Poor adherence to antihypertensive medication has been recognized as a major reason for poor control of hypertension. This study aimed to describe the prescribing pattern of antihypertensive agents in 2 public primary care clinics and assess its appropriateness in relation to current evidence and guidelines. Methods: A cross-sectional survey to describe the prescribing pattern of antihypertensive agents was carried out in 2 publicprimary care clinics in Selangor from May to June 2009. Hypertensive patients on pharmacological treatment for ≥1 year who attended the clinics within the study period of 7 weeks were selected. Appropriate use of antihypertensive agents was defined based on current evidence and the recommendations by the Malaysian Clinical Practice Guidelines (CPG on the Management of Hypertension, 2008. Data were obtained from patients’ medical records and were analysed using the SPSS software version 16.0. Results: A total of 400 hypertensive patients on treatment were included. Mean age was 59.5 years (SD ±10.9, range 28 to91 years, of which 52.8% were females and 47.2% were males. With regards to pharmacotherapy, 45.7% were on monotherapy,43.3% were on 2 agents and 11.0% were on ≥3 agents. Target blood pressure of <140/90mmHg was achieved in 51.4% of patients on monotherapy, and 33.2% of patients on combination of ≥2 agents. The commonest monotherapy agents being prescribed were β-blockers (atenolol or propranolol, followed by the short-acting calcium channel blocker (nifedipine. The commonest combination of 2-drug therapy prescribed was β-blockers and short-acting calcium channel blocker. Conclusion: This study shows that the prescribing pattern of antihypertensive agents in the 2 primary care clinics was not in accordance with current evidence and guidelines. �

SUPPLY OF ANTIHYPERTEN SIVE DRUG S AND CARDIOVA SCULAR MORTALITY IN POLAND IN 2000–2010

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K. Baranski

2016-05-01

Full Text Available Background and objective. In Poland, the sale of antihypertensive drugs has significantly increased since 2000. According to that fact, the aim of our study was to determine if the increased use of antihypertensive drugs correlates with the decreasing mortality due to cardiovascular diseases (CVD including hypertension (HT. Methods. The analysis is based on data on annual national sales (million units of four types of antihypertensive drugs in 2000–2010. For the same period standardized mortality rates were calculated based on the data available from the Central Statistical Office in Poland. Data analysis involved correlation analysis between annual mortality rates due CVD and HT and country-wide annual sales of antihypertensive drugs (2000–2010. Results. In the period 2000–2010, standardized mortality rates of CVD in the whole population followed a decreasing trend. Analysis of correlation of CVD with specific drug provided the following findings: diuretics (r=-0.97; p<0.0001 beta-blockers (r=-1.0; p<0.0001 renin-angiotensin system (RAS inhibitors (r=-0.72 p=0.01 calcium-channel blockers (r=-0.82; p=0.001 Standardized mortality rates for the HT showed fluctuating trend. Correlations of that mortality with global sale of these drugs were no longer negative: r=0.54; p=0.08, r=0.56; p=0.08 r=0.55; p=0.07; r=0.63; p=0.03, respectively. Conclusions. In Poland, in 2000–2010, an improved access to pharmacological control of HT was associated with an apparent reduction in mortality from CVD but not from HT. The latter findings might reflect imprecise definition of HT as a cause of death or the fact that HT leads to other cardiologic events usually reported as a cause of death.

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.

Classifying insulin regimens

DEFF Research Database (Denmark)

Neu, A; Lange, K; Barrett, T

2015-01-01

Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1...

Short-term Risk of Serious Fall Injuries in Older Adults Initiating and Intensifying Treatment with Antihypertensive Medication

Science.gov (United States)

Shimbo, Daichi; Bowling, C. Barrett; Levitan, Emily B.; Deng, Luqin; Sim, John J.; Huang, Lei; Reynolds, Kristi; Muntner, Paul

2016-01-01

Background Antihypertensive medication use has been associated with an increased risk of falls in some but not all studies. Few data are available on the short-term risk of falls following antihypertensive medication initiation and intensification. Methods and Results We examined the association between initiating and intensifying antihypertensive medication and serious fall injuries in a case-crossover study of 90,127 Medicare beneficiaries who were ≥65 years old and had a serious fall injury between July 1, 2007 and December 31, 2012, based on emergency department and inpatient claims. Antihypertensive medication initiation was defined by a prescription fill with no fills in the prior year. Intensification was defined by the addition of a new antihypertensive class, and, separately, titration by the addition of a new class or increase in dosage of a current class. Exposures were ascertained for the 15 days before the fall (case period) and six 15-day earlier periods (control periods). Overall, 272, 1508, and 3113 Medicare beneficiaries initiated, added a new class of antihypertensive medication or titrated therapy, respectively, within 15 days of their serious fall injury. The odds for a serious fall injury was increased during the 15 days following antihypertensive medication initiation [odds ratio, OR, 1.36 (95% CI 1.19, 1.55)], adding a new class [OR 1.16 (95% CI 1.10, 1.23)], and titration [OR 1.13 (95% CI 1.08, 1.18)]. These associations were attenuated beyond 15 days. Conclusions Antihypertensive medication initiation and intensification was associated with a short-term, but not long-term, increased risk of serious fall injuries among older adults. PMID:27166208

Is the use of ABPM justified in patients on 1 or 2 antihypertensive medications?

Science.gov (United States)

Mathur, Gaurav; Prasad, Rachana; Robinson, Anne; Rodrigues, Erwin; Wong, Peter

2008-03-28

We studied the utility of ABPM in patients with elevated clinic BP on 1-2 antihypertensive medications (group B, N=117), compared with those on no medications (group A, N=76) and on > or =3 medications (group C, N=110). 35% of patients in group B had adequately controlled 24-h BP based on ABPM, compared with 22.4% in group A (P=0.06) and 19.1% in group C (P=0.007). Antihypertensive treatment was not escalated in patients with adequately controlled BP. This suggests that ABPM has an important role in therapeutic decision-making for patients on 1-2 antihypertensive medications.

COMPARATIVE STUDY OF NEW DRUG OF LONG ACTING METOPROLOL TARTRATE - EGILOK RETARD AND ORIGINAL DRUG OF METOPROLOL SUCCINATE – BETALOC ZOK IN PATIENTS WITH MILD TO MODERATE ARTERIAL HYPERTENSION

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J. V. Lukina

2015-12-01

Full Text Available Aim. To study efficiency and safety of new drug of long acting metoprolol tartrate, “Egilok retard” (ER in patients with mild to moderate arterial hypertension (AH in comparison with the original drug of metoprolol succinat, “Betaloc ZOK” (BZ, possibility of reaching target blood pressure (BP level with treatment with each drug.Material and methods. 30 patients (11 men and 19 women with mild to moderate AH took part in randomized, open, cross over study. Previous antihypertensive treatment had been canceled for all the patients 10-14 days before the study started. Each patient by turns was treated during 6 weeks with ER and BZ 50-100 mg daily. After cancellation of the previous antihypertensive therapy, BZ and ER were prescribed (according to the randomization table in dose 50 mg daily. Drugs were taken once per day. 29 patients completed therapy with the first drug of randomization, 25 patients – with the second. After 2 weeks efficiency of treatment was assessed by target BP level achievement (< 140/90 mmHg. If efficiency of beta-adrenoblocker (BB was not sufficient, the dose of the drug was doubled to 100 mg daily, if target level was reached – the dose remained unchanged. Treatment with the settled dose was held within next 4 weeks. After 6-week treatment with the first randomized drug antihypertensive therapy was canceled for 10-14 days depending on the BB dose. At each visit office BP and heart rate were assessed, EKG was registered. Side-effects were registered according to the self-control diary, questionnaire results, examination and EKG data.Results. After 6-week treatment with ER and BZ average level of systolic BP reduced by 15,7 and 15,2 mmHg, of diastolic BP – by 8,0 and 4,5 mmHg, heart rate – by 4,1 and 4,3 beat/min respectively. Differences between antihypertensive and heart rate lowering effect of the studied drugs were not significant. Target BP level with treatment with both drugs was reached in approximately

COMPARATIVE STUDY OF NEW DRUG OF LONG ACTING METOPROLOL TARTRATE - EGILOK RETARD AND ORIGINAL DRUG OF METOPROLOL SUCCINATE – BETALOC ZOK IN PATIENTS WITH MILD TO MODERATE ARTERIAL HYPERTENSION

Directory of Open Access Journals (Sweden)

J. V. Lukina

2005-01-01

Full Text Available Aim. To study efficiency and safety of new drug of long acting metoprolol tartrate, “Egilok retard” (ER in patients with mild to moderate arterial hypertension (AH in comparison with the original drug of metoprolol succinat, “Betaloc ZOK” (BZ, possibility of reaching target blood pressure (BP level with treatment with each drug.Material and methods. 30 patients (11 men and 19 women with mild to moderate AH took part in randomized, open, cross over study. Previous antihypertensive treatment had been canceled for all the patients 10-14 days before the study started. Each patient by turns was treated during 6 weeks with ER and BZ 50-100 mg daily. After cancellation of the previous antihypertensive therapy, BZ and ER were prescribed (according to the randomization table in dose 50 mg daily. Drugs were taken once per day. 29 patients completed therapy with the first drug of randomization, 25 patients – with the second. After 2 weeks efficiency of treatment was assessed by target BP level achievement (< 140/90 mmHg. If efficiency of beta-adrenoblocker (BB was not sufficient, the dose of the drug was doubled to 100 mg daily, if target level was reached – the dose remained unchanged. Treatment with the settled dose was held within next 4 weeks. After 6-week treatment with the first randomized drug antihypertensive therapy was canceled for 10-14 days depending on the BB dose. At each visit office BP and heart rate were assessed, EKG was registered. Side-effects were registered according to the self-control diary, questionnaire results, examination and EKG data.Results. After 6-week treatment with ER and BZ average level of systolic BP reduced by 15,7 and 15,2 mmHg, of diastolic BP – by 8,0 and 4,5 mmHg, heart rate – by 4,1 and 4,3 beat/min respectively. Differences between antihypertensive and heart rate lowering effect of the studied drugs were not significant. Target BP level with treatment with both drugs was reached in approximately

Rationale for combination therapy in hypertension management: focus on angiotensin receptor blockers and thiazide diuretics.

Science.gov (United States)

Nash, David T

2007-04-01

Despite recognition that hypertension is a major risk factor for cardiovascular events and mortality, blood pressure control rates remain low in the US population. Reflecting clinical trial results, hypertension management guidelines assert the clinical benefit of achieving current blood pressure goals and indicate that most patients will require 2 or more drugs to reach goal. Well-designed drug combinations counter hypertension via complementary mechanisms that increase antihypertensive efficacy, potentially with lower rates of adverse events than higher dose monotherapy regimens. Lower adverse event rates, in turn, may contribute to greater adherence with treatment. The combination of a low-dose diuretic with agents that block the effects of the renin-angiotensin system (RAS), such as angiotensin receptor blockers, has been found in numerous clinical trials to be highly effective for lowering blood pressure in patients with uncomplicated as well as high-risk hypertension, with a comparable favorable side effect profile compared with monotherapy. Moreover, agents that block the RAS are associated with a lower risk of new-onset diabetes mellitus than other antihypertensive classes. Complementary combinations of antihypertensive agents provide an efficient and effective approach to hypertension management.

A new analgesia regimen after (adeno) tonsillectomy in children: a pilot study.

Science.gov (United States)

Syed, M I; Magos, T A; Singh, J; Montague, M L

2016-12-01

The objective was to ascertain the efficacy of a new analgesic regimen introduced in children undergoing (adeno)tonsillectomy in view of the ban on codeine use in children codeine, albeit one should bear in mind that parental concerns and adverse effects of the drug were seen in a minority of patients (n = 11) and anaesthetists were reluctant to prescribe the drug in cases of severe OSA or associated central apnoeas (n = 7). © 2015 John Wiley & Sons Ltd.

High-resolution crystal structures of Drosophila melanogaster angiotensin-converting enzyme in complex with novel inhibitors and antihypertensive drugs.

Science.gov (United States)

Akif, Mohd; Georgiadis, Dimitris; Mahajan, Aman; Dive, Vincent; Sturrock, Edward D; Isaac, R Elwyn; Acharya, K Ravi

2010-07-16

Angiotensin I-converting enzyme (ACE), one of the central components of the renin-angiotensin system, is a key therapeutic target for the treatment of hypertension and cardiovascular disorders. Human somatic ACE (sACE) has two homologous domains (N and C). The N- and C-domain catalytic sites have different activities toward various substrates. Moreover, some of the undesirable side effects of the currently available and widely used ACE inhibitors may arise from their targeting both domains leading to defects in other pathways. In addition, structural studies have shown that although both these domains have much in common at the inhibitor binding site, there are significant differences and these are greater at the peptide binding sites than regions distal to the active site. As a model system, we have used an ACE homologue from Drosophila melanogaster (AnCE, a single domain protein with ACE activity) to study ACE inhibitor binding. In an extensive study, we present high-resolution structures for native AnCE and in complex with six known antihypertensive drugs, a novel C-domain sACE specific inhibitor, lisW-S, and two sACE domain-specific phosphinic peptidyl inhibitors, RXPA380 and RXP407 (i.e., nine structures). These structures show detailed binding features of the inhibitors and highlight subtle changes in the orientation of side chains at different binding pockets in the active site in comparison with the active site of N- and C-domains of sACE. This study provides information about the structure-activity relationships that could be utilized for designing new inhibitors with improved domain selectivity for sACE. 2010 Elsevier Ltd. All rights reserved.

Antihypertensive agents and risk of Parkinson's disease, essential tremor and dementia: a population-based prospective study (NEDICES).

Science.gov (United States)

Louis, Elan D; Benito-León, Julián; Bermejo-Pareja, Félix

2009-01-01

Recent interest in antihypertensive agents, especially calcium channel blockers, has been sparked by the notion that these medications may be neuroprotective. A modest literature, with mixed results, has examined whether these medications might lower the odds or risk of Parkinson's disease (PD) or dementia. There are no data for essential tremor (ET). To examine the association between antihypertensive use (defined broadly and by individual subclasses) and ET, PD and dementia. For each disorder, we used cross-sectional data (association with prevalent disease) and prospective data (association with incident disease). Prospective population-based study in Spain enrolling 5,278 participants at baseline. Use of antihypertensive medications (aside from beta-blockers) was similar in prevalent ET cases and controls. Baseline use of antihypertensive agents was not associated with reduced risk of incident ET. Antihypertensive medication use was not associated with prevalent or incident PD. Calcium channel blocker use was marginally reduced in prevalent dementia cases (OR(adjusted) = 0.63, p = 0.06) but was not associated with reduced risk of incident dementia (RR(adjusted) = 1.02, p = 0.95). We did not find evidence of a protective effect of antihypertensive medications in these three neurodegenerative disorders. Copyright 2009 S. Karger AG, Basel.

β-Blocker-Associated Risks in Patients With Uncomplicated Hypertension Undergoing Noncardiac Surgery

DEFF Research Database (Denmark)

Jørgensen, Mads E; Hlatky, Mark A; Køber, Lars Valeur

2015-01-01

IMPORTANCE: Perioperative β-blocker strategies are important to reduce risks of adverse events. Effectiveness and safety may differ according to patients' baseline risk. OBJECTIVE: To determine the risk of major adverse cardiovascular events (MACEs) associated with long-term β-blocker therapy...... antihypertensive drugs (β-blockers, thiazides, calcium antagonists, or renin-angiotensin system [RAS] inhibitors) undergoing noncardiac surgery between 2005 and 2011. INTERVENTIONS: Various antihypertensive treatment regimens, chosen as part of usual care. MAIN OUTCOMES AND MEASURES: Thirty-day risk of MACEs...... (cardiovascular death, nonfatal ischemic stroke, nonfatal myocardial infarction) and all-cause mortality, assessed using multivariable logistic regression models and adjusted numbers needed to harm (NNH). RESULTS: The baseline characteristics of the 14,644 patients who received β-blockers (65% female, mean [SD...

The 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE trial: study protocol for a randomized controlled trial

Directory of Open Access Journals (Sweden)

Park Kyung

2012-03-01

Full Text Available Abstract Background Second-generation drug-eluting stents (DES have raised the bar of clinical performance. These stents are mostly made from cobalt chromium alloy. A newer generation DES has been developed from platinum chromium alloy, but clinical data regarding the efficacy and safety of the platinum chromium-based everolimus-eluting stent (PtCr-EES is limited, with no comparison data against the cobalt chromium-based zotarolimus-eluting stent (CoCr-ZES. In addition, an antiplatelet regimen is an integral component of medical therapy after percutaneous coronary intervention (PCI. A 1-week duration of doubling the dose of clopidogrel (double-dose antiplatelet therapy (DDAT was shown to improve outcome at 1 month compared with conventional dose in acute coronary syndrome (ACS patients undergoing PCI. However in Asia, including Korea, the addition of cilostazol (triplet antiplatelet therapy (TAT is used more commonly than doubling the dose of clopidogrel in high-risk patients. Methods In the 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE trial, approximately 3,750 patients are being prospectively and randomly assigned in a 2 × 2 factorial design according to the type of stent (PtCr-EES vs CoCr-ZES and antiplatelet regimen (TAT vs DDAT. The first primary endpoint is target lesion failure at 1 year for the stent comparison, and the second primary endpoint is net clinical outcome at 1 month for comparison of antiplatelet therapy regimen. Discussion The HOST-ASSURE trial is the largest study yet performed to directly compare the efficacy and safety of the PtCr-EES versus CoCr-ZES in an 'all-comers' population. In addition, this study will also compare the clinical outcome of TAT versus DDAT for 1-month post PCI. Trial registration ClincalTrials.gov number NCT01267734.

The effects of anti-hypertensives and type 2 diabetes on salivary flow and total antioxidant capacity.

Science.gov (United States)

Djukić, L J; Roganović, J; Brajović, M D; Bokonjić, D; Stojić, D

2015-07-01

The present cross-sectional study aimed to determine the effect of first-line anti-hypertensive drugs (enalapril, metoprolol, and combinations of enalapril with metoprolol and/or hydrochlorothiazide) on salivary gland function and salivary total antioxidant capacity (TAC) in hypertensive patients with/without diabetes mellitus (DM) type 2. Salivary gland function was measured as xerostomia (interview) and unstimulated whole saliva flow rate (UWSFR) in 447 subjects (387 hypertensive and 60 healthy). Salivary TAC was evaluated by spectrophotometric assay. Enalapril is not xerogenic, while metoprolol and drug combinations are. In the presence of DM type 2, all drugs, except metoprolol, had pronounced xerogenic effect. Binary logistic regression analysis found enalapril to be significantly associated with decreased risk of xerogenic effect development, while DM type 2 with increased risk. In the presence of enalapril in hypertensive patients with/without DM type 2 salivary TAC was similar to that in healthy subjects, while for metoprolol was reduced. Enalapril is not xerogenic but is antioxidant, which moderately reduces the risk of xerogenic effect development even in the presence of DM type 2. However, metoprolol and drug combinations exhibit xerogenic effect. In DM type 2, xerogenic effect of all drugs was pronounced except of metoprolol. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Vaginal drug distribution modeling.

Science.gov (United States)

Katz, David F; Yuan, Andrew; Gao, Yajing

2015-09-15

This review presents and applies fundamental mass transport theory describing the diffusion and convection driven mass transport of drugs to the vaginal environment. It considers sources of variability in the predictions of the models. It illustrates use of model predictions of microbicide drug concentration distribution (pharmacokinetics) to gain insights about drug effectiveness in preventing HIV infection (pharmacodynamics). The modeling compares vaginal drug distributions after different gel dosage regimens, and it evaluates consequences of changes in gel viscosity due to aging. It compares vaginal mucosal concentration distributions of drugs delivered by gels vs. intravaginal rings. Finally, the modeling approach is used to compare vaginal drug distributions across species with differing vaginal dimensions. Deterministic models of drug mass transport into and throughout the vaginal environment can provide critical insights about the mechanisms and determinants of such transport. This knowledge, and the methodology that obtains it, can be applied and translated to multiple applications, involving the scientific underpinnings of vaginal drug distribution and the performance evaluation and design of products, and their dosage regimens, that achieve it. Copyright © 2015 Elsevier B.V. All rights reserved.

131-I treatment in patients with hyperthyroidism using low fixed dose regimen

International Nuclear Information System (INIS)

Bochev, P.; Klisarova, A.; Chaushev, B.; Hristozov, K.; Tsvetanova, B.

2007-01-01

Treatment of hyperthyroidism is one of the major problems in thyroidology. The well known and widely exploited treatment modalities in patients with hyperthyroidism are antithyroid drugs, radioiodine treatment and thyroid surgery, the latter two being considered definitive. Radioiodine treatment is effective and well tolerated treating modality, which major disadvantage is the impossibility of exact calculation of the dose needed. Lots of dosage regimens are approved, including empirically chosen fixed dose regimen. The aim of the study is to define the overall success rate in patients with hyperthyroidism in subgroups Grave's disease and toxic nodular goiter treated with fixed dose 185MBq regimen. Of all treated patients a low fixed dose regimen was chosen in 43. All the patients were followed up clinically, with ultrasonography and hormone levels for a period of minimum 1 year. Part of the patients with persistent hyperthyroidism 6 months after the initial treatment receive a second dose of 185MBq 131-1. The overall success rate in the subgroup with Grave's disease was 87% by the time of the study, compared to a considerably lower success of 62% in patients with toxic nodular goiter. (authors)

Antihypertensive activity of peptides identified in the in vitro gastrointestinal digest of pork meat.

Science.gov (United States)

Escudero, Elizabeth; Toldrá, Fidel; Sentandreu, Miguel Angel; Nishimura, Hitoshi; Arihara, Keizo

2012-07-01

This study investigated the in vivo antihypertensive activity of three novel peptides identified in the in vitro digest of pork meat. These peptides were RPR, KAPVA and PTPVP and all of them showed significant antihypertensive activity after oral administration to spontaneously hypertensive rats, RPR being the peptide with the greatest in vivo activity. To our knowledge, this is the first report showing the in vivo antihypertensive action of the three peptides from nebulin (RPR) and titin (KAPVA and PTPVP), thus confirming their reported in vitro angiotensin I-converting enzyme (ACE) inhibitory activity. These findings suggest that pork meat could constitute a source of bioactive constituents that could be utilized in functional foods or nutraceuticals. Copyright © 2012 Elsevier Ltd. All rights reserved.

Drug Pricing Evolution in Hepatitis C.

Science.gov (United States)

Vernaz, Nathalie; Girardin, François; Goossens, Nicolas; Brügger, Urs; Riguzzi, Marco; Perrier, Arnaud; Negro, Francesco

2016-01-01

We aimed to determine the association between the stepwise increase in the sustained viral response (SVR) and Swiss and United States (US) market prices of drug regimens for treatment-naive, genotype 1 chronic hepatitis C virus (HCV) infection in the last 25 years. We identified the following five steps in the development of HCV treatment regimens: 1) interferon (IFN)-α monotherapy in the early '90s, 2) IFN-α in combination with ribavirin (RBV), 3) pegylated (peg) IFN-α in combination with RBV, 4) the first direct acting antivirals (DAAs) (telaprevir and boceprevir) in combination with pegIFN-α and RBV, and 5) newer DAA-based regimens, such as sofosbuvir (which is or is not combined with ledipasvir) and fixed-dose combination of ritonavir-boosted paritaprevir and ombitasvir in combination with dasabuvir. We performed a linear regression and mean cost analysis to test for an association between SVRs and HCV regimen prices. We conducted a sensitivity analysis using US prices at the time of US drug licensing. We selected randomized clinical trials of drugs approved for use in Switzerland from 1997 to July 2015 including treatment-naïve patients with HCV genotype 1 infection. We identified a statistically significant positive relationship between the proportion of patients achieving SVRs and the costs of HCV regimens in Switzerland (with a bivariate ordinary least square regression yielding an R2 measure of 0.96) and the US (R2 = 0.95). The incremental cost per additional percentage of SVR was 597.14 USD in Switzerland and 1,063.81 USD in the US. The pricing of drugs for HCV regimens follows a value-based model, which has a stable ratio of costs per achieved SVR over 25 years. Health care systems are struggling with the high resource use of these new agents despite their obvious long-term advantages for the overall health of the population. Therefore, the pharmaceutical industry, health care payers and other stakeholders are challenged with finding new drug

Antihypertensive Activity of Residue From “Gebto Arekei”. Locally ...

African Journals Online (AJOL)

Antihypertensive Activity of Residue From “Gebto Arekei”. Locally Distilled Medicinal Spirit From a Brew Containing Lupinus albus Seeds in Renovascular Hypertensive Guines-Pigs. Cherinet Ambaye, Tesfaye Tolessa, Abebe Abera, Hassen Taha Sherief, Dawit Abebe, Kelbessa Urga ...

Use of antihypertensive medications and diagnostic tests among privately insured adolescents and young adults with primary versus secondary hypertension.

Science.gov (United States)

Yoon, Esther Y; Cohn, Lisa; Freed, Gary; Rocchini, Albert; Kershaw, David; Ascione, Frank; Clark, Sarah

2014-07-01

To compare the use of antihypertensive medications and diagnostic tests among adolescents and young adults with primary versus secondary hypertension. We conducted retrospective cohort analysis of claims data for adolescents and young adults (12-21 years of age) with ≥3 years of insurance coverage (≥11 months/year) in a large private managed care plan during 2003-2009 with diagnosis of primary hypertension or secondary hypertension. We examined their use of antihypertensive medications and identified demographic characteristics and the presence of obesity-related comorbidities. For the subset receiving antihypertensive medications, we examined their diagnostic test use (echocardiograms, renal ultrasounds, and electrocardiograms). The study sample included 1,232 adolescents and young adults; 84% had primary hypertension and 16% had secondary hypertension. The overall prevalence rate of hypertension was 2.6%. One quarter (28%) with primary hypertension had one or more antihypertensive medications, whereas 65% with secondary hypertension had one or more antihypertensive medications. Leading prescribers of antihypertensives for subjects with primary hypertension were primary care physicians (80%), whereas antihypertensive medications were equally prescribed by primary care physicians (43%) and sub-specialists (37%) for subjects with secondary hypertension. The predominant hypertension diagnosis among adolescents and young adults is primary hypertension. Antihypertensive medication use was higher among those with secondary hypertension compared with those with primary hypertension. Further study is needed to determine treatment effectiveness and patient outcomes associated with differential treatment patterns used for adolescents and young adults with primary versus secondary hypertension. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Safety of Temporary Discontinuation of Antihypertensive Medication in Patients With Difficult-to-Control Hypertension.

Science.gov (United States)

Beeftink, Martine M A; van der Sande, Nicolette G C; Bots, Michiel L; Doevendans, Pieter A; Blankestijn, Peter J; Visseren, Frank L J; Voskuil, Michiel; Spiering, Wilko

2017-05-01

Successful control of blood pressure relies on identification of secondary causes and contributing factors of hypertension. As antihypertensive medication can interfere with diagnostic investigations, temporary discontinuation of medication is advised. However, there are concerns about the safety of temporary discontinuation of antihypertensive medication in patients with difficult-to-control hypertension. We assessed the occurrence of adverse cardiovascular and cerebrovascular events potentially attributable to temporary discontinuation of antihypertensive medication between February 2010 and March 2016 (n=604) in our Analysis of Complicated Hypertension screening program. A reference group (n=604) was extracted from the SMART study (Second Manifestations of Arterial Disease) cohort (comprising a similar cohort at our hospital in whom medication was not stopped) and individually matched for blood pressure, age, sex, and history of cardiovascular disease. Discontinuation of medication was well tolerated; 62% reported no complaints, 24% had mild discomfort that could be left untreated, and 14% experienced complaints that required prescription of antihypertensive escape medication. Three major adverse events were observed in the Analysis of Complicated Hypertension group between discontinuation of medication and 30 days after restart of medication (event rate=31.2 events per 1000 patient-year). In the reference cohort, 5 cardiovascular events were observed during a similar follow-up period (event rate=51.2 events per 1000 patient-year). In conclusion, discontinuation of antihypertensive medication for the diagnostic evaluation of hypertension does not increase the acute risk of cardiovascular events when performed in a well-controlled setting in specialized hospitals with appropriate protocols for monitoring safety. © 2017 American Heart Association, Inc.

Antihypertensive properties of lactoferricin B-derived peptides.

Science.gov (United States)

Ruiz-Giménez, Pedro; Ibáñez, Aida; Salom, Juan B; Marcos, Jose F; López-Díez, Jose Javier; Vallés, Salvador; Torregrosa, Germán; Alborch, Enrique; Manzanares, Paloma

2010-06-09

A set of eight lactoferricin B (LfcinB)-derived peptides was examined for inhibitory effects on angiotensin I-converting enzyme (ACE) activity and ACE-dependent vasoconstriction, and their hypotensive effect in spontaneously hypertensive rats (SHR). Peptides were derived from different elongations both at the C-terminal and N-terminal ends of the representative peptide LfcinB(20-25), which is known as the LfcinB antimicrobial core. All of the eight LfcinB-derived peptides showed in vitro inhibitory effects on ACE activity with different IC(50) values. Moreover, seven of them showed ex vivo inhibitory effects on ACE-dependent vasoconstriction. No clear correlation between in vitro and ex vivo inhibitory effects was found. Only LfcinB(20-25) and one of its fragments, F1, generated after a simulated gastrointestinal digestion, showed significant antihypertensive effects in SHR after oral administration. Remarkably, F1 did not show any effect on ACE-dependent vasoconstriction in contrast to the inhibitory effect showed by LfcinB(20-25). In conclusion, two LfcinB-derived peptides lower blood pressure and exhibit potential as orally effective antihypertensive compounds, yet a complete elucidation of the mechanism(s) involved deserves further ongoing research.

Drugs for treatment of very high blood pressure during pregnancy.

Science.gov (United States)

Duley, Lelia; Meher, Shireen; Jones, Leanne

2013-07-31

Very high blood pressure during pregnancy poses a serious threat to women and their babies. The aim of antihypertensive therapy is to lower blood pressure quickly but safety, to avoid complications. Antihypertensive drugs lower blood pressure but their comparative effectiveness and safety, and impact on other substantive outcomes is uncertain. To compare different antihypertensive drugs for very high blood pressure during pregnancy. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (9 January 2013). Studies were randomised trials. Participants were women with severe hypertension during pregnancy. Interventions were comparisons of one antihypertensive drug with another. Two review authors independently assessed trials for inclusion and assessed trial quality. Two review authors extracted data and checked them for accuracy. Thirty-five trials (3573 women) with 15 comparisons were included. Women allocated calcium channel blockers were less likely to have persistent high blood pressure compared to those allocated hydralazine (six trials, 313 women; 8% versus 22%; risk ratio (RR) 0.37, 95% confidence interval (CI) 0.21 to 0.66). Ketanserin was associated with more persistent high blood pressure than hydralazine (three trials, 180 women; 27% versus 6%; RR 4.79, 95% CI 1.95 to 11.73), but fewer side-effects (three trials, 120 women; RR 0.32, 95% CI 0.19 to 0.53) and a lower risk of HELLP (haemolysis, elevated liver enzymes and lowered platelets) syndrome (one trial, 44 women; RR 0.20, 95% CI 0.05 to 0.81).Labetalol was associated with a lower risk of hypotension compared to diazoxide (one trial 90 women; RR 0.06, 95% CI 0.00 to 0.99) and a lower risk of caesarean section (RR 0.43, 95% CI 0.18 to 1.02), although both were borderline for statistical significance.Both nimodipine and magnesium sulphate were associated with a high incidence of persistent high blood pressure, but this risk was lower for nimodipine compared to magnesium sulphate (one trial

Comparison of adherence to generic multi-tablet regimens vs. brand multi-tablet and brand single-tablet regimens likely to incorporate generic antiretroviral drugs by breaking or not fixed-dose combinations in HIV-infected patients.

Science.gov (United States)

Rwagitinywa, Joseph; Lapeyre-Mestre, Maryse; Bourrel, Robert; Montastruc, Jean-Louis; Sommet, Agnès

2018-03-05

Adherence to antiretroviral (ARV) is crucial to achieve viral load suppression in HIV-infected patients. This study aimed to compare adherence to generic multi-tablet regimens (MTR) vs. brand MTR likely to incorporate ARV drugs without breaking fixed-dose combinations (FDC) and brand single-tablet regimens (STR) likely to incorporate generics by breaking the FDC. Patients aged of 18 years or over exposed to one of the generic or the brand of lamivudine (3TC), zidovudine/lamivudine (AZT/TC), nevirapine (NVP), or efavirenz (EFV), or the brand STR of efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF). Adherence was measured by medication possession ratio (MPR) using both defined daily dose (DDD) and daily number of tablet recommended for adults (DNT). Adherence to generic MTR vs. brand MTR and brand STR was compared using Kruskal-Wallis. The overall median adherence was 0.97 (IQR 0.13) by DNT method and 0.97 (0.14) by DDD method. Adherence in patients exposed to generic MTR (n = 165) vs. brand MTR (n = 481) and brand STR (n = 470) was comparable by DNT and DDD methods. In conclusion, adherence to generic MTR was high and comparable with adherence to brand MTR and to STR. Utilization of DDD instead DNT to measure the MPR led to small but nonsignificant difference that has no clinical impact. © 2018 Société Française de Pharmacologie et de Thérapeutique.

Improved Therapeutic Regimens for Treatment of Post-Traumatic Ocular Infections

Science.gov (United States)

2011-05-01

cystoid macular oedema in uveitis . Clin. Exp. Ophthalmol. 29, 2–6 (2001). 36 Campochiaro PA, Lim JI. Aminoglycoside toxicity in the treatment of...TELEPHONE NUMBER (include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Improved Therapeutic Regimens for Treatment of...injury and adequate treatment . This proposal was designed to analyze the effectiveness of antibiotics, anti-inflammatory drugs, and non-conventional

Blood Pressure, Antihypertensive Polypharmacy, Frailty, and Risk for Serious Fall Injuries Among Older Treated Adults With Hypertension.

Science.gov (United States)

Bromfield, Samantha G; Ngameni, Cedric-Anthony; Colantonio, Lisandro D; Bowling, C Barrett; Shimbo, Daichi; Reynolds, Kristi; Safford, Monika M; Banach, Maciej; Toth, Peter P; Muntner, Paul

2017-08-01

Antihypertensive medication and low systolic blood pressure (BP) and diastolic BP have been associated with an increased falls risk in some studies. Many older adults have indicators of frailty, which may increase their risk for falls. We contrasted the association of systolic BP, diastolic BP, number of antihypertensive medication classes taken, and indicators of frailty with risk for serious fall injuries among 5236 REGARDS study (Reasons for Geographic and Racial Difference in Stroke) participants ≥65 years taking antihypertensive medication at baseline with Medicare fee-for-service coverage. Systolic BP and diastolic BP were measured, and antihypertensive medication classes being taken assessed through a pill bottle review during a study visit. Indicators of frailty included low body mass index, cognitive impairment, depressive symptoms, exhaustion, impaired mobility, and history of falls. Serious fall injuries were defined as fall-related fractures, brain injuries, or joint dislocations using Medicare claims through December 31, 2014. Over a median of 6.4 years, 802 (15.3%) participants had a serious fall injury. The multivariable-adjusted hazard ratio for a serious fall injury among participants with 1, 2, or ≥3 indicators of frailty versus no frailty indicators was 1.18 (95% confidence interval, 0.99-1.40), 1.49 (95% confidence interval, 1.19-1.87), and 2.04 (95% confidence interval, 1.56-2.67), respectively. Systolic BP, diastolic BP, and number of antihypertensive medication classes being taken at baseline were not associated with risk for serious fall injuries after multivariable adjustment. In conclusion, indicators of frailty, but not BP or number of antihypertensive medication classes, were associated with increased risk for serious fall injuries among older adults taking antihypertensive medication. © 2017 American Heart Association, Inc.

Prescription patterns and utilisation of antihypertensive drugs in a ...

African Journals Online (AJOL)

The aim of the study is to investigate the prescribing pattern and drug use in the management of essential hypertension in a specialist hospital and its conformity to the JNC VII and WHO/ISH management guidelines. A total of 1572 prescriptions from 490 case files of hypertensive patients (> 18 years) attending the ...

Effect of discontinuation of antihypertensive medication on orthostatic hypotension in older persons with mild cognitive impairment: the DANTE Study Leiden.

Science.gov (United States)

Moonen, Justine E F; Foster-Dingley, Jessica C; de Ruijter, Wouter; van der Grond, Jeroen; de Craen, Anton J M; van der Mast, Roos C

2016-03-01

the relationship between antihypertensive medication and orthostatic hypotension in older persons remains ambiguous, due to conflicting observational evidence and lack of data of clinical trials. to assess the effect of discontinuation of antihypertensive medication on orthostatic hypotension in older persons with mild cognitive impairment. a total of 162 participants with orthostatic hypotension were selected from the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study. This randomised clinical trial included community-dwelling participants aged ≥75 years, with mild cognitive impairment, using antihypertensive medication and without serious cardiovascular disease. Participants were randomised to discontinuation or continuation of antihypertensive treatment (ratio 1:1). Orthostatic hypotension was defined as a drop of at least 20 mmHg in systolic blood pressure and/or 10 mmHg in diastolic blood pressure on standing from a seated position. Outcome was the absence of orthostatic hypotension at 4-month follow-up. Relative risks (RR) were calculated by intention-to-treat and per-protocol analyses. at follow-up, according to intention-to-treat analyses, of the 86 persons assigned to discontinuation of antihypertensive medication, 43 (50%) were free from orthostatic hypotension, compared with 29 (38%) of the 76 persons assigned to continuation of medication [RR 1.31 (95% confidence interval (CI) 0.92-1.87); P = 0.13]. Per-protocol analysis showed that recovery from orthostatic hypotension was significantly higher in persons who completely discontinued all antihypertensive medication (61%) compared with the continuation group (38%) [RR 1.60 (95% CI 1.10-2.31); P = 0.01]. in older persons with mild cognitive impairment and orthostatic hypotension receiving antihypertensive medication, discontinuation of antihypertensive medication may increase the probability of recovery from orthostatic hypotension. © The Author 2016. Published by Oxford

Comparing two service delivery models for the prevention of mother-to-child transmission (PMTCT of HIV during transition from single-dose nevirapine to multi-drug antiretroviral regimens

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Mugwaneza Placidie

2010-12-01

Full Text Available Abstract Background Mother-to-child transmission (MTCT of HIV has been eliminated from the developed world with the introduction of multi-drug antiretroviral (md-ARV regimens for the prevention of MTCT (PMTCT; but remains the major cause of HIV infection among sub-Saharan African children. This study compares two service delivery models of PMTCT interventions and documents the lessons learned and the challenges encountered during the transition from single-dose nevirapine (sd-nvp to md-ARV regimens in a resource-limited setting. Methods Program data collected from 32 clinical sites was used to describe trends and compare the performance (uptake of HIV testing, CD4 screening and ARV regimens initiated during pregnancy of sites providing PMTCT as a stand-alone service (stand-alone site versus sites providing PMTCT as well as antiretroviral therapy (ART (full package site. CD4 cell count screening, enrolment into ART services and the initiation of md-ARV regimens during pregnancy, including dual (zidovudine [AZT] +sd-nvp prophylaxis and highly active antiretroviral therapy (HAART were analysed. Results From July 2006 to December 2008, 1,622 pregnant women tested HIV positive (HIV+ during antenatal care (ANC. CD4 cell count screening during pregnancy increased from 60% to 70%, and the initiation of md-ARV regimens increased from 35.5% to 97% during this period. In 2008, women attending ANC at full package sites were 30% more likely to undergo CD4 cell count assessment during pregnancy than women attending stand-alone sites (relative risk (RR = 1.3; 95% confidence interval (CI: 1.1-1.4. Enrolment of HIV+ pregnant women in ART services was almost twice as likely at full package sites than at stand-alone sites (RR = 1.9; 95% CI: 1.5-2.3. However, no significant differences were detected between the two models of care in providing md-ARV (RR = 0.9; 95% CI: 0.9-1.0. Conclusions All sites successfully transitioned from sd-nvp to md-ARV regimens for PMTCT

Camptothecin-Based Regimens for Treatment of Ewing Sarcoma: sPast Studies and Future Directions

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Lars Wagner

2011-01-01

Full Text Available New therapies are needed to improve survival for patients with Ewing sarcoma. Over the past decade, camptothecin agents such as topotecan and irinotecan have demonstrated activity against Ewing sarcoma, especially in combination with alkylating agents. Previous studies have shown camptothecin-based combinations to be tolerable outpatient strategies that are attractive for salvage therapy. This paper highlights important issues related to drug dosing, schedule of administration, pharmacokinetics, toxicity, and activity of commonly used camptothecin-based regimens. Also discussed are strategies for incorporating these regimens into therapy for newly diagnosed patients, including several potential possibilities for combination with targeted agents.

Regimen durability in HIV-infected children and adolescents initiating first-line ART in a large public sector HIV cohort in South Africa.

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Bonawitz, Rachael; Brennan, Alana T; Long, Lawrence; Heeren, Timothy; Maskew, Mhairi; Sanne, Ian; Fox, Matthew P

2018-04-15

In April 2010 tenofovir and abacavir replaced stavudine in public-sector first-line antiretroviral therapy (ART) for children under 20 years old in South Africa. The association of both abacavir and tenofovir with fewer side-effects and toxicities compared to stavudine could translate to increased durability of tenofovir or abacavir-based regimens. We evaluated changes over time in regimen durability for pediatric patients 3 to 19 years of age at 8 public sector clinics in Johannesburg, South Africa. Cohort analysis of treatment naïve, non-pregnant pediatric patients from 3 to 19 years old initiated on ART between April 2004-December 2013. First-line ART regimens before April 2010 consisted of stavudine or zidovudine with lamivudine and either efavirenz or nevirapine. Tenofovir and/or abacavir was substituted for stavudine after April 2010 in first-line ART. We evaluated the frequency and type of single-drug substitutions, treatment interruptions, and switches to second-line therapy. Fine and Gray competing risk regression models were used to evaluate the association of antiretroviral drug type with single-drug substitutions, treatment interruptions, and second-line switches in the first 24-months on treatment. 398 (15.3%) single-drug substitutions, 187 (7.2%) treatment interruptions and 86 (3.3%) switches to second-line therapy occurred among 2602 pediatric patients over 24-months on ART. Overall, the rate of single-drug substitutions started to increase in 2009, peaked in 2011 at 25%, then declined to 10% in 2013, well after the integration of tenofovir into pediatric regimens; no patients over the age of 3 were initiated on abacavir for first-line therapy. Competing risk regression models showed patients on zidovudine or stavudine had upwards of a 5-fold increase in single-drug substitution vs. patients initiated on tenofovir in the first 24-months on ART. Older adolescents also had a 2-3-fold increase in treatment interruptions and switches to second

Economic evaluation of a shortened standardised treatment regimen of antituberculosis drugs for patients with multidrug-resistant tuberculosis (STREAM): study protocol

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Gama, Elvis; Madan, Jason; Langley, Ivor; Girma, Mamo; Evans, Denise; Rosen, Sydney; Squire, S Bertel

2016-01-01

Introduction:\\ud Multidrug-resistant tuberculosis (MDR-TB) poses a serious financial challenge to health systems and patients. The current treatment for patients with MDR-TB takes up to 24 months to complete. Evidence for a shorter regimen which differs from the standard WHO recommended MDR-TB regimen and typically lasts between 9 and 12 months has been reported from Bangladesh. This evaluation aims to assess the economic impact of a shortened regimen on patients and health systems. This eval...

Effects of autogenic training and antihypertensive agents on circadian and circaseptan variation of blood pressure.

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Watanabe, Yoshihiko; Cornélissen, Germaine; Watanabe, Misako; Watanabe, Fumihiko; Otsuka, Kuniaki; Ohkawa, Shi-ichiro; Kikuchi, Takenori; Halberg, Franz

2003-10-01

Even when the daily blood pressure mean is acceptable, too large a circadian amplitude of blood pressure largely increases cardiovascular disease risk. Autogenic training (N = 11), a non-pharmacologic intervention capable of lowering an excessive blood pressure variability, may be well-suited for MESOR-normotensive patients diagnosed with circadian-hyper-amplitude-tension (CHAT). Not all anti-hypertensive drugs affect blood pressure variability. Accordingly, long-acting carteolol (N = 11) and/or atenolol (N = 8) may be preferred to captopril retard (N = 13), nilvadipine (N = 8), or amlodipine (N = 7) for midline-estimating statistic of rhythm (MESOR)-hypertensive patients with CHAT. Prospective outcome studies are needed to assess whether the relative merits of these treatments are in keeping with their effects on blood pressure and blood pressure variability.

Treatment of Hypertension in Renal Transplant Recipients in Four Independent Cross-Sectional Analyses

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Izabella Kuźmiuk-Glembin

2018-01-01

Full Text Available Background/Aims: This retrospective study analysed hypertension management and adherence to blood pressure (BP targets among renal transplant recipients (RTRs under specialized care in the Outpatient Transplantation Unit in the Department of Nephrology, Transplantology and Internal Medicine at Gdansk University Hospital. Methods: Medical records of 101, 316, 639 and 818 RTRs diagnosed with hypertension, who received outpatient care in 2001, 2006, 2011 and 2014, respectively were analysed in four independent cross-sectional surveys. All RTRs received antihypertensive regimens. Results: The overall most commonly used antihypertensive agents were beta-blockers (BB (range 66.3-82.5% followed by calcium channel blockers (CCB (range 52.8-64.2%. Whilst a significant, upward tendency of BB usage (p<0.01 was observed, CCB usage (p<0.001 displayed a downward tendency as a first line therapy in the subsequent years. The average number of antihypertensive agents used per patient increased significantly from 2.24±1.03 in 2001 to 2.55±1.25 in 2014 (p<0.05. The most frequently used combination of hypotensive therapy consisted of two or three antihypertensive drugs depending on the survey. The most common two drug combination consisted of BB and CCB followed by BB accompanied by angiotensin converting enzyme inhibitors. A significant, upward tendency in the use of four (p<0.001 and five (p<0.05 antihypertensive drugs simultaneously, was observed in subsequent years. The target values of BP i.e. <140/90 mmHg were accomplished in 47, 58, 60 and 46% of RTRs in subsequent years. In a secondary - stratified analysis of data from 2014, younger patients (p<0.05, patients with better graft function (p<0.001, patients treated with a higher number of antihypertensive agents (p<0.001 and those not treated with BB (p<0.01 were shown to reach the BP target of below 140/90 mmHg more often. Conclusion: The study showed intensification of hypertension treatment in RTRs in

Cost-effectiveness analysis of granisetron-based versus standard antiemetic regimens in low-emetogenic chemotherapy: a hospital-based perspective from Malaysia.

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Keat, Chan Huan; Ghani, Norazila Abdul

2013-01-01

In a prospective cohort study of antiemetic therapy conducted in Malaysia, a total of 94 patients received low emetogenic chemotherapy (LEC) with or without granisetron injections as the primary prophylaxis for chemotherapy-induced nausea and vomiting (CINV). This study is a retrospective cost analysis of two antiemetic regimens from the payer perspective. This cost evaluation refers to 2011, the year in which the observation was conducted. Direct costs incurred by hospitals including the drug acquisition, materials and time spent for clinical activities from prescribing to dispensing of home medications were evaluated (MYR 1=$0.32 USD). As reported to be significantly different between two regimens (96.1% vs 81.0%; p=0.017), the complete response rate of acute emesis which was defined as a patient successfully treated without any emesis episode within 24 hours after LEC was used as the main indicator for effectiveness. Antiemetic drug acquisition cost per patient was 40.7 times higher for the granisetron-based regimen than for the standard regimen (MYR 64.3 vs 1.58). When both the costs for materials and clinical activities were included, the total cost per patient was 8.68 times higher for the granisetron-based regimen (MYR 73.5 vs 8.47). Considering the complete response rates, the mean cost per successfully treated patient in granisetron group was 7.31 times higher (MYR 76.5 vs 10.5). The incremental cost-effectiveness ratio (ICER) with granisetron-based regimen, relative to the standard regimen, was MYR 430.7. It was found to be most sensitive to the change of antiemetic effects of granisetron-based regimen. While providing a better efficacy in acute emesis control, the low incidence of acute emesis and high ICER makes use of granisetron as primary prophylaxis in LEC controversial.

A randomized trial comparing initial HAART regimens of nelfinavir/nevirapine and ritonavir/saquinavir in combination with two nucleoside reverse transcriptase inhibitors

DEFF Research Database (Denmark)

Kirk, Ole; Lundgren, Jens D; Pedersen, Court

2003-01-01

BACKGROUND: A triple-class HAART regimen may be associated with a better virological effect than conventional regimens, but may also lead to toxicity and more profound resistance. METHODS: Randomized, controlled, open-label trial of 233 protease inhibitor- and non-nucleoside reverse transcriptase...... inhibitor-naive HIV-infected patients allocated to a regimen of nelfinavir and nevirapine (1250/200 mg twice daily; n = 118) or ritonavir and saquinavir (400/400 mg twice daily; n = 115), both in combination with two nucleoside reverse transcriptase inhibitors. The primary end-point was HIV RNA ... the long-term consequences of triple class HAART regimens, including the development of broad drug resistance....

EVALUASI DRUG RELATED PROBLEMS PADA PASIEN GERIATRI DENGAN HIPERTENSI DISERTAI VERTIGO DI RS PANTI RINI YOGYAKARTA AGUSTUS 2013

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Kresensiana Yosriani

2016-04-01

Full Text Available Abstract : This study aimed to evaluate Drug Related Problems (DRPs among hypertensive geriatric patients with vertigo co morbid at Panti Rini Hospital Yogyakarta. This is a non-experimental research descriptive evaluative design using a retrospective medical record data. Collected data including patient's identity; initial, final, and complication diagnosis; cardiovascular system drugs and antivertigo, laboratory data. The inclusion criteria were ≥ 60 years with an initial diagnosis of hypertension with vertigo co morbid, used a diuretic drug, and had creatinine test result. Data were analyzed case by case using selected literatur. There were 20 cases found. Result of the study showed that 100% of patients used antihypertensive as the cardiovascular system drugs and 80% patients used antivertigo as nervous system drugs. There were 18 cases of DRPs found related to the use of antihypertensive and antivertigo. 1 case of dosage too low, 8 cases of adverse drug reaction, and 9 cases of dosege too high. Keywords : hypertension with vertigo co morbid, geriatrics, Drug Related Problems

A Review of Moxifloxacin for the Treatment of Drug-Susceptible Tuberculosis.

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Naidoo, Anushka; Naidoo, Kogieleum; McIlleron, Helen; Essack, Sabiha; Padayatchi, Nesri

2017-11-01

Moxifloxacin, an 8-methoxy quinolone, is an important drug in the treatment of multidrug-resistant tuberculosis and is being investigated in novel drug regimens with pretomanid, bedaquiline, and pyrazinamide, or rifapentine, for the treatment of drug-susceptible tuberculosis. Early results of these studies are promising. Although current evidence does not support the use of moxifloxacin in treatment-shortening regimens for drug-susceptible tuberculosis, it may be recommended in patients unable to tolerate standard first-line drug regimens or for isoniazid monoresistance. Evidence suggests that the standard 400-mg dose of moxifloxacin used in the treatment of tuberculosis may be suboptimal in some patients, leading to worse tuberculosis treatment outcomes and emergence of drug resistance. Furthermore, a drug interaction with the rifamycins results in up to 31% reduced plasma concentrations of moxifloxacin when these are combined for treatment of drug-susceptible tuberculosis, although the clinical relevance of this interaction is unclear. Moxifloxacin exhibits extensive interindividual pharmacokinetic variability. Higher doses of moxifloxacin may be needed to achieve drug exposures required for improved clinical outcomes. Further study is, however, needed to determine the safety of proposed higher doses and clinically validated targets for drug exposure to moxifloxacin associated with improved tuberculosis treatment outcomes. We discuss in this review the evidence for the use of moxifloxacin in drug-susceptible tuberculosis and explore the role of moxifloxacin pharmacokinetics, pharmacodynamics, and drug interactions with rifamycins, on tuberculosis treatment outcomes when used in first-line tuberculosis drug regimens. © 2017, The American College of Clinical Pharmacology.

Requirement for aspartate-cleaved bid in apoptosis signaling by DNA-damaging anti-cancer regimens

NARCIS (Netherlands)

Werner, Arlette B.; Tait, Stephen W. G.; de Vries, Evert; Eldering, Eric; Borst, Jannie

2004-01-01

Lymphoid malignancies can escape from DNA-damaging anti-cancer drugs and gamma-radiation by blocking apoptosis-signaling pathways. How these regimens induce apoptosis is incompletely defined, especially in cells with nonfunctional p53. We report here that the BH3-only Bcl-2 family member Bid is

Drug Pricing Evolution in Hepatitis C

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Vernaz, Nathalie; Girardin, François; Goossens, Nicolas; Brügger, Urs; Riguzzi, Marco; Perrier, Arnaud; Negro, Francesco

2016-01-01

Objective We aimed to determine the association between the stepwise increase in the sustained viral response (SVR) and Swiss and United States (US) market prices of drug regimens for treatment-naive, genotype 1 chronic hepatitis C virus (HCV) infection in the last 25 years. We identified the following five steps in the development of HCV treatment regimens: 1) interferon (IFN)-α monotherapy in the early '90s, 2) IFN-α in combination with ribavirin (RBV), 3) pegylated (peg) IFN-α in combination with RBV, 4) the first direct acting antivirals (DAAs) (telaprevir and boceprevir) in combination with pegIFN-α and RBV, and 5) newer DAA-based regimens, such as sofosbuvir (which is or is not combined with ledipasvir) and fixed-dose combination of ritonavir-boosted paritaprevir and ombitasvir in combination with dasabuvir. Design We performed a linear regression and mean cost analysis to test for an association between SVRs and HCV regimen prices. We conducted a sensitivity analysis using US prices at the time of US drug licensing. We selected randomized clinical trials of drugs approved for use in Switzerland from 1997 to July 2015 including treatment-naïve patients with HCV genotype 1 infection. Results We identified a statistically significant positive relationship between the proportion of patients achieving SVRs and the costs of HCV regimens in Switzerland (with a bivariate ordinary least square regression yielding an R2 measure of 0.96) and the US (R2 = 0.95). The incremental cost per additional percentage of SVR was 597.14 USD in Switzerland and 1,063.81 USD in the US. Conclusion The pricing of drugs for HCV regimens follows a value-based model, which has a stable ratio of costs per achieved SVR over 25 years. Health care systems are struggling with the high resource use of these new agents despite their obvious long-term advantages for the overall health of the population. Therefore, the pharmaceutical industry, health care payers and other stakeholders are

Therapeutic strategies to improve control of hypertension.

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Armario, Pedro; Waeber, Bernard

2013-03-01

Blood pressure is poorly controlled in most European countries and the control rate is even lower in high-risk patients such as patients with chronic kidney disease, diabetic patients or previous coronary heart disease. Several factors have been associated with poor control, some of which involve the characteristic of the patients themselves, such as socioeconomic factors, or unsuitable life-styles, other factors related to hypertension or to associated comorbidity, but there are also factors directly associated with antihypertensive therapy, mainly involving adherence problems, therapeutic inertia and therapeutic strategies unsuited to difficult-to-control hypertensive patients. It is common knowledge that only 30% of hypertensive patients can be controlled using monotherapy; all the rest require a combination of two or more antihypertensive drugs, and this can be a barrier to good adherence and log-term persistence in patients who also often need to use other drugs, such as antidiabetic agents, statins or antiplatelet agents. The fixed combinations of three antihypertensive agents currently available can facilitate long-term control of these patients in clinical practice. If well tolerated, a long-term therapeutic regimen that includes a diuretic, an ACE inhibitor or an angiotensin receptor blocker, and a calcium channel blocker is the recommended optimal triple therapy.

[Influence of dose regimen on gentamycin nephrotoxicity in rats].

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Oliveira, V C; Tejos, C R; Hosaka, E M; Andrade, S C; Araújo, M; Vattimo, M F

2001-06-01

The acute renal failure (ARF), that still presents a right mortality rate (50%) can be defined as an abrupt decline of the glomerular filtration, resultant of ischemic or toxicity event. The drugs nephrotoxicity is one of the most frequent cause (27%) of ARF and it is suggested that the interval of administration of the drug can interfere in this side effect, however the best administration regimen is not very well established. This study evaluated the renal function of rats that received gentamicin (100 mg/kg) in one dose or in two doses (2 x 50 mg/kg), by intraperitoneal infusion. The results obtained in this research, indicated that the single infusion of gentamicin determined smaller nephrotoxicity by the reduction of serum concentration of this drug in 24 hours, decreasing the intracellular accumulation of this gentamicin, which is one of the main cellular mechanisms of this renal injury. The single dose treatment regime, otherwise, shows advantages not only related to the nephrotoxicity effect, but also it is relevant to the cost and safety, which can be rationable factors in the administration of this drug.

Health services research in the public healthcare system in Hong Kong: an analysis of over 1 million antihypertensive prescriptions between 2004-2007 as an example of the potential and pitfalls of using routinely collected electronic patient data.

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Wong, Martin C S; Jiang, Johnny Y; Tang, Jin-ling; Lam, Augustine; Fung, Hong; Mercer, Stewart W

2008-06-25

Increasing use is being made of routinely collected electronic patient data in health services research. The aim of the present study was to evaluate the potential usefulness of a comprehensive database used routinely in the public healthcare system in Hong Kong, using antihypertensive drug prescriptions in primary care as an example. Data on antihypertensive drug prescriptions were retrieved from the electronic Clinical Management System (e-CMS) of all primary care clinics run by the Health Authority (HA) in the New Territory East (NTE) cluster of Hong Kong between January 2004 and June 2007. Information was also retrieved on patients' demographic and socioeconomic characteristics, visit type (new or follow-up), and relevant diseases (International Classification of Primary Care, ICPC codes). 1,096,282 visit episodes were accessed, representing 93,450 patients. Patients' demographic and socio-economic details were recorded in all cases. Prescription details for anti-hypertensive drugs were missing in only 18 patients (0.02%). However, ICPC-code was missing for 36,409 patients (39%). Significant independent predictors of whether disease codes were applied included patient age > or = 70 years (OR 2.18), female gender (OR 1.20), district of residence (range of ORs in more rural districts; 0.32-0.41), type of clinic (OR in Family Medicine Specialist Clinics; 1.45) and type of visit (OR follow-up visit; 2.39). In the 57,041 patients with an ICPC-code, uncomplicated hypertension (ICPC K86) was recorded in 45,859 patients (82.1%). The characteristics of these patients were very similar to those of the non-coded group, suggesting that most non-coded patients on antihypertensive drugs are likely to have uncomplicated hypertension. The e-CMS database of the HA in Hong Kong varies in quality in terms of recorded information. Potential future health services research using demographic and prescription information is highly feasible but for disease-specific research dependant

Rare Acute Pancreatitis Cases Due to Different Antihypertensive Drugs: Four Cases

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Gökhan Celbek

2014-03-01

Full Text Available The most important reasons of acute pancreatitis (AP are benign biliary tract diseases, metabolic diseases and alcoholism. Some drugs also(sulfonamides, thiazides, lysinopril, captopril, estrogens and tetracyclines can induce AP. We herein report four cases of AP patients who were using different drugs. The first case was 73 years old male patient who has been using zofenopril for 4 weeks and the second patient was 24 years old female who was using furosemide after her pregnancy. Third one was using valsartan for one month. Fourth patient was using lysinopril for six weeks and resulted in AP. All patients had no known risk factors for pancreatitis. After cessation of the drugs, four patients recovered in a few days without any complications. AP due to zofenopril was firstly reported in our manuscript in the literature.

Effects of intense aerobic exercise and/or antihypertensive medication in individuals with metabolic syndrome.

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Ramirez-Jimenez, M; Morales-Palomo, F; Ortega, J F; Mora-Rodriguez, R

2018-05-17

We studied the blood pressure lowering effects of a bout of exercise and/or antihypertensive medicine with the goal of studying if exercise could substitute or enhance pharmacologic hypertension treatment. Twenty-three hypertensive metabolic syndrome patients chronically medicated with angiotensin II receptor 1 blockade antihypertensive medicine underwent 24-hr monitoring in four separated days in a randomized order; a) after taking their habitual dose of antihypertensive medicine (AHM trial), b) substituting their medicine by placebo medicine (PLAC trial), c) placebo medicine with a morning bout of intense aerobic exercise (PLAC+EXER trial) and d) combining the exercise and antihypertensive medicine (AHM+EXER trial). We found that in trials with AHM subjects had lower plasma aldosterone/renin activity ratio evidencing treatment compliance. Before exercise, the trials with AHM displayed lower systolic (130±16 vs 133±15 mmHg; P=0.018) and mean blood pressures (94±11 vs 96±10 mmHg; P=0.036) than trials with placebo medication. Acutely (i.e., 30 min after treatments) combining AHM+EXER lowered systolic blood pressure (SBP) below the effects of PLAC+EXER (-8.1±1.6 vs -4.9±1.5 mmHg; P=0.015). Twenty-four hour monitoring revealed no differences among trials in body motion. However, PLAC+EXER and AHM lowered SBP below PLAC during the first 10 hours, time at which PLAC+EXER effects faded out (i.e., at 19 PM). Adding exercise to medication (i.e., AHM+EXER) resulted in longer reductions in SBP than with exercise alone (PLAC+EXER). In summary, one bout of intense aerobic exercise in the morning cannot substitute the long-lasting effects of antihypertensive medicine in lowering blood pressure, but their combination is superior to exercise alone. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Pharmacokinetics and pharmacodynamics of qinghaosu derivatives: how do they impact on the choice of drug and the dosage regimens?

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Kyle, D E; Teja-Isavadharm, P; Li, Q; Leo, K

1998-01-01

The critical decisions of which artemisinin derivative(s) to use and by which route(s) of administration for falciparum malaria are complex scientifically and politically. Despite the need for additional pharmacokinetic, pharmacodynamic and toxicokinetic data, these drugs are too important to delay concise, rational recommendations any longer. These types of decisions must be made now, implemented on a multinational level with WHO leadership, and revised as new findings emerge. For acute, uncomplicated disease, per os dosing of artesunate or artemether for three days is recommended, but only in combination with other antimalarial drugs like mefloquine. For severe falciparum malaria, intravenous administration is the preferred route, yet current formulations for intravenous dosing are not optimal and should be an area for future development emphasis. Clearly intramuscular administration of artemether has proven effective for severe disease, yet dosing regimens shouldn't be designed with ultimate parasitological cure as the aim and the problem of bioavailability of the sesame oil formulations must be examined further. Once the life-saving reduction in parasitemia and pathophysiological sequelae have been achieved, the patient can be given oral medication to affect radical cure. Much more data will be required to define the role of per rectum dosing for the treatment of severe malaria, yet this approach holds great promise as a life-saving intervention in rural areas where this disease has it most dramatic impact.

Clinical Implications of Complex Pharmacokinetics for Daratumumab Dose Regimen in Patients With Relapsed/Refractory Multiple Myeloma

DEFF Research Database (Denmark)

Xu, Xu Steven; Yan, Xiaoyu; Puchalski, Thomas

2017-01-01

New therapeutic strategies are urgently needed to improve clinical outcomes in patients with multiple myeloma (MM). Daratumumab is a first-in-class, CD38 human immunoglobulin G1κ monoclonal antibody approved for treatment of relapsed or refractory MM. Identification of an appropriate dose regimen...... for daratumumab is challenging due to its target-mediated drug disposition, leading to time- and concentration-dependent pharmacokinetics. We describe a thorough evaluation of the recommended dose regimen for daratumumab in patients with relapsed or refractory MM. This article is protected by copyright. All...

Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study.

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Phairote Teeranaipong

Full Text Available Etravirine(ETR can be used for patients who have failed NNRTI-based regimen. In Thailand, ETR is approximately 45 times more expensive than rilpivirine(RPV. However, there are no data of RPV use in NNRTI failure. Therefore, we assessed the susceptibility and mutation patterns of first line NNRTI failure and the possibility of using RPV compared to ETV in patients who have failed efavirenz(EFV- and nevirapine(NVP-based regimens.Clinical samples with confirmed virological failure from EFV- or NVP-based regimens were retrospectively analyzed. Resistance-associated mutations (RAMs were interpreted by IAS-USA Drug Resistance Mutations. Susceptibility of ETR and RPV were interpreted by DUET, Monogram scoring system, and Stanford University HIV Drug Resistance Database.1,279 and 528 patients failed EFV- and NVP-based regimens, respectively. Y181C was the most common NVP-associated RAM (54.3% vs. 14.7%, p<0.01. K103N was the most common EFV-associated RAM (56.5% vs. 19.1%, P<0.01. The results from all three scoring systems were concordant. 165(11.1% and 161(10.9% patients who failed NVP-based regimen were susceptible to ETR and RPV, respectively (p = 0.85. 195 (32.2% and 191 (31.6% patients who failed EFV-based regimen, were susceptible to ETR and RPV, respectively (p = 0.79. The susceptibility of ETV and RPV in EFV failure was significantly higher than NVP failure (p<0.01.The mutation patterns for ETR and RPV were similar but 32% and 11% of patients who failed EFV and NVP -based regimen, respectivly were susceptible to RPV. This finding suggests that RPV can be used as the alternative antiretroviral agent in patients who have failed EFV-based regimen.

Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study.

Science.gov (United States)

Teeranaipong, Phairote; Sirivichayakul, Sunee; Mekprasan, Suwanna; Ohata, Pirapon June; Avihingsanon, Anchalee; Ruxrungtham, Kiat; Putcharoen, Opass

2016-01-01

Etravirine(ETR) can be used for patients who have failed NNRTI-based regimen. In Thailand, ETR is approximately 45 times more expensive than rilpivirine(RPV). However, there are no data of RPV use in NNRTI failure. Therefore, we assessed the susceptibility and mutation patterns of first line NNRTI failure and the possibility of using RPV compared to ETV in patients who have failed efavirenz(EFV)- and nevirapine(NVP)-based regimens. Clinical samples with confirmed virological failure from EFV- or NVP-based regimens were retrospectively analyzed. Resistance-associated mutations (RAMs) were interpreted by IAS-USA Drug Resistance Mutations. Susceptibility of ETR and RPV were interpreted by DUET, Monogram scoring system, and Stanford University HIV Drug Resistance Database. 1,279 and 528 patients failed EFV- and NVP-based regimens, respectively. Y181C was the most common NVP-associated RAM (54.3% vs. 14.7%, p<0.01). K103N was the most common EFV-associated RAM (56.5% vs. 19.1%, P<0.01). The results from all three scoring systems were concordant. 165(11.1%) and 161(10.9%) patients who failed NVP-based regimen were susceptible to ETR and RPV, respectively (p = 0.85). 195 (32.2%) and 191 (31.6%) patients who failed EFV-based regimen, were susceptible to ETR and RPV, respectively (p = 0.79). The susceptibility of ETV and RPV in EFV failure was significantly higher than NVP failure (p<0.01). The mutation patterns for ETR and RPV were similar but 32% and 11% of patients who failed EFV and NVP -based regimen, respectivly were susceptible to RPV. This finding suggests that RPV can be used as the alternative antiretroviral agent in patients who have failed EFV-based regimen.

THE EVALUATION OF COMPLIANCE TO ANTIHYPERTENSIVE THERAPY IN PATIENTS AFTER STROKE AND POSTSTROKE DEPRESSION DURING ANTIDEPRESSANT THERAPY

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B. B. Fishman

2010-01-01

Full Text Available Aim. To study the effect of the antidepressant paroxetine on the compliance to antihypertensive therapy in patients with arterial hypertension (HT and post-stroke depression.Material and methods. Patients (n=24 aged 55-73 with controlled HT (blood pressure, BP<140/90 mm Hg and with subclinical poststroke depression after rehabilitation course were included into the study. Patients were split into two groups. Patients of group 1 (n=12 received adequate antihypertensive therapy and selective serotonin reuptake inhibitor paroxetine. Patients of group 2 (n=12 received antihypertensive therapy only. The study duration was 16 weeks. Patient compliance to antihypertensive therapy, BP and severity of depressive disorders, motor and intellectual functions was evaluated initially and after 16 weeks.Results. BP>140/80 mmHg after 16 weeks was found in 10 (41.6% patients. Clinical post-stroke depression was found in 7 (30.4% patients, 5 (41.6% of them were from group 2 (OR=0.35, 95% CI 0.12-0.78. High treatment compliance was in 15 (65.2% patients, and 9 (81.8% of them were from group 1. Nine (39.1% patients did not receive an adequate antihypertensive therapy, 5 (41.6% of them were from group 2 and could not explain their refusal from medication. General index of intellectual function was higher in patients of group 1 (p=0.034 than this in group 2; index of motor function did not change significantly (p>0.05.Conclusion. Reduction of compliance to antihypertensive therapy and rehabilitation in hypertensive patients after stroke is associated with unmotivated refusal from treatment because of clinical post-stroke depression.

Hepatitis C Virus Resistance to Direct-Acting Antiviral Drugs in Interferon-Free Regimens.

Science.gov (United States)

Pawlotsky, Jean-Michel

2016-07-01

Treatment of hepatitis C virus (HCV) infection has progressed considerably with the approval of interferon-free, direct-acting antiviral (DAA)-based combination therapies. Although most treated patients achieve virological cure, HCV resistance to DAAs has an important role in the failure of interferon-free treatment regimens. The presence of viral variants resistant to NS5A inhibitors at baseline is associated with lower rates of virological cure in certain groups of patients, such as those with genotype 1a or 3 HCV, those with cirrhosis, and/or prior nonresponders to pegylated interferon-based regimens. DAA-resistant HCV is generally dominant at virological failure (most often relapse). Viruses resistant to NS3-4A protease inhibitors disappear from peripheral blood in a few weeks to months, whereas NS5A inhibitor-resistant viruses persist for years. Re-treatment options are available, but first-line treatment strategies should be optimized to efficiently prevent treatment failure due to HCV resistance. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Patient adherence to antihypertensive therapy and its individual psychological factors

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Lidia Trachuk

2016-09-01

Full Text Available Background. In the treatment of chronic, especially asymptomatic pathology one of the main problem is the adherence to therapy. Patients with arterial hypertension need long-term, often lifelong medication, and how strictly they adhere to prescriptions often determines the course of the disease and the medical measures effectiveness. According to statistics, more than half of patients with hypertension are characterized by low compliance, which leads to complications of this disease. The objective of the research is to identify and analize the individual psychological factors that determine patient adherence to antihypertensive therapy. Methods and materials. This study was conducted during 2011-2013 at the cardiology departments of the Kyiv Alexander Hospital, polyclinics number 2 Shevchenko district in Kyiv, Desnyanskiy clinic №3 district in Kyiv, medical center "Adonis plus". We examined 203 patients with arterial hypertension (average age 53,5 ± 4,5 years. Methods: socio-demographic, clinical, clinical and psychological, psychodiagnostical, mathematical and statistical methods. Psychodiagnostical method included: 8-item Morisky medical adherence scale (Morisky D. E., 2008; self-assessment anxiety scale Charles D. Spielberger – Y.L Hanin (A.V. Batarshev, 2005; the Minnesota Multiphasic Personality Inventory questionnaire (MMRI (F.B. Berezin, 1994; "The level of subjective control" (A.A. Rean, 2001; "Index of attitudes to health" (S.D. Deryabo, VA Yasvin, 2000. Results. According to the results of 8-item Morisky medical adherence scale patients were divided into 3 groups according to the level of compliance - with high (26.11%, average (24.14% and low (49.75% levels of adherence to antihypertensive therapy. The individual-psychological predictors of poor adherence to antihypertensive therapy include the following personal characteristics of patients: a low level of intensity of attitude to health, internal type of subjective control, a

Antihypertensive efficacy and tolerability of lercanidipine in daily clinical practice. The ELYPSE Study. Eficacia de Lercanidipino y su Perfil de Seguridad.

Science.gov (United States)

Barrios, Vivencio; Navarro, Angel; Esteras, Antonio; Luque, Manuel; Romero, Joaquima; Tamargo, Juan; Prieto, Luis; Carrasco, Jose Luis; Herranz, Inmaculada; Navarro-Cid, Josefa; Ruilope, Luis M

2002-01-01

Lercanidipine, a long-acting dihydropyridine with a good antihypertensive efficacy and tolerability in clinical use. With the aim to determine the efficacy and tolerability of this drug in usual clinical practice we performed the ELYPSE trial. Grade 1 or 2 essential hypertensive patients in whom their physicians considered to prescribe a dihydropyridine were conferred to Lercanidipine 10 mg once daily with a 3-month follow-up; 9059 patients were included (age: 63 +/- 11 years; 58% women, 60% over 60 years, 56% grade 2 hypertensives and 69% previously treated with other antihypertensive drugs). A subgroup of 1267 patients (14%) who were included in the study had experienced adverse reactions with other drugs. Electronic case-report forms and a central database (Internet) were used in this trial. At baseline, blood pressure (BP) was 160.1 +/- 10.2/95.6 +/- 6.6 mmHg; and heart rate (HR) 77.3 +/- 9.3 beats/min. Significant reductions in both systolic and diastolic BP were attained at 1 month with slight additional decreases 2 months later. At 3 months, BP was 141.4 +/- 11.3/ 83.1 +/- 6.9 mmHg, and HR 75.2 +/- 8.2 beats/min (p < 0.001 versus baseline). At the study end. 64% of the patients achieved a diastolic BP < 90 mmHg, BP control (< 140/90 mmHg) was attained in 32%. In the subgroup of diabetics (n = 1269) an adequate BP control (< 130/85) was attained in only 16.4%. The overall incidence of adverse events was 6.5%, of which the most frequent were headache (2.9%), ankle oedema (1.2%), flushing (1.1%) and palpitations (0.6%). Withdrawal rate was < 1%. The efficacy and tolerability in the subgroup of patients included in the study due to adverse events with other drugs were similar to the whole study group. In this study Lercanidipine has shown a good efficacy and tolerability in daily clinical practice. These findings are concordant with those reported in randomized controlled trials.

Effect of antihypertensive agents - captopril and nifedipine - on the functional properties of rat heart mitochondria

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Ivana Kancirová

2016-06-01

Full Text Available Objective(s: Investigation of acute effect on cellular bioenergetics provides the opportunity to characterize the possible adverse effects of drugs more comprehensively. This study aimed to investigate the changes in biochemical and biophysical properties of heart mitochondria induced by captopril and nifedipine antihypertensive treatment. Materials and Methods: Male, 12-week-old Wistar rats in two experimental models (in vivo and in vitro were used. In four groups, the effects of escalating doses of captopril, nifedipine and combination of captopril + nifedipine added to the incubation medium (in vitro or administered per os to rat (in vivo on mitochondrial ATP synthase activity and membrane fluidity were monitored. Results: In the in vitro model we observed a significant inhibitory effect of treatment on the ATP synthase activity (P

Drug therapy in spinal tuberculosis.

Science.gov (United States)

Rajasekaran, S; Khandelwal, Gaurav

2013-06-01

Although the discovery of effective anti-tuberculosis drugs has made uncomplicated spinal tuberculosis a medical disease, the advent of multi-drug-resistant Mycobacterium tuberculosis and the co-infection of HIV with tuberculosis have led to a resurgence of the disease recently. The principles of drug treatment of spinal tuberculosis are derived from our experience in treating pulmonary tuberculosis. Spinal tuberculosis is classified to be a severe form of extrapulmonary tuberculosis and hence is included in Category I of the WHO classification. The tuberculosis bacilli isolated from patients are of four different types with different growth kinetics and metabolic characteristics. Hence multiple drugs, which act on the different groups of the mycobacteria, are included in each anti-tuberculosis drug regimen. Prolonged and uninterrupted chemotherapy (which may be 'short course' and 'intermittent' but preferably 'directly observed') is effective in controlling the infection. Spinal Multi-drug-resistant TB and spinal TB in HIV-positive patients present unique problems in management and have much poorer prognosis. Failure of chemotherapy and emergence of drug resistance are frequent due to the failure of compliance hence all efforts must be made to improve patient compliance to the prescribed drug regimen.

A review of drug-drug interactions in older HIV-infected patients.

Science.gov (United States)

Chary, Aarthi; Nguyen, Nancy N; Maiton, Kimberly; Holodniy, Mark

2017-12-01

The number of older HIV-infected people is growing due to increasing life expectancies resulting from the use of antiretroviral therapy (ART). Both HIV and aging increase the risk of other comorbidities, such as cardiovascular disease, osteoporosis, and some malignancies, leading to greater challenges in managing HIV with other conditions. This results in complex medication regimens with the potential for significant drug-drug interactions and increased morbidity and mortality. Area covered: We review the metabolic pathways of ART and other medications used to treat medical co-morbidities, highlight potential areas of concern for drug-drug interactions, and where feasible, suggest alternative approaches for treating these conditions as suggested from national guidelines or articles published in the English language. Expert commentary: There is limited evidence-based data on ART drug interactions, pharmacokinetics and pharmacodynamics in the older HIV-infected population. Choosing and maintaining effective ART regimens for older adults requires consideration of side effect profile, individual comorbidities, interactions with concurrent prescriptions and non-prescription medications and supplements, dietary patterns with respect to dosing, pill burden and ease of dosing, cost and affordability, patient preferences, social situation, and ART resistance history. Practitioners must remain vigilant for potential drug interactions and intervene when there is a potential for harm.

Individual patient data meta-analysis of antiplatelet regimens after noncardioembolic stroke or TIA : Rationale and design

NARCIS (Netherlands)

Greving, Jacoba P.; Diener, Hans Christoph; Csiba, László; Hacke, Werner; Kappelle, L. Jaap; Koudstaal, Peter J.; Leys, Didier; Mas, Jean Louis; Sacco, Ralph L.; Sivenius, Juhani; Algra, Ale

2015-01-01

Background: The Cerebrovascular Antiplatelet Trialists' Collaborative Group was formed to obtain and analyze individual patient data from the major randomized trials of common antiplatelet regimens after cerebral ischemia. Although the risk of stroke can be reduced by antiplatelet drugs, there

Mechanisms underlying the antihypertensive properties of Urtica dioica.

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Qayyum, Rahila; Qamar, Hafiz Misbah-Ud-Din; Khan, Shamim; Salma, Umme; Khan, Taous; Shah, Abdul Jabbar

2016-09-01

Urtica dioica has traditionally been used in the management of cardiovascular disorders especially hypertension. The aim of this study was to explore pharmacological base of its use in hypertension. Crude methanolic extract of U. dioica (Ud.Cr) and its fractions (Ud.EtAc, Ud.nHex, Ud.Chl and Ud.Aq) were tested in vivo on normotensive and hypertensive rats under anesthesia for blood pressure lowering effect. In-vitro experiments on rat and rabbit aortae were employed to probe the vasorelaxation mechanism(s). The responses were measured using pressure and force transducers connected to PowerLab Data Acquisition System. Ud.Cr and fractions were found more effective antihypertensive in hypertensive rats than normotensive with remarkable potency exhibited by the ethyl acetate fraction. The effect was same in the presence of atropine. In isolated rat aortic rings, Ud.Cr and all its fractions exhibited L-NAME sensitive endothelium-dependent vasodilator effect and also inhibit K(+) (80 mM)-induced pre-contractions. In isolated rabbit thoracic aortic rings Ud.Cr and its fractions induced relaxation with more potency against K(+) (80 mM) than phenylephrine (1 µM) like verapamil, showing Ud.EtAc fraction the most potent one. Pre-incubation of aortic rings with Ud.Cr and its fractions exhibited Ca(2+) channel blocking activity comparable with verapamil by shifting Ca(2+) concentration response curves to the right. Ud.Cr and its fractions also ablated the intracellular Ca(2+) release by suppressing PE peak formation in Ca(2+) free medium. When tested on basal tension, the crude extract and all fractions were devoid of any vasoconstrictor effect. These data indicate that crude methanolic extract and its fractions possess antihypertensive effect. Identification of NO-mediated vasorelaxation and calcium channel blocking effects explain the antihypertensive potential of U. dioica and provide a potential pharmacological base to its medicinal use in the management of hypertension.

[Dissociation of antihypertensive and metabolic response to losartan and spironolactone in experimental rats with metabolic sindrome].

Science.gov (United States)

Machado, Hussen; Pinheiro, Helady Sanders; Terra, Marcella Martins; Guerra, Martha de Oliveira; de Paula, Rogerio Baumgratz; Peters, Vera Maria

2012-01-01

The treatment of arterial hypertension (AH) in patients with metabolic syndrome (MS) is a challenge, since non drug therapies are difficult to implement and optimal pharmacological treatment is not fully established. To assess the blockade of the rennin angiotensin aldosterone system (RAAS) in blood pressure (BP) in renal function and morphology in an experimental model of MS induced by high fat diet. Wistar rats were fed on high fat diet from the fourth week of life, for 20 weeks. The groups received Losartan or Spironolactone from the eighth week of life. We weekly evaluated the body weight and BP by tail plethysmography. At the end of the experiment oral glucose tolerance, lipid profile, creatinine clearance tests, and the direct measurement of BP were performed. A morphometric kidney analysis was performed. The administration of high-fat diet was associated with the development of MS, characterized by central fat accumulation, hypertension, hyperglycemia and hypertriglyceridemia. In this model there were no changes in renal histomorphometry. The blockade of angiotensin II (Ang II) receptor AT1 prevented the development of hypertension. The mineralocorticoid blockage did not have antihypertensive efficacy but was associated with reduction of abdominal fat. The dissociation of the antihypertensive response to the blockades of Ang II receptors and mineralocorticoid indicates the involvement of Ang II in the pathogenesis of hypertension associated with obesity. Reduction of central obesity with Spironolactone suggests the presence of mineralocorticoid adipogenic effect.

Characterization of HIV-1 from patients with virological failure to a boosted protease inhibitor regimen

DEFF Research Database (Denmark)

Lillemark, Marie Rathcke; Gerstoft, Jan; Obel, Niels

2011-01-01

The use of highly active antiretroviral treatment (HAART) regimens with unboosted protease inhibitors (PIs) has resulted in a high level of virological failure primarily due to the development of resistant virus. Current boosted PI regimens combine successfully low-dose ritonavir (r) with a second.......3%) experienced virological failure, of whom 19 (83%) started PI/r treatment before 2001. Patients from Copenhagen (n=19) were selected to study the development of protease (PR) and gag cleavage site (CS) mutations during PI/r treatment and PI plasma levels at the time of virological failure. Three patients (16......%) developed major PI resistance mutations. Mutations in the p7/p1 and p1/p6 gag CS only developed in patients with major or minor mutations in PR. Drug concentrations were low or undetectable in 10 out of the 19 patients. In total PR resistance mutations and low drug levels could account for 12 (63...

Early antihypertensive treatment and clinical outcomes in acute ischemic stroke: subgroup analysis by baseline blood pressure.

Science.gov (United States)

He, William J; Zhong, Chongke; Xu, Tan; Wang, Dali; Sun, Yingxian; Bu, Xiaoqing; Chen, Chung-Shiuan; Wang, Jinchao; Ju, Zhong; Li, Qunwei; Zhang, Jintao; Geng, Deqin; Zhang, Jianhui; Li, Dong; Li, Yongqiu; Yuan, Xiaodong; Zhang, Yonghong; Kelly, Tanika N

2018-06-01

We studied the effect of early antihypertensive treatment on death, major disability, and vascular events among patients with acute ischemic stroke according to their baseline SBP. We randomly assigned 4071 acute ischemic stroke patients with SBP between 140 and less than 220 mmHg to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. A composite primary outcome of death and major disability and secondary outcomes were compared between treatment and control stratified by baseline SBP levels of less than 160, 160-179, and at least 180 mmHg. At 24 h after randomization, differences in SBP reductions were 8.8, 8.6 and 7.8 mmHg between the antihypertensive treatment and control groups among patients with baseline SBP less than 160, 160-179, and at least 180 mmHg, respectively (P baseline SBP subgroups on death (P = 0.02): odds ratio (95% CI) of 2.42 (0.74-7.89) in patients with baseline SBP less than 60 mmHg and 0.34 (0.11-1.09) in those with baseline SBP at least 180 mmHg. At the 3-month follow-up, the primary and secondary clinical outcomes were not significantly different between the treatment and control groups by baseline SBP levels. Early antihypertensive treatment had a neutral effect on clinical outcomes among acute ischemic stroke patients with various baseline SBP levels. Future clinical trials are warranted to test BP-lowering effects in acute ischemic stroke patients by baseline SBP levels. ClinicalTrials.gov Identifier: NCT01840072.

Improved pregnancy outcome in type 1 diabetic women with microalbuminuria or diabetic nephropathy: effect of intensified antihypertensive therapy?

DEFF Research Database (Denmark)

Nielsen, Lene Ringholm; Damm, Peter; Mathiesen, Elisabeth R

2009-01-01

To describe pregnancy outcome in type 1 diabetic women with normoalbuminuria, microalbuminuria, or diabetic nephropathy after implementation of an intensified antihypertensive therapeutic strategy.......To describe pregnancy outcome in type 1 diabetic women with normoalbuminuria, microalbuminuria, or diabetic nephropathy after implementation of an intensified antihypertensive therapeutic strategy....

Ambulatory blood pressure monitoring in clinical trials with antihypertensive agents

NARCIS (Netherlands)

A.H. van den Meiracker (Anton)

1995-01-01

textabstractAmbulatory blood pressure monitoring (ABPM) is being used increasingly for the evaluation of antihypertensive agents in clinical trials. In this brief review several aspects of ABPM are discussed. In particular, attention is paid to the extent to which ABPM is subject to a placebo

Etravirine and Rilpivirine Drug Resistance Among HIV-1 Subtype C Infected Children Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens in South India.

Science.gov (United States)

Saravanan, Shanmugam; Kausalya, Bagavathi; Gomathi, Selvamurthi; Sivamalar, Sathasivam; Pachamuthu, Balakrishnan; Selvamuthu, Poongulali; Pradeep, Amrose; Sunil, Solomon; Mothi, Sarvode N; Smith, Davey M; Kantor, Rami

2017-06-01

We have analyzed reverse transcriptase (RT) region of HIV-1 pol gene from 97 HIV-infected children who were identified as failing first-line therapy that included first-generation non-nucleoside RT inhibitors (Nevirapine and Efavirenz) for at least 6 months. We found that 54% and 65% of the children had genotypically predicted resistance to second-generation non-nucleoside RT inhibitors drugs Etravirine (ETR) and Rilpivirine, respectively. These cross-resistance mutations may compromise future NNRTI-based regimens, especially in resource-limited settings. To complement these investigations, we also analyzed the sequences in Stanford database, Monogram weighted score, and DUET weighted score algorithms for ETR susceptibility and found almost perfect agreement between the three algorithms in predicting ETR susceptibility from genotypic data.

Prognostic evaluation of primary biliary cirrhosis and its value in guiding therapeutic regimens

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HUANG Chunyang

2016-07-01

Full Text Available Prognostic evaluation of patients with primary biliary cirrhosis (PBC and how to improve the prognosis have attracted much attention. Further therapeutic regimens for PBC patients with poor prognosis has become the direction of clinical and scientific studies. This article summarizes the association between baseline indices and prognosis and prognostic evaluation of patients undergoing ursodeoxycholic acid (UDCA treatment, introduces the current status of UDCA combined with budesonide, fibrates, and obeticholic acid for patients with poor response to UDCA and the drugs being developed, and analyzes the influencing factors for prognosis and efficacy of UDCA. It is pointed out that prognosis and efficacy should be evaluated before and during UDCA treatment, and that therapeutic regimens should be adjusted in time to improve prognosis.

Triple Active Antiretroviral Regimen Including Enfuvirtide Via the Biojector is Effective and Safe

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Mona Loutfy

2007-01-01

Full Text Available For full HIV virological suppression, three fully active antiretroviral agents are required. New drug classes should be included to ensure that agents are fully active. The addition of enfuvirtide and efavirenz to the present patient’s new antiretroviral regimen ensured that two fully active agents were in use in the setting of a moderate degree of nucleoside resistance and a high level of protease resistance, and where non-nucleoside reverse transcriptase inhibitors were still fully active. Both viral load and CD4 count responded favourably to this regimen. The patient received support from physicians and clinic staff in the introduction and use of enfuvirtide. To reduce injection site reactions, a needle-free injection system (Biojector proved effective.

Successful Treatment of Disseminated Bacillus Calmette-Guérin Disease in an HIV-Infected Child with a Linezolid-Containing Regimen

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Srđan Roglić

2016-01-01

Full Text Available Upon HIV infection diagnosis, an 8-month-old boy was transferred for evaluation of worsening respiratory distress requiring mechanical ventilation. Pneumocystis jirovecii pneumonia (PCP was diagnosed; the boy also had a nonhealing ulcer at the site of vaccination with Statens Serum Institut (Danish strain Bacillus Calmette-Guérin (BCG vaccine and associated axillary lymphadenopathy. PCP treatment resulted in weaning from mechanical ventilation. Antimycobacterial treatment was immediately attempted but was discontinued because of hepatotoxicity. Over several months, he developed splenic lesions and then disseminated skin and cystic bone lesions. M. bovis was repeatedly cultured from both skin and bone lesions despite various multidrug antimycobacterial regimens which included linezolid. Eventually, treatment with a regimen of rifabutin, isoniazid, ethambutol, and linezolid led to definitive cure. Clinicians should consider a linezolid-containing regimen for treatment of severe disseminated BCG infection, especially if other drug regimens have failed. Although drug toxicity is a particular concern for young children, this patient received linezolid for 13 months without serious toxicity. This case also highlights the need for universal screening among pregnant women to prevent vertical transmission of HIV. Finally, routine immunization with BCG vaccine at birth should be questioned in countries with low and declining burden of tuberculosis.

Antihypertensive and antioxidant effects of hydroalcoholic extract from the aerial parts of Kelussia odoratissima Mozaff. in dexamethasone-induced hypertensive rats

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Leila Safaeian

2016-01-01

Conclusions: These results suggest antihypertensive and antioxidant effects of K. odoratissima extract in Dex-induced hypertension. Further studies are needed to elucidate the exact mechanism of the antihypertensive effect of this herbal medicine.

Comparison between Efficacy of Ciprofioxacin -Doxycycline with Rifampin – Doxycycline Regimens inrelapse of Brucellosis

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Hossein Sarmadian

2014-08-01

Full Text Available Background: Brucellosis is one of the endemic diseases in Iran that has a worldwide spread and is associated with chronic disabilities in humans. Combination therapy of Brucellosis leads to recovery of symptoms, shortening of the symptomatic intervals, and decrease in the rate of relapse and drug resistance. Considering the use of rifampin in the treatment of tuberculosis, and the necessity for an alternative treatment in regions endemic for both tuberculosis and brucellosis, the aim ofthis study was to compare the efficiency of the regimen of rifampin-Doxycycline with ciprofloxacin-Doxycycline in relapse of brucellosis. Materials and methods: This randomized controlled trial was performed on 90 patients, older than 17 years old, affected with brucellosis, which were referred to the Infectious Disease Clinics at ArakUniversity of medical sciences between the years 1384-1387. The patients were randomly divided into two groups: the DR groups, receiving 100 mg of Doxycycline twice a day and 300 mg of rifampin Bid daily for eight weeks and the CD group, receiving 100 mg of Doxycycline plus 500 mg of ciprofloxacin twice a day for eight weeks. The patients were analyzed for the relief of symptoms, drug side effects, and laboratory findings during the treatment. Results:In this study, the rate of relapse in both groups were similar. The relapse was seen in 4.5% and 3.2% of the patients for the DR and CD groups, respectively (P=0.168. The drug side effects were slight in both of groups, with no significant difference, and did not lead to discontinuation of the therapy. Conclusion: According to the same rate of relapse in both CD and DR regimens in the treatment of brucellosis and considering the usage of rifampin in regions with high prevalence of tuberclusis, the CD regimen is recommended as an appropriate one.

Safety and efficacy of a drug regimen to control heart rate during 64-slice ECG-gated coronary CTA in children

International Nuclear Information System (INIS)

Rigsby, Cynthia K.; Nicholas, Angela C.; deFreitas, R.A.; Leidecker, Christianne; Johanek, Andrew J.; Anley, Peter; Wang, Deli; Uejima, Tetsu

2010-01-01

The adult practice for ECG-gated single-source 64-slice coronary CTA (CCTA) includes administering beta-blockers to reduce heart rate. There are limited data on this process in children. To evaluate the safety and efficacy of a drug regimen to decrease heart rate before performing CCTA in children. IV remifentanil and esmolol infusion were chosen to decrease heart rate in 41 children (mean age 6.5 years) while they were under general anesthesia (GA) for CCTA. Drug doses, changes in heart rate and procedural complications were recorded. CCTA image quality was graded on a scale of 1 to 5. The relationships between image quality and heart rate and image quality and age were evaluated. Patient effective radiation doses were calculated. Heart rates were lowered utilizing esmolol (4 children), remifentanil (2 children) or both (35 children); 26 children received nitroglycerin for coronary vasodilation. The mean decrease in heart rate was 26%. There were no major complications. The average image-quality score was 4.4. Higher heart rates were associated with worse image quality (r = 0.67, P < 0.0001). Older age was associated with better image quality (r = 0.66, P < 0.0001). Effective radiation doses were 0.7 to 7.0 mSv. Heart rate reduction for pediatric CCTA can be safely and effectively achieved while yielding high-quality images. (orig.)

Effect of antihypertensive treatment on progression of incipient diabetic nephropathy

DEFF Research Database (Denmark)

Christensen, Cramer; Mogensen, C E

1985-01-01

of urinary albumin excretion before and during 2.6 years +/- 1.0 (SD) of treatment. The blood pressure was depressed by the treatment (systolic blood pressure from 135 mm Hg +/- 8.6 to 124 mm Hg +/- 6.2, NS; mean blood pressure from 107 mm Hg +/- 7.6 to 97 mm Hg +/- 3.4, 2p less than 0.05; diastolic blood......The aim of the study was to clarify whether antihypertensive treatment with a selective beta blocker would have an effect on the progression rate of kidney disease in patients with incipient diabetic nephropathy. Six male patients with juvenile-onset diabetes with incipient nephropathy (urinary...... albumin excretion above 15 micrograms/min and total protein excretion below 0.5 g/24 hr) were treated with metoprolol (200 mg daily). At the start of the antihypertensive treatment the mean age was 32 years +/- 4.2 (SD). The patients were followed a mean 5.4 years +/- 3.1 (SD) with repeated measurements...

Drug-resistant tuberculosis

African Journals Online (AJOL)

statistics show that almost half a million new ... testing for second-line drugs, no international consensus has been reached about .... Given the high background rates of TB and MDR-TB in several countries, regimens are often constructed ...

Impact of body weight on virological and immunological responses to efavirenz-containing regimens in HIV-infected, treatment-naive adults

DEFF Research Database (Denmark)

Marzolini, Catia; Sabin, Caroline; Raffi, François

2015-01-01

OBJECTIVE: The prevalence of overweight and obesity is increasing among HIV-infected patients. Whether standard antiretroviral drug dosage is adequate in heavy individuals remains unresolved. We assessed the virological and immunological responses to initial efavirenz (EFV)-containing regimens...... individuals had significantly higher CD4 cell count at baseline, CD4 cell recovery at 6 and 12 months after EFV initiation was comparable to normal-weight individuals. CONCLUSION: Virological and immunological responses to initial EFV-containing regimens were not impaired in heavy individuals, suggesting...

Aggressive chemotherapy and the selection of drug resistant pathogens.

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Silvie Huijben

2013-09-01

Full Text Available Drug resistant pathogens are one of the key public health challenges of the 21st century. There is a widespread belief that resistance is best managed by using drugs to rapidly eliminate target pathogens from patients so as to minimize the probability that pathogens acquire resistance de novo. Yet strong drug pressure imposes intense selection in favor of resistance through alleviation of competition with wild-type populations. Aggressive chemotherapy thus generates opposing evolutionary forces which together determine the rate of drug resistance emergence. Identifying treatment regimens which best retard resistance evolution while maximizing health gains and minimizing disease transmission requires empirical analysis of resistance evolution in vivo in conjunction with measures of clinical outcomes and infectiousness. Using rodent malaria in laboratory mice, we found that less aggressive chemotherapeutic regimens substantially reduced the probability of onward transmission of resistance (by >150-fold, without compromising health outcomes. Our experiments suggest that there may be cases where resistance evolution can be managed more effectively with treatment regimens other than those which reduce pathogen burdens as fast as possible.

Left Ventricular Structure during Antihypertensive Treatment in Patients with Chronic Kidney Disease

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Batir T. Daminov

2016-03-01

Full Text Available The aim of our study was to investigate the left ventricular (LV echocardiographic parameters and estimate the antiremodeling efficacy of eprosartan and lercanidipine in patients with CKD, depending on the presence or absence of diabetic nephropathy (DN. Materials and Methods: The study included 121 patients (mean age 52.4±5.7 years with CKD stage 3 (KDOQI, 2002. Patients were distributed in two groups according to the etiology of CKD. Group 1 consisted of 67 patients with non-diabetic CKD. Group 2 consisted of 54 CKD patients with DN. All patients had arterial hypertension grade 1 or 2 (ESH/ESC, 2013. All patients underwent clinical examination, echocardiography; GFR was estimated by the Cockcroft-Gault formula. Stages of chronic kidney disease (CKD were determined according to the KDOQI 2002 classification. Eprosartan and lercanidipine were prescribed to patients after one week of lavage from previous antihypertensive therapy. This 6-month follow-up study compared the effectiveness of two courses of treatment. Results: LVH was observed in all CKD patients regardless of the presence or absence of DN. Eprosartan and lercanidipine showed the high antihypertensive efficacy expressing a reliable decrease in absolute values of SBP and DBP. In CKD patients with DN, on the background of a comparable antihypertensive effect, eprosartan, in comparison with lercanidipine, showed a more pronounced effect on the LV echocardiographic parameters associated with LVH regression.

Appropriateness of Bolus Antihypertensive Therapy for Elevated Blood Pressure in the Emergency Department.

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Miller, Joseph B; Arter, Andrew; Wilson, Suprat S; Janke, Alexander T; Brody, Aaron; Reed, Brian P; Levy, Phillip D

2017-08-01

While moderate to severely elevated blood pressure (BP) is present in nearly half of all emergency department (ED) patients, the incidence of true hypertensive emergencies in ED patients is low. Administration of bolus intravenous (IV) antihypertensive treatment to lower BP in patients without a true hypertensive emergency is a wasteful practice that is discouraged by hypertension experts; however, anecdotal evidence suggests this occurs with relatively high frequency. Accordingly, we sought to assess the frequency of inappropriate IV antihypertensive treatment in ED patients with elevated BP absent a hypertensive emergency. We performed a retrospective cohort study from a single, urban, teaching hospital. Using pharmacy records, we identified patients age 18-89 who received IV antihypertensive treatment in the ED. We defined treatment as inappropriate if documented suspicion for an indicated cardiovascular condition or acute end-organ injury was lacking. Data abstraction included adverse events and 30-day readmission rates, and analysis was primarily descriptive. We included a total of 357 patients over an 18-month period. The mean age was 55; 51% were male and 93% black, and 127 (36.4%) were considered inappropriately treated. Overall, labetalol (61%) was the most commonly used medication, followed by enalaprilat (18%), hydralazine (18%), and metoprolol (3%). There were no significant differences between appropriate and inappropriate BP treatment groups in terms of clinical characteristics or adverse events. Hypotension or bradycardia occurred in three (2%) patients in the inappropriate treatment cohort and in two (1%) patients in the appropriately treated cohort. Survival to discharge and 30-day ED revisit rates were equivalent. More than one in three patients who were given IV bolus antihypertensive treatment in the ED received such therapy inappropriately by our definition, suggesting that significant resources could perhaps be saved through education of

Appropriateness of Bolus Antihypertensive Therapy for Elevated Blood Pressure in the Emergency Department

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Joseph B. Miller

2017-07-01

Full Text Available Introduction: While moderate to severely elevated blood pressure (BP is present in nearly half of all emergency department (ED patients, the incidence of true hypertensive emergencies in ED patients is low. Administration of bolus intravenous (IV antihypertensive treatment to lower BP in patients without a true hypertensive emergency is a wasteful practice that is discouraged by hypertension experts; however, anecdotal evidence suggests this occurs with relatively high frequency. Accordingly, we sought to assess the frequency of inappropriate IV antihypertensive treatment in ED patients with elevated BP absent a hypertensive emergency. Methods: We performed a retrospective cohort study from a single, urban, teaching hospital. Using pharmacy records, we identified patients age 18–89 who received IV antihypertensive treatment in the ED. We defined treatment as inappropriate if documented suspicion for an indicated cardiovascular condition or acute end-organ injury was lacking. Data abstraction included adverse events and 30-day readmission rates, and analysis was primarily descriptive. Results: We included a total of 357 patients over an 18-month period. The mean age was 55; 51% were male and 93% black, and 127 (36.4% were considered inappropriately treated. Overall, labetalol (61% was the most commonly used medication, followed by enalaprilat (18%, hydralazine (18%, and metoprolol (3%. There were no significant differences between appropriate and inappropriate BP treatment groups in terms of clinical characteristics or adverse events. Hypotension or bradycardia occurred in three (2% patients in the inappropriate treatment cohort and in two (1% patients in the appropriately treated cohort. Survival to discharge and 30-day ED revisit rates were equivalent. Conclusion: More than one in three patients who were given IV bolus antihypertensive treatment in the ED received such therapy inappropriately by our definition, suggesting that significant

Uso de antihipertensivos en Cantabria (1995-2002: el desfase con las evidencias Use of antihypertensive agents in Cantabria, Spain [1995-2002]: discrepancy with the published evidence

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Luis Vara

2004-10-01

Full Text Available Objetivo: Conocer el patrón de prescripción de los fármacos antihipertensivos en Cantabria y su variación según las nuevas evidencias publicadas entre 1995 y 2002. Método: Se realiza una revisión de la base de datos del Sistema Informático de Gestión de Farmacia, del Servicio Cántabro de Salud, acerca del consumo y coste de los medicamentos que tienen como indicación el tratamiento de la hipertensión arterial. El consumo se expresa en dosis diarias definidas por 1.000 habitantes y día (DHD. Resultados: En 1995, el consumo de antihipertensivos se situó en 130,2 DHD y fue de 235 DHD en 2002. La contribución de los diuréticos al consumo total disminuyó del 34,3% en 1995 al 25,8% en 2002, y la de los bloqueadores beta del 6,5% en 1995 al 5,9% en 2002. El grupo más utilizado en todos los años fue el de los inhibidores de la enzima de conversión de la angiotensina, que representó el 36,8% en 2002. Los antagonistas de los receptores de la angiotensina experimentaron el mayor incremento y originaron el 13,2% de las prescripciones en 2002, que supuso el 26% del gasto en antihipertensivos. Excepto enalapril, no varió la tendencia de uso de ninguno de los fármacos utilizados en los principales estudios publicados en este período o incluso disminuyó. Conclusiones: Se comprueba un notable incremento de la prescripción de antihipertensivos con un cambio en su patrón de consumo. Este diferente patrón no cambia en armonía con la publicación de los grandes ensayos clínicos y podría tener importantes implicaciones económicas.Objective: To ascertain the pattern of prescription of antihypertensive drugs in Cantabria and its variation from published evidence between 1995 and 2002. Method: We reviewed the database of the pharmaceutical data processing system of the Cantabrian Health Service on the consumption and cost of the drugs indicated in the treatment of hypertension. Consumption data is expressed in defined daily doses per

A phase II clinical trial evaluating the use of two sequential, four-drug combination chemotherapy regimens in ambulatory bronchogenic adenocarcinoma patients.

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Broder, L E; Sridhar, K S; Selawry, O S; Charyulu, K N; Rao, R K; Saldana, M J; Lenz, C

1992-12-01

Forty-three ambulatory patients with locally advanced or metastatic bronchogenic adenocarcinoma were sequentially treated with two potentially mutually non-cross-resistant chemotherapy regimens. A new regimen, MVPF (mitomycin-c, vinblastine, procarbazine, and 5-fluorouracil), was given until progressive disease occurred. Then, a second regimen--MOCC (methotrexate, vincristine [Oncovin], cyclophosphamide, and CCNU)--was initiated. At further progression, regional disease patients received radiotherapy, whereas extensive disease patients received Phase II agents. Of the 43 patients entered on the study, 40 were evaluable. Three patients withdrew early due to poor tolerance of the regimen. The response rate for MVPF was 33% (12 of 40 PR, 1 of 40 CR) compared to a 4% (1 of 23 PR) response for MOCC (difference: p < or = .03), for a total response rate of 35%. Although there was an initial improvement in survival for responders (31.7 weeks) versus nonresponders (15.7 weeks) at the 75th percentile (p < or = .05), there was no significant difference in median survival. The hematologic toxicity was equivalent for both groups, whereas nonhematologic toxicity revealed a high incidence of nausea and vomiting in the MVPF group. It is concluded that this approach lent itself well to ambulatory care, and MVPF could be considered an alternative to cyclophosphamide-based regimens. However, the absence of a meaningful CR rate and lack of influence of response on median survival were factors limiting its effectiveness.

The effect of how outcomes are framed on decisions about whether to take antihypertensive medication: a randomized trial.

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Cheryl L L Carling

Full Text Available BACKGROUND: We conducted an Internet-based randomized trial comparing three valence framing presentations of the benefits of antihypertensive medication in preventing cardiovascular disease (CVD for people with newly diagnosed hypertension to determine which framing presentation resulted in choices most consistent with participants' values. METHODS AND FINDINGS: In this second in a series of televised trials in cooperation with the Norwegian Broadcasting Company, adult volunteers rated the relative importance of the consequences of taking antihypertensive medication using visual analogue scales (VAS. Participants viewed information (or no information to which they were randomized and decided whether or not to take medication. We compared positive framing over 10 years (the number escaping CVD per 1000; negative framing over 10 years (the number that will have CVD and negative framing per year over 10 years of the effects of antihypertensive medication on the 10-year risk for CVD for a 40 year-old man with newly diagnosed hypertension without other risk factors. Finally, all participants were shown all presentations and detailed patient information about hypertension and were asked to decide again. We calculated a relative importance score (RIS by subtracting the VAS-scores for the undesirable consequences of antihypertensive medication from the VAS-score for the benefit of CVD risk reduction. We used logistic regression to determine the association between participants' RIS and their choice. 1,528 participants completed the study. The statistically significant differences between the groups in the likelihood of choosing to take antihypertensive medication in relation to different values (RIS increased as the RIS increased. Positively framed information lead to decisions most consistent with those made by everyone for the second, more fully informed decision. There was a statistically significant decrease in deciding to take antihypertensives on

The effect of how outcomes are framed on decisions about whether to take antihypertensive medication: a randomized trial.

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Carling, Cheryl L L; Kristoffersen, Doris Tove; Oxman, Andrew D; Flottorp, Signe; Fretheim, Atle; Schünemann, Holger J; Akl, Elie A; Herrin, Jeph; MacKenzie, Thomas D; Montori, Victor M

2010-03-01

We conducted an Internet-based randomized trial comparing three valence framing presentations of the benefits of antihypertensive medication in preventing cardiovascular disease (CVD) for people with newly diagnosed hypertension to determine which framing presentation resulted in choices most consistent with participants' values. In this second in a series of televised trials in cooperation with the Norwegian Broadcasting Company, adult volunteers rated the relative importance of the consequences of taking antihypertensive medication using visual analogue scales (VAS). Participants viewed information (or no information) to which they were randomized and decided whether or not to take medication. We compared positive framing over 10 years (the number escaping CVD per 1000); negative framing over 10 years (the number that will have CVD) and negative framing per year over 10 years of the effects of antihypertensive medication on the 10-year risk for CVD for a 40 year-old man with newly diagnosed hypertension without other risk factors. Finally, all participants were shown all presentations and detailed patient information about hypertension and were asked to decide again. We calculated a relative importance score (RIS) by subtracting the VAS-scores for the undesirable consequences of antihypertensive medication from the VAS-score for the benefit of CVD risk reduction. We used logistic regression to determine the association between participants' RIS and their choice. 1,528 participants completed the study. The statistically significant differences between the groups in the likelihood of choosing to take antihypertensive medication in relation to different values (RIS) increased as the RIS increased. Positively framed information lead to decisions most consistent with those made by everyone for the second, more fully informed decision. There was a statistically significant decrease in deciding to take antihypertensives on the second decision, both within groups and

Is the fixed-dose combination of telmisartan and hydrochlorothiazide a good approach to treat hypertension?

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Marc P Maillard

2007-07-01

Full Text Available Marc P Maillard, Michel BurnierService of Nephrology, Department of Internal Medicine, Lausanne University Hospital, SwitzerlandAbstract: Blockade of the renin-angiotensin system with selective AT1 receptor antagonists is recognized as an effective mean to lower blood pressure in hypertensive patients. Among the class of AT1 receptor antagonists, telmisartan offers the advantage of a very long half-life. This enables blood pressure control over 24 hours using once-daily administration. The combination of telmisartan with hydrochlorothiazide is a logical step because numerous previous studies have demonstrated that sodium depletion enhances the antihypertensive efficacy of drugs interfering with the activity of the renin-angiotensin system (RAS. In accordance with past experience using similar compounds blocking the RAS, several controlled studies have now demonstrated that the fixed-dose combination of telmisartan/hydrochlorothiazide is superior in lowering blood pressure than either telmisartan or hydrochlorothiazide alone. Of clinical interest also is the observation that the excellent clinical tolerance of the angiotensin II receptor antagonist is not affected by the association of the low-dose thiazide. Thus telmisartan/hydrochlorothiazide is an effective and well-tolerated antihypertensive combination. Finally, the development of fixed-dose combinations should improve drug adherence because of the one-pill-a-day regimen.Keywords: telmisartan, hydrochlorothiazide, fixed-dose combinations, antihypertensive agent, safety, compliance

Impact of overweight and obesity on cardiac benefit of antihypertensive treatment

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Gerdts, E; de Simone, G; Lund, Birthe

2013-01-01

BACKGROUND AND AIMS: Increased body mass index (BMI) has been associated with increased cardiovascular morbidity and mortality in hypertension. Less is known about the impact of BMI on improvement in left ventricular (LV) structure and function during antihypertensive treatment. METHODS AND RESULTS...

Individual and work-unit measures of psychological demands and decision latitude and the use of antihypertensive medication

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Daugaard, S; Andersen, J H; Grynderup, Matias Brødsgaard

2015-01-01

were associated with the purchase of prescribed antihypertensive medication among women. This effect was present on both the work-unit and the individual level. Among men there were no associations. The lack of interaction between psychological demands and decision latitude did not support the job......PURPOSE: To analyse whether psychological demands and decision latitude measured on individual and work-unit level were related to prescription of antihypertensive medication. METHODS: A total of 3,421 women and 897 men within 388 small work units completed a questionnaire concerning psychological...... working conditions according to the job strain model. Mean levels of psychological demands and decision latitude were computed for each work unit to obtain exposure measures that were less influenced by reporting bias. Dispensed antihypertensive medication prescriptions were identified in The Danish...

Pharmacokinetic-pharmacodynamic modeling of the antihypertensive interaction between azilsartan medoxomil and chlorthalidone in spontaneously hypertensive rats.

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Kumar Puttrevu, Santosh; Ramakrishna, Rachumallu; Bhateria, Manisha; Jain, Moon; Hanif, Kashif; Bhatta, Rabi Sankar

2017-05-01

A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to describe the time course of blood pressure following oral administration of azilsartan medoxomil (AZM) and/or chlorthalidone (CLT) in spontaneously hypertensive (SH) rats. The drug concentration and pharmacological effects, including systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and tail-cuff manometry, respectively. Sequential PK-PD analysis was performed, wherein the plasma concentration-time data was modeled by one compartmental analysis. Subsequently PD parameters were calculated to describe the time-concentration-response relationship using indirect response (IDR) PK-PD model. The combination of AZ and CLT had greater BP lowering effect compared to AZ or CLT alone, despite of no pharmacokinetic interaction between two drugs. These findings suggest synergistic antihypertensive pharmacodynamic interaction between AZ and CLT noncompetitively, which was simulated by inhibitory function of AZ and stimulatory function of CLT after concomitant administration of the two drugs. The present model was able to capture the turnover of blood pressure adequately at different time points at two different dose levels. The current PK-PD model was successfully utilized in the simulation of PD effect at a dose combination of 0.5 and 2.5 mg/kg for AZ and CLT, respectively. The developed preclinical PK-PD model may provide guidance in the optimization of dose ratio of individual drugs in the combined pharmacotherapy of AZ and CLT at clinical situations.

Antihypertensive Effects of Probiotics.

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Robles-Vera, Iñaki; Toral, Marta; Romero, Miguel; Jiménez, Rosario; Sánchez, Manuel; Pérez-Vizcaíno, Francisco; Duarte, Juan

2017-04-01

The present review focuses in the hypertension-associated changes in the microbiota and the current insights regarding the impact of probiotics on blood pressure in animal models and in human hypertensive patients. Gut dysbiosis in hypertension is characterized by (i) the gut microbioma that is less diverse and less rich with an increased Firmicutes/Bacteroidetes ratio and (ii) a decrease in acetate- and butyrate-producing bacteria and an increase in lactate-producing bacterial populations. The meta-analysis of the human studies supports that supplementation with probiotics reduces blood pressure. The mechanism of this antihypertensive effect of probiotics and its protective effect on endothelial function has not been fully elucidated. Further investigations are needed to clarify if the effects of probiotic bacteria result from the changes in the gut microbiota and its metabolic by-products; the restoration of the gut barrier function; and the effects on endotoxemia, inflammation, and renal sympathetic nerve activity.

5-FU Metabolism in Cancer and Orally-Administrable 5-FU Drugs

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Iwao Sasaki

2010-09-01

Full Text Available 5-Fluorouracil (5-FU is a key anticancer drug that for its broad antitumor activity, as well as for its synergism with other anticancer drugs, has been used to treat various types of malignancies. In chemotherapeutic regimens, 5-FU has been combined with oxaliplatin, irinotecan and other drugs as a continuous intravenous infusion. Recent clinical chemotherapy studies have shown that several of the regimens with oral 5-FU drugs are not inferior compared to those involving continuous 5-FU infusion chemotherapy, and it is probable that in some regimens continuous 5-FU infusion can be replaced by oral 5-FU drugs. Historically, both the pharmaceutical industry and academia in Japan have been involved in the development of oral 5-FU drugs, and this review will focus on the current knowledge of 5-FU anabolism and catabolism, and the available information about the various orally-administrable 5-FU drugs, including UFT, S-1 and capecitabine. Clinical studies comparing the efficacy and adverse events of S-1 and capecitabine have been reported, and the accumulated results should be utilized to optimize the treatment of cancer patients. On the other hand, it is essential to elucidate the pharmacokinetic mechanism of each of the newly-developed drugs, to correctly select the drugs for each patient in the clinical setting, and to further develop optimized drug derivatives.

The target-specific transporter and current status of diuretics as antihypertensive.

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Ali, Syed Salman; Sharma, Pramod Kumar; Garg, Vipin Kumar; Singh, Avnesh Kumar; Mondal, Sambhu Charan

2012-04-01

The currently available diuretics increase the urinary excretion of sodium chloride by selective inhibition of specific sodium transporters in the loop of Henle and distal nephron. In recent years, the molecular cloning of the diuretic-sensitive sodium transporters at distal convoluted tubule has improved our understanding of the cellular mechanisms of action of each class of diuretics. Diuretics are tools of considerable therapeutic importance. First, they effectively reduce blood pressure. Loop and thiazide diuretics are secreted from the proximal tubule via the organic anion transporter-1 and exert their diuretic action by binding to the Na(+)-K(+)-2Cl(-) co-transporter type 2 in the thick ascending limb and the Na(+)-Cl(-) co-transporter in the distal convoluted tubule, respectively. Recent studies in animal models suggest that abundance of these ion transporters is affected by long-term diuretic administration. The WHO/ISH guidelines point out that diuretics enhance the efficacy of antihypertensive drugs and will most often be a component of combination therapy. © 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

Therapeutic drug monitoring of aminoglycosides in neonates

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Touw, Daniël J; Westerman, Elsbeth M; Sprij, Arwen J

2009-01-01

The efficacy and toxicity of aminoglycosides show a strong direct positive relationship with blood drug concentrations, therefore, therapy with aminoglycosides in adults is usually guided by therapeutic drug monitoring. Dosing regimens in adults have evolved from multiple daily dosing to

Predictive tools for designing new insulins and treatment regimens

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Klim, Søren

The thesis deals with the development of "Predictive tools for designing new insulins and treatments regimens" and consists of two parts: A model based approach for bridging properties of new insulin analogues from glucose clamp experiments to meal tolerance tests (MTT) and a second part that des......The thesis deals with the development of "Predictive tools for designing new insulins and treatments regimens" and consists of two parts: A model based approach for bridging properties of new insulin analogues from glucose clamp experiments to meal tolerance tests (MTT) and a second part...... that describes an implemented software program able to handle stochastic differential equations (SDEs) with mixed effects. The thesis is supplemented with scientific papers published during the PhD. Developing an insulin analogue from candidate molecule to a clinical drug consists of a development programme...... and efficacy are investigated. Numerous methods are used to quantify dose and efficacy in Phase II - especially of interest is the 24-hour meal tolerance test as it tries to portray near normal living conditions. Part I describes an integrated model for insulin and glucose which is aimed at simulating 24-hour...

Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators

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Sever, P S; Dahlöf, B; Poulter, N R

2001-01-01

To test the primary hypothesis that a newer antihypertensive treatment regimen (calcium channel blocker +/- an angiotensin converting enzyme inhibitor) is more effective than an older regimen (beta-blocker +/- a diuretic) in the primary prevention of coronary heart disease (CHD). To test a second...

Durability of the first combined antiretroviral regimen in patients with AIDS at a reference center in Belo Horizonte, Brazil, from 1996 to 2005

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Flávia Andrade Ribeiro

Full Text Available Finding a better first antiretroviral regimen is one of the strategies used to improve span and quality of life of HIV/AIDS patients. 891 patients were followed during 24 months or until interruption/abandonment of treatment, changing regimen or death. At the end of 6 months, 69% of the patients were still being treated with the first regimen, 54% at 12 months, 48% at 18 months and 39% at 24 months. AZT-3TC-EFV was the most prescribed regimen and with the lesser discontinuation. NNRTI regimens showed high effectiveness and durability compared to PI regimens. Irregular medication dispensation was the only risk factor for failure/interruption of treatment in multivariate analyses. Intolerance/adverse effects were mainly responsible for first regimen discontinuation, followed by abandonment/non-adherence and virologic failure. Results showed significant difference between causes of interruption of first HAART with higher percentage of intolerance/adverse effects with PI regimens and higher immunologic failure with NNRTI regimens. Even with the availability of more potent and tolerable drugs, lack of adherence to HAART and high level of adverse effects are still the most important barriers to prolonged success of treatment. This study adds relevant information about durability and effectiveness of HAART in the first decade of its use in Brazil.

One patient with schizophrenia showed reduced drug-induced extrapyramidal symptoms as a result of an alternative regimen of treatment with paliperidone 3 and 6 mg every other day.

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Suzuki, Hidenobu; Hibino, Hiroyuki; Inoue, Yuichi; Matsumoto, Hideo; Mikami, Katsunaka

2017-01-01

Schizophrenia is a chronic disease that requires long-term management with antipsychotics. Antipsychotic drugs are given by tapering their dose, extending the dosing interval, and so on, as part of a treatment strategy to minimize the adverse effects while at the same time maintaining efficacy. We report the case of one patient with schizophrenia in whom the clinical symptoms were alleviated after treatment with 6 mg paliperidone. However, the patient developed extrapyramidal syndrome, for which 3 and 6 mg paliperidone were administered alternately every other day. Extrapyramidal syndrome was assessed using the Drug-Induced Extrapyramidal Symptoms Scale, Abnormal Involuntary Movement Scale, or Barnes Akathisia Scale. There was improvement in Drug-Induced Extrapyramidal Symptoms Scale score and Abnormal Involuntary Movement Scale score. However, there was almost no change in the Positive and Negative Syndrome Scale total score, positive score, negative score, or general score. The results indicate the possibility of lessened adverse effects as a result of an alternative regimen of treatment with paliperidone 3 and 6 mg every other day in the maintenance phase.

Comparison between chloral hydrate and propofol-ketamine as sedation regimens for pediatric auditory brainstem response testing.

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Abulebda, Kamal; Patel, Vinit J; Ahmed, Sheikh S; Tori, Alvaro J; Lutfi, Riad; Abu-Sultaneh, Samer

2017-10-28

The use of diagnostic auditory brainstem response testing under sedation is currently the "gold standard" in infants and young children who are not developmentally capable of completing the test. The aim of the study is to compare a propofol-ketamine regimen to an oral chloral hydrate regimen for sedating children undergoing auditory brainstem response testing. Patients between 4 months and 6 years who required sedation for auditory brainstem response testing were included in this retrospective study. Drugs doses, adverse effects, sedation times, and the effectiveness of the sedative regimens were reviewed. 73 patients underwent oral chloral hydrate sedation, while 117 received propofol-ketamine sedation. 12% of the patients in the chloral hydrate group failed to achieve desired sedation level. The average procedure, recovery and total nursing times were significantly lower in the propofol-ketamine group. Propofol-ketamine group experienced higher incidence of transient hypoxemia. Both sedation regimens can be successfully used for sedating children undergoing auditory brainstem response testing. While deep sedation using propofol-ketamine regimen offers more efficiency than moderate sedation using chloral hydrate, it does carry a higher incidence of transient hypoxemia, which warrants the use of a highly skilled team trained in pediatric cardio-respiratory monitoring and airway management. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

VASCULAR REMODELING AND HEART RATE VARIABILITY IN DIFFERENT ANTIHYPERTENSIVE THERAPIES

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E. D. Golovanova

2008-01-01

Full Text Available Aim. To study the effect of the long-term antihypertensive monotherapy with indapamide (Arifon Retard, 1,5 mg/d, metoprolol tartrate (Egilok Retard, 50 mg/d and combined therapy with indapamide and perindopril (Noliprel Forte, 1 tab/d: perindopril 4 mg and indapamide 1,25 mg on pulse wave velocity (PWV, cardio-ankle vascular index (CAVI and the sympathetic system activity.Material and methods. 88 patients, aged 30-59 y.o. (32 normotensive patients, 56 with arterial hypertension [HT] of 1-2 grades were examined. Biological age (BA was determined by the linear regression and the vascular wall age (VWA was estimated with the use of volume sphygmography (“VaSera-1000”, “Fucuda Denshi”, Japan. 39 patients with HT were randomized into 3 parallel groups with studied therapies lasted for 6 months. PWV, CAVI of the vessels of elastic, muscular and mixed types, blood pressure, measured in upper and lower extremities and heart rate variability (HRV were determined before and at the end of the therapies.Results. BA and VWA were elevated in all of patients with HT as compared with normotensive patients. The reduction in PWV and CAVI of the vessels of elastic and mixed types, HRV increase were found in patients with Arifon Retard monotherapy. Monotherapy with metoprolol significantly improved HVR without any influence on the vascular remodeling. Noliprel Forte significantly decreased in blood pressure in the upper and lower extremities, PWV and CAVI of the vessels of all types, decreased in VWA and increased in parasympathetic drive.Conclusion. Long-term therapy with Arifon Retard and Noliprel Forte resulted in decrease in vascular remodeling and increase in HRV simultaneously with significant antihypertensive effect in patients with HT. Metoprolol low doses therapy resulted in normalization of autonomic drive independently on antihypertensive action.

Prognostic value of microalbuminuria during antihypertensive treatment in essential hypertension.

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Pascual, Jose Maria; Rodilla, Enrique; Costa, Jose Antonio; Garcia-Escrich, Miguel; Gonzalez, Carmen; Redon, Josep

2014-12-01

Whether changes over time of urinary albumin excretion have prognostic value is a matter of discussion. The objective was to assess the prognostic value of changes in urinary albumin excretion over time in cardiovascular risk during antihypertensive treatment. Follow-up study of 2835 hypertensives in the absence of previous cardiovascular disease (mean age 55 years, 47% men, BP 138/80 mm Hg, 19.1% diabetics, and calibrated systemic coronary risk estimation 5 or >10.6%). Usual-care of antihypertensive treatment was implemented to maintain blood pressure<140/90 mm Hg. Urinary albumin excretion was assessed yearly, and the values were expressed as the creatinine ratio. Incidence of cardiovascular events, fatal and nonfatal, was recorded during the follow-up. During a median follow-up of 4.7 years (17 028 patients-year), 294 fatal and first nonfatal cardiovascular events were recorded (1.73 CVD per 100 patients/year). Independently of blood pressure, estimated glomerular filtration rate, level of cardiovascular risk, and antihypertensive treatment, microalbuminuria at baseline and at any time during the follow-up resulted in higher risk for events, hazard ratio (HR) 1.35 (95% confidence interval [CI], 1.08-1.79) and HR 1.49 (95% CI, 1.14-1.94), respectively. Likewise, development of microalbuminuria (HR 1.60; 95% CI, 1.04-2.46) or persistence from the beginning (1.53; 95% CI, 1.13-2.06) had a significantly higher rate of events than if remained normoalbuminuric (HR 1) or regress to normoalbuminuria (HR 1.37; 95% CI, 0.92-2.06) with an 18%, 18%, 8%, and 11% events, respectively, P<0.001. The study supports the value of urinary albumin excretion assessment as a prognostic factor for cardiovascular risk, but also opens the way to consider it as an intermediate objective in hypertension. © 2014 American Heart Association, Inc.

Cost-effectiveness of Antihypertensive Medication: Exploring Race and Sex Differences Using Data From the REasons for Geographic and Racial Differences in Stroke Study.

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Tajeu, Gabriel S; Mennemeyer, Stephen; Menachemi, Nir; Weech-Maldonado, Robert; Kilgore, Meredith

2017-06-01

Antihypertensive medication decreases risk of cardiovascular disease (CVD) events in adults with hypertension. Although black adults have higher prevalence of hypertension and worse CVD outcomes compared with whites, limited attention has been given to the cost-effectiveness of antihypertensive medication for blacks. To compare the cost-effectiveness of antihypertensive medication treatment versus no-treatment in white and black adults. We constructed a State Transition Model to assess the costs and quality-adjusted life-years (QALYs) associated with either antihypertensive medication treatment or no-treatment using data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study and published literature. CVD events and health states considered in the model included stroke, coronary heart disease, heart failure, chronic kidney disease, and end-stage renal disease. White and black adults with hypertension in the United States, 45 years of age and above. Yearly risk of CVD was determined using REGARDS data and published literature. Antihypertensive medication costs were determined using Medicare claims. Event and health state costs were estimated from published literature. All costs were adjusted to 2012 US dollars. Effectiveness was assessed using QALYs. Antihypertensive medication treatment was cost-saving and increased QALYs compared with no-treatment for white men ($7387; 1.14 QALYs), white women ($7796; 0.89 QALYs), black men ($8400; 1.66 QALYs), and black women ($10,249; 1.79 QALYs). Antihypertensive medication treatment is cost-saving and increases QALYs for all groups considered in the model, particularly among black adults.

Blood pressure and antihypertensive medication profile in a multiethnic Asian population of stable chronic kidney disease patients.

Science.gov (United States)

Teo, Boon Wee; Chua, Horng Ruey; Wong, Weng Kin; Haroon, Sabrina; Subramanian, Srinivas; Loh, Ping Tyug; Sethi, Sunil; Lau, Titus

2016-05-01

Clinical practice guidelines recommend different blood pressure (BP) goals for chronic kidney disease (CKD) patients. Usage of antihypertensive medication and attainment of BP targets in Asian CKD patients remain unclear. This study describes the profile of antihypertensive agents used and BP components in a multiethnic Asian population with stable CKD. Stable CKD outpatients with variability of serum creatinine levels 3 months apart, were recruited. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using automated manometers, according to practice guidelines. Serum creatinine was assayed and the estimated glomerular filtration rate (GFR) calculated using the CKD Epidemiology Collaboration equation. BP and antihypertensive medication profile was examined using univariate analyses. 613 patients (55.1% male; 74.7% Chinese, 6.4% Indian, 11.4% Malay; 35.7% diabetes mellitus) with a mean age of 57.8 ± 14.5 years were recruited. Mean SBP was 139 ± 20 mmHg, DBP was 74 ± 11 mmHg, serum creatinine was 166 ± 115 µmol/L and GFR was 53 ± 32 mL/min/1.73 m(2). At a lower GFR, SBP increased (p < 0.001), whereas DBP decreased (p = 0.0052). Mean SBP increased in tandem with the number of antihypertensive agents used (p < 0.001), while mean DBP decreased when ≥ 3 antihypertensive agents were used (p = 0.0020). Different targets are recommended for each BP component in CKD patients. A majority of patients cannot attain SBP targets and/or exceed DBP targets. Research into monitoring and treatment methods is required to better define BP targets in CKD patients. Copyright: © Singapore Medical Association.

Oral antidiabetic therapy in a large Italian sample: drug supply and compliance for different therapeutic regimens

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Vittorino Gaddi, A; Capello, F; Di Pietro, C; Cinconze, E; Rossi, E; De Sando, V; Cevenini, M; D'Alò, G

2014-01-01

Objectives: To define the main features of patients treated with oral antidiabetics, evaluating monotherapy (MT), loose-dose combination therapy (LDCT) and fixed-dose combination therapy (FDCT); to describe medication adherence to the different therapies; and to evaluate the differences in compliance with the prescribed therapy regimen among prevalent and incident patient cohorts. Study design: This study was a retrospective cohort analysis based on the ARNO database, a national record that tracks reimbursable prescription claims submitted from selected pharmacies to the Italian national health system. In total, 169,375 subjects, from an overall population of 4,040,624 were included in this study. The patients represented 12 different local health units. Each patient had at least one oral antidiabetic prescription claim (A10B ATC code). Methods: Patients were divided into four groups according to their treatment regimen during the recruitment period (1 January 2008-31 December 2008): MT, FDCT, LDCT and swi...

The relationship between visfatin and HOMA-IR in hypertensive patients, and the effect of antihypertensive drugs on visfatin and HOMA-IR in hypertensive patients with insulin resistance.

Science.gov (United States)

Lan, Jianjun; Chen, Xiaoni; Chen, Xiaoping; Wang, Si; Zhang, Xin; Wu, Kai; He, Sen; Peng, Yong; Jiang, Lingyun; Li, Longxin; Wan, Liyan

2011-10-01

To investigate the correlation between serum visfatin and insulin resistance (IR) in non-diabetic essential hypertensive (EH) patients with and without IR, and to evaluate the effect of antihypertensive treatment on serum visfatin and IR in these patients. A total of 81 non-diabetic EH patients, including 54 with IR and 27 without IR, were enrolled. After two weeks wash-out, patients with IR were randomly assigned to telmisartan (group T) or amlodipine (group A) for 6 months. Blood samples were taken before and after treatment for measurement of routine biochemical parameters, visfatin and insulin resistance (measured by HOMA-IR). Visfatin was independently correlated with HOMA-IR (r=0.845, P=0.000). After 6 months of treatment, both drugs lowered HOMA-IR, more significantly so in group T than group A (P=0.010). Serum visfatin levels increased in group T but decreased in group A. Serum visfatin levels were higher in non-diabetic EH patients with IR compared with those without IR. Visfatin is independently correlated with HOMA-IR. Telmisartan lowers HOMA-IR to a greater extent than amlodipine. Interestingly, serum visfatin increased with telmisartan yet decreased with amlodipine treatment. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Left ventricular hypertrophy in normoalbuminuric type 2 diabetic patients not taking antihypertensive treatment

DEFF Research Database (Denmark)

Sato, A; Tarnow, L; Nielsen, F S

2005-01-01

BACKGROUND: Left ventricular hypertrophy (LVH) is an independent risk factor for myocardial ischaemia, cardiac arrhythmia, sudden death, and heart failure, all common findings in patients with type 2 diabetes. AIM: To determine the prevalence of, and risk factors for, LVH in normoalbuminuric type 2...... diabetic patients not taking antihypertensive treatment. DESIGN: Cross-sectional study. METHODS: From 1994 to 1998, M-mode echocardiography was performed by one experienced examiner in 262 consecutive, normoalbuminuric Caucasian type 2 diabetic patients, all with blood pressure ... of diabetes and blood pressure were not. Similar results were obtained for left ventricular mass index. DISCUSSION: LVH was frequent in our normoalbuminuric type 2 diabetic patients not taking antihypertensive treatment. Several potentially modifiable risk factors, such as raised BMI, poor glycaemic control...

Pharmacokinetic/pharmacodynamic modeling for the determination of a cimicoxib dosing regimen in the dog.

Science.gov (United States)

Jeunesse, Elisabeth C; Schneider, Marc; Woehrle, Frederique; Faucher, Mathieu; Lefebvre, Herve P; Toutain, Pierre-Louis

2013-12-11

Cimicoxib is a new coxib anti-inflammatory drug for use in the dog. To determine a preclinical dosage regimen for cimicoxib in dog, a reversible model of kaolin-induced paw inflammation was used. Dosage regimens were established using pharmacokinetic/pharmacodynamic (PK/PD) modeling approach (indirect response model). Analgesic, anti-inflammatory and antipyretic endpoints investigated with the inflammation model established the efficacy of cimicoxib at a dose of 2 mg/kg administered orally (single dose) in 12 beagle dogs.For both the oral and IV route of administration two groups of dogs to be identified namely Poor Metabolizers (PM) and Extensive Metabolizers (EM).The terminal half-life after oral administration was 8.0 ± 0.6 h for the PM and 4.6 ± 2.6 h for the EM groups, with the corresponding values after the IV route being 5.6 ± 1.7 h and 2.7 ± 0.9 h (mean ± SD).The main pharmacodynamic parameters (potency, efficacy, and sensitivity) were estimated for four endpoints (body temperature, creeping speed, ground vertical reaction force and clinical lameness score). The plasma concentration corresponding to half the maximum of the indirect effect were 239 μg/L for creeping speed, 284 μg/L for the lameness score, 161 μg/L for the ground reaction vertical force and 193 μg/L for the body temperature.To document possible polymorphism of the cimicoxib disposition in the target dog population, cimicoxib was administered by the intravenous route to 40 dogs (four different sized breeds). The cimicoxib half-lives in these 40 dogs were of same order of the magnitude as those of the EM beagle dogs. Thus pharmacokinetic and pharmacodynamic parameters obtained from the EM beagle dogs were selected to simulate the dose-effect relationship of cimicoxib after an oral administration allowing a dosage regimen to be selected for confirmation by a clinical trial. Cimicoxib was an efficacious anti-inflammatory, antipyretic and analgesic drug and a dosage regimen of 2 mg

Claims in advertisements for antihypertensive drugs in a Dutch medical journal

NARCIS (Netherlands)

Greving, Jacoba P; Denig, Petra; de Zeeuw, Dick; Haaijer-Ruskamp, Flora M

2007-01-01

BACKGROUND: Advertising claims must not conflict with the official summary of product characteristics. After a drug has been approved, new clinical evidence may become available. AIMS: To determine how the pharmaceutical industry deals with evolving clinical evidence in advertising claims for

Use of fall risk increasing drugs in residents of retirement villages: a pilot study of long term care and retirement home residents in Ontario, Canada.

Science.gov (United States)

Rojas-Fernandez, Carlos; Dadfar, Farzan; Wong, Andrea; Brown, Susan G

2015-10-14

Falls continue to be a problem for older people in long-term care (LTC) and retirement home (RH) settings and are associated with significant morbidity and health care use. Fall-risk increasing drugs (FRIDs) are known to increase fall risk and represent modifiable risk factors. There are limited data regarding the use of FRIDs in contemporary LTC and RH settings, and it has not been well documented to what extent medication regimens are reviewed and modified for those who have sustained falls. The objective of this study is to characterize medication related fall risk factors in LTC and RH residents and on-going use of medications known to increase fall risk. Retrospective chart review of residents aged >65 who sustained one or more falls living in LTC or RH settings. 105 residents who fell one or more times during 2009-2010 were identified with a mean age of 89 years, a mean of nine scheduled medications and seven diagnoses, and 83% were women. Residents in LTC were ostensibly at higher risk for falls relative to those in RH settings as suggested by higher proportion of residents with multiple falls, multiple comorbidities, comorbidities that increase fall risk and visual impairment. Post fall injuries were sustained by 42% of residents, and residents in RH sustained more injuries relative to LTC residents (47 vs 34%). Use of FRIDs such as benzodiazepines, antipsychotic, antidepressant and various antihypertensive drugs was common in the present sample. No medication regimen changes were noted in the 6-month post fall period. The present study documented common use FRIDs by LTC and RH residents with multiple falls. These potentially modifiable falls risk factors are not being adequately addressed in contemporary practice, demonstrating that there is much room for improvement with regards to the safe and appropriate use of medications in LTC and RH residents.

Chrono pharmacotherapy: A pulsatile Drug Delivery

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Huma Hameed

2015-01-01

Full Text Available Chronopharmacotherapy refers to a treatment in which controlled drug delivery is achieved according to circadian rhythms of disease by enhancing therapeutic outcomes and minimizing side effects. Colon targeting has gained great importance not only for the treatment of local diseases such as Crohn’s disease, inflammatory bowel disease and ulcerative colitis but also very important in systemic delivery of proteins/peptides, antiasthmatic drugs, antidiabetic agents and antihypertensive drugs, which mostly show their efficacy based on circadian rhythms of the body.Colon drug delivery is one of the difficult approaches to achieve the targeted and desired outcomes through pulsatile drug delivery by avoiding dose dumping.The main reasonbehind the use of pulsatile delivery is provision ofconstant drug release where a zero-order release is notpreferred. Chronopharmacotherapy in colon targeting play its role bymany systems such ascapsular systems, pulsatile system and osmotic systems, which are based on use of rupturable membranes and biodegradable polymers.The objective of this review article is to provide latest knowledge about drugs with chrono-pharmacological behavior entails night time dosing specially to the colon.

The impact of anti hypertensive drug groups on urinary albumin excretion in a non-diabetic population

NARCIS (Netherlands)

Monster, TBM; Janssen, WMT; de Jong, PE; de Jong-van den Berg, LTW

Aims Microalbuminuria (30-300 mg 24 h(-1)) is recognized to be independently associated with renal and cardiovascular risk. Antihypertensives may lower microalbuminuria. We questioned whether the use of different anti hypertensive drug classes in general practice influences microalbuminuria as

Multidrug resistant to extensively drug resistant tuberculosis: What is ...

Indian Academy of Sciences (India)

Prakash

The modern, ... World Health Organization is based on a four-drug regimen ... Better management and control of tuberculosis specially drug resistant TB by experienced and qualified .... a comprehensive approach including the major DOTS.

Immunotherapy with mutated onchocystatin fails to enhance the efficacy of a sub-lethal oxytetracycline regimen against Onchocerca ochengi.

Science.gov (United States)

Bah, Germanus S; Tanya, Vincent N; Makepeace, Benjamin L

2015-08-15

Human onchocerciasis (river blindness), caused by the filarial nematode Onchocerca volvulus, has been successfully controlled by a single drug, ivermectin, for over 25 years. Ivermectin prevents the disease symptoms of severe itching and visual impairment by killing the microfilarial stage, but does not eliminate the adult parasites, necessitating repeated annual treatments. Mass drug administration with ivermectin does not always break transmission in forest zones and is contraindicated in individuals heavily co-infected with Loa loa, while reports of reduced drug efficacy in Ghana and Cameroon may signal the development of resistance. An alternative treatment for onchocerciasis involves targeting the essential Wolbachia symbiont with tetracycline or its derivatives, which are adulticidal. However, implementation of antibiotic therapy has not occurred on a wide scale due to the prolonged treatment regimen required (several weeks). In the bovine Onchocerca ochengi system, it has been shown previously that prolonged oxytetracycline therapy increases eosinophil counts in intradermal nodules, which kill the adult worms by degranulating on their surface. Here, in an "immunochemotherapeutic" approach, we sought to enhance the efficacy of a short, sub-lethal antibiotic regimen against O. ochengi by prior immunotherapy targeting onchocystatin, an immunomodulatory protein located in the adult female worm cuticle. A key asparagine residue in onchocystatin was mutated to ablate immunomodulatory activity, which has been demonstrated previously to markedly improve the protective efficacy of this vaccine candidate when used as an immunoprophylactic. The immunochemotherapeutic regimen was compared with sub-lethal oxytetracycline therapy alone; onchocystatin immunotherapy alone; a gold-standard prolonged, intermittent oxytetracycline regimen; and no treatment (negative control) in naturally infected Cameroonian cattle. Readouts were collected over one year and comprised adult

Controlled release and angiotensin-converting enzyme inhibition properties of an antihypertensive drug based on a perindopril erbumine-layered double hydroxide nanocomposite

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Hussein Al Ali SH

2012-04-01

Full Text Available Samer Hasan Hussein Al Ali1, Mothanna Al-Qubaisi2, Mohd Zobir Hussein1,3, Maznah Ismail2,4, Zulkarnain Zainal1, Muhammad Nazrul Hakim51Department of Chemistry, Faculty of Science, 2Laboratory of Molecular Biomedicine, Institute of Bioscience, 3Advanced Materials and Nanotechnology Laboratory, Institute of Advanced Technology, 4Department of Nutrition and Dietetics, Faculty of Medicine and Health Science, 5Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaBackground: The intercalation of perindopril erbumine into Zn/Al-NO3-layered double hydroxide resulted in the formation of a host-guest type of material. By virtue of the ion-exchange properties of layered double hydroxide, perindopril erbumine was released in a sustained manner. Therefore, this intercalated material can be used as a controlled-release formulation.Results: Perindopril was intercalated into the interlayers and formed a well ordered, layered organic-inorganic nanocomposite. The basal spacing of the products was expanded to 21.7 Å and 19.9 Å by the ion-exchange and coprecipitation methods, respectively, in a bilayer and a monolayer arrangement, respectively. The release of perindopril from the nanocomposite synthesized by the coprecipitation method was slower than that of its counterpart synthesized by the ion-exchange method. The rate of release was governed by pseudo-second order kinetics. An in vitro antihypertensive assay showed that the intercalation process results in effectiveness similar to that of the antihypertensive properties of perindopril.Conclusion: Intercalated perindopril showed better thermal stability than its free counterpart. The resulting material showed sustained-release properties and can therefore be used as a controlled-release formulation.Keywords: perindopril erbumine, layered double hydroxides, ion-exchange, coprecipitation, sustained release, angiotensin-converting enzyme

Evaluation of Hypotensive and Antihypertensive Effects of Velvet Bean (Mucuna pruriens L.) Hydrolysates.

Science.gov (United States)

Chel-Guerrero, Luis; Galicia-Martínez, Saulo; Acevedo-Fernández, Juan José; Santaolalla-Tapia, Jesus; Betancur-Ancona, David

2017-01-01

Hypertension could cause significant worldwide health problems that affect 15-20% of all adults; according to National Health and Nutrition Examination Survey, about 29% of the adult population in the United States are hypertensive. Recent research has shown that peptides derived from the hydrolysis of food proteins can decrease blood pressure. This study was carried out to evaluate the hypotensive and antihypertensive potential of Mucuna pruriens protein hydrolysates in in vitro and in vivo models. M. pruriens protein concentrate was prepared by wet fractionation and enzymatically hydrolyzed using Alcalase ® , Flavourzyme ® , and the sequential system Alcalase-Flavourzyme at different times (5-120 min). The biological potential was measured in vitro based on the IC 50 value as well as in vivo effect, measuring the systolic (SBP) and diastolic (DBP) blood pressure in normotensive and antihypertensive Wistar-Kyoto rats by the tail-cuff method. Hydrolysis of M. pruriens protein concentrates with commercial enzymes generated extensive hydrolysates with angiotensin-converting enzyme (ACE-I) inhibitory activity (IC 50 : 0.589-0.993 mg/mL) and hypotensive (SBP: 0.6-47.43%, DBP: 1.94-43.47%) and antihypertensive (SBP: 8.84-27.29% DBP: 16.1-29.37%) effect. These results indicate that Mucuna pruriens protein hydrolysate (MPPH) could be used as a functional ingredient to prevent blood pressure increase.

The influence of patient beliefs and treatment satisfaction on the discontinuation of current first-line antiretroviral regimens.

Science.gov (United States)

Casado, J L; Marín, A; Romero, V; Bañón, S; Moreno, A; Perez-Elías, M J; Moreno, S; Rodriguez-Sagrado, M A

2016-01-01

Large cohort studies have shown a high rate of first-line combination antiretroviral therapy (cART) regimen discontinuation in HIV-infected patients, attributed to characteristics of the cART regimen or toxicity. A cohort study of 274 patients receiving a first-line regimen was carried out. Patients' perceptions and beliefs prior to initiation were assessed using an attitude towards medication scale (0-15 points), and their satisfaction during therapy was assessed using an HIV treatment satisfaction questionnaire (HIVTSQ). Treatment discontinuation was defined as any switch in the cART regimen. During 474.8 person-years of follow-up, 63 (23%) patients changed their cART regimen, mainly because of toxicity/intolerance (42; 67%). The overall rate of change was 13.2 per 100 patient-years [95% confidence interval (CI) 11.1-16.4 per 100 patient-years]. An efavirenz (EFV)-based single tablet regimen showed the highest rate of adverse events (27%), but the lowest rate of change (16%; 7.44 per 100 patient-years). Cox regression revealed a decreased hazard of first regimen termination with better initial attitude towards drugs [hazard ratio (HR) 0.76; 95% CI 0.62-0.93; P satisfaction (HR 0.94; 95% CI 0.89-0.99; P = 0.01), and an increased hazard of termination with the presence of adverse events (HR 7.7; 95% CI 2.4-11.6; P patients (18 of 59; 31%) with mild/moderate adverse events (which were mainly central nervous system symptoms) continued the regimen; these patients, compared with those discontinuing therapy, showed better perception of therapy (mean score 14.4 versus 12.1, respectively; P = 0.05) and greater satisfaction during therapy (mean score 50.6 versus 44.6, respectively; P = 0.04). Patients' beliefs and satisfaction with therapy influence the durability of the first antiretroviral regimen. These patient-related factors modulate the impact of mild adverse events, and could explain differences in the rate of discontinuation. © 2015 British HIV

Reduced prevalence of early preterm delivery in women with Type 1 diabetes and microalbuminuria--possible effect of early antihypertensive treatment during pregnancy

DEFF Research Database (Denmark)

Nielsen, L R; Kragh-Müller, Claus; Damm, P

2006-01-01

In normotensive women with Type 1 diabetes and microalbuminuria we previously found preterm delivery (pregnancies. Antihypertensive treatment was initiated in late pregnancy when preeclampsia was diagnosed and diastolic blood pressure > 90 mmHg. From April 2000 our routine...... was changed and early antihypertensive treatment with methyldopa was initiated if antihypertensive treatment was given prior to pregnancy, if urinary albumin excretion (UAE) was > 2 g/24 h, or blood pressure > 140/90 mmHg. The present study describes the impact of this more aggressive antiypertensive...

Drug treatment of metabolic syndrome.

Science.gov (United States)

Altabas, Velimir

2013-08-01

The metabolic syndrome is a constellation of risk factors for cardiovascular diseases including: abdominal obesity, a decreased ability to metabolize glucose (increased blood glucose levels and/or presence of insulin resistance), dyslipidemia, and hypertension. Patients who have developed this syndrome have been shown to be at an increased risk of developing cardiovascular disease and/or type 2 diabetes. Genetic factors and the environment both are important in the development of the metabolic syndrome, influencing all single components of this syndrome. The goals of therapy are to treat the underlying cause of the syndrome, to reduce morbidity, and to prevent complications, including premature death. Lifestyle modification is the preferred first-step treatment of the metabolic syndrome. There is no single effective drug treatment affecting all components of the syndrome equally known yet. However, each component of metabolic syndrome has independent goals to be achieved, so miscellaneous types of drugs are used in the treatment of this syndrome, including weight losing drugs, antidiabetics, antihypertensives, antilipemic and anticlothing drugs etc. This article provides a brief insight into contemporary drug treatment of components the metabolic syndrome.

Prediction of resistance development against drug combinations by collateral responses to component drugs

DEFF Research Database (Denmark)

Munck, Christian; Gumpert, Heidi; Nilsson Wallin, Annika

2014-01-01

the genomes of all evolved E. coli lineages, we identified the mutational events that drive the differences in drug resistance levels and found that the degree of resistance development against drug combinations can be understood in terms of collateral sensitivity and resistance that occurred during...... adaptation to the component drugs. Then, using engineered E. coli strains, we confirmed that drug resistance mutations that imposed collateral sensitivity were suppressed in a drug pair growth environment. These results provide a framework for rationally selecting drug combinations that limit resistance......Resistance arises quickly during chemotherapeutic selection and is particularly problematic during long-term treatment regimens such as those for tuberculosis, HIV infections, or cancer. Although drug combination therapy reduces the evolution of drug resistance, drug pairs vary in their ability...

Drug cocktail optimization in chemotherapy of cancer.

Directory of Open Access Journals (Sweden)

Saskia Preissner

Full Text Available BACKGROUND: In general, drug metabolism has to be considered to avoid adverse effects and ineffective therapy. In particular, chemotherapeutic drug cocktails strain drug metabolizing enzymes especially the cytochrome P450 family (CYP. Furthermore, a number of important chemotherapeutic drugs such as cyclophosphamide, ifosfamide, tamoxifen or procarbazine are administered as prodrugs and have to be activated by CYP. Therefore, the genetic variability of these enzymes should be taken into account to design appropriate therapeutic regimens to avoid inadequate drug administration, toxicity and inefficiency. OBJECTIVE: The aim of this work was to find drug interactions and to avoid side effects or ineffective therapy in chemotherapy. DATA SOURCES AND METHODS: Information on drug administration in the therapy of leukemia and their drug metabolism was collected from scientific literature and various web resources. We carried out an automated textmining approach. Abstracts of PubMed were filtered for relevant articles using specific keywords. Abstracts were automatically screened for antineoplastic drugs and their synonyms in combination with a set of human CYPs in title or abstract. RESULTS: We present a comprehensive analysis of over 100 common cancer treatment regimens regarding drug-drug interactions and present alternatives avoiding CYP overload. Typical concomitant medication, e.g. antiemetics or antibiotics is a preferred subject to improvement. A webtool, which allows drug cocktail optimization was developed and is publicly available on http://bioinformatics.charite.de/chemotherapy.

One-Week Antihypertensive Effect of Ile-Gln-Pro in Spontaneously Hypertensive Rats

NARCIS (Netherlands)

Lu, Jun; Sawano, Yoriko; Miyakawa, Takuya; Xue, You-Lin; Cai, Mu-Yi; Egashira, Yukari; Ren, Di-Feng; Tanokura, Masaru

2011-01-01

The antihypertensive effect of an angiotensin I-converting enzyme (ACE) inhibitory peptide lie-Gin-Pro (IQP), whose sequence was derived from Spirulina platensis, was investigated in spontaneously hypertensive rats (SHRs) for 1 week. The weighted systolic blood pressure (SBP) and diastolic blood

The impact of South Korea's new drug-pricing policy on market competition among off-patent drugs.

Science.gov (United States)

Kwon, Hye-Young; Kim, Hyungmin; Godman, Brian; Reich, Michael R

2015-01-01

A new pricing policy was introduced in Korea in April 2012 with the aim of strengthening competition among off-patent drugs by eliminating price gaps between originators and generics. Examine the effect of newly implemented pricing policy. Retrospectively examining the effects through extracting from the National Health Insurance claims data a 30-month panel dataset (January 2011-June 2013) containing consumption data in four major therapeutic classes (antihypertensives, lipid-lowering drugs, antiulcerants and antidepressants). Proxies for market competition were examined before and after the policy. The new pricing policy did not enhance competition among off-patent drugs. In fact, price dispersion significantly decreased as opposed to the expected change. Originator-to-generic utilization increased 6.12 times (p = 0.000) after the new policy. The new pricing policy made no impact on competition among off-patent drugs. Competition in the off-patent market cannot be enhanced unless both supply and demand side measures are coordinated.

Emerging drugs and alternative possibilities in the treatment of tuberculosis

NARCIS (Netherlands)

Hofman, S.; Segers, M.M.; Ghimire, S.; Bolhuis, M.S.; Sturkenboom, M.G.; Soolingen, D. van; Alffenaar, J.W.

2016-01-01

INTRODUCTION: Tuberculosis (TB) remains a global health problem. Drug resistance, treatment duration, complexity, and adverse drug reactions associated with anti-TB regimens are associated with treatment failure, prolonged infectiousness and relapse. With the current set of anti-TB drugs the goal to

Emerging drugs and alternative possibilities in the treatment of tuberculosis

NARCIS (Netherlands)

Hofman, S.; Segers, M. M.; Ghimire, S.; Bolhuis, M. S.; Sturkenboom, M. G. G.; Van Soolingen, D.; Alffenaar, J. W. C.

2016-01-01

Introduction: Tuberculosis (TB) remains a global health problem. Drug resistance, treatment duration, complexity, and adverse drug reactions associated with anti-TB regimens are associated with treatment failure, prolonged infectiousness and relapse. With the current set of anti-TB drugs the goal to

ANTIHYPERTENSIVE THERAPY AND CLIMACTERIC DISORDERS IN POSTMENOPAUSAL WOMEN

Directory of Open Access Journals (Sweden)

A. A. Kirichenko

2008-01-01

Full Text Available Aim. To study efficacy and tolerability of antihypertensive therapy with enalapril (Berlipril®, Berlin-Chemie AG/Menarini Group and diltiazem (Altiazem® PP, Berlin-Chemie AG/Menarini Group in postmenopausal women with arterial hypertension (HT and climacteric disorders.Material and methods. 60 postmenopausal women (aged 56,8±3,9 y.o. with HT of 1-3 degrees were included into the study. They were split in two groups. Patients of the first group (30 people received enalapril (Berlipril® 20 mg/daily, patients of the second group (30 people – diltiazem (Altiazem® PP 180-360 mg/daily. Observation period was 6 months. Ambulatory blood pressure monitoring (ABPM was performed before treatment and after 3 weeks, 1, 3 and 6 months of therapy. Climacteric syndrome severity and urodynamic disorders was estimated as well as psychic status according to score of depression and anxiety.Results. Office and ambulance blood pressure decreased after 6 months of therapy in all patients of both groups. A number of complaints on headache and giddiness reduced significantly. Severity of climacteric syndrome also decreased. Enalapril (Berlipril® monotherapy and especially combined therapy with hydrochlorothiazide led to aggravation of urodinamic disorders. On the contrary both monotherapy with diltiazem (Altiazem® PP or its combination with hydrochlorothiazide had positive effect on urodinamics. Both therapies reduced depression and anxiety levels significantly.Conclusion. All spectrum of pharmacology effects should be taken into account during antihypertensive therapy of patients with climacteric disorders.

INFLUENCE OF COMBINED ANTIHYPERTENSIVE AND ANTIDEPRESSANT THERAPY ON LEFT VENTRICULAR REMODELING IN PATIENTS WITH ARTERIAL HYPERTENSION, ANXIETY AND DEPRESSION

Directory of Open Access Journals (Sweden)

Y. A. Vasyuk

2008-01-01

Full Text Available Aim. To assess influence of combined antihypertensive (captopril or metoprolol and antidepressant (thianeptin or sertralin therapy on clinical status, blood pressure (BP and myocardial function in patients with arterial hypertension (HT and affective disorders (AD.Material and methods. 106 patients with HT were involved in the study. 64 patients (60,4% had concomitant AD. All patients were divided into 3 groups. 46 patients with HT and AD were included in the 1-st group. They received metoprolol or captopril in combination with tianeptine or sertaline. The 2-nd group included 18 patients with HT and AD who received only antihypertensive therapy. The 3-rd group consisted of 42 patients with HT without AD. They also received only antihypertensive therapy.Results. After 6 month therapy patients of the 1-st and the 3-rd groups had more significant clinical improvement and BP reduction (according to 24- hour BP monitoring as well as more farourable structural and functional changes of left ventricular in comparison with patients of the 2-nd group.Conclusion. In patients with HT and concomitant AD combined antihypertensive and antidepressant therapy result in favourable clinical changes, effectively reduce BP, improve left ventricular structure and function.

Factors Affecting Compliance to Antihypertensive Treatment among Adults in a Tertiary Care Hospital in Mumbai.

Science.gov (United States)

Shah, Ayushi Jayesh; Singh, Vijaykumar; Patil, Subita P; Gadkari, Mithila R; Ramchandani, Varun; Doshi, Karan Janak

2018-01-01

Compliance to antihypertensive therapy reduces the risk of complications. It is important to understand the factors affecting compliance in patients so that the goal of successful treatment is not jeopardized. To determine the proportion of participants' compliant to treatment and various factors associated with compliance of antihypertensive treatment. A cross-sectional study of 330 hypertensive patients on treatment attending the outpatient department of a tertiary care hospital in Mumbai. It was conducted over 8 weeks using a validated, pretested questionnaire including information on the individual's sociodemographic profile, compliance to antihypertensive therapy and lifestyle advice assessed using a 4-point Likert scale. Data were entered into MS Excel 2007 and analyzed using SPSS 20. Participants' mean age was 55.2 ± 12.6 years. 39.4% were compliant to their treatment. Common reasons for frequently skipping the dose - forgetfulness (41.2%) and discontinued the medication when feeling well (30.3%). Factors positively associated with compliance were gender and illiteracy. The proportion of noncompliance among smokers and alcoholics was statistically significant. Forgetfulness and subjective feeling of wellness were the prevalent reasons for noncompliance. Controlling habits such as smoking and alcohol may prove as key factors for compliance.

EVALUATIN OF ANTIHYPERTENSIVE ACTIVITY OF SONCHUS ASPER L. IN RATS.

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Mushtaq, Muhammad Naveed; Akhtar, Muhammad Shoaib; Alamgeer; Ahmad, Taseer; Khan, Hafeez Ullah; Maheen, Safirah; Ahsan, Haseeb; Naz, Huma; Asif, Hira; Younis, Waqas; Tabassum, Nazia

2016-01-01

The present investigation was carried out to evaluate the effect of aerial parts of Sonchus asper L. in normotensive, glucose and egg feed diet induced hypertensive rats. Aqueous-methanolic extract of Sonchus asper in 250, 500 and 1000 mg/kg doses was studied in normotensive and glucose induced hypertensive rats using the non-invasive technique. The results obtained showed that the extract has significantly (p < 0.5 - p < 0.001) decreased the blood pressure and heart rate in dose dependent manner. The dose 1000 mg/kg of the extract produced the maximum antihypertensive effect and was selected for further experiments. The extract was found to prevent the rise in blood pressure of egg and glucose fed rats as compared to control group in 21 days study. The LD50 of the plant extract was 3500 mg/kg b.w. in mice and sub-chronic toxicity study showed that there was no significant alteration in the blood chemistry of the extract treated rats. It is conceivable, therefore, that the aqueous-methanolic extract of Sonchus asper has exerted considerable antihypertensive activity in rats and has duly supported traditional medicinal use of plant in hypertension.

Interactions of renin-angiotensin system gene polymorphisms and antihypertensive effect of benazepril in Chinese population.

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Chen, Qing; Yu, Can-Qing; Tang, Xun; Chen, Da-Fang; Tian, Jun; Cao, Yang; Fan, Wen-Yi; Cao, Wei-Hua; Zhan, Si-Yan; Lv, Jun; Guo, Xiao-Xia; Hu, Yong-Hua; Lee, Li-Ming

2011-05-01

Angiotensin-converting enzyme inhibitors are widely used antihypertensive drugs with individual response variation. We studied whether interactions of AGT, AGTR1 and ACE2 gene polymorphisms affect this response. Our study is based on a 3-year field trial with 1831 hypertensive patients prescribed benazepril. Generalized multifactor dimensionality reduction was used to explore interaction models and logistic regressions were used to confirm them. A two-locus model involving the AGT and ACE2 genes was found in males, the sensitive genotypes showed an odds ratio (OR) of 1.9 (95% CI: 1.3-2.8) when compared with nonsensitive genotypes. Two AGT-AGTR1 models were found in females, with an OR of 3.5 (95% CI: 2.0-5.9) and 3.1 (95% CI: 1.8-5.3). Gender-specific gene-gene interactions of the AGT, AGTR1 and ACE2 genes were associated with individual variation of response to benazepril. Further studies are needed to confirm this finding.

Synthesis of Benzimidazole Derivatives: As Anti-hypertensive Agents

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Jat Rakesh Kumar

2006-01-01

Full Text Available A new series of non peptide angiotensin(A-II receptor antagonist has been prepared. This N-(biphenyl methyl imidazoles e.g. 5-substituted (amino -2- phenyl-1-(2ʼcarboxy biphenyl-4-yl benzimidazoles differ from the previously reported and related compounds in that they produce a potent hypertensive effect upon oral administration. The earlier series were generally active only when administered intravenously. It has been found that 2’-position of biphenyl is essential. Only ortho substituted acid possess both high affinity for the AII receptor and oral anti-hypertensive potency.

Drugs in breast milk.

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Hervada, A R; Feit, E; Sagraves, R

1978-09-01

The amount of drug excreted into breast milk is dependent upon the lipid solubility of the medication, the mechanism of transport, the degree of ionization, and change in plasma pH. The higher the lipid solubility, the greater the concentration in human milk. The majority of drugs are transported into mammary blood capillaries by passive diffusion. The rest are transported by reverse pinocytosis. Once the drug has entered the epithelial cells of breast tissue, the drug molecules are excreted into the human milk by active transport, passive diffusion, or apocrine secretion. The amount of free (active) drug available for transport depends on the degree of protein binding the plasma pH. Another factor affecting excretion of drugs is the time when breast feeding occurs. In the 1st few days of life, when colostrum is present, water-soluble drugs pass through the breast more easily than afterwards when milk is produced. Then lipid-soluble drugs cross in higher concentrations. The effect on nursing infants is dependent on the amount excreted into the milk, the total amount absorbed by the infant, and the toxicity of the drug. The use of the following drugs in breast feeding mothers is reviewed: anticoagulants, antihypertensives and diuretics, antimicrobials, drugs affecting the central nervous system (alcohol, chloral hydrate, meprobamate, lithium, and aspirin), marijuana, other drugs (antihistamines, atropine, ergot alkaloids, laxatives, nicotine, iodides, propylthiouracil, theophylline), hormones (insulin, thyroxine, and oral contraceptives), and radiopharmaceuticals.

The association of antihypertensives with postural blood pressure and falls among seniors residing in the community: a case-control study.

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Zia, Anam; Kamaruzzaman, Shahrul B; Myint, Phyo K; Tan, Maw P

2015-10-01

A drop in postural blood pressure (BP) may contribute to falls, while antihypertensives have been considered to induce postural drop or orthostatic hypotension (OH) and falls among older people. However, this relationship between antihypertensives, postural BP and the risk of falls has never been evaluated in a single study. To examine the association of postural BP changes and BP therapy with the risk of falls among community-dwelling older people in a case-control manner. Cases (n = 202) included participants aged ≥ 65 years with two falls or one injurious fall while controls (n = 156) included participants ≥ 65 years with no falls in the preceding 12 months. Antihypertensives usage and medical history were recorded. Supine BP measurements were obtained at 10 min rest and at 1, 2 and 3 min after standing. Orthostatic hypotension was defined as a reduction in BP of 20/10 mmHg within 3 min of standing. Individual antihypertensive classes were not associated with falls. Minimal standing systolic BP (SBP) was significantly lower among fallers [128 (± 27·3) vs. 135·7 (± 24·7) mmHg; P = 0·01], but fallers were not more likely to fulfil the diagnostic criteria for OH. Diuretics were associated with OH and α-blockers were associated with minimal standing SBP. Univariate analysis revealed that the use of ≥ 2 antihypertensives was associated with recurrent and injurious falls [OR,1.97;CI,1.2-3.1], which was no longer significant aftermultivariateadjustment for age and number of comorbidities [OR, 1.6; CI, 0.95-2.6]. Minimal standing SBP or a lower SBP at 2 or 3minutes standing was associated with falls rather than OH using consensus definition. Association between ≥ 2 antihypertensives and falls was attenuated by increasing age and comorbidities. Our findings challenge previous assumptions that OH or the use of antihypertensives is associated with falls. Future studies should now seek to link these findings prospectively with falls in order to guide decision

Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration

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Soo-Yon Rhee

2017-04-01

Full Text Available Tenofovir disoproxil fumarate (TDF genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT mutations selected in individuals with VF on such a regimen is not known. To identify TDF regimen-associated mutations (TRAMs, we compared the proportion of each RT mutation in 2873 individuals with VF on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-naïve individuals. To identify TRAMs specifically associated with TDF-selection pressure, we compared the proportion of each TRAM to its proportion in a cohort of 5805 individuals with VF on a first-line thymidine analog-containing regimen. We identified 83 TRAMs including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12 – A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F – were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. These 12 TDF-selected TRAMs will be important for monitoring TDF-associated transmitted drug-resistance and for determining the extent of reduced TDF susceptibility in individuals with VF on a TDF-containing regimen.

In vivo antihypertensive and antidyslipidemic effects of the crude extracts and fractions of Moringa stenopetala (Baker f. Cufod. leaves in rats.

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Bekesho eGeleta

2016-04-01

Full Text Available Moringa stenopetala (Baker f. Cufod. is a medicinal plant that has been used in Ethiopian traditional medicine as a remedy for treatment of hypertension and diabetes. The aim of this study was to evaluate antihypertensive and antihyperlipidemic effect in fructose induced hypertensive rats.Rats were randomly divided into control and treatment groups (n=6. Treatment groups were given daily extracts (250, 500, and 1000 mg/kg orally with fructose. Whereas, positive, negative and normal control groups were received captopril (20 mg/kg/day with fructose, only fructose (66% w/v ad libitum and distilled water ad libitum for 15 days, respectively. The blood pressure was measured every 5th day using tail cuff blood pressure analyzer, and on the 16th day the blood was sampled to evaluate antihyperlipidemic effect using clinical chemistry analyzer. The study showed that aqueous and 70% ethanol extracts significantly prevented blood pressure increment in a dose dependent manner comparable to that of the standard drug. Similarly, the extracts suppressed increment in lipid profile (cholesterol, glucose and triglycerides compared with negative control. The biochemical test revealed that extracts produced a rise in liver but no effect on kidney function indicators compared with normal control.These findings revealed that both crude extracts of Moringa stenopetala (Baker f. Cufod. possess antihypertensive and antihyperlipidemic effect.

Predicting Optimal Dihydroartemisinin-Piperaquine Regimens to Prevent Malaria During Pregnancy for Human Immunodeficiency Virus-Infected Women Receiving Efavirenz.

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Wallender, Erika; Vucicevic, Katarina; Jagannathan, Prasanna; Huang, Liusheng; Natureeba, Paul; Kakuru, Abel; Muhindo, Mary; Nakalembe, Mirium; Havlir, Diane; Kamya, Moses; Aweeka, Francesca; Dorsey, Grant; Rosenthal, Philip J; Savic, Radojka M

2018-03-05

A monthly treatment course of dihydroartemisinin-piperaquine (DHA-PQ) effectively prevents malaria during pregnancy. However, a drug-drug interaction pharmacokinetic (PK) study found that pregnant human immunodeficiency virus (HIV)-infected women receiving efavirenz-based antiretroviral therapy (ART) had markedly reduced piperaquine (PQ) exposure. This suggests the need for alternative DHA-PQ chemoprevention regimens in this population. Eighty-three HIV-infected pregnant women who received monthly DHA-PQ and efavirenz contributed longitudinal PK and corrected QT interval (QTc) (n = 25) data. Population PK and PK-QTc models for PQ were developed to consider the benefits (protective PQ coverage) and risks (QTc prolongation) of alternative DHA-PQ chemoprevention regimens. Protective PQ coverage was defined as maintaining a concentration >10 ng/mL for >95% of the chemoprevention period. PQ clearance was 4540 L/day. With monthly DHA-PQ (2880 mg PQ), 96% of women, respectively. All regimens were safe, with ≤2% of women predicted to have ≥30 msec QTc increase. For HIV-infected pregnant women receiving efavirenz, low daily DHA-PQ dosing was predicted to improve protection against parasitemia and reduce risk of toxicity compared to monthly dosing. NCT02282293. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Efficacy of a brief multifactorial adherence-based intervention on reducing the blood pressure of patients with poor adherence: protocol for a randomized clinical trial

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Llobera Joan

2010-09-01

Full Text Available Abstract Background Lowering of blood pressure by antihypertensive drugs reduces the risks of cardiovascular events, stroke, and total mortality. However, poor adherence to antihypertensive medications reduces their effectiveness and increases the risk of adverse events. In terms of relative risk reduction, an improvement in medication adherence could be as effective as the development of a new drug. Methods/Design The proposed randomized controlled trial will include patients with a low adherence to medication and uncontrolled blood pressure. The intervention group will receive a multifactorial intervention during the first, third, and ninth months, to improve adherence. This intervention will include motivational interviews, pill reminders, family support, blood pressure self-recording, and simplification of the dosing regimen. Measurement The primary outcome is systolic blood pressure. The secondary outcomes are diastolic blood pressure, proportion of patients with adequately controlled blood pressure, and total cost. Discussion The trial will evaluate the impact of a multifactorial adherence intervention in routine clinical practice. Ethical approval was given by the Ethical Committee on Human Research of Balearic islands, Spain (approval number IB 969/08 PI. Trial registration Current controlled trials ISRCTN21229328

Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial.

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Azizi, Michel; Sapoval, Marc; Gosse, Philippe; Monge, Matthieu; Bobrie, Guillaume; Delsart, Pascal; Midulla, Marco; Mounier-Véhier, Claire; Courand, Pierre-Yves; Lantelme, Pierre; Denolle, Thierry; Dourmap-Collas, Caroline; Trillaud, Hervé; Pereira, Helena; Plouin, Pierre-François; Chatellier, Gilles

2015-05-16

Conflicting blood pressure-lowering effects of catheter-based renal artery denervation have been reported in patients with resistant hypertension. We compared the ambulatory blood pressure-lowering efficacy and safety of radiofrequency-based renal denervation added to a standardised stepped-care antihypertensive treatment (SSAHT) with the same SSAHT alone in patients with resistant hypertension. The Renal Denervation for Hypertension (DENERHTN) trial was a prospective, open-label randomised controlled trial with blinded endpoint evaluation in patients with resistant hypertension, done in 15 French tertiary care centres specialised in hypertension management. Eligible patients aged 18-75 years received indapamide 1·5 mg, ramipril 10 mg (or irbesartan 300 mg), and amlodipine 10 mg daily for 4 weeks to confirm treatment resistance by ambulatory blood pressure monitoring before randomisation. Patients were then randomly assigned (1:1) to receive either renal denervation plus an SSAHT regimen (renal denervation group) or the same SSAHT alone (control group). The randomisation sequence was generated by computer, and stratified by centres. For SSAHT, after randomisation, spironolactone 25 mg per day, bisoprolol 10 mg per day, prazosin 5 mg per day, and rilmenidine 1 mg per day were sequentially added from months two to five in both groups if home blood pressure was more than or equal to 135/85 mm Hg. The primary endpoint was the mean change in daytime systolic blood pressure from baseline to 6 months as assessed by ambulatory blood pressure monitoring. The primary endpoint was analysed blindly. The safety outcomes were the incidence of acute adverse events of the renal denervation procedure and the change in estimated glomerular filtration rate from baseline to 6 months. This trial is registered with ClinicalTrials.gov, number NCT01570777. Between May 22, 2012, and Oct 14, 2013, 1416 patients were screened for eligibility, 106 of those were randomly assigned to treatment

Provider knowledge of treatment policy and dosing regimen with artemether-lumefantrine and quinine in malaria-endemic areas of western Kenya

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Watsierah Carren A

2012-12-01

Full Text Available Abstract Background Due to widespread anti-malarial drug resistance in many countries, Kenya included, artemisinin-based Combination Therapy (ACT has been adopted as the most effective treatment option against malaria. Artemether-lumefantrine (AL is the first-line ACT for treatment of uncomplicated malaria in Kenya, while quinine is preferred for complicated and severe malaria. Information on the providers’ knowledge and practices prior to or during AL and quinine implementation is scanty. The current study evaluated providers’ knowledge and practices of treatment policy and dosing regimens with AL and quinine in the public, private and not-for-profit drug outlets. Methods A cross-sectional survey using three-stage sampling of 288 (126 public, 96 private and 66 not-for-profits providers in drug outlets was conducted in western Kenya in two Plasmodium falciparum-endemic regions with varying malarial risk. Information on provider in-service training, knowledge (qualification, treatment policy, dosing regimen, recently banned anti-malarials and on practices (request for written prescription, prescription of AL, selling partial packs and advice given to patients after prescription, was collected. Results Only 15.6% of providers in private outlets had received any in-service training on AL use. All (100% in public and majority (98.4% in not-for-profit outlets mentioned AL as first line-treatment drug. Quinine was mentioned as second-line drug by 47.9% in private outlets. A total of 92.0% in public, 57.3% in private and 78.8% in not-for-profit outlets stated correct AL dose for adults. A total of 85.7% of providers in public, 30.2% in private and 41.0% in not-for-profit outlets were aware that SP recommendations changed from treatment for mild malaria to IPTp in high risk areas. In-service training influenced treatment regimen for uncomplicated malaria (P = 0.039 and P = 0.039 and severe malaria (P P = 0.002 in children and adults

Effect of variations in treatment regimen and liver cirrhosis on exposure to benzodiazepines during treatment of alcohol withdrawal syndrome

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Pavel Gershokovich

2015-08-01

Full Text Available Purpose: Benzodiazepines (BDZs are the drugs of choice to prevent the symptoms of alcohol withdrawal syndrome (AWS. Various treatment protocols are published and have been shown to be effective in both office-managed and facility-managed treatment of AWS. The aim of this scientific commentary is to demonstrate the differences in the expected exposure to BDZs during AWS treatment using different treatment regimens available in the literature, in patients with or without alcoholic liver cirrhosis. Methods: Diazepam and lorazepam AWS protocols were examined and reviewed in the literature, and blood plasma levels were examined and compared, respectively. Results: Considerable variation in the blood levels with the different dosing schedules was found. Because the drugs are metabolized differently, we have also shown that liver disease affects the blood levels of diazepam, but not of lorazepam. Conclusions: Differences in treatment regimens, the choice of BDZ, as well as the presence of liver cirrhosis can substantially alter the exposure of patients to drugs used for AWS treatment. Outpatient treatment of AWS has been shown to be relatively safe and effective for the treatment of AWS but patients should be carefully monitored.

Selection of Parasites with Diminished Drug Sensitivity by Amodiaquine-Containing Antimalarial Regimens in Uganda

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Nawaz, Fatima; Nsobya, Samuel L.; Kiggundu, Moses; Joloba, Moses; Rosenthal, Philip J.

2009-01-01

Background Amodiaquine (AQ) is paired with artesunate (AS) or sulfadoxine-pyrimethamine (SP) in recommended antimalarial regimens. It is unclear how readily AQ resistance will be selected with combination chemotherapy. Methods We collected 61 Plasmodium falciparum samples from a cohort of Ugandan children randomized to treatment with AQ/SP, AS/AQ, or artemether-lumefantrine (AL) for uncomplicated malaria. In vitro sensitivity to monodesethylamodiaquine (MDAQ) was measured with a histidine rich protein-2-based ELISA, and potential resistance-mediating polymorphisms pfmdr-1were evaluated. Results Parasites from subjects previously treated with AQ/SP or AS/AQ within 12 weeks were less sensitive to MDAQ (n=18; mean IC50 62.9 nM; range 12.7–158.3 nM) than parasites from those not treated within 12 weeks (n=43; mean IC50 37.5 nM; range 6.3–184.7 nM; p=0.0085) or only those in the treatment arm that did not contain AQ (n=20; mean IC50 28.8 nM; range 6.3–121.8 nM; p=0.0042). The proportion of strains with polymorphisms expected to mediate diminished response to AQ (pfmdr-1 86Y and 1246Y) increased after prior AQ therapy, although differences were not significant. Conclusions Prior therapy selected for diminished response to MDAQ, suggesting that AQ-containing regimens may rapidly lose efficacy in Africa. The mechanism of diminished MDAQ response is not fully explained by known mutations in pfmdr-1. PMID:19905933

Drug-drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems.

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Kumar, Santosh; Rao, P S S; Earla, Ravindra; Kumar, Anil

2015-03-01

Substance abuse is a common problem among HIV-infected individuals. Importantly, addictions as well as moderate use of alcohol, smoking, or other illicit drugs have been identified as major reasons for non-adherence to antiretroviral therapy (ART) among HIV patients. The literature also suggests a decrease in the response to ART among HIV patients who use these substances, leading to failure to achieve optimal virological response and increased disease progression. This review discusses the challenges with adherence to ART as well as observed drug interactions and known toxicities with major drugs of abuse, such as alcohol, smoking, methamphetamine, cocaine, marijuana, and opioids. The lack of adherence and drug interactions potentially lead to decreased efficacy of ART drugs and increased ART, and drugs of abuse-mediated toxicity. As CYP is the common pathway in metabolizing both ART and drugs of abuse, we discuss the possible involvement of CYP pathways in such drug interactions. We acknowledge that further studies focusing on common metabolic pathways involving CYP and advance research in this area would help to potentially develop novel/alternate interventions and drug dose/regimen adjustments to improve medication outcomes in HIV patients who consume drugs of abuse.

Adherence to antihypertensive treatment and its determinants among urban slum dwellers in Kolkata, India.

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Bhandari, Subhasis; Sarma, P Sankara; Thankappan, Kavumpurathu R

2015-03-01

A cross-sectional study was conducted to determine the prevalence and predictors of adherence to modern antihypertensive pharmacotherapy among slum dwellers in Kolkata, India. Prevalence of adherence based on patient self-reports of consuming ≥80% of the prescribed medications over a recall period of 1 week was found to be 73% (95% confidence interval = 68%-78%). Compared with their counterparts, the following patients were more likely to be adherent to treatment: patients hypertensive for ≥5 years (2.98 times), those whose hypertension was detected during checkups for conditions related to hypertension (2.35 times), those living with ≤4 family members (2.01 times), those with family income of ≥3000 rupees (2.56 times), those who were getting free drugs (4.16 times), patients perceiving current blood pressure to be under control (2.23 times), and those satisfied with current treatment (3.77). Those adherent to their prescribed medications were 1.71 times more likely to achieve adequate control of hypertension compared with those who were not adherent. © 2011 APJPH.

Factors affecting compliance to antihypertensive treatment among adults in a tertiary care hospital in Mumbai

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Ayushi Jayesh Shah

2018-01-01

Full Text Available Background: Compliance to antihypertensive therapy reduces the risk of complications. It is important to understand the factors affecting compliance in patients so that the goal of successful treatment is not jeopardized. Objectives: To determine the proportion of participants' compliant to treatment and various factors associated with compliance of antihypertensive treatment. Settings and Design: A cross-sectional study of 330 hypertensive patients on treatment attending the outpatient department of a tertiary care hospital in Mumbai. Subjects and Methods: It was conducted over 8 weeks using a validated, pretested questionnaire including information on the individual's sociodemographic profile, compliance to antihypertensive therapy and lifestyle advice assessed using a 4-point Likert scale. Statistical Analysis: Data were entered into MS Excel 2007 and analyzed using SPSS 20. Results: Participants' mean age was 55.2 ± 12.6 years. 39.4% were compliant to their treatment. Common reasons for frequently skipping the dose – forgetfulness (41.2% and discontinued the medication when feeling well (30.3%. Factors positively associated with compliance were gender and illiteracy. The proportion of noncompliance among smokers and alcoholics was statistically significant. Conclusion: Forgetfulness and subjective feeling of wellness were the prevalent reasons for noncompliance. Controlling habits such as smoking and alcohol may prove as key factors for compliance.

Antihypertensive and organ-protective effects of benazepril.

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Barrios, Vivencio; Escobar, Carlos

2010-12-01

Benazepril is a nonsulfhydryl ACE inhibitor with favorable pharmacodynamic and pharmacokinetic properties, well-established antihypertensive effects and a good tolerability profile. Recent clinical studies have demonstrated that patients treated with benazepril alone or in combination with hydrochlorothiazide or amlodipine may achieve beneficial renal outcomes that extend beyond blood pressure control. Furthermore, the recent Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed decreased cardiovascular morbidity and mortality with benazepril when administered as a cotreatment. An additional novel therapeutic area for benazepril is atrial fibrillation. Differences between combination therapies have implications for which patients may be best suited to particular interventions, and further studies are required to fully ascertain this potential.

Sustainability of first-line antiretroviral regimens: findings from a large HIV treatment program in western Kenya.

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Braitstein, Paula; Ayuo, Paul; Mwangi, Ann; Wools-Kaloustian, Kara; Musick, Beverly; Siika, Abraham; Kimaiyo, Sylvester

2010-02-01

To describe first change or discontinuation in combination antiretroviral treatment (cART) among previously treatment naive, HIV-infected adults in a resource-constrained setting. The United States Agency for International Development-Academic Model Providing Access to Healthcare Partnership has enrolled >90,000 HIV-infected patients at 18 clinics throughout western Kenya. Patients in this analysis were aged > or =18 years, previously antiretroviral treatment naive, and initiated to cART between January 2006 and November 2007, with at least 1 follow-up visit. A treatment change or discontinuation was defined as change of regimen including single drug substitutions or a complete halting of cART. There were 14,162 patients eligible for analysis and 10,313 person-years of follow-up, of whom 1376 changed or stopped their cART. Among these, 859 (62%) changed their regimen (including 514 patients who had a single drug substitution) and 517 (38%) completely discontinued cART. The overall incidence rate (IR) of cART changes or stops per 100 person-years was 13.3 [95% confidence interval (CI): 12.7-14.1]. The incidence was much higher in the first year of post-cART initiation (IR: 25.0, 95% CI: 23.6-26.3) compared with the second year (IR: 2.4, 95% CI: 2.0-2.8). The most commonly cited reason was toxicity (46%). In multivariate regression, individuals were more likely to discontinue cART if they were World Health Organization stage III/IV [adjusted hazard ratio (AHR): 1.37, 95% CI: 1.11-1.69] or were receiving a zidovudine-containing regimen (AHR: 4.44, 95% CI: 3.35-5.88). Individuals were more likely to change their regimen if they were aged > or =38 years (AHR: 1.44, 95% CI: 1.23-1.69), had to travel more than 1 hour to clinic (AHR: 1.34, 95% CI: 1.15-1.57), had a CD4 at cART initiation < or =111 cells/mm3 (AHR: 1.51, 95% CI: 1.29-1.77), or had been receiving a zidovudine-containing regimen (AHR: 3.73, 95% CI: 2.81-4.95). Those attending urban clinics and those receiving

Tradução e validação para o português do Medication Regimen Complexity Index Translation and validation into portuguese Language of the Medication Regimen Complexity Index

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Ana Carolina Melchiors

2007-10-01

Full Text Available FUNDAMENTO: A complexidade da farmacoterapia consiste de múltiplas características do regime prescrito, incluindo o número de diferentes medicações no esquema, o número de unidades de dosagem por dose, o número total de doses por dia e os cuidados na administração dos medicamentos. O Medication Regimen Complexity Index (MRCI é um instrumento específico, validado e utilizado para medir a complexidade da farmacoterapia, desenvolvido originalmente em língua inglesa. OBJETIVO: Tradução transcultural e validação desse instrumento para o português do Brasil. MÉTODOS: Foi desenvolvido um estudo transversal envolvendo 95 pacientes com diabete do tipo 2 utilizando múltiplas medicações. O processo de validação teve início pela tradução, retrotradução e pré-teste do instrumento, gerando uma versão adaptada chamada Índice de Complexidade da Farmacoterapia (ICFT. Em seguida foram analisados parâmetros psicométricos, incluindo validade convergente, validade divergente, confiabilidade entre avaliadores e teste-reteste. RESULTADOS: A complexidade da farmacoterapia medida pelo ICFT obteve média de 15,7 pontos (desvio padrão = 8,36. O ICFT mostrou correlação significativa com o número de medicamentos em uso (r = 0,86; p BACKGROUND: The complexity of pharmacotherapy is a result of a multiplicity of prescribed regimen factors, including the number of different drugs in the regimen, the number of dosage units per dose, the total number of prescribed doses per day and administration instructions. The Medication Regimen Complexity Index (MRCI is a specific, reliable and valid tool used to measure the complexity of pharmacotherapy, originally developed in English language. OBJECTIVE: Transcultural translation and validation of this tool into Brazilian Portuguese. METHODS: A cross-sectional study was developed with 95 type-2 diabetes patients, receiving multiple medications. The validation process included translation into

Body friendly, safe and effective regimen of MgSO4 for eclampsia

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Gautam S. Aher, Urmila Gavali

2013-01-01

Full Text Available Pre-eclampsia and eclampsia are major health problems in developing countries. MgSO4 is the standard drug in the control of convulsions in eclampsia. Our study carried out at PDVVPF’s hospital is based on the low dose regimen than Pritchard, which is suitable for Indian women who are of smaller built thanwomen in western world. This prospective study included 50 eclampsia patients receiving low dose MgSO4 therapy. The loading dose of MgSO4 was 9gm. Following this 2.5 gm was given intramuscularly every 6 hourly for 24 hours after administration of the loading dose. Patients were monitored hourly by observing their respiratory rate, knee jerk and urine output. Out of 50, two patients required Pritchard regimen, rest completely recovered from eclampsia. The maternal and perinatal morbidity and mortality were comparable to those of the standard Pritchard regime. The study did not find a single case of magnesium related toxicity with low dose MgSO4 regime. Low dose magnesium sulphate regime was found to be safe and effective in eclampsia

Treating tuberculosis with high doses of anti-TB drugs: mechanisms and outcomes.

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Xu, Yuhui; Wu, Jianan; Liao, Sha; Sun, Zhaogang

2017-10-03

Tuberculosis (TB) is considered as one of the most serious threats to public health in many parts of the world. The threat is even more severe in the developing countries where there is a lack of advanced medical amenities and contemporary anti-TB drugs. In such situations, dosage optimization of existing medication regimens seems to be the only viable option. Therapeutic drug monitoring study results suggest that high-dose treatment regimens can compensate the low serum concentration of anti-TB drugs and shorten the therapy duration. The article presents a critical review on the possible changes that occur in the host and the pathogen upon the administration of standard and high-dose regimens. Some of the most common factors that are responsible for low anti-TB drug concentrations in the serum are differences in hosts' body weight, metabolic processing of the drug, malabsorption and/or drug-drug interaction. Furthermore, failure to reach the cavitary pulmonary and extrapulmonary tissues also contributes to the therapeutic inefficiency of the drugs. In such conditions, administration of higher doses can help in compensating the pathogenic outcomes of enhancement of the pathogen's physical barriers, efflux pumps and genetic mutations. The present article also presents a summary of the recorded treatment outcomes of clinical trials that were conducted to test the efficacy of administration of high dose of anti-tuberculosis drugs. This review will help physicians across the globe to understand the underlying pathophysiological changes (including side effects) that dictate the clinical outcomes in patients administered with standard and/or high dose anti-TB drugs.

Classifying new anti-tuberculosis drugs: rationale and future perspectives

Directory of Open Access Journals (Sweden)

Simon Tiberi

2017-03-01

Full Text Available The classification of anti-tuberculosis (TB drugs is important as it helps the clinician to build an appropriate anti-TB regimen for multidrug-resistant (MDR and extensively drug-resistant (XDR TB cases that do not fulfil the criteria for the shorter MDR-TB regimen. The World Health Organization (WHO has recently approved a revision of the classification of new anti-TB drugs based on current evidence on each drug. In the previous WHO guidelines, the choice of drugs was based on efficacy and toxicity in a step-down manner, from group 1 first-line drugs and groups 2–5 second-line drugs, to group 5 drugs with potentially limited efficacy or limited clinical evidence. In the revised WHO classification, exclusively aimed at managing drug-resistant cases, medicines are again listed in hierarchical order from group A to group D. In parallel, a possible future classification is independently proposed. The aim of this viewpoint article is to describe the evolution in WHO TB classification (taking into account an independently proposed new classification and recent changes in WHO guidance, while commenting on the differences between them. The latest evidence on the ex-group 5 drugs is also discussed.

No impact of HIV-1 protease minority resistant variants on the virological response to a first-line PI-based regimen containing darunavir or atazanavir.

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Perrier, Marine; Visseaux, Benoit; Landman, Roland; Joly, Véronique; Todesco, Eve; Yazdanpanah, Yazdan; Calvez, Vincent; Marcelin, Anne-Geneviève; Descamps, Diane; Charpentier, Charlotte

2018-01-01

To evaluate, in a clinical cohort of HIV-1-infected patients, the prevalence of PI minority resistant variants (MRV) at ART baseline and their impact on the virological response to a first-line PI-based regimen. In an observational single-centre cohort, we assessed all ART-naive patients initiating a first-line regimen including two NRTI and one boosted PI, darunavir/ritonavir or atazanavir/ritonavir, between January 2012 and March 2015. Ultra-deep sequencing of the pol gene was performed using Illumina® technology. Protease mutations were identified using the WHO transmitted drug resistance list and major PI resistance mutations (IAS-USA drug resistance mutations list). Ninety-four and 16 patients initiating a darunavir/ritonavir-based regimen and an atazanavir/ritonavir-based regimen, respectively, were assessed. Twenty-eight percent of the patients were HIV-1 subtype B, 39% CRF02_AG and 33% other non-B subtypes. Thirteen patients (13.8%) in the darunavir group and three patients (18.8%) in the atazanavir group experienced a virological failure (VF). Overall, 13 (11.8%) subjects had PI MRV at baseline in the median proportion of 1.3% (IQR = 1.1-1.7). The most prevalent PI MRV were G73C (n = 5) and M46I (n = 3). The proportion of patients harbouring baseline PI MRV was similar between those with virological success (10.6%) and those experiencing VF (18.8%) (P = 0.40). No difference was observed in the rate of PI MRV by viral subtype (P = 0.51) or by PI drug (P = 0.40). This study showed a prevalence of 11.8% of PI MRV among 110 ART-naive subjects, without significant impact on the virological response to a first-line PI-based regimen containing darunavir or atazanavir. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cost-effectiveness of adding bedaquiline to drug regimens for the treatment of multidrug-resistant tuberculosis in the UK.

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Lara J Wolfson

Full Text Available To evaluate the cost-effectiveness of adding bedaquiline to a background regimen (BR of drugs for multidrug-resistant tuberculosis (MDR-TB in the United Kingdom (UK.A cohort-based Markov model was developed to estimate the incremental cost-effectiveness ratio of bedaquiline plus BR (BBR versus BR alone (BR in the treatment of MDR-TB, over a 10-year time horizon. A National Health Service (NHS and personal social services perspective was considered. Cost-effectiveness was evaluated in terms of Quality-Adjusted Life Years (QALYs and Disability-Adjusted Life Years (DALYs. Data were sourced from a phase II, placebo-controlled trial, NHS reference costs, and the literature; the US list price of bedaquiline was used and converted to pounds (£18,800. Costs and effectiveness were discounted at a rate of 3.5% per annum. Probabilistic and deterministic sensitivity analysis was conducted.The total discounted cost per patient (pp on BBR was £106,487, compared with £117,922 for BR. The total discounted QALYs pp were 5.16 for BBR and 4.01 for BR. The addition of bedaquiline to a BR resulted in a cost-saving of £11,434 and an additional 1.14 QALYs pp over a 10-year period, and is therefore considered to be the dominant (less costly and more effective strategy over BR. BBR remained dominant in the majority of sensitivity analyses, with a 81% probability of being dominant versus BR in the probabilistic analysis.In the UK, bedaquiline is likely to be cost-effective and cost-saving, compared with the current MDR-TB standard of care under a range of scenarios. Cost-savings over a 10-year period were realized from reductions in length of hospitalization, which offset the bedaquiline drug costs. The cost-benefit conclusions held after several sensitivity analyses, thus validating assumptions made, and suggesting that the results would hold even if the actual price of bedaquiline in the UK were higher than in the US.

Phytochemical and in vitro and in vivo biological investigation on the antihypertensive activity of mango leaves (Mangifera indica L.).

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Ronchi, Silas Nascimento; Brasil, Girlandia Alexandre; do Nascimento, Andrews Marques; de Lima, Ewelyne Miranda; Scherer, Rodrigo; Costa, Helber B; Romão, Wanderson; Boëchat, Giovanna Assis Pereira; Lenz, Dominik; Fronza, Marcio; Bissoli, Nazaré Souza; Endringer, Denise Coutinho; de Andrade, Tadeu Uggere

2015-10-01

The aim of this study was to investigate the antihypertensive effect of leaves Mangifera indica L. using in vitro and in vivo assays. The ethanol extract of leaves of M. indica was fractionated to dichloromethanic, n-butyl alcohol and aqueous fractions. The chemical composition of ethanolic extract and dichloromethanic fraction were evaluated by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Antioxidant activity was evaluated in the DPPH scavenging activity assay. Angiotensin-converting enzyme (ACE) inhibitory activity was investigated using in vitro and in vivo assays. The chronic antihypertensive assay was performed in spontaneously hypertensive rats (SHRs) and Wistar rats treated with enalapril (10 mg/kg), dichloromethanic fraction (100 mg/kg; twice a day) or vehicle control for 30 days. The baroreflex sensitivity was evaluated through the use of sodium nitroprusside and phenylephrine. Cardiac hypertrophy was evaluated by morphometric analysis. The dichloromethanic fraction exhibited the highest flavonoid, total phenolic content and high antioxidant activity. Dichloromethanic fraction elicited ACE inhibitory activity in vitro (99 ± 8%) similar to captopril. LC-MS/MS analysis revealed the presence of ferulic acid (48.3 ± 0.04 µg/g) caffeic acid (159.8 ± 0.02 µg/g), gallic acid (142.5 ± 0.03 µg/g), apigenin (11.0 ± 0.01 µg/g) and quercetin (203.3 ± 0.05 µg/g). The chronic antihypertensive effects elicited by dichloromethanic fraction were similar to those of enalapril, and the baroreflex sensitivity was normalized in SHR. Plasma ACE activity and cardiac hypertrophy were comparable with animals treated with enalapril. Dichloromethanic fraction of M. indica presented an antihypertensive effect, most likely by ACE inhibition, with benefits in baroreflex sensitivity and cardiac hypertrophy. Altogether, the results of the present study suggest that the dichloromethanic fraction of M. indica leaves may have potential as a promoting

mtct regimen choice, drug resistance and the treatment of hiv

African Journals Online (AJOL)

risk of transmission is highest during labour and delivery, ... will have a major impact on controlling perinatally acquired HIV infection. ... could result in the development of drug resistance with potential .... dosing, pharmacokinetics and safety.

Short communication: Assessing antihypertensive activity in native and model Queso Fresco cheeses.

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Paul, M; Van Hekken, D L

2011-05-01

Hispanic-style cheeses are one of the fastest growing varieties in the United States, making up approximately 2% of the total cheese production in this country. Queso Fresco is one of most popular Hispanic-style cheeses. Protein extracts from several varieties of Mexican Queso Fresco and model Queso Fresco were analyzed for potential antihypertensive activity. Many Quesos Frescos obtained from Mexico are made from raw milk and therefore the native microflora is included in the cheese-making process. Model Queso Fresco samples were made from pasteurized milk and did not utilize starter cultures. Water-soluble protein extracts from 6 Mexican Quesos Frescos and 12 model cheeses were obtained and assayed for their ability to inhibit angiotensin-converting enzyme, implying potential as foods that can help to lower blood pressure. All model cheeses displayed antihypertensive activity, but mainly after 8 wk of aging when they were no longer consumable, whereas the Mexican samples did display some angiotensin-converting enzyme inhibitory action after minimal aging. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Angiotensin converting enzyme (ACE) inhibitory and antihypertensive activities of protein hydrolysate from meat of Kacang goat (Capra aegagrus hircus).

Science.gov (United States)

Mirdhayati, Irdha; Hermanianto, Joko; Wijaya, Christofora H; Sajuthi, Dondin; Arihara, Keizo

2016-08-01

The meat of Kacang goat has potential for production of a protein hydrolysate. Functional ingredients from protein hydrolysate of Kacang goat meat were determined by the consistency of angiotensin-converting enzyme (ACE) inhibitory activity and antihypertensive effect. This study examined the potency of Kacang goat protein hydrolysate in ACE inhibition and antihypertensive activity. Protein hydrolysates of Kacang goat meat were prepared using sequential digestion of endo-proteinase and protease complex at several concentrations and hydrolysis times. The highest ACE inhibitory activity resulted from a hydrolysate that was digested for 4 h with 5 g kg(-1) of both enzymes. An ACE inhibitory peptide was purified and a novel peptide found with a sequence of Phe-Gln-Pro-Ser (IC50 value of 27.0 µmol L(-1) ). Both protein hydrolysates and a synthesised peptide (Phe-Gln-Pro-Ser) demonstrated potent antihypertensive activities in spontaneously hypertensive rats. Protein hydrolysate of Kacang goat meat produced by sequential digestion with endo-proteinase and protease complex has great potential as a functional ingredient, particularly as an antihypertensive agent. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Identification of validated questionnaires to measure adherence to pharmacological antihypertensive treatments

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Pérez-Escamilla, Beatriz; Franco-Trigo, Lucía; Moullin, Joanna C; Martínez-Martínez, Fernando; García-Corpas, José P

2015-01-01

Background Low adherence to pharmacological treatments is one of the factors associated with poor blood pressure control. Questionnaires are an indirect measurement method that is both economic and easy to use. However, questionnaires should meet specific criteria, to minimize error and ensure reproducibility of results. Numerous studies have been conducted to design questionnaires that quantify adherence to pharmacological antihypertensive treatments. Nevertheless, it is unknown whether questionnaires fulfil the minimum requirements of validity and reliability. The aim of this study was to compile validated questionnaires measuring adherence to pharmacological antihypertensive treatments that had at least one measure of validity and one measure of reliability. Methods A literature search was undertaken in PubMed, the Excerpta Medica Database (EMBASE), and the Latin American and Caribbean Health Sciences Literature database (Literatura Latino-Americana e do Caribe em Ciências da Saúde [LILACS]). References from included articles were hand-searched. The included papers were all that were published in English, French, Portuguese, and Spanish from the beginning of the database’s indexing until July 8, 2013, where a validation of a questionnaire (at least one demonstration of the validity and at least one of reliability) was performed to measure adherence to antihypertensive pharmacological treatments. Results A total of 234 potential papers were identified in the electronic database search; of these, 12 met the eligibility criteria. Within these 12 papers, six questionnaires were validated: the Morisky–Green–Levine; Brief Medication Questionnaire; Hill-Bone Compliance to High Blood Pressure Therapy Scale; Morisky Medication Adherence Scale; Treatment Adherence Questionnaire for Patients with Hypertension (TAQPH); and Martín–Bayarre–Grau. Questionnaire length ranged from four to 28 items. Internal consistency, assessed by Cronbach’s α, varied from 0

The effect of anti-hypertensive drugs on the obstructive pancreatitis in rats Efeitos de fármacos anti-hipertensivos sobre pancreatite obstrutiva em ratos

Directory of Open Access Journals (Sweden)

Roberto de Barros Silva

2010-10-01

Full Text Available PURPOSE: To investigate the effect of ACE inhibitor, lisinopril and AT1 blocker, losartan, on the obstructive pancreatitis in rat. METHODS: Acute pancreatitis in rats (n=21 was induced for a common hepatic duct were ligated proximal to its entry into the pancreas and the common bile - pancreatic duct were also ligated near its junction with the duodenum, under ether anesthesia, after which the abdomen were closed. The animals was divided in tree groups, being two treated and control group. The animals was treated with Losartan and Lisinopril at the dose of 10µg/Kg body weight per day, i.p., in a proportional volume, for five days, before and after treatement. RESULTS: The inflammation, collagen deposition in the pancreas of treated animals were smaller, suggesting that the use of antihypertensive agents interfered positively in the depletion of the injury of the pancreas. Scythe showed a correlation between activity of pancreatic stellate cells (PSCs lower in treated animals when compared to control. CONCLUSION: The pancreatic stellate cells strength are involved in collagen production during acute pancreatitis and why antihypertensive drugs such as lisinopril and losartan may possibly have beneficial effects in reducing pancreatic fibrosis in models of experimental obstructive pancreatitis.OBJETIVO: Investigar o efeito de um inibidor da ECA, lisinopril e bloqueador AT1, losartan, a pancreatite obstrutiva em ratos. MÉTODOS: Pancreatite aguda em ratos (n = 21 foi induzida por um ducto hepático comum foram ligados proximal à sua entrada no pâncreas e da bílis comum - ducto pancreático também foram ligados perto de sua junção com o duodeno, sob anestesia com éter, após o que abdome foram fechadas. Os animais foram divididos em três grupos, sendo dois tratados eo grupo controle. Os animais foram tratados com lisinopril e losartan na dose de 10µg/Kg de peso corporal por dia, IP, em um volume proporcional, por cinco dias, antes e depois

Potential drug-drug and drug-disease interactions in well-functioning community-dwelling older adults.

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Hanlon, J T; Perera, S; Newman, A B; Thorpe, J M; Donohue, J M; Simonsick, E M; Shorr, R I; Bauer, D C; Marcum, Z A

2017-04-01

There are few studies examining both drug-drug and drug-disease interactions in older adults. Therefore, the objective of this study was to describe the prevalence of potential drug-drug and drug-disease interactions and associated factors in community-dwelling older adults. This cross-sectional study included 3055 adults aged 70-79 without mobility limitations at their baseline visit in the Health Aging and Body Composition Study conducted in the communities of Pittsburgh PA and Memphis TN, USA. The outcome factors were potential drug-drug and drug-disease interactions as per the application of explicit criteria drawn from a number of sources to self-reported prescription and non-prescription medication use. Over one-third of participants had at least one type of interaction. Approximately one quarter (25·1%) had evidence of had one or more drug-drug interactions. Nearly 10·7% of the participants had a drug-drug interaction that involved a non-prescription medication. % The most common drug-drug interaction was non-steroidal anti-inflammatory drugs (NSAIDs) affecting antihypertensives. Additionally, 16·0% had a potential drug-disease interaction with 3·7% participants having one involving non-prescription medications. The most common drug-disease interaction was aspirin/NSAID use in those with history of peptic ulcer disease without gastroprotection. Over one-third (34·0%) had at least one type of drug interaction. Each prescription medication increased the odds of having at least one type of drug interaction by 35-40% [drug-drug interaction adjusted odds ratio (AOR) = 1·35, 95% confidence interval (CI) = 1·27-1·42; drug-disease interaction AOR = 1·30; CI = 1·21-1·40; and both AOR = 1·45; CI = 1·34-1·57]. A prior hospitalization increased the odds of having at least one type of drug interaction by 49-84% compared with those not hospitalized (drug-drug interaction AOR = 1·49, 95% CI = 1·11-2·01; drug-disease interaction AOR = 1·69, CI = 1·15-2�

A controlled clinical trial testing two potentially non-cross-resistant chemotherapeutic regimens in small-cell carcinoma of the lung.

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Broder, L E; Selawry, O S; Charyulu, K N; Ng, A; Bagwell, S

1981-03-01

With the objectives of improving response rate, duration of response, and survival in small-cell carcinoma of the lung, 39 patients were randomized to remission-induction with either one of two potentially non-cross-resistant drug combinations: APE (consisting of adriamycin, 35 mg/m2 IV, D1 Q 3 weeks; procarbazine, 60 mg/m2 PO, D1-10 Q 3 weeks; and the epipodophyllotoxin (VP16-213), 130 mg/m2 IV, D8, 15 Q 3 weeks) or MOCC (composed of methotrexate, 15 mg/m2 IV (with [vincristine] Oncovin) or PO twice weekly D8-21 Q 3 weeks; Oncovin, 1.5 mg/m2 IV, D8, 15 Q 3 weeks; cyclophosphamide, 600 mg/m2 IV, D1 Q 3 weeks, and CCNU, 60 mg/m2 PO Q 6 weeks). A fixed crossover to the alternate regimen occurred at three months. Radiotherapy was delivered to the primary tumor (locoregional disease only) by a split course technique (1,750 rads for five days with a three-week split, followed by 3,400 rads over 17 days). The median survival including both arms was 11 months for regional and nine months for extensive disease. The chemotherapeutic activity of both regimens was comparable, with 15/17 (88 percent) of the patients responding to APE (including six complete) and 14/17 (82 percent) responding to MOCC (including five complete). The median survival for the complete responders was 11.7 months, while the partial responders survived for a median of 9.7 months. There were 2/9 (22 percent) responders to the alternate regimen at progressive disease. The overall incidence of CNS progression was 17 percent. The toxicity of the regimens was moderate, except for one instance of granulocytopenic death. This study establishes two equipotent drug combinations for the treatment of small-cell carcinoma of the lung.

What are the ideal properties for functional food peptides with antihypertensive effect? A computational peptidology approach.

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Zhou, Peng; Yang, Chao; Ren, Yanrong; Wang, Congcong; Tian, Feifei

2013-12-01

Peptides with antihypertensive potency have long been attractive to the medical and food communities. However, serving as food additives, rather than therapeutic agents, peptides should have a good taste. In the present study, we explore the intrinsic relationship between the angiotensin I-converting enzyme (ACE) inhibition and bitterness of short peptides in the framework of computational peptidology, attempting to find out the appropriate properties for functional food peptides with satisfactory bioactivities. As might be expected, quantitative structure-activity relationship modeling reveals a significant positive correlation between the ACE inhibition and bitterness of dipeptides, but this correlation is quite modest for tripeptides and, particularly, tetrapeptides. Moreover, quantum mechanics/molecular mechanics analysis of the structural basis and energetic profile involved in ACE-peptide complexes unravels that peptides of up to 4 amino acids long are sufficient to have efficient binding to ACE, and more additional residues do not bring with substantial enhance in their ACE-binding affinity and, thus, antihypertensive capability. All of above, it is coming together to suggest that the tripeptides and tetrapeptides could be considered as ideal candidates for seeking potential functional food additives with both high antihypertensive activity and low bitterness. Copyright © 2013 Elsevier Ltd. All rights reserved.

Open-label observational study to assess the efficacy and safety of aprepitant for chemotherapy-induced nausea and vomiting prophylaxis in Indian patients receiving chemotherapy with highly emetogenic chemotherapy/moderately emetogenic chemotherapy regimens

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Hingmire Sachin

2015-01-01

Full Text Available Context: Currently, there is limited data on the prevention of chemotherapy-induced nausea and vomiting (CINV in Indian population with aprepitant containing regimens. Aims: The aim was to assess the Efficacy and Safety of Aprepitant for the prevention of nausea and vomiting associated with highly emetogenic chemotherapy/moderately emetogenic chemotherapy (HEC/MEC regimens. Settings and Design: Investigator initiated, multicentric, open-label, prospective, noncomparative, observational trial. Subjects and Methods: Triple drug regimen with aprepitant, palonosetron, and dexamethasaone administration was assessed for the prevention of CINV during acute, delayed, and the overall phase (OP for HEC/MEC Regimens. The primary endpoint was complete response (CR; no emesis and no use of rescue medication and the key secondary endpoint was the complete control (CC; no emesis, no rescue medication and no more than mild nausea during the OP. Statistical Analysis Used: Perprotocol efficacy was analyzed for the first cycle with results represented in terms of CR/CC rates using descriptive statistics. Results: Seventy-five patients were included in the study with median age of 49.7 years and 89.7% being females. The CR rate (OP for patients administered HEC or MEC regimens during the first cycle were 92% and 90.9%, respectively. Similarly, the CC rates (OP were 75% and 90% for these regimens, respectively. 7 (9.2% patients reported adverse drug reactions that were mild and transient with no reports of any serious adverse events. Conclusions: Use of aprepitant containing regimen for patients receiving HEC/MEC regimen resulted in significantly high CR and CC response rates, which further consolidate its potential role to improve patient quality of life and compliance to disease management.

Safety of specific immunotherapy using an ultra-rush induction regimen in bee and wasp allergy.

Science.gov (United States)

Bożek, Andrzej; Kołodziejczyk, Krzysztof

2018-02-01

Specific allergen immunotherapy to Hymenoptera venom (VIT) is a basic treatment for patients allergic to Hymenoptera venom. The aim of the study was to evaluate the safety of an ultra-rush regimen compared with the rush and conventional protocols. In 31 patients with an allergy to bee venom and 82 with an allergy to wasp venom, the allergic adverse reactions during VIT were monitored. Patients were selected based on the criteria established by EAACI (European Academy of Allergy and Clinical Immunology) recommendations. Adverse reactions during the ultra-rush immunotherapy were measured, documented and classified according to the criteria of Mueller. Ultra-rush, rush or conventional protocols of the initial phase VIT using the Venomenhal vaccine (Hal Allergy, Leiden, Netherlands) were conducted. Six (13.7%) patients on the ultra-rush regimen, 5 (14.3%) patients on the rush regimen and 9 (26.5%) on conventional VIT experienced an allergic reaction. There were no associations between the adverse allergic reactions and the following factors: gender, total IgE and allergen-specific IgE to wasp or bee venom before the VIT and cardiological drugs that were used. We found that the ultra-rush protocol (similar to the rush protocol) using the Venomenhal vaccine is safer than the conventional protocol.

Hypertension Prevalence, Cardiac Complications, and Antihypertensive Medication Use in Children.

Science.gov (United States)

Dobson, Craig P; Eide, Matilda; Nylund, Cade M

2015-07-01

To determine the prevalence of hypertension diagnosis in children of US military members and quantify echocardiography evaluations, cardiac complications, and antihypertensive prescriptions in the post-2004 guideline era. Using billing data from military health insurance (TRICARE) enrollees, hypertension cases were defined as 2 or more visits with a primary or unspecified hypertension diagnosis during any calendar year or 1 such visit if with a cardiologist or nephrologist. During 2006-2011, the database contained an average 1.3 million subjects aged 2-18 years per year. A total of 16 322 met the definition of hypertension (2.6/1000). The incidence of hypertension increased by 17% between 2006 and 2011 (from 2.3/1000 to 2.7/1000; P Hypertension was more common in adolescents aged 12-18 years than in younger children (5.4/1000 vs 0.9/1000). Among patients with hypertension, 5585 (34%) underwent echocardiography. The frequency of annual echocardiograms increased from 22.7% to 27.7% (P hypertension, 6353 (38.9%) received an antihypertensive medication. The prevalence of hypertension in children has increased. Compliance with national guidelines is poor. Of pediatric patients with hypertension who receive an echocardiogram, 1 in 12 had identified cardiac complications, supporting the current recommendations for echocardiography in children with hypertension. Less than one-half of children with hypertension are treated with medication. Published by Elsevier Inc.

Novel diagnostics and therapeutics for drug-resistant tuberculosis.

Science.gov (United States)

Toosky, Melody; Javid, Babak

2014-06-01

Drug-resistant tuberculosis (DR-TB) is associated with increased mortality and morbidity. This is at least partly due to late diagnosis and ineffective treatment of drug-resistant status. Selective search of the literature on DR-TB supplemented by recent guidelines from the World Health Organization. Better and more rapid diagnosis of DR-TB by new techniques such as Xpert Mtb/RIF are likely to make a substantial impact on the disease. New therapeutics for DR-TB are entering, or about to enter the market for the first time in decades. It is not clear whether new treatments should be restricted for DR-TB or also used for drug-susceptible tuberculosis. With several new agents on the horizon, there is the real possibility of an entirely new regimen for tuberculosis. An inexpensive 'near-patient' diagnostic test is still needed. Optimizing new drug combination regimens in a timely manner is urgently required. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Why do hypertensive patients of African ancestry respond better to calcium blockers and diuretics than to ACE inhibitors and β-adrenergic blockers? A systematic review

Science.gov (United States)

2013-01-01

Background Clinicians are encouraged to take an individualized approach when treating hypertension in patients of African ancestry, but little is known about why the individual patient may respond well to calcium blockers and diuretics, but generally has an attenuated response to drugs inhibiting the renin-angiotensin system and to β-adrenergic blockers. Therefore, we systematically reviewed the factors associated with the differential drug response of patients of African ancestry to antihypertensive drug therapy. Methods Using the methodology of the systematic reviews narrative synthesis approach, we sought for published or unpublished studies that could explain the differential clinical efficacy of antihypertensive drugs in patients of African ancestry. PUBMED, EMBASE, LILACS, African Index Medicus and the Food and Drug Administration and European Medicines Agency databases were searched without language restriction from their inception through June 2012. Results We retrieved 3,763 papers, and included 72 reports that mainly considered the 4 major classes of antihypertensive drugs, calcium blockers, diuretics, drugs that interfere with the renin-angiotensin system and β-adrenergic blockers. Pharmacokinetics, plasma renin and genetic polymorphisms did not well predict the response of patients of African ancestry to antihypertensive drugs. An emerging view that low nitric oxide and high creatine kinase may explain individual responses to antihypertensive drugs unites previous observations, but currently clinical data are very limited. Conclusion Available data are inconclusive regarding why patients of African ancestry display the typical response to antihypertensive drugs. In lieu of biochemical or pharmacogenomic parameters, self-defined African ancestry seems the best available predictor of individual responses to antihypertensive drugs. PMID:23721258

Regimen Change: Gilead's TAF Drugs Toppling TDFs in HIV Treatment.

Science.gov (United States)

Reinke, Thomas

2017-09-01

Truvada is getting a new lease on life as a preventive agent. It is the only drug approved to prevent HIV infections, and Truvada is the key pharmaceutical component of pre-exposure prophylaxis, which is aimed at preventing, rather than treating, HIV infection and transmission.

A fixed-dose 24-hour regimen of artesunate plus sulfamethoxypyrazine-pyrimethamine for the treatment of uncomplicated Plasmodium falciparum malaria in eastern Sudan

DEFF Research Database (Denmark)

Adam, Ishag; Magzoub, Mamoun; Osman, Maha E

2006-01-01

-sulfamethoxypyrazine-pyrimethamine (AS+SMP f) administered at time intervals of 12 hours for a 24-hour therapy was compared with the efficacy of the same drug given as a loose combination (AS+SMP l) with a dose interval of 24 hours for 3 days for the treatment of uncomplicated Plasmodium falciparum malaria in eastern Sudan. RESULTS...... of the patients. CONCLUSION: both regimens of AS+SMP were effective and safe for the treatment of uncomplicated P. falciparum malaria in eastern Sudan. Due to its simplicity, the fixed dose one-day treatment regimen may improve compliance and therefore may be the preferred choice....

[Considerations about the efficiency of treatment regimens with fixed Rifampicin-Isoniazid combinations in pulmonary tuberculosis].

Science.gov (United States)

Munteanu, Ioana; Husar, Iulia; Didilescu, C; Stoicescu, I P

2004-01-01

Here are presented the results of a prospective, randomized study regarding the efficiency of regimens with fixed drug combination Rifampicin-Isoniazide manufactured by Antibiotics S.A. of Iasi in comparison with single drugs routinely used in treatment of patients with pulmonary tuberculosis. Newly diagnosed (confirmed by smear and culture) pulmonary tuberculosis patients were selected, and those who accepted to be included in the study, were admitted to the National Institute of Pneumology "Marius Nasta" between August 2001 and September 2002. At the time of admission, they were randomized into two groups: 20 patients received fixed drug combination RMP300 HIN150, and 18 patients received RMP and HIN in single drug tablets (2 patients were excluded). The follow-up of the patients was for one year from the date of enclosure. The smear conversion rate was 83,3% for the patients using single drug tablets, and 70% for those using fixed drug combination, motivated with some more severe TB patterns. The success rate was 100% for all TB patients. Although the present study was done for few patients, we can say that it demonstrated the same efficiency of fixed drug combination produced in Romania, with the single drug tablets, and it suggests a better compliance to treatment with a lower price.

Variation in training regimens in professional showjumping yards

NARCIS (Netherlands)

Lönnell, A C; Bröjer, J; Nostell, K; Hernlund, E; Roepstorff, L; Tranquille, C A; Murray, R C; Oomen, A; van Weeren, René; Bitschnau, C; Montavon, S; Weishaupt, M A; Egenvall, A

2014-01-01

REASONS FOR PERFORMING STUDY: Training regimens of showjumping horses under field conditions are largely undocumented. OBJECTIVES: The aims of this study were to quantify and compare training regimens used in professional-level showjumping yards, with respect to time exercised and type of activity.

Cost/efficacy analysis of preferred Spanish AIDS study group regimens and the dual therapy with lopinavir/ritonavir plus lamivudine for initial ART in HIV infected adults.

Science.gov (United States)

Gatell Artigas, Josep María; Arribas López, José Ramón; Lázaro Y de Mercado, Pablo; Blasco Bravo, Antonio Javier

2016-01-01

The National AIDS Plan and the Spanish AIDS study group (GESIDA) proposes "preferred regimens" (PR) of antiretroviral treatment (ART) as initial therapy in HIV-infected patients. In 2013, the recommended regimens were all triple therapy regimens. The Gardel Study assessed the efficacy of a dual therapy (DT) combination of lopinavir/ritonavir (LPV/r) plus lamivudine (3TC). Our objective is to evaluate the GESIDA PR and the DT regimen LPV/r+3TC cost/efficacy ratios. Decision tree models were built. probability of having viral load cost: costs of ART, adverse effects, and drug resistance tests during the first 48 weeks. Cost/efficacy ratios varied between 5,817 and 13,930 euros per responder at 48 weeks, for the DT of LPV/r+3TC and tenofovir DF/emtricitabine+raltegravir, respectively. Taking into account the official Spanish prices of ART, the most efficient regimen was DT of LPV/r+3TC, followed by the triple therapy with non-nucleoside containing regimens. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension.

Science.gov (United States)

Fadl Elmula, Fadl Elmula M; Hoffmann, Pavel; Larstorp, Anne C; Fossum, Eigil; Brekke, Magne; Kjeldsen, Sverre E; Gjønnæss, Eyvind; Hjørnholm, Ulla; Kjaer, Vibeke N; Rostrup, Morten; Os, Ingrid; Stenehjem, Aud; Høieggen, Aud

2014-05-01

We aimed to investigate for the first time the blood pressure (BP)-lowering effect of renal sympathetic denervation (RDN) versus clinically adjusted drug treatment in true treatment-resistant hypertension (TRH) after excluding patients with confounding poor drug adherence. Patients with apparent TRH (n=65) were referred for RDN, and those with secondary and spurious hypertension (n=26) were excluded. TRH was defined as office systolic BP (SBP) >140 mm Hg, despite maximally tolerated doses of ≥3 antihypertensive drugs including a diuretic. In addition, ambulatory daytime SBP >135 mm Hg after witnessed intake of antihypertensive drugs was required, after which 20 patients had normalized BP and were excluded. Patients with true TRH were randomized and underwent RDN (n=9) performed with Symplicity Catheter System versus clinically adjusted drug treatment (n=10). The study was stopped early for ethical reasons because RDN had uncertain BP-lowering effect. Office SBP and diastolic BP in the drug-adjusted group changed from 160±14/88±13 mm Hg (±SD) at baseline to 132±10/77±8 mm Hg at 6 months (P<0.0005 and P=0.02, SBP and diastolic BP, respectively) and in the RDN group from 156±13/91±15 to 148±7/89±8 mm Hg (P=0.42 and P=0.48, SBP and diastolic BP, respectively). SBP and diastolic BP were significantly lower in the drug-adjusted group at 6 months (P=0.002 and P=0.004, respectively), and absolute changes in SBP were larger in the drug-adjusted group (P=0.008). Ambulatory BPs changed in parallel to office BPs. Our data suggest that adjusted drug treatment has superior BP lowering effects compared with RDN in patients with true TRH. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01673516.

Antihypertensive treatment and risk of atrial fibrillation

DEFF Research Database (Denmark)

Marott, Sarah C W; Nielsen, Sune F; Benn, Marianne

2014-01-01

AIMS: To examine the associations between antihypertensive treatment with angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs), β-blockers, diuretics, or calcium-antagonists, and risk of atrial fibrillation. We examined these associations using the entire Danish...... population from 1995 through 2010. METHODS AND RESULTS: Excluding medication used in atrial fibrillation, we matched individuals on ACEi monotherapy 1:1 with individuals on β-blocker (n = 48 658), diuretic (n = 69 630), calcium-antagonist (n = 57 646), and ARB monotherapy (n = 20 158). Likewise, individuals...... on ARB monotherapy were matched 1:1 with individuals on β-blocker (n = 20 566), diuretic (n = 20 832), calcium-antagonist (n = 20 232), and ACEi monotherapy (n = 20 158). All were free of atrial fibrillation and of predisposing diseases like heart failure, ischaemic heart disease, diabetes mellitus...

Drug Utilisation Pattern and Adverse Events in Patients with Chronic Kidney Disease Undergoing Maintenance Haemodialysis at a Tertiary Care Hospital of Odisha

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P. Ansuman Abhisek

2017-10-01

Full Text Available Introduction: The number of patients receiving renal replacement therapy in the form of dialysis or transplant has been increasing in recent years. Increased frequency of monitoring due to complex therapeutic regimen and inappropriate use of drugs may lead to increased Adverse Events (AEs, hospital stay, cost of treatment as well as increased morbidity and mortality. Aim: To analyse utilisation pattern of drugs and AEs in Chronic Kidney Disease (CKD patients undergoing maintenance haemodialysis. Materials and Methods: This prospective, observational study was conducted in the Department of Pharmacology in collaboration with Department of Nephrology, SCB Medical College and Hospital, Cuttack, from 1st June to 31st December, 2015. Demographic, clinical and medicine details were collected from patients’ case sheet, matched with nursing case records and tabulated in a predesigned case study form. The data were analysed in a descriptive manner using percentage calculation and Spearman’s correlation, multiple logistic regression using trial version SPSS v24. Results: A total number of 115 cases were included in this study. Average number of drugs used, per prescription was 12.8 during the dialysis and non-dialysis days. Most frequently used drugs were antihypertensives, 25% dextrose and heparin (before dialysis and on dialysis days were prescribed to all patients followed by haematinics in 90.43% of the patients and proton pump inhibitors were prescribed in 70.43% of the patients. Among 1472 drugs prescribed, 40.96% of the drugs were prescribed in generic name. It was observed that 72.62% of the prescribed drugs were from National List of Essential Medicine. AEs were observed with varying severity in all the patients. Frequently observed AEs as per the laboratory investigations were hyperphosphataemia, hyponatraemia, metabolic acidosis, hyperkalemia, hypoglycaemia, hypocalcaemia and hypokalemia. AEs were statistically significant with age group

Hypofractionation Regimens for Stereotactic Radiotherapy for Large Brain Tumors

International Nuclear Information System (INIS)

Yuan Jiankui; Wang, Jian Z.; Lo, Simon; Grecula, John C.; Ammirati, Mario; Montebello, Joseph F.; Zhang Hualin; Gupta, Nilendu; Yuh, William T.C.; Mayr, Nina A.

2008-01-01

Purpose: To investigate equivalent regimens for hypofractionated stereotactic radiotherapy (HSRT) for brain tumor treatment and to provide dose-escalation guidance to maximize the tumor control within the normal brain tolerance. Methods and Materials: The linear-quadratic model, including the effect of nonuniform dose distributions, was used to evaluate the HSRT regimens. The α/β ratio was estimated using the Gammaknife stereotactic radiosurgery (GKSRS) and whole-brain radiotherapy experience for large brain tumors. The HSRT regimens were derived using two methods: (1) an equivalent tumor control approach, which matches the whole-brain radiotherapy experience for many fractions and merges it with the GKSRS data for few fractions; and (2) a normal-tissue tolerance approach, which takes advantages of the dose conformity and fractionation of HSRT to approach the maximal dose tolerance of the normal brain. Results: A plausible α/β ratio of 12 Gy for brain tumor and a volume parameter n of 0.23 for normal brain were derived from the GKSRS and whole-brain radiotherapy data. The HSRT prescription regimens for the isoeffect of tumor irradiation were calculated. The normal-brain equivalent uniform dose decreased as the number of fractions increased, because of the advantage of fractionation. The regimens for potential dose escalation of HSRT within the limits of normal-brain tolerance were derived. Conclusions: The designed hypofractionated regimens could be used as a preliminary guide for HSRT dose prescription for large brain tumors to mimic the GKSRS experience and for dose escalation trials. Clinical studies are necessary to further tune the model parameters and validate these regimens

APF530 versus ondansetron, each in a guideline-recommended three-drug regimen, for the prevention of chemotherapy-induced nausea and vomiting due to anthracycline plus cyclophosphamide–based highly emetogenic chemotherapy regimens: a post hoc subgroup analysis of the Phase III randomized MAGIC trial

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Schnadig ID

2017-05-01

Full Text Available Ian D Schnadig1, Richy Agajanian2, Christopher Dakhil3, Nashat Gabrail4, Jeffrey Vacirca5, Charles Taylor6, Sharon Wilks7, Eduardo Braun8, Michael C Mosier9, Robert B Geller10, Lee Schwartzberg11, Nicholas Vogelzang12 1Compass Oncology, US Oncology Research, Tualatin, OR, 2The Oncology Institute of Hope and Innovation, Whittier, CA, 3Cancer Center of Kansas, Wichita, KS, 4Gabrail Cancer Center, Canton, OH, 5North Shore Hematology Oncology, East Setauket, NY, 6Tulsa Cancer Institute, Tulsa, OK, 7Cancer Care Centers of South Texas, San Antonio, TX, 8Michiana Hematology Oncology, Westville, IN, 9Biostatistics, EMB Statistical Solutions, LLC, Overland Park, KS, 10Medical Affairs, Heron Therapeutics, Inc., San Diego, CA, 11West Cancer Center, Germantown, TN, 12Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA Background: APF530, a novel extended-release granisetron injection, was superior to ondansetron in a guideline-recommended three-drug regimen in preventing delayed-phase chemotherapy-induced nausea and vomiting (CINV among patients receiving highly emetogenic chemotherapy (HEC in the double-blind Phase III Modified Absorption of Granisetron In the prevention of CINV (MAGIC trial.Patients and methods: This MAGIC post hoc analysis evaluated CINV prevention efficacy and safety of APF530 versus ondansetron, each with fosaprepitant and dexamethasone, in patient subgroup receiving an anthracycline plus cyclophosphamide (AC regimen. Patients were randomized 1:1 to APF530 500 mg subcutaneously (granisetron 10 mg or ondansetron 0.15 mg/kg intravenously (IV (≤16 mg; stratification was by planned cisplatin ≥50 mg/m2 (yes/no. Patients were to receive fosaprepitant 150 mg IV and dexamethasone 12 mg IV on day 1, then dexamethasone 8 mg orally once daily on day 2 and twice daily on days 3 and 4. Patients were mostly younger females (APF530 arm, mean age 54.1 years, female, 99.3%; ondansetron arm, 53.8 years, female 98.3%. The primary

Analysis of access to hypertensive and diabetic drugs in the Family Health Strategy, State of Pernambuco, Brazil.

Science.gov (United States)

Barreto, Maria Nelly Sobreira de Carvalho; Cesse, Eduarda Ângela Pessoa; Lima, Rodrigo Fonseca; Marinho, Michelly Geórgia da Silva; Specht, Yuri da Silva; de Carvalho, Eduardo Maia Freese; Fontbonne, Annick

2015-01-01

To evaluate the access to drugs for hypertension and diabetes and the direct cost of buying them among users of the Family Health Strategy (FHS) in the state of Pernambuco, Brazil. Population-based, cross-sectional study of a systematic random sample of 785 patients with hypertension and 823 patients with diabetes mellitus who were registered in 208 randomly selected FHS teams in 35 municipalities of the state of Pernambuco. The selected municipalities were classified into three levels with probability proportional to municipality size (LS, large-sized; MS, medium-sized; SS, small-sized). To verify differences between the cities, we used the χ2 test. Pharmacological treatment was used by 91.2% patients with hypertension whereas 85.6% patients with diabetes mellitus used oral antidiabetic drugs (OADs), and 15.4% used insulin. The FHS team itself provided antihypertensive medications to 69.0% patients with hypertension, OADs to 75.0% patients with diabetes mellitus, and insulin treatment to 65.4%. The 36.9% patients with hypertension and 29.8% with diabetes mellitus that had to buy all or part of their medications reported median monthly cost of R$ 18.30, R$ 14.00, and R$ 27.61 for antihypertensive drugs, OADs, and insulin, respectively. It is necessary to increase efforts to ensure access to these drugs in the primary health care network.

Analysis of access to hypertensive and diabetic drugs in the Family Health Strategy, State of Pernambuco, Brazil

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Maria Nelly Sobreira de Carvalho Barreto

2015-06-01

Full Text Available OBJECTIVE: To evaluate the access to drugs for hypertension and diabetes and the direct cost of buying them among users of the Family Health Strategy (FHS in the state of Pernambuco, Brazil.METHODS: Population-based, cross-sectional study of a systematic random sample of 785 patients with hypertension and 823 patients with diabetes mellitus who were registered in 208 randomly selected FHS teams in 35 municipalities of the state of Pernambuco. The selected municipalities were classified into three levels with probability proportional to municipality size (LS, large-sized; MS, medium-sized; SS, small-sized. To verify differences between the cities, we used the χ2 test.RESULTS: Pharmacological treatment was used by 91.2% patients with hypertension whereas 85.6% patients with diabetes mellitus used oral antidiabetic drugs (OADs, and 15.4% used insulin. The FHS team itself provided antihypertensive medications to 69.0% patients with hypertension, OADs to 75.0% patients with diabetes mellitus, and insulin treatment to 65.4%. The 36.9% patients with hypertension and 29.8% with diabetes mellitus that had to buy all or part of their medications reported median monthly cost of R$ 18.30, R$ 14.00, and R$ 27.61 for antihypertensive drugs, OADs, and insulin, respectively.CONCLUSION: It is necessary to increase efforts to ensure access to these drugs in the primary health care network.

Antimicrobial Drugs in Fighting against Antimicrobial Resistance

OpenAIRE

Cheng, Guyue; Dai, Menghong; Ahmed, Saeed; Hao, Haihong; Wang, Xu; Yuan, Zonghui

2016-01-01

The outbreak of antimicrobial resistance, together with the lack of newly developed antimicrobial drugs, represents an alarming signal for both human and animal healthcare worldwide. Selection of rational dosage regimens for traditional antimicrobial drugs based on pharmacokinetic/pharmacodynamic principles as well as development of novel antimicrobials targeting new bacterial targets or resistance mechanisms are key approaches in tackling AMR. In addition to the cellular level resistance (i....

Inappropriate Tuberculosis Treatment Regimens in Chinese Tuberculosis Hospitals

NARCIS (Netherlands)

Xue He, Guang; van den Hof, Susan; van der Werf, Marieke J.; Guo, Hui; Hu, Yuan Lian; Fan, Ji Huan; Zhang, Wei Min; Tostado, Christopher P.; Borgdorff, Martien W.

2011-01-01

This investigation of tuberculosis (TB) treatment regimens in 6 TB hospitals in China showed that only 18% of patients with new cases and 9% of patients with retreatment cases were prescribed standard TB treatment regimens. Adherence to treatment guidelines needs to be improved in TB hospitals to

Understanding drugs in breast cancer through drug sensitivity screening.

Science.gov (United States)

Uhr, Katharina; Prager-van der Smissen, Wendy J C; Heine, Anouk A J; Ozturk, Bahar; Smid, Marcel; Göhlmann, Hinrich W H; Jager, Agnes; Foekens, John A; Martens, John W M

2015-01-01

With substantial numbers of breast tumors showing or acquiring treatment resistance, it is of utmost importance to develop new agents for the treatment of the disease, to know their effectiveness against breast cancer and to understand their relationships with other drugs to best assign the right drug to the right patient. To achieve this goal drug screenings on breast cancer cell lines are a promising approach. In this study a large-scale drug screening of 37 compounds was performed on a panel of 42 breast cancer cell lines representing the main breast cancer subtypes. Clustering, correlation and pathway analyses were used for data analysis. We found that compounds with a related mechanism of action had correlated IC50 values and thus grouped together when the cell lines were hierarchically clustered based on IC50 values. In total we found six clusters of drugs of which five consisted of drugs with related mode of action and one cluster with two drugs not previously connected. In total, 25 correlated and four anti-correlated drug sensitivities were revealed of which only one drug, Sirolimus, showed significantly lower IC50 values in the luminal/ERBB2 breast cancer subtype. We found expected interactions but also discovered new relationships between drugs which might have implications for cancer treatment regimens.

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.

Prophylactic antibiotic regimens in tumour surgery (PARITY)

DEFF Research Database (Denmark)

Petersen, Michael Mørk; Hettwer, Werner H; Grum-Schwensen, Tomas

2015-01-01

-day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours. METHODS: We performed a pilot international multi-centre RCT. We used central randomisation...... to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. RESULTS: We screened 96 patients and enrolled 60 participants......% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all post-operative doses were administered per protocol. CONCLUSIONS: It is feasible to conduct a definitive multi-centre RCT of post...

Assessment of non-standard HIV antiretroviral therapy regimens at ...

African Journals Online (AJOL)

2016-03-06

Mar 6, 2016 ... Most patients were transitioned to standard regimens, ... In cases of first-line regimen treatment failure, ..... tute; National Heart, Lung, and Blood Institute; National. Institute of Dental & Craniofacial Research; National Insti-.

Impedance cardiography – optimization and efficacy evaluation of antihypertensive treatment

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Katarzyna Panasiuk-Kamińska

2016-09-01

Full Text Available Background . Hypertension is a civilization disease which currently affects about 10.5 m people in Poland. The number of patients with diagnosed, untreated hypertension amounts to 18%, and as many as 45% of patients are treated ineffectively whereas only 26% are treated effectively. Impedance cardiography (IC is an important tool both in diagnostics and the treatment of hypertensive patients, particularly in the case of antihypertensive treatment resistance. This method allows for the individualized treatment of each patient on the basis of hemodynamic parameters, monitoring of hypertensive patients in the outpatient care setting, and the assessment of cardiovascular risk factors. Objectives . The aim of the study was to evaluate the efficacy of hypotensive medications in patients with hypertension using impedance cardiography. Material and methods. The study involved 60 hypertensive patients, treated with antihypertensives, who failed to achieve the required blood pressure values. The modification of hypertension therapy was based on EBM (evidence-based medicine and on hemodynamic parameters obtained using impedance cardiography. Results . It was found that high blood pressure therapy based on impedance cardiography parameters has a significant influence on blood pressure reduction compared to EM B-based therapy: below 140/90: 66.8 vs. 55.1% and below 130/80: 23.5 vs. 18.9%. Conclusions . On the basis of this study it was confirmed that impedance cardiography allows for a significant reduction of hypertension and the selection of the most effective therapeutic strategy, providing for the optimization and efficacy of hypertension treatment.

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.

Mathematical modeling of efficacy and safety for anticancer drugs clinical development.

Science.gov (United States)

Lavezzi, Silvia Maria; Borella, Elisa; Carrara, Letizia; De Nicolao, Giuseppe; Magni, Paolo; Poggesi, Italo

2018-01-01

Drug attrition in oncology clinical development is higher than in other therapeutic areas. In this context, pharmacometric modeling represents a useful tool to explore drug efficacy in earlier phases of clinical development, anticipating overall survival using quantitative model-based metrics. Furthermore, modeling approaches can be used to characterize earlier the safety and tolerability profile of drug candidates, and, thus, the risk-benefit ratio and the therapeutic index, supporting the design of optimal treatment regimens and accelerating the whole process of clinical drug development. Areas covered: Herein, the most relevant mathematical models used in clinical anticancer drug development during the last decade are described. Less recent models were considered in the review if they represent a standard for the analysis of certain types of efficacy or safety measures. Expert opinion: Several mathematical models have been proposed to predict overall survival from earlier endpoints and validate their surrogacy in demonstrating drug efficacy in place of overall survival. An increasing number of mathematical models have also been developed to describe the safety findings. Modeling has been extensively used in anticancer drug development to individualize dosing strategies based on patient characteristics, and design optimal dosing regimens balancing efficacy and safety.

Clinical Management of HIV Drug Resistance

Science.gov (United States)

Cortez, Karoll J.; Maldarelli, Frank

2011-01-01

Combination antiretroviral therapy for HIV-1 infection has resulted in profound reductions in viremia and is associated with marked improvements in morbidity and mortality. Therapy is not curative, however, and prolonged therapy is complicated by drug toxicity and the emergence of drug resistance. Management of clinical drug resistance requires in depth evaluation, and includes extensive history, physical examination and laboratory studies. Appropriate use of resistance testing provides valuable information useful in constructing regimens for treatment-experienced individuals with viremia during therapy. This review outlines the emergence of drug resistance in vivo, and describes clinical evaluation and therapeutic options of the individual with rebound viremia during therapy. PMID:21994737

Secondary Prevention Services for Clients Who Are Low Risk in Drug Court: A Conceptual Model

Science.gov (United States)

DeMatteo, David S.; Marlowe, Douglas B.; Festinger, David S.

2006-01-01

The drug court model assumes that most drug offenders are addicts, and that drug use fuels other criminal activity. As a result, drug court clients must satisfy an intensive regimen of treatment and supervisory obligations. However, research suggests that roughly one third of drug court clients do not have a clinically significant substance use…

New dosing strategies for an old antibiotic: pharmacodynamics of front-loaded regimens of colistin at simulated pharmacokinetics in patients with kidney or liver disease.

Science.gov (United States)

Rao, Gauri G; Ly, Neang S; Haas, Curtis E; Garonzik, Samira; Forrest, Alan; Bulitta, Jurgen B; Kelchlin, Pamela A; Holden, Patricia N; Nation, Roger L; Li, Jian; Tsuji, Brian T

2014-01-01

Increasing evidence suggests that colistin monotherapy is suboptimal at currently recommended doses. We hypothesized that front-loading provides an improved dosing strategy for polymyxin antibiotics to maximize killing and minimize total exposure. Here, we utilized an in vitro pharmacodynamic model to examine the impact of front-loaded colistin regimens against a high bacterial density (10(8) CFU/ml) of Pseudomonas aeruginosa. The pharmacokinetics were simulated for patients with hepatic (half-life [t1/2] of 3.2 h) or renal (t1/2 of 14.8 h) disease. Front-loaded regimens (n=5) demonstrated improvement in bacterial killing, with reduced overall free drug areas under the concentration-time curve (fAUC) compared to those with traditional dosing regimens (n=14) with various dosing frequencies (every 12 h [q12h] and q24h). In the renal failure simulations, front-loaded regimens at lower exposures (fAUC of 143 mg · h/liter) obtained killing activity similar to that of traditional regimens (fAUC of 268 mg · h/liter), with an ∼97% reduction in the area under the viable count curve over 48 h. In hepatic failure simulations, front-loaded regimens yielded rapid initial killing by up to 7 log10 within 2 h, but considerable regrowth occurred for both front-loaded and traditional regimens. No regimen eradicated the high bacterial inoculum of P. aeruginosa. The current study, which utilizes an in vitro pharmacodynamic infection model, demonstrates the potential benefits of front-loading strategies for polymyxins simulating differential pharmacokinetics in patients with hepatic and renal failure at a range of doses. Our findings may have important clinical implications, as front-loading polymyxins as a part of a combination regimen may be a viable strategy for aggressive treatment of high-bacterial-burden infections.

Dabigatran - Metabolism, Pharmacologic Properties and Drug Interactions.

Science.gov (United States)

Antonijevic, Nebojsa M; Zivkovic, Ivana D; Jovanovic, Ljubica M; Matic, Dragan M; Kocica, Mladen J; Mrdovic, Igor B; Kanjuh, Vladimir I; Culafic, Milica D

2017-01-01

The superiority of dabigatran has been well proven in the standard dosing regimen in prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) and extended venous thromboembolism (VTE) treatment. Dabigatran, an anticoagulant with a good safety profile, reduces intracranial bleeding in patients with atrial fibrillation and decreases major and clinically relevant non-major bleeding in acute VTE treatment. However, several important clinical issues are not fully covered by currently available directions with regard to dabigatran administration. The prominent one is reflected in the fact that dynamic impairment in renal function due to dehydratation may lead to haemorragic complications on the one hand, while on the other hand glomerular hyperfiltration may be a possible cause of dabigatran subdosing, hence reducing the drug's efficacy. Furthermore, limitations of the Cockcroft-Gault formula, considered a standard equation for assessing the renal function, may imply that other calculations are likely to obtain more accurate estimates of the kidney function in specific patient populations. Method and Conclusions: Although not routinely recommended, a possibility of monitoring dabigatran in special clinical settings adds to optimization of its dosage regimens, timely perioperative care and administration of urgently demanded thrombolytic therapy, therefore significantly improving this drug's safety profile. Despite the fact that dabigatran has fewer reported interactions with drugs, food constituents, and dietary supplements, certain interactions still remain, requiring considerable caution, notably in elderly, high bleeding risk patients, patients with decreased renal function and those on complex drug regimens. Additionally, upon approval of idarucizumab, an antidote to dabigatran solution, hitherto being a major safety concern, has been finally reached, which plays a vital role in life-threatening bleeding and emergency

Drug-drug interactions involving antidepressants: focus on desvenlafaxine.

Science.gov (United States)

Low, Yvette; Setia, Sajita; Lima, Graca

2018-01-01

Psychiatric and physical conditions often coexist, and there is robust evidence that associates the frequency of depression with single and multiple physical conditions. More than half of patients with depression may have at least one chronic physical condition. Therefore, antidepressants are often used in cotherapy with other medications for the management of both psychiatric and chronic physical illnesses. The risk of drug-drug interactions (DDIs) is augmented by complex polypharmacy regimens and extended periods of treatment required, of which possible outcomes range from tolerability issues to lack of efficacy and serious adverse events. Optimal patient outcomes may be achieved through drug selection with minimal potential for DDIs. Desvenlafaxine is a serotonin-norepinephrine reuptake inhibitor approved for the treatment of adults with major depressive disorder. Pharmacokinetic studies of desvenlafaxine have shown a simple metabolic profile unique among antidepressants. This review examines the DDI profiles of antidepressants, particularly desvenlafaxine, in relation to drugs of different therapeutic areas. The summary and comparison of information available is meant to help clinicians in making informed decisions when using desvenlafaxine in patients with depression and comorbid chronic conditions.

Antihypertensive treatment with β-blockade in patients with asymptomatic aortic stenosis and association with cardiovascular events

DEFF Research Database (Denmark)

Bang, Casper N.; Greve, Anders M.; Rossebø, Anne B.

2017-01-01

Background--Patients with aortic stenosis (AS) often have concomitant hypertension. Antihypertensive treatment with a β-blocker (Bbl) is frequently avoided because of fear of depression of left ventricular function. However, it remains unclear whether antihypertensive treatment with a Bbl...... is associated with increased risk of cardiovascular events in patients with asymptomatic mild to moderate AS. Methods and Results--We did a post hoc analysis of 1873 asymptomatic patients with mild to moderate AS and preserved left ventricular ejection fraction in the SEAS (Simvastatin and Ezetimibe in Aortic...... Stenosis) study. Propensity-matched Cox regression and competing risk analyses were used to assess risk ratios for all-cause mortality, sudden cardiac death, and cardiovascular death. A total of 932 (50%) patients received Bbl at baseline. During a median follow-up of 4.3±0.9 years, 545 underwent aortic...

[New drug developments of snake venom polypeptides and progress].

Science.gov (United States)

Fu, Sihai; Feng, Mei; Xiong, Yan

2017-11-28

The value of snake venom polypeptides in clinical application has drawn extensive attention, and the development of snake polypeptides into new drugs with anti-tumor, anti-inflammatory, antithrombotic, analgesic or antihypertensive properties has become the recent research hotspot. With the rapid development of molecular biology and biotechnology, the mechanisms of snake venom polypeptides are also gradually clarified. Numerous studies have demonstrated that snake venom polypeptides exert their pharmacological effects by regulating ion channels, cell proliferation, apoptosis, intracellular signaling pathway, and expression of cytokine as well as binding to relevant active sites or receptors.

Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects.

Science.gov (United States)

Shi, Nianmin; Zhang, Yibin; Zheng, Huizhen; Zhu, Zhenggang; Wang, Dingming; Li, Sihai; Li, Yuhua; Yang, Liqing; Zhang, Junnan; Bai, Yunhua; Lu, Qiang; Zhang, Zheng; Luo, Fengji; Yu, Chun; Li, Li

2017-06-03

To compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, Zagreb or Essen regimen. Serum samples were collected before vaccination and on days 7, 14, 42, 180 and 365 post vaccination. Solicited adverse events were recorded for 7 d following each vaccine dose, and unsolicited adverse events throughout the entire study period. This study was registered with ClinicalTrials.gov (NCT01821911 and NCT01827917). No serious adverse events were reported. Although Zagreb regimen had a higher incidence of adverse reactions than Essen regimen at the first and second injection, the incidence was similar at the third and fourth injection between these 2 groups as well. At day 42, 100% subjects developed adequate rabies virus neutralizing antibody concentrations (≥ 0.5IU/ml) for both regimens. At days 180 and 365, the antibody level decreased dramatically, however, the percentage of subjects with adequate antibody concentrations still remained high (above 75% and 50% respectively). None of confirmed rabies virus exposured subjects had rabies one year later, and percentage of subjects with adequate antibody concentrations reached 100% at days 14 and 42. Rabies post-exposure prophylaxis vaccination with PVRV following a Zagreb regimen had a similar safety, immunogenicity and long-term effect to the Essen regimen in China.

Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials.

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Phillips, Patrick P J; Mendel, Carl M; Burger, Divan A; Crook, Angela M; Crook, Angela; Nunn, Andrew J; Dawson, Rodney; Diacon, Andreas H; Gillespie, Stephen H

2016-02-04

Despite recent increased clinical trials activity, no regimen has proved able to replace the standard 6-month regimen for drug-sensitive tuberculosis. Understanding the relationship between microbiological markers measured during treatment and long-term clinical outcomes is critical to evaluate their usefulness for decision-making for both individual patient care and for advancing novel regimens into time-consuming and expensive pivotal phase III trials. Using data from the randomized controlled phase III trial REMoxTB, we evaluated sputum-based markers of speed of clearance of bacilli: time to smear negative status; time to culture negative status on LJ or in MGIT; daily rate of change of log10(TTP) to day 56; and smear or culture results at weeks 6, 8 or 12; as individual- and trial-level surrogate endpoints for long-term clinical outcome. Time to culture negative status on LJ or in MGIT, time to smear negative status and daily rate of change in log10(TTP) were each independent predictors of clinical outcome, adjusted for treatment (p limited role in decision-making for advancing regimens into phase III trials or in predicting the outcome of treatment for individual patients. REMoxTB ClinicalTrials.gov number: NCT00864383.

Antioxidant and Antihypertensive Potential of Protein Fractions from Flour and Milk Substitutes from Canary Seeds (Phalaris canariensis L.).

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Valverde, María Elena; Orona-Tamayo, Domancar; Nieto-Rendón, Blanca; Paredes-López, Octavio

2017-03-01

Canary seed (Phalaris canariensis) is used to feed birds but it has been recently considered a promising cereal with nutraceutical potential for humans. The aim of this work was to analyze the protein fractions from canary seed flour and from milk substitutes (prepared by soaking the seeds in water 12 and 24 h), and to evaluate antioxidant and antihypertensive capacity of peptides obtained after in vitro digestion. Prolamins were the major protein fraction, followed by glutelins. After digestion, albumins and prolamins fractions from milks presented higher levels of peptides than flour, globulins showed more peptides in flour and glutelins were found in similar concentrations in all samples; 24 h milk prolamins had the highest concentration of peptides. Purification by high performance liquid chromatography (HPLC), sequencing of peptides, in vitro antioxidant ABTS (2,2'-azino-bis, 3-ethylbenzothiazoline-6-sulphonic acid) and DPPH (2,2-diphenyl-1-picrylhydrazyl) assays, and antihypertensive capacity (angiotensin converting enzyme (ACE) assay), indicated that peptides from canary seed prolamins were the most efficient compounds with antioxidant and antihypertensive activity. Canary seeds may be considered an accessible and cheap source to prepare milk substitutes with high contents of bioactive peptides with remarkable functional properties to promote better human health and healthy ageing.

Development of antibiotic regimens using graph based evolutionary algorithms.

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Corns, Steven M; Ashlock, Daniel A; Bryden, Kenneth M

2013-12-01

This paper examines the use of evolutionary algorithms in the development of antibiotic regimens given to production animals. A model is constructed that combines the lifespan of the animal and the bacteria living in the animal's gastro-intestinal tract from the early finishing stage until the animal reaches market weight. This model is used as the fitness evaluation for a set of graph based evolutionary algorithms to assess the impact of diversity control on the evolving antibiotic regimens. The graph based evolutionary algorithms have two objectives: to find an antibiotic treatment regimen that maintains the weight gain and health benefits of antibiotic use and to reduce the risk of spreading antibiotic resistant bacteria. This study examines different regimens of tylosin phosphate use on bacteria populations divided into Gram positive and Gram negative types, with a focus on Campylobacter spp. Treatment regimens were found that provided decreased antibiotic resistance relative to conventional methods while providing nearly the same benefits as conventional antibiotic regimes. By using a graph to control the information flow in the evolutionary algorithm, a variety of solutions along the Pareto front can be found automatically for this and other multi-objective problems. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

TH-302, a hypoxia-activated prodrug with broad in vivo preclinical combination therapy efficacy: optimization of dosing regimens and schedules.

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Liu, Qian; Sun, Jessica D; Wang, Jingli; Ahluwalia, Dharmendra; Baker, Amanda F; Cranmer, Lee D; Ferraro, Damien; Wang, Yan; Duan, Jian-Xin; Ammons, W Steve; Curd, John G; Matteucci, Mark D; Hart, Charles P

2012-06-01

Subregional hypoxia is a common feature of tumors and is recognized as a limiting factor for the success of radiotherapy and chemotherapy. TH-302, a hypoxia-activated prodrug selectively targeting hypoxic regions of solid tumors, delivers a cytotoxic warhead to the tumor, while maintaining relatively low systemic toxicity. The antitumor activity, different dosing sequences, and dosing regimens of TH-302 in combination with commonly used conventional chemotherapeutics were investigated in human tumor xenograft models. Seven chemotherapeutic drugs (docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide) were tested in combination with TH-302 in eleven human xenograft models, including non-small cell lung cancer (NSCLC), colon cancer, prostate cancer, fibrosarcoma, melanoma, and pancreatic cancer. The antitumor activity of docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide was increased when combined with TH-302 in nine out of eleven models tested. Administration of TH-302 2-8 h prior to the other chemotherapeutics yielded superior efficacy versus other sequences tested. Simultaneous administration of TH-302 and chemotherapeutics increased toxicity versus schedules with dosing separations. In a dosing optimization study, TH-302 administered daily at 50 mg/kg intraperitoneally for 5 days per week in the H460 NSCLC model showed the optimal response with minimal toxicity. TH-302 enhances the activity of a wide range of conventional anti-neoplastic agents in a broad panel of in vivo xenograft models. These data highlight in vivo effects of schedule and order of drug administration in regimen efficacy and toxicity and have relevance to the design of human regimens incorporating TH-302.

Effectiveness of Ritonavir-Boosted Protease Inhibitor Monotherapy in Clinical Practice Even with Previous Virological Failures to Protease Inhibitor-Based Regimens.

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Luis F López-Cortés

Full Text Available Significant controversy still exists about ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv as a simplification strategy that is used up to now to treat patients that have not experienced previous virological failure (VF while on protease inhibitor (PI -based regimens. We have evaluated the effectiveness of two mtPI/rtv regimens in an actual clinical practice setting, including patients that had experienced previous VF with PI-based regimens.This retrospective study analyzed 1060 HIV-infected patients with undetectable viremia that were switched to lopinavir/ritonavir or darunavir/ritonavir monotherapy. In cases in which the patient had previously experienced VF while on a PI-based regimen, the lack of major HIV protease resistance mutations to lopinavir or darunavir, respectively, was mandatory. The primary endpoint of this study was the percentage of participants with virological suppression after 96 weeks according to intention-to-treat analysis (non-complete/missing = failure.A total of 1060 patients were analyzed, including 205 with previous VF while on PI-based regimens, 90 of whom were on complex therapies due to extensive resistance. The rates of treatment effectiveness (intention-to-treat analysis and virological efficacy (on-treatment analysis at week 96 were 79.3% (CI95, 76.8-81.8 and 91.5% (CI95, 89.6-93.4, respectively. No relationships were found between VF and earlier VF while on PI-based regimens, the presence of major or minor protease resistance mutations, the previous time on viral suppression, CD4+ T-cell nadir, and HCV-coinfection. Genotypic resistance tests were available in 49 out of the 74 patients with VFs and only four patients presented new major protease resistance mutations.Switching to mtPI/rtv achieves sustained virological control in most patients, even in those with previous VF on PI-based regimens as long as no major resistance mutations are present for the administered drug.

Carotid angiodysplasia complicated by the use of anti-hypertensive drugs during pregnancy: a case report

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Tavares Beatriz

2011-08-01

highlights the need for constant supervision of blood pressure levels during the use of anti-hypertensive medications.

Characteristics of HIV antiretroviral regimen and treatment adherence

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Vera Lúcia da Silveira

Full Text Available The relationship between characteristics of HIV antiretroviral regimens and treatment adherence was studied in adolescent and adult patients who underwent antiretroviral therapy from January 1998 to September 2000, at the Service for Specialized Assistance in Pelotas. The patients were interviewed on two occasions, and the use of antiretrovirals during the previous 48 hours was investigated by a self-report. Adherence was defined as use of 95% or more of the prescribed medication. Social-demographic variables were collected through direct questionnaires. The antiretroviral regimen and clinical data were copied from the patients' records. Associations between the independent variables and adherence were analyzed by means of logistic regression. The multivariate analysis included characteristics of the antiretroviral regimens, social-demographic variables, as well as perception of negative effects, negative physiological states, and adverse effects of the treatment. Among the 224 selected patients, 194 participated in our study. Their ages varied from 17 to 67 years; most patients were men, with few years of schooling and a low family income. Only 49% adhered to the treatment. Adherence to treatment regimens was reduced when more daily doses were indicated: three to four doses (odds ratio of adherence to treatment (OR=0.47, 95% confidence interval (CI 0.22-1.01 and five to six (OR=0.24, 95% CI 0.09-0.62; two or more doses taken in a fasting state (OR=0.59, 95% CI 0.11-0.68, and for patients who reported adverse effects to the treatment (OR=0.39, 95% CI 0.19-0.77. Most of the regimens with more than two daily doses of medication included at least one dose apart from mealtimes. The results suggest that, if possible, regimens with a reduced number of doses should be chosen, with no compulsory fasting, and with few adverse effects. Strategies to minimize these effects should be discussed with the patients.

Virological failure of staggered and simultaneous treatment interruption in HIV patients who began Efavirenz-based regimens after allergic reactions to nevirapine

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Siripassorn Krittaecho

2013-01-01

Full Text Available Abstract Objective The objective of this work was to study the virological outcomes associated with two different types of treatment interruption strategies in patients with allergic reactions to nevirapine (NVP. We compared the virological outcomes of (1 HIV-1-infected patients who discontinued an initial NVP-based regimen because of cutaneous allergic reactions to NVP; different types of interruption strategies were used, and second-line regimen was based on efavirenz (EFV; and (2 HIV-1-infected patients who began an EFV-based regimen as a first-line therapy (controls. Methods This retrospective cohort included patients who began an EFV-based regimen, between January 2002 and December 2008, as either an initial regimen or as a subsequent regimen after resolving a cutaneous allergic reaction against an initial NVP-based regimen. The study ended in March 2010. The primary outcome was virological failure, which was defined as either (a two consecutive plasma HIV-1 RNA levels >400 copies/mL or (b a plasma HIV-1 RNA level >1,000 copies/mL plus any genotypic resistance mutation. Results A total of 559 patients were stratified into three groups: (a Simultaneous Interruption, in which the subjects simultaneously discontinued all the drugs in an NVP-based regimen following an allergic reaction (n=161; (b Staggered Interruption, in which the subjects discontinued NVP treatment while continuing nucleoside reverse transcriptase inhibitor (NRTI backbone therapy for a median of 7 days (n=82; and (c Control, in which the subjects were naïve to antiretroviral therapy (n=316. The overall median follow-up time was 43 months. Incidence of virological failure in Simultaneous Interruption was 12.9 cases per 1,000 person-years, which trended toward being higher than the incidences in Staggered Interruption (5.4 and Control (6.6. However, differences were not statistically significant. Conclusions Among the patients who had an acute allergic reaction to first

Effects and Mechanisms of Radiofrequency Ablation of Renal Sympathetic Nerve on Anti-Hypertension in Canine

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Wei Chen

Full Text Available Abstract Background: Radiofrequency ablation of renal sympathetic nerve (RDN shows effective BP reduction in hypertensive patients while the specific mechanisms remain unclear. Objective: We hypothesized that abnormal levels of norepinephrine (NE and changes in NE-related enzymes and angiotensinconverting enzyme 2 (ACE2, angiotensin (Ang-(1-7 and Mas receptor mediate the anti-hypertensive effects of RDN. Methods: Mean values of systolic blood pressure (SBP, diastolic blood pressure (DBP and mean arterial pressure (MAP were assessed at baseline and follow-up. Plasma and renal norepinephrine (NE concentrations were determined using highperformance liquid chromatography with electrochemical detection, and levels of NE-related enzyme and ACE2-Ang(1-7- Mas were measured using real time PCR, Western blot and immunohistochemistry or Elisa in a hypertensive canine model fed with high-fat diet and treated with RDN. The parameters were also determined in a sham group treated with renal arteriography and a control group fed with normal diet. Results: RDN decreased SBP, DBP, MAP, plasma and renal NE. Compared with the sham group, renal tyrosine hydroxylase (TH expression was lower and renalase expression was higher in the RDN group. Compared with the control group, renal TH and catechol-o-methyl transferase (COMT were higher and renalase was lower in the sham group. Moreover, renal ACE2, Ang-(1-7 and Mas levels of the RDN group were higher than those of the sham group, which were lower than those of the control group. Conclusion: RDN shows anti-hypertensive effect with reduced NE and activation of ACE2-Ang(1-7-Mas, indicating that it may contribute to the anti-hypertensive effect of RDN.