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Sample records for tolerated antihypertensive drug

  1. Efficacy and tolerability of antihypertensive drugs in diabetic and nondiabetic patients

    Directory of Open Access Journals (Sweden)

    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

  2. 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.

  3. [Classical antihypertensive drugs: diuretics].

    Science.gov (United States)

    Nagy, Viktor László

    2017-03-01

    The diuretics are essential medicaments of antihypertensive therapy. They reduce blood pressure and cardiovascular events optimally. With increasing doses of thiazides and thiazide analogs do not come further powerful effect of reducing blood pressure or cardiovascular mortality and morbidity, but clearly elevate the side effects. Because of it, the minimum effective dose level and the fixed-dose combination therapy should be preferred. The use these drugs leads to especially positive outcome in elder patients, isolated systolic hypertension, heart failure, after stroke and in black population. Loop diuretics as antihypertensive therapy can be used only by renal impairment. The use of aldosterone antagonists can have a good effect not only on heart failure but also on prevention of atrial fibrillation. Furthermore, using it in a combination therapy with thiazides, it reduces the risk of hypokalemia. Therefore, the diuretic treatment in hypertension is flourishing again. Orv. Hetil., 2017, 158(11), 403-408.

  4. Cost Evaluation of Commonly Prescribed Antihypertensive Drugs ...

    African Journals Online (AJOL)

    It was also concluded that generic prescription should be encouraged among prescribers to lessen the financial burden of patients because drugs marketed under generic names are usually cheaper than those with brand names. Key words: Brand, Generic,Prescription, Antihypertensives,Cost. [Nig. Jnl Health & Biomedical ...

  5. Prescribing Patterns and Cost of Antihypertensive Drugs in Private ...

    African Journals Online (AJOL)

    Nx 6110

    Antihypertensive agents are used to prevent morbidity and mortality related to hypertension. Prescribing patterns and the cost of some antihypertensive were studied for 600 patients attending medical clinics in four private hospitals in Dar es. Salaam using the WHO drug use indicator forms. The average number of drugs ...

  6. Use of antihypertensive drugs during pregnancy in the Netherlands

    NARCIS (Netherlands)

    De Jong, Josta; Bos, Jens H.J.; Schuiling-Veninga, Catharina C.M.; De Jong-Van Den Berg, Lolkje T.W.

    2016-01-01

    Background: Antihypertensive drugs are used during pregnancy for both chronic hypertension and gestational hypertension. Methyldopa, labetalol and nifedipine are considered safe for the fetus during pregnancy and are therefore recommended in the Dutch guidelines. Objectives: To determine how often

  7. Drug Therapy Problems in Patients on Antihypertensives and ...

    African Journals Online (AJOL)

    Drug therapy problems (DTPs), with the associated risks inherent in antihypertensive and antidiabetic therapy require utmost attention. This present study was aimed at assessing the DTPs observed in the management of hypertension and diabetes mellitus (DM) in two tertiary health facilities in Niger Delta region. In this ...

  8. PHARMACOECONOMIC ANALYSIS OF ANTIHYPERTENSIVE DRUG COMBINATIONS USE

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    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.

  9. [Generic drugs and the consumption trends of antihypertensives in Morocco].

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    Berrada El Azizi, Ghizlane; Ahid, Samir; Ghanname, Imane; Ghannam, Imane; Belaiche, Abdelmajid; Hassar, Mohammed; Cherrah, Yahia

    2013-01-01

    To evaluate the evolution of consumption of antihypertensive drugs generic among 1991-2010, to assess the impacts after the institution of Mandatory Health Insurance and the marketing of generic drugs. We used sales data from the Moroccan subsidiary of IMS Health Intercontinental Marketing Service. Consumption of generic antihypertensive drugs increased from 0.08 to 10.65 DDD/1 000 inhabitants/day between 1991 and 2010. In 2010, generic of the calcium channel blockers (CCBs) represented 4.08 DDD/1 000 inhabitants/day (82.09%), followed by angiotensin converting enzyme inhibitors (ACEI) by 2.40 DDD/1 000 inhabitants/day (48.29%). The generics market of CCBs is the most dominant and represented in 2010, 79.21% in volume and 62.58% in value. In developing countries like Morocco, the generic drug is a key element for access to treatment especially for the poor population. © 2013 Société Française de Pharmacologie et de Thérapeutique.

  10. Translating data on antihypertensive drugs into clinical practice.

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    Weber, M A

    1998-06-01

    Two problems in the treatment of hypertension continue to be largely unsolved. The first, and more simple, is our inability to adequately control blood pressure in the majority of hypertensive patients. This not only reflects the difficulty of retaining patients in effective treatment programs, but also of convincing physicians to strive for optimal blood pressure levels. There is a continuing need for new antihypertensive drugs and combinations to help accomplish these goals. The second major problem is that the major clinical endpoints, including coronary events and renal failure, have not been adequately reduced by traditional therapies. Standard regimens, particularly those including diuretics, have protected against strokes and heart failure. Our improved understanding of vascular biology in hypertension has directed interest to the mechanisms in hypertensive patients that might accelerate atherosclerosis and vascular events in these individuals. This involves addressing the concomitant metabolic risk factors that comprise the "Hypertension Syndrome," and, perhaps of equal importance, finding therapies that directly inhibit unwanted types of growth and proliferative activities within the walls of critical arteries. Many substances within the endothelium and the vascular wall may participate as initiators or mediators of pathology, but most information thus far has focused on the renin-angiotensin system. Angiotensin converting enzyme inhibitors (and potentially angiotensin receptor blockers) have provided coronary and renal protection in various cardiovascular conditions, though not yet in formal hypertension trials. Calcium channel blockers have also shown promise, including recent stroke and cardiovascular benefits in patients with isolated systolic hypertension, but, again, definitive coronary data in hypertension are awaited. Unless concomitant conditions mandate the selection of a particular antihypertensive drug class, physicians currently have a dilemma

  11. The efficacy of antihypertensive drugs in chronic intermittent hypoxia conditions

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    Diogo, Lucilia N.; Monteiro, Emília C.

    2014-01-01

    Sleep apnea/hypopnea disorders include centrally originated diseases and obstructive sleep apnea (OSA). This last condition is renowned as a frequent secondary cause of hypertension (HT). The mechanisms involved in the pathogenesis of HT can be summarized in relation to two main pathways: sympathetic nervous system stimulation mediated mainly by activation of carotid body (CB) chemoreflexes and/or asphyxia, and, by no means the least important, the systemic effects of chronic intermittent hypoxia (CIH). The use of animal models has revealed that CIH is the critical stimulus underlying sympathetic activity and hypertension, and that this effect requires the presence of functional arterial chemoreceptors, which are hyperactive in CIH. These models of CIH mimic the HT observed in humans and allow the study of CIH independently without the mechanical obstruction component. The effect of continuous positive airway pressure (CPAP), the gold standard treatment for OSA patients, to reduce blood pressure seems to be modest and concomitant antihypertensive therapy is still required. We focus this review on the efficacy of pharmacological interventions to revert HT associated with CIH conditions in both animal models and humans. First, we explore the experimental animal models, developed to mimic HT related to CIH, which have been used to investigate the effect of antihypertensive drugs (AHDs). Second, we review what is known about drug efficacy to reverse HT induced by CIH in animals. Moreover, findings in humans with OSA are cited to demonstrate the lack of strong evidence for the establishment of a first-line antihypertensive regimen for these patients. Indeed, specific therapeutic guidelines for the pharmacological treatment of HT in these patients are still lacking. Finally, we discuss the future perspectives concerning the non-pharmacological and pharmacological management of this particular type of HT. PMID:25295010

  12. Opportunities for Web-based Drug Repositioning: Searching for Potential Antihypertensive Agents with Hypotension Adverse Events.

    Science.gov (United States)

    Wang, Kejian; Wan, Mei; Wang, Rui-Sheng; Weng, Zuquan

    2016-04-01

    Drug repositioning refers to the process of developing new indications for existing drugs. As a phenotypic indicator of drug response in humans, clinical side effects may provide straightforward signals and unique opportunities for drug repositioning. We aimed to identify drugs frequently associated with hypotension adverse reactions (ie, the opposite condition of hypertension), which could be potential candidates as antihypertensive agents. We systematically searched the electronic records of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) through the openFDA platform to assess the association between hypotension incidence and antihypertensive therapeutic effect regarding a list of 683 drugs. Statistical analysis of FAERS data demonstrated that those drugs frequently co-occurring with hypotension events were more likely to have antihypertensive activity. Ranked by the statistical significance of frequent hypotension reporting, the well-known antihypertensive drugs were effectively distinguished from others (with an area under the receiver operating characteristic curve > 0.80 and a normalized discounted cumulative gain of 0.77). In addition, we found a series of antihypertensive agents (particularly drugs originally developed for treating nervous system diseases) among the drugs with top significant reporting, suggesting the good potential of Web-based and data-driven drug repositioning. We found several candidate agents among the hypotension-related drugs on our list that may be redirected for lowering blood pressure. More important, we showed that a pharmacovigilance system could alternatively be used to identify antihypertensive agents and sustainably create opportunities for drug repositioning.

  13. 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 ...

  14. 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.

  15. 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

  16. Prevalence of the use of antihypertensive medications in Greenland: a study of quality of care amongst patients treated with antihypertensive drugs

    DEFF Research Database (Denmark)

    Bundgaard, M.; Jarbol, D. E.; Paulsen, M. S.

    2012-01-01

    in January 2011. Only patients aged 20 or above were included. The age-and gender-specific prevalence of patients in antihypertensive treatment was calculated using the population as it was 1 January 2010 in Greenland as background population. A subsample consisting of patients in antihypertensive treatment...... and blood pressure level, respectively. Results. The total number of patients in treatment with antihypertensive drugs was 4,462 (1,998 males and 2,464 females) corresponding to a prevalence of 11.4% (4,462/39,231). The prevalence was higher among females than among males. The prevalence increased with age...... and differed among the 5 health regions. The percentage of patients in antihypertensive treatment with minimum 1 follow-up visit within 1 year (blood pressure measured and registered in a health clinic) was only 77.7%. Some 45% of patients in antihypertensive treatment achieved blood pressure below 140/90 mm...

  17. 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....

  18. Do advertisements for antihypertensive drugs in Australia promote quality prescribing? A cross-sectional study

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    Spurling Geoffrey K

    2008-05-01

    Full Text Available Abstract Background Antihypertensive medications are widely prescribed by doctors and heavily promoted by the pharmaceutical industry. Despite strong evidence of the effectiveness and cost-effectiveness of thiazide diuretics, trends in both promotion and prescription of antihypertensive drugs favour newer, less cost-effective agents. Observational evidence shows correlations between exposure to pharmaceutical promotion and less ideal prescribing. Our study therefore aimed to determine whether print advertisements for antihypertensive medications promote quality prescribing in hypertension. Methods We performed a cross-sectional study of 113 advertisements for antihypertensive drugs from 4 general practice-oriented Australian medical publications in 2004. Advertisements were evaluated using a quality checklist based on a review of hypertension management guidelines. Main outcome measures included: frequency with which antihypertensive classes were advertised, promotion of thiazide class drugs as first line agents, use of statistical claims in advertisements, mention of harms and prices in the advertisements, promotion of assessment and treatment of cardiovascular risk, promotion of lifestyle modification, and targeting of particular patient subgroups. Results Thiazides were the most frequently advertised drug class (48.7% of advertisements, but were largely promoted in combination preparations. The only thiazide advertised as a single agent was the most expensive, indapamide. No advertisement specifically promoted any thiazide as a better first-line drug. Statistics in the advertisements tended to be expressed in relative rather than absolute terms. Drug costs were often reported, but without cost comparisons between drugs. Adverse effects were usually reported but largely confined to the advertisements' small print. Other than mentioning drug interactions with alcohol and salt, no advertisements promoted lifestyle modification. Few

  19. Do advertisements for antihypertensive drugs in Australia promote quality prescribing? A cross-sectional study.

    Science.gov (United States)

    Montgomery, Brett D; Mansfield, Peter R; Spurling, Geoffrey K; Ward, Alison M

    2008-05-20

    Antihypertensive medications are widely prescribed by doctors and heavily promoted by the pharmaceutical industry. Despite strong evidence of the effectiveness and cost-effectiveness of thiazide diuretics, trends in both promotion and prescription of antihypertensive drugs favour newer, less cost-effective agents. Observational evidence shows correlations between exposure to pharmaceutical promotion and less ideal prescribing. Our study therefore aimed to determine whether print advertisements for antihypertensive medications promote quality prescribing in hypertension. We performed a cross-sectional study of 113 advertisements for antihypertensive drugs from 4 general practice-oriented Australian medical publications in 2004. Advertisements were evaluated using a quality checklist based on a review of hypertension management guidelines. Main outcome measures included: frequency with which antihypertensive classes were advertised, promotion of thiazide class drugs as first line agents, use of statistical claims in advertisements, mention of harms and prices in the advertisements, promotion of assessment and treatment of cardiovascular risk, promotion of lifestyle modification, and targeting of particular patient subgroups. Thiazides were the most frequently advertised drug class (48.7% of advertisements), but were largely promoted in combination preparations. The only thiazide advertised as a single agent was the most expensive, indapamide. No advertisement specifically promoted any thiazide as a better first-line drug. Statistics in the advertisements tended to be expressed in relative rather than absolute terms. Drug costs were often reported, but without cost comparisons between drugs. Adverse effects were usually reported but largely confined to the advertisements' small print. Other than mentioning drug interactions with alcohol and salt, no advertisements promoted lifestyle modification. Few advertisements (2.7%) promoted the assessment of cardiovascular risk

  20. 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.

  1. Prescribing patterns of antihypertensive drugs in geriatric population in tertiary care hospital

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    Renoy Philip

    2016-03-01

    Full Text Available Hypertension is one of the major chronic diseases with high mortality and morbidity in the today’s world. Present study was to assess the prescribing pattern of antihypertensive medications in geriatric population suffering mainly from hypertension with or without co morbidities like Diabetes Mellitus (DM. A prospective observational study was carried out for a period of six months in an in-patient general medicine department. Elderly patients who have been diagnosed with pure hypertension as per JNC 7 guidelines and hypertension with co- morbid condition like diabetes mellitus and patients receiving or prescribed with antihypertensive drugs were included. A total of 150 prescriptions were analyzed. The present study revealed that there were 93 patients with pure Hypertension and 57 patients with co morbid conditions like Diabetes Mellitus (DM. Among antihypertensive drugs in pure hypertensive cases, 53.76% of cases were prescribed with monotherapy, followed by 46.23% by combination therapy. The commonly prescribed antihypertensive monotherapy is calcium channel blockers. The most commonly prescribed combination therapy in severe cases was angiotensin receptor blockers with diuretics. This prescribing pattern of antihypertensives was as per Joint National Committee-7report on hypertension. In case of geriatric patients suffering from hypertension with Type 2 diabetes mellitus, most commonly prescribed antihypertensive as monotherapy was found to be amlodipine and combination therapy was telmisartan + hydrochlorothiazide.

  2. Baseline Antihypertensive Drug Count and Patient Response to Hypertension Medication Management.

    Science.gov (United States)

    Crowley, Matthew J; Olsen, Maren K; Woolson, Sandra L; King, Heather A; Oddone, Eugene Z; Bosworth, Hayden B

    2016-04-01

    Telemedicine-based medication management improves hypertension control, but has been evaluated primarily in patients with low antihypertensive drug counts. Its impact on patients taking three or more antihypertensive agents is not well-established. To address this evidence gap, the authors conducted an exploratory analysis of an 18-month, 591-patient trial of telemedicine-based hypertension medication management. Using general linear models, the effect of medication management on blood pressure for patients taking two or fewer antihypertensive agents at study baseline vs those taking three or more was compared. While patients taking two or fewer antihypertensive agents had a significant reduction in systolic blood pressure with medication management, those taking three or more had no such response. The between-subgroup effect difference was statistically significant at 6 months (-6.4 mm Hg [95% confidence interval, -12.2 to -0.6]) and near significant at 18 months (-6.0 mm Hg [95% confidence interval, -12.2 to 0.2]). These findings suggest that baseline antihypertensive drug count may impact how patients respond to hypertension medication management and emphasize the need to study management strategies specifically in patients taking three or more antihypertensive medications. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  3. 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.

  4. Change in antihypertensive drug prescribing after guideline implementation: a controlled before and after study

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    Helin-Salmivaara Arja

    2011-08-01

    Full Text Available Abstract Background Antihypertensive drug choices and treatment levels are not in accordance with the existing guidelines. We aimed to assess the impact of a guideline implementation intervention on antihypertensive drug prescribing. Methods In this controlled before and after study, the effects of a multifaceted (education, audit and feedback, local care pathway quality programme was evaluated. The intervention was carried out in a health centre between 2002 and 2003. From each health care unit (n = 31, a doctor-nurse pair was trained to act as peer facilitators in the intervention. All antihypertensive drugs prescribed by 25 facilitator general practitioners (intervention GPs and 53 control GPs were retrieved from the nationwide Prescription Register for three-month periods in 2001 and 2003. The proportions of patients receiving specific antihypertensive drugs and multiple antihypertensive drugs were measured before and after the intervention for three subgroups of hypertension patients: hypertension only, with coronary heart disease, and with diabetes. Results In all subgroups, the use of multiple concurrent medications increased. For intervention patients with hypertension only, the odds ratio (OR was 1.12 (95% CI 0.99, 1.25; p = 0.06 and for controls 1.13 (1.05, 1.21; p = 0.002. We observed no statistically significant differences in the change in the prescribing of specific antihypertensive agents between the intervention and control groups. The use of agents acting on the renin-angiotensin-aldosterone system increased in all subgroups (hypertension only intervention patients OR 1.19 (1.06, 1.34; p = 0.004 and controls OR 1.24 (1.15, 1.34; p Conclusions A multifaceted guideline implementation intervention does not necessarily lead to significant changes in prescribing performance. Rigorous planning of the interventions and quality projects and their evaluation are essential.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. Drug-Drug Multicomponent Solid Forms: Cocrystal, Coamorphous and Eutectic of Three Poorly Soluble Antihypertensive Drugs Using Mechanochemical Approach.

    Science.gov (United States)

    Haneef, Jamshed; Chadha, Renu

    2017-08-01

    The present study deals with the application of mechanochemical approach for the preparation of drug-drug multicomponent solid forms of three poorly soluble antihypertensive drugs (telmisartan, irbesartan and hydrochlorothiazide) using atenolol as a coformer. The resultant solid forms comprise of cocrystal (telmisartan-atenolol), coamorphous (irbesartan-atenolol) and eutectic (hydrochlorothiazide-atenolol). The study emphasizes that solid-state transformation of drug molecules into new forms is a result of the change in structural patterns, diminishing of dimers and creating new facile hydrogen bonding network based on structural resemblance. The propensity for heteromeric or homomeric interaction between two different drugs resulted into diverse solid forms (cocrystal/coamorphous/eutectics) and become one of the interesting aspects of this research work. Evaluation of these solid forms revealed an increase in solubility and dissolution leading to better antihypertensive activity in deoxycorticosterone acetate (DOCA) salt-induced animal model. Thus, development of these drug-drug multicomponent solid forms is a promising and viable approach to addressing the issue of poor solubility and could be of considerable interest in dual drug therapy for the treatment of hypertension.

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

    OpenAIRE

    Beune, E.J.A.J.; Haafkens, J.A.; Agyemang, C.; Schuster, J.S.; Willems, D.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 patients without comorbidity who were prescribed antihypertensives. RESULTS: Patients in all the ethnic groups actively decided how to manage their prescribed antihypertensive regimens. In all the ...

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

    Directory of Open Access Journals (Sweden)

    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

  12. [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.

  13. 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 ...

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  2. 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.

  3. 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.

  4. 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

  5. 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.

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

    Science.gov (United States)

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

    2008-04-01

    To explore and compare how Ghanaian, African-Surinamese (Surinamese), and White-Dutch patients perceive and manage antihypertensive drug treatment in Amsterdam, the Netherlands. Qualitative study was conducted using detailed interviews with a purposive sample of 46 hypertensive patients without comorbidity who were prescribed antihypertensives. Patients in all the ethnic groups actively decided how to manage their prescribed antihypertensive regimens. In all the groups, confidence in the doctor and beneficial effects of medication were reasons for taking prescribed antihypertensive dosage. Particularly, ethnic-minority patients reported lowering or leaving off the prescribed medication dosage. Explanations for altering prescribed dosage comprised disliking chemical medications, fear of side effects and preference for alternative treatment. Surinamese and Ghanaian men also worried about the negative effects of antihypertensives on their sexual performance. Some Ghanaians mentioned fear of addiction or lack of money as explanations for altering prescribed dosage. Surinamese and Ghanaians often discontinued medication when visiting their homeland. Some respondents from all ethnic groups preferred natural treatments although treatment type varied. Patients' explanations for their decisions regarding the use of antihypertensives are often influenced by sociocultural issues and in ethnic-minority groups also by migration-related issues. Self-alteration of prescribed medication among Surinamese and Ghanaians may contribute to the low blood pressure (BP) control rate and high rate of malignant hypertension reported among these populations in the Netherlands. This study provides new information, which can help clinicians to understand how patients of diverse ethnic populations think about managing antihypertensive drug treatment and to address ethnic disparities in medication adherence and BP control.

  7. 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...

  8. 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.

  9. 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

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

    Science.gov (United States)

    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.

  11. 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

  12. 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

  13. 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

  14. Anti-hypertensive drug treatment of patients with and the metabolic syndrome and obesity: a review of evidence, meta-analysis, post hoc and guidelines publications.

    Science.gov (United States)

    Owen, Jonathan G; Reisin, Efrain

    2015-06-01

    Epidemiological studies have shown an increasing prevalence of obesity and the metabolic syndrome worldwide. Lifestyle modifications that include dietary changes, weight reduction, and exercise are the cornerstones in the treatment of this pathology. However, adherence to this approach often meets with failure in clinical practice; therefore, drug therapy should not be delayed. The ideal pharmacological antihypertensive regimen should target the underlying mechanisms involved in this syndrome, including sympathetic activation, increased renal tubular sodium reabsorption, and overexpression of the renin-angiotensin-aldosterone system by the adipocyte. Few prospective trials have been conducted in the search of the ideal antihypertensive regimen in patients with obesity and the metabolic syndrome. We summarize previously published ad hoc studies, prospective studies, and guideline publications regarding the treatment of hypertension in patients with obesity and the metabolic syndrome. We conclude that the optimal antihypertensive drug therapy in these patients has not been defined. Though caution exists regarding the use of thiazide diuretics due to potential metabolic derangements, there is insufficient data to show worsened cardiovascular or renal outcomes in patients treated with these drugs. In regard to beta blockers, the risk of accelerating conversion to diabetes and worsening of inflammatory mediators described in patients treated with traditional beta blockers appears much less pronounced or absent when using the vasodilating beta blockers. Renin-angiotensin-aldosterone system (RAAS) inhibition with an ACE or an ARB and treatment with calcium channel blockers appears safe and well tolerated in obesity-related hypertension and in patients with metabolic syndrome. Future prospective pharmacological studies in this population are needed.

  15. 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.

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

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    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.

  17. 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

  18. Safety, Tolerability, and Antihypertensive Effect of SER100, an Opiate Receptor-Like 1 (ORL-1) Partial Agonist, in Patients With Isolated Systolic Hypertension.

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    Kantola, Ilkka; Scheinin, Mika; Gulbrandsen, Trygve; Meland, Nils; Smerud, Knut T

    2017-11-01

    The purpose of the present trial was to evaluate safety, tolerability, and effect on systolic blood pressure (SBP) of SER100 in a small group of patients with isolated systolic hypertension (ISH) in treatment with at least 1 antihypertensive drug. Eligible patients were randomized to either SER100 (10 mg) or placebo in a crossover design, and 2 doses were given subcutaneously (SC), 8 hours apart, on 2 consecutive days. On all treatment days patients were monitored with an ambulatory blood pressure measurement device for 12 daytime hours. Seventeen patients completed treatment. There were no serious or severe adverse events. Relative to placebo SER100 induced an average reduction of SBP during the 2 treatment days of 7.0 mm Hg (P = 0.0032), whereas the average reduction of diastolic blood pressure (DBP) over the same period was 3.8 mm Hg (P = 0.0011). For patients with ISH, this short-term cross-over study of SC SER100 demonstrated an acceptable safety profile and consistent, significant lowering of SBP and DBP. As initial clinical proof of concept for a new class of drugs, a nociceptin agonist peptide, the results were encouraging and warrant further research. © 2016, The American College of Clinical Pharmacology.

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

    Science.gov (United States)

    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.

  20. 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

  1. 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

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

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    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.

  3. 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.

  4. 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...

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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...

  10. 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

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

    Directory of Open Access Journals (Sweden)

    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

  12. 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.

  13. [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.

  14. Tolerability and safety of antifungal drugs

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    Francesco Scaglione

    2013-08-01

    Full Text Available When treating critically ill patients, as those with fungal infections, attention should be focused on the appropriate use of drugs, especially in terms of dose, safety, and tolerability. The fungal infection itself and the concomitant physiological disorders concur to increase the risk of mortality in these patients, therefore the use of any antifungal agent should be carefully evaluated, considering both the direct action on the target fungus and the adverse effects eventually caused. Among antifungal drugs, echinocandins have the greatest tolerability. In fact, unlike amphotericin B, showing nephrotoxicity, and azoles, which are hepatotoxic, the use of echinocandins doesn’t result in major adverse events.http://dx.doi.org/10.7175/rhc.v4i2s.873

  15. 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  18. 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.

  19. 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.

    Directory of Open Access Journals (Sweden)

    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. 

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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

  2. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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

  6. 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

  7. Carotid angiodysplasia complicated by the use of anti-hypertensive drugs during pregnancy: a case report

    Directory of Open Access Journals (Sweden)

    Tavares Beatriz

    2011-08-01

    highlights the need for constant supervision of blood pressure levels during the use of anti-hypertensive medications.

  8. Sex differences in the subjective tolerability of antipsychotic drugs

    NARCIS (Netherlands)

    Barbui, Corrado; Nosè, Michela; Bindman, Jonathan; Schene, Aart; Becker, Thomas; Mazzi, Maria A.; Kikkert, Martijn; Camara, Jayne; Born, Anja; Tansella, Michele

    2005-01-01

    In recent years, research efforts have been directed to better characterize the Subjective experience of taking psychotropic drugs. This Study investigated the sex difference in the subjective tolerability of antipsychotic drugs. Participants were recruited from patients under the care of

  9. 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.

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

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    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.

  11. 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...

  12. 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.

  13. 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

  14. Persistence and drug tolerance in pathogenic yeast

    DEFF Research Database (Denmark)

    Bojsen, Rasmus Kenneth; Regenberg, Birgitte; Folkesson, Sven Anders

    2017-01-01

    In this review, we briefly summarize the current understanding of how fungal pathogens can persist antifungal treatment without heritable resistance mutations by forming tolerant persister cells. Fungal infections tolerant to antifungal treatment have become a major medical problem. One mechanism...

  15. Antihypertensive effect of low-frequency transcutaneous electrical nerve stimulation (TENS) in comparison with drug treatment.

    Science.gov (United States)

    Silverdal, Jonas; Mourtzinis, Georgios; Stener-Victorin, Elisabet; Mannheimer, Clas; Manhem, Karin

    2012-10-01

    Hypertension is a major risk factor for vascular disease, yet blood pressure (BP) control is unsatisfactory low, partly due to side-effects. Transcutaneous electrical nerve stimulation (TENS) is well tolerated and studies have demonstrated BP reduction. In this study, we compared the BP lowering effect of 2.5 mg felodipin once daily with 30 min of bidaily low-frequency TENS in 32 adult hypertensive subjects (mean office BP 152.7/90.0 mmHg) in a randomized, crossover design. Office BP and 24-h ambulatory BP monitoring (ABPM) were performed at baseline and at the end of each 4-week treatment and washout period. Felodipin reduced office BP by 10/6 mmHg (p TENS reduced office BP by 5/1.5 mmHg (p TENS washout, BP was further reduced and significantly lower than at baseline, but at levels similar to BP after felodipin washout and therefore reasonably caused by factors other than the treatment per se. ABPM revealed a significant systolic reduction of 3 mmHg by felodipin, but no significant changes were noted after TENS. We conclude that our study does not present any solid evidence of BP reduction of TENS.

  16. 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.

  17. 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.

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

    Science.gov (United States)

    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

  19. 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.

  20. 77 FR 72254 - New Animal Drugs; Updating Tolerances for Residues of New Animal Drugs in Food

    Science.gov (United States)

    2012-12-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 500, 520, 522, 524, 529, 556, and 558 [Docket No. FDA-2012-N-1067] RIN 0910-AG17 New Animal Drugs; Updating Tolerances for Residues of New Animal Drugs in Food AGENCY: Food and Drug Administration, HHS. ACTION...

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

  5. 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...

  6. Enhancement of the bioavailability of an antihypertensive drug by transdermal protransfersomal system: formulation and in vivo study.

    Science.gov (United States)

    Morsi, Nadia M; Aboelwafa, Ahmed A; Dawoud, Marwa H S

    2018-06-01

    Timolol Maleate (TiM), a nonselective β-adrenergic blocker, is a potent highly effective agent for management of hypertension. The drug suffers from poor oral bioavailability (50%) due to its first pass effect and a short elimination half-life of 4 h; resulting in its frequent administration. Transdermal formulation may circumvent these problems in the form of protransfersomes. The aim of this study is to develop and optimize transdermal protransfersomal system of Timolol Maleate by film deposition on carrier method where protransfersomes were converted to transfersomes upon skin hydration following transdermal application under occlusive conditions. Two 2 3 full factorial designs were employed to investigate the influence of three formulation variables which were; phosphatidyl choline: surfactant molar ratio, carrier: mixture and the type of SAA each on particle size, drug entrapment efficiency and release rate. The optimized formulation was evaluated regarding permeation through hairless rat skin and compared with oral administration of aqueous solution on male Wistar rats. Optimized protransfersomal system had excellent permeation rate through shaved rat skin (780.69 μg/cm 2 /h) and showed six times increase in relative bioavailability with prolonged plasma profile up to 72 h. A potential protransfresomal transdermal system was successfully developed and factorial design was found to be a smart tool in its optimization.

  7. Behavior of sartans (antihypertensive drugs) in wastewater treatment plants, their occurrence and risk for the aquatic environment.

    Science.gov (United States)

    Bayer, Anne; Asner, Robert; Schüssler, Walter; Kopf, Willi; Weiß, Klaus; Sengl, Manfred; Letzel, Marion

    2014-09-01

    Pharmaceuticals and other anthropogenic trace contaminants reach wastewaters and are often not satisfactorily eliminated in sewage treatment plants. These contaminants and/or their degradation products may reach surface waters, thus influencing aquatic life. In this study, the behavior of five different antihypertonic pharmaceuticals from the sartan group (candesartan, eprosartan, irbesartan, olmesartan and valsartan) is investigated in lab-scale sewage plants. The elimination of the substances with related structures varied broadly from 17 % for olmesartan up to 96 % for valsartan. Monitoring data for these drugs in wastewater effluents of six different sewage treatment plants (STPs) in Bavaria, and at eight rivers, showed median concentrations for, e.g. valsartan of 1.1 and 0.13 μg L(-1), respectively. Predicted environmental concentrations (PEC) were calculated and are mostly consistent with the measured environmental concentrations (MEC). The selected sartans and the mixture of the five sartans showed no ecotoxic effects on aquatic organisms in relevant concentrations. Nevertheless, the occurrence of pharmaceuticals in the environment should be reduced to minimize the risk of their distribution in surface waters, ground waters and bank filtrates used for drinking water.

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

    Science.gov (United States)

    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.

  9. 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

  10. A theory of drug tolerance and dependence II: the mathematical model.

    Science.gov (United States)

    Peper, Abraham

    2004-08-21

    The preceding paper presented a model of drug tolerance and dependence. The model assumes the development of tolerance to a repeatedly administered drug to be the result of a regulated adaptive process. The oral detection and analysis of exogenous substances is proposed to be the primary stimulus for the mechanism of drug tolerance. Anticipation and environmental cues are in the model considered secondary stimuli, becoming primary in dependence and addiction or when the drug administration bypasses the natural-oral-route, as is the case when drugs are administered intravenously. The model considers adaptation to the effect of a drug and adaptation to the interval between drug taking autonomous tolerance processes. Simulations with the mathematical model demonstrate the model's behaviour to be consistent with important characteristics of the development of tolerance to repeatedly administered drugs: the gradual decrease in drug effect when tolerance develops, the high sensitivity to small changes in drug dose, the rebound phenomenon and the large reactions following withdrawal in dependence. The present paper discusses the mathematical model in terms of its design. The model is a nonlinear, learning feedback system, fully satisfying control theoretical principles. It accepts any form of the stimulus-the drug intake-and describes how the physiological processes involved affect the distribution of the drug through the body and the stability of the regulation loop. The mathematical model verifies the proposed theory and provides a basis for the implementation of mathematical models of specific physiological processes.

  11. A theory of drug tolerance and dependence I: a conceptual analysis.

    Science.gov (United States)

    Peper, Abraham

    2004-08-21

    A mathematical model of drug tolerance and its underlying theory is presented. The model extends a first approach, published previously. The model is essentially more complex than the generally used model of homeostasis, which is demonstrated to fail in describing tolerance development to repeated drug administrations. The model assumes the development of tolerance to a repeatedly administered drug to be the result of a regulated adaptive process. The oral detection and analysis of exogenous substances is proposed to be the primary stimulus for the mechanism of drug tolerance. Anticipation and environmental cues are in the model considered secondary stimuli, becoming primary only in dependence and addiction or when the drug administration bypasses the natural-oral-route, as is the case when drugs are administered intravenously. The model considers adaptation to the effect of a drug and adaptation to the interval between drug taking autonomous tolerance processes. Simulations with the mathematical model demonstrate the model's behavior to be consistent with important characteristics of the development of tolerance to repeatedly administered drugs: the gradual decrease in drug effect when tolerance develops, the high sensitivity to small changes in drug dose, the rebound phenomenon and the large reactions following withdrawal in dependence. The mathematical model verifies the proposed theory and provides a basis for the implementation of mathematical models of specific physiological processes. In addition, it establishes a relation between the drug dose at any moment, and the resulting drug effect and relates the magnitude of the reactions following withdrawal to the rate of tolerance and other parameters involved in the tolerance process. The present paper analyses the concept behind the model. The next paper discusses the mathematical model.

  12. ADVERSE PREGNANCY OUTCOMES ASSOCIATED WITH MATERNAL ENALAPRIL ANTIHYPERTENSIVE TREATMENT

    Science.gov (United States)

    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...

  13. Antihypertensive effects of astaxanthin

    Directory of Open Access Journals (Sweden)

    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

  14. Efficacy and tolerability of a single-pill combination of telmisartan 80 mg and hydrochlorothiazide 25 mg according to age, gender, race, hypertension severity, and previous antihypertensive use: planned analyses of a randomized trial

    Directory of Open Access Journals (Sweden)

    Zhu D

    2013-04-01

    previously treated with two or more antihypertensive agents respectively. Treatment was generally well tolerated across the patient subgroups. Conclusion: The T80/H25 single-pill combination provides consistent BP reductions and higher goal attainment rates versus T80 across a range of hypertensive patient subgroups, which are likely to have a positive impact on patients’ cardiovascular risk. Keywords: grade 2 and 3 hypertension, age, race, gender, telmisartan, hydrochlorothiazide

  15. 77 FR 3653 - Import Tolerances for Residues of Unapproved New Animal Drugs in Food

    Science.gov (United States)

    2012-01-25

    ... find a safe import tolerance. It could look at toxicity and residue data and build in a conservative... drugs covered by import tolerances are manufactured under good manufacturing practices (GMP)-like... resistant bacteria in or on the target animal and the potential impact on human health. C. International...

  16. Systematic comparison of drug-tolerant assays for anti-drug antibodies in a cohort of adalimumab-treated rheumatoid arthritis patients

    NARCIS (Netherlands)

    Bloem, Karien; van Leeuwen, Astrid; Verbeek, Gerrit; Nurmohamed, Michael T.; Wolbink, Gerrit Jan; van der Kleij, Desiree; Rispens, Theo

    2015-01-01

    Drug interference complicates assessment of immunogenicity of biologicals and results in an underestimation of anti-drug antibody (ADA) formation. Drug-tolerant assays have the potential to overcome such limitations. However, to which extent drug-tolerant assays provide an unbiased picture of the

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

    Directory of Open Access Journals (Sweden)

    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

  18. Tolerance

    DEFF Research Database (Denmark)

    Tønder, Lars

    is linked to a different set of circumstances than the ones suggested by existing models in contemporary democratic theory. Reorienting the discussion of tolerance, the book raises the question of how to disclose new possibilities within our given context of affect and perception. Once we move away from......Tolerance: A Sensorial Orientation to Politics is an experiment in re-orientation. The book is based on the wager that tolerance exceeds the more prevalent images of self-restraint and repressive benevolence because neither precludes the possibility of a more “active tolerance” motivated...... by the desire to experiment and to become otherwise. The objective is to discuss what gets lost, conceptually as well as politically, when we neglect the subsistence of active tolerance within other practices of tolerance, and to develop a theory of active tolerance in which tolerance's mobilizing character...

  19. 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)

  20. Antihypertensive Effects of Probiotics.

    Science.gov (United States)

    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.

  1. Tolerability of continuous subcutaneous octreotide used in combination with other drugs.

    Science.gov (United States)

    Mercadante, S

    1995-01-01

    Continuous subcutaneous infusion of octreotide combined with other drugs has proved to be useful in some circumstances in palliative care setting when theoral route is no longer available. Forty-four patients were administered octreotide alone or in combination with other drugs in the same syringe driver for symptom control in advanced cancer patients. Good tolerability and compatibility were observed without visual drug precipitation for a period of 48 hours at room temperature, the standard clinical situation in patients' homes. Such a combination of drugs administered by the subcutaneous route makes possible the adequate control of symptoms in the final days of life.

  2. Tolerance

    DEFF Research Database (Denmark)

    Tønder, Lars

    Tolerance: A Sensorial Orientation to Politics is an experiment in re-orientation. The book is based on the wager that tolerance exceeds the more prevalent images of self-restraint and repressive benevolence because neither precludes the possibility of a more “active tolerance” motivated by the d...... these alternatives by returning to the notion of tolerance as the endurance of pain, linking this notion to exemplars and theories relevant to the politics of multiculturalism, religious freedom, and free speech....

  3. 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...

  4. [The effect of prolonged treatment of hypertensive rats with antihypertensive drugs of various actions on the arterial tension and noradrenaline level in the myocardium, brain and aortal].

    Science.gov (United States)

    Kiriakov, A; Khlebarova, M; Staneva-stoicheva, D; Panova, I

    1975-01-01

    The authors examined the changes in arterial blood pressure and the content of Noradrenaline in the myocardium, brain and aorta of rats with hypertension due to nephrectomy and treatment with desoxycorticosterone and NaCl, and after a chronic 6-month treatment of hypertension with various antihypertensive means. The most significant reduction of noradrenaline in the three of the examined tissues was found in rats, which received dic. sulfyram (100 mg/kg per os). Clondine (10 mkg/kg, per os) manifested the strongest hypotensive effect and lowered the level of noradrenaline in the myocardium, while it was raised in the aorta. Reserpine (10 mkg/kg, s. c) induced a clear reduction of Noradrenaline content in the brain, but an increase in the other two tissues. Insignificant hypotensive effect was observed in animals, treated with guanetidine (0.5 mg/kg, per os), which did not affect substantially noradrenaline in the examined organs. The increase of noradrenaline level was established in the three of the organs of animals, treated with alpha-methyl-DOFA (25 mg/kg, per os). Furosemide (1 mg/kg, s.c.) induced a statistically significant elevation of noradrenaline in the aorta, but was noneffective to noradrenaline in the myocardium and brain.

  5. Rational Prescribing in Primary care (RaPP: process evaluation of an intervention to improve prescribing of antihypertensive and cholesterol-lowering drugs

    Directory of Open Access Journals (Sweden)

    Oxman Andrew D

    2006-08-01

    Full Text Available Abstract Background A randomised trial of a multifaceted intervention for improving adherence to clinical practice guidelines for the pharmacological management of hypertension and hypercholesterolemia increased prescribing of thiazides, butdetected no impact onthe use of cardiovascular risk assessment toolsor achievement of treatment targets. We carried out a predominantly quantitative process evaluation to help explain and interpret the trial-findings. Methods Several data-sources were used including: questionnaires completed by pharmacists immediately after educational outreach visits, semi-structured interviews with physicians subjected to the intervention, and data extracted from their electronic medical records. Multivariate regression analyses were conducted to explore the association between possible explanatory variables and the observed variation across practices for the three main outcomes. Results The attendance rate during the educational sessions in each practice was high; few problems were reported, and the physicians were perceived as being largely supportive of the recommendations we promoted, except for some scepticism regarding the use of thiazides as first-line antihypertensive medication. Multivariate regression models could explain only a small part of the observed variation across practices and across trial-outcomes, and key factors that might explain the observed variation in adherence to the recommendations across practices were not identified. Conclusion This study did not provide compelling explanations for the trial results. Possible reasons for this include a lack of statistical power and failure to include potential explanatory variables in our analyses, particularly organisational factors. More use of qualitative research methods in the course of the trial could have improved our understanding.

  6. Therapeutic indications and other use-case-driven updates in the drug ontology: anti-malarials, anti-hypertensives, opioid analgesics, and a large term request

    OpenAIRE

    Hogan, William R.; Hanna, Josh; Hicks, Amanda; Amirova, Samira; Bramblett, Baxter; Diller, Matthew; Enderez, Rodel; Modzelewski, Timothy; Vasconcelos, Mirela; Delcher, Chris

    2017-01-01

    Background The Drug Ontology (DrOn) is an OWL2-based representation of drug products and their ingredients, mechanisms of action, strengths, and dose forms. We originally created DrOn for use cases in comparative effectiveness research, primarily to identify historically complete sets of United States National Drug Codes (NDCs) that represent packaged drug products, by the ingredient(s), mechanism(s) of action, and so on contained in those products. Although we had designed DrOn from the outs...

  7. Therapeutic indications and other use-case-driven updates in the drug ontology: anti-malarials, anti-hypertensives, opioid analgesics, and a large term request.

    Science.gov (United States)

    Hogan, William R; Hanna, Josh; Hicks, Amanda; Amirova, Samira; Bramblett, Baxter; Diller, Matthew; Enderez, Rodel; Modzelewski, Timothy; Vasconcelos, Mirela; Delcher, Chris

    2017-03-03

    The Drug Ontology (DrOn) is an OWL2-based representation of drug products and their ingredients, mechanisms of action, strengths, and dose forms. We originally created DrOn for use cases in comparative effectiveness research, primarily to identify historically complete sets of United States National Drug Codes (NDCs) that represent packaged drug products, by the ingredient(s), mechanism(s) of action, and so on contained in those products. Although we had designed DrOn from the outset to carefully distinguish those entities that have a therapeutic indication from those entities that have a molecular mechanism of action, we had not previously represented in DrOn any particular therapeutic indication. In this work, we add therapeutic indications for three research use cases: resistant hypertension, malaria, and opioid abuse research. We also added mechanisms of action for opioid analgesics and added 108 classes representing drug products in response to a large term request from the Program for Resistance, Immunology, Surveillance and Modeling of Malaria in Uganda (PRISM) project. The net result is a new version of DrOn, current to May 2016, that represents three major therapeutic classes of drugs and six new mechanisms of action. A therapeutic indication of a drug product is represented as a therapeutic function in DrOn. Adverse effects of drug products, as well as other therapeutic uses for which the drug product was not designed are dispositions. Our work provides a framework for representing additional therapeutic indications, adverse effects, and uses of drug products beyond their design. Our work also validated our past modeling decisions for specific types of mechanisms of action, namely effects mediated via receptor and/or enzyme binding. DrOn is available at: http://purl.obolibrary.org/obo/dron.owl . A smaller version without NDCs is available at: http://purl.obolibrary.org/obo/dron/dron-lite.owl.

  8. 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.

  9. Demonstration of safety in Alzheimer's patients for intervention with an anti-hypertensive drug Nilvadipine: results from a 6-week open label study.

    LENUS (Irish Health Repository)

    Kennelly, S P

    2012-02-01

    BACKGROUND: Nilvadipine may lower rates of conversion from mild-cognitive impairment to Alzheimer\\'s disease (AD), in hypertensive patients. However, it remains to be determined whether treatment with nilvadipine is safe in AD patients, given the higher incidence of orthostatic hypotension (OH) in this population, who may be more likely to suffer from symptoms associated with the further exaggeration of a drop in BP. OBJECTIVE: The aim of this study was to investigate the safety and tolerability of nilvadipine in AD patients. METHODS: AD patients in the intervention group (n = 56) received nilvadipine 8 mg daily over 6-weeks, compared to the control group (n = 30) who received no intervention. Differences in systolic (SBP) and diastolic (DBP) blood pressure, before and after intervention, was assessed using automated sphygmomanometer readings and ambulatory BP monitors (ABP), and change in OH using a finometer. Reporting of adverse events was monitored throughout the study. RESULTS: There was a significant reduction in the SBP of treated patients compared to non-treated patients but no significant change in DBP. Individuals with higher initial blood pressure (BP) had greater reduction in BP but individuals with normal BP did not experience much change in their BP. While OH was present in 84% of the patients, there was no further drop in BP recorded on active stand studies. There were no significant differences in adverse event reporting between groups. CONCLUSION: Nilvadipine was well tolerated by patients with AD. This study supports further investigation of its efficacy as a potential treatment for AD.

  10. 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.

  11. 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.

  12. Just don`t do it: zero tolerance alcohol and drug policy in place

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1997-10-01

    Safety policies in effect on the Hibernia offshore platform in the Hibernia Field, 300 km off the Newfoundland coast, were described, especially with regard to alcohol and drugs. No alcohol of any type is allowed on the platform. Each employee departing for the platform must take a breathalyzer test prior to boarding the helicopter. The tolerance level at the heliport is .05 per cent and anyone exceeding that is not permitted to board the aircraft. Employees must also be drug-free to be permitted to travel offshore. There is a policy of random testing on the platform for illicit or `recreational` drugs. All employees must agree in writing to taking these tests through provision of a urine sample on demand, as a condition of employment. The use of alcohol offshore or the detection of illegal drugs through the random testing program are grounds for dismissal, although team leaders have some discretion to judge each situation on its own set of circumstances. The company also has the right to search individuals, their sleeping quarters, lockers and other property for alcohol, drugs or other controlled substances in situations where reasonable doubt exists. To date there has been very little resistance within Hibernia to its random testing and zero tolerance policies. Employees understand that this is a safety issue and that they serve to protect everyone who works on the offshore platform.

  13. [The problems of antihypertensive balneotherapy].

    Science.gov (United States)

    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.

  14. Therapeutic Drug Monitoring of Lacosamide in Norway: Focus on Pharmacokinetic Variability, Efficacy and Tolerability.

    Science.gov (United States)

    Svendsen, Torleiv; Brodtkorb, Eylert; Baftiu, Arton; Burns, Margrete Larsen; Johannessen, Svein I; Johannessen Landmark, Cecilie

    2017-07-01

    Lacosamide (LCM) is a new antiepileptic drug (AED). Experience from therapeutic drug monitoring (TDM) in clinical practice is limited. The purpose of this study is to evaluate the pharmacokinetic variability of LCM in relation to efficacy and tolerability in patients with refractory epilepsy in a real-life setting. Variables included age, gender, daily doses and serum concentrations of LCM and other AEDs from the TDM-database at the National Center for Epilepsy in Norway. Clinical data regarding efficacy and tolerability were collected from medical records. The Norwegian Prescription Database (NorPD) was used to include population-based numbers of users. TDM-data from 344 patients were included. The median dose, serum concentration, and concentration/dose (C/D)-ratio of LCM was 350 (range 25-700) mg/day, 19.7 (range 8.1-56.2) µmol/L, and 0.06 (0.02-0.82) µmol/L/mg, respectively. Serum concentrations were reduced by 28% by concomitant use of enzyme inducers and increased by 30% in patients aged >65 years. Efficacy and tolerability were assessed in 227 patients: 29% had >50% seizure reduction (eight seizure free), 30% had no effect, and 44% reported adverse effects. In Norway, there were on average 500 patients per year using LCM in this period based on NorPD. The study demonstrated pharmacokinetic variability and use of TDM of LCM in Norway. Data were collected from multiple sources for improved pharmacovigilance. Serum concentrations were influenced by enzyme inducers and ageing, indicating the usefulness of TDM. Effect and tolerability were favorable within a suggested reference range of 10-40 µmol/L given drug-fasting conditions.

  15. 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.

  16. [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.

  17. New-onset diabetes and antihypertensive treatment

    Directory of Open Access Journals (Sweden)

    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

  18. Hypericum perforatum: pharmacokinetic, mechanism of action, tolerability, and clinical drug-drug interactions.

    Science.gov (United States)

    Russo, Emilio; Scicchitano, Francesca; Whalley, Benjamin J; Mazzitello, Carmela; Ciriaco, Miriam; Esposito, Stefania; Patanè, Marinella; Upton, Roy; Pugliese, Michela; Chimirri, Serafina; Mammì, Maria; Palleria, Caterina; De Sarro, Giovambattista

    2014-05-01

    Hypericum perforatum (HP) belongs to the Hypericaceae family and is one of the oldest used and most extensively investigated medicinal herbs. The medicinal form comprises the leaves and flowering tops of which the primary ingredients of interest are naphthodianthrones, xanthones, flavonoids, phloroglucinols (e.g. hyperforin), and hypericin. Although several constituents elicit pharmacological effects that are consistent with HP's antidepressant activity, no single mechanism of action underlying these effects has thus far been found. Various clinical trials have shown that HP has a comparable antidepressant efficacy as some currently used antidepressant drugs in the treatment of mild/moderate depression. Interestingly, low-hyperforin-content preparations are effective in the treatment of depression. Moreover, HP is also used to treat certain forms of anxiety. However, HP can induce various cytochrome P450s isozymes and/or P-glycoprotein, of which many drugs are substrates and which are the main origin of HP-drug interactions. Here, we analyse the existing evidence describing the clinical consequence of HP-drug interactions. Although some of the reported interactions are based on findings from in vitro studies, the clinical importance of which remain to be demonstrated, others are based on case reports where causality can, in some cases, be determined to reveal clinically significant interactions that suggest caution, consideration, and disclosure of potential interactions prior to informed use of HP. Copyright © 2013 John Wiley & Sons, Ltd.

  19. Quality risk management of top spray fluidized bed process for antihypertensive drug formulation with control strategy engendered by Box-behnken experimental design space.

    Science.gov (United States)

    Mukharya, Amit; Patel, Paresh U; Shenoy, Dinesh; Chaudhary, Shivang

    2013-01-01

    Lacidipine (LCDP) is a very low soluble and highly biovariable calcium channel blocker used in the treatment of hypertension. To increase its apparent solubility and to reduce its biovariability, solid dispersion fluid bed processing technology was explored, as it produces highly dispersible granules with a characteristic porous structure that enhances dispersibility, wettability, blend uniformity (by dissolving and spraying a solution of actives), flow ability and compressibility of granules for tableting and reducing variability by uniform drug-binder solution distribution on carrier molecules. Main object of this quality risk management (QRM) study is to provide a sophisticated "robust and rugged" Fluidized Bed Process (FBP) for the preparation of LCDP tablets with desired quality (stability) and performance (dissolution) by quality by design (QbD) concept. THIS STUDY IS PRINCIPALLY FOCUSING ON THOROUGH MECHANISTIC UNDERSTANDING OF THE FBP BY WHICH IT IS DEVELOPED AND SCALED UP WITH A KNOWLEDGE OF THE CRITICAL RISKS INVOLVED IN MANUFACTURING PROCESS ANALYZED BY RISK ASSESSMENT TOOLS LIKE: Qualitative Initial Risk-based Matrix Analysis (IRMA) and Quantitative Failure Mode Effective Analysis (FMEA) to identify and rank parameters with potential to have an impact on In Process/Finished Product Critical Quality Attributes (IP/FP CQAs). These Critical Process Parameters (CPPs) were further refined by DoE and MVDA to develop design space with Real Time Release Testing (RTRT) that leads to implementation of a control strategy to achieve consistent finished product quality at lab scale itself to prevent possible product failure at larger manufacturing scale.

  20. 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.

  1. A safety and tolerability study of differently-charged nanoparticles for local pulmonary drug delivery

    International Nuclear Information System (INIS)

    Harush-Frenkel, Oshrat; Bivas-Benita, Maytal; Nassar, Taher; Springer, Chaim; Sherman, Yoav; Avital, Avraham; Altschuler, Yoram; Borlak, Jurgen; Benita, Simon

    2010-01-01

    Nanoparticle (NP) based drug delivery systems provide promising opportunities in the treatment of lung diseases. Here we examined the safety and tolerability of pulmonary delivered NPs consisting of PEG-PLA as a function of particle surface charge. The rationale for such a comparison should be attributed to the differential pulmonary toxicity of positively and negatively charged PEG-PLA NP. Thus, the local and systemic effects of pulmonary administered NPs were investigated following 5 days of daily endotracheal instillation to BALB/c mice that were euthanized on the eighth or nineteenth day of the experiment. We collected bronchoalveolar lavages and studied hematological as well as histochemistry parameters. Notably, the cationic stearylamine based PEG-PLA NPs elicited increased local and systemic toxic effects both on the eighth and nineteenth day. In contrast, anionic NPs of similar size were much better tolerated with local inflammatory effects observed only on the eighth experimental day after pulmonary instillation. No systemic toxicity effect was observed although a moderate change was noted in the platelet count that was not considered to be of clinical significance. No pathological observations were detected in the internal organs following instillation of anionic NPs. Overall these observations suggest that anionic PEG-PLA NPs are useful pulmonary drug carriers that should be considered as a promising therapeutic drug delivery system.

  2. Local tolerance testing of parenteral drugs: how to put into practice.

    Science.gov (United States)

    Jochims, Karin; Kemkowski, Joerg; Nolte, Thomas; Bartels, Thomas; Heusener, Alexander

    2003-10-01

    Notwithstanding that there are national and international guidelines about local tolerance testing of parenteral drugs in animals, in particular to mention CPMP/SWP/2145/00 (Note for Guidance on Non-Clinical Local Tolerance Testing of Medicinal Products), very heterogeneous study designs have been established in the past. A working group including experts of the leading pharmaceutical industry from German-language countries, named "Arbeitskreis Lokale Verträglichkeit," has been intensively discussing the experimental procedures in detail for a period of six years and has been considering their pros and cons. This team of experts now feels confident to give some recommendations for study conduct besides describing different materials and methods for this type of toxicological study. Special knowledge from toxicologists as well as pathologists from our working group has been taken into account. This paper deals with choice of species, number of animals used, controls, administration sites, volumes, rate and frequency, length of observation period, termination, clinical, macroscopic and histopathological examinations and, finally, overall assessment criteria and conclusion. Our purpose is that this paper may be of value for: *The study director who is inexperienced in the conduction of local tolerance testing and who may need a standard design as his first step into this new field. *The well-versed study director who would like to know how others have done in the past, who may examine self-critically his own practice and who is open to our team's recommendations, tips and tricks from practice. *The specialist at a regulatory authority who, finally, reviews study reports, assesses their format and content and, above all, decides on the approval of a drug product.

  3. ASSESSMENT OF AMLODIPINE ANTIHYPERTENSIVE EFFECT HOMOGENEITY IN CONTROLLED TRIAL

    Directory of Open Access Journals (Sweden)

    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.

  4. Interventional procedures and future drug therapy for hypertension

    Science.gov (United States)

    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

  5. 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.

  6. 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.

  7. 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

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

    Science.gov (United States)

    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.

  9. Contribution of the Chromosomal ccdAB Operon to Bacterial Drug Tolerance.

    Science.gov (United States)

    Gupta, Kritika; Tripathi, Arti; Sahu, Alishan; Varadarajan, Raghavan

    2017-10-01

    One of the first identified and best-studied toxin-antitoxin (TA) systems in Escherichia coli is the F-plasmid-based CcdAB system. This system is involved in plasmid maintenance through postsegregational killing. More recently, ccdAB homologs have been found on the chromosome, including in pathogenic strains of E. coli and other bacteria. However, the functional role of chromosomal ccdAB genes, if any, has remained unclear. We show that both the native ccd operon of the E. coli O157 strain ( ccd O157 ) and the ccd operon from the F plasmid ( ccd F ), when inserted on the E. coli chromosome, lead to protection from cell death under multiple antibiotic stress conditions through formation of persisters, with the O157 operon showing higher protection. While the plasmid-encoded CcdB toxin is a potent gyrase inhibitor and leads to bacterial cell death even under fully repressed conditions, the chromosomally encoded toxin leads to growth inhibition, except at high expression levels, where some cell death is seen. This was further confirmed by transiently activating the chromosomal ccd operon through overexpression of an active-site inactive mutant of F-plasmid-encoded CcdB. Both the ccd F and ccd O157 operons may share common mechanisms for activation under stress conditions, eventually leading to multidrug-tolerant persister cells. This study clearly demonstrates an important role for chromosomal ccd systems in bacterial persistence. IMPORTANCE A large number of free-living and pathogenic bacteria are known to harbor multiple toxin-antitoxin systems, on plasmids as well as on chromosomes. The F-plasmid CcdAB system has been extensively studied and is known to be involved in plasmid maintenance. However, little is known about the function of its chromosomal counterpart, found in several pathogenic E. coli strains. We show that the native chromosomal ccd operon of the E. coli O157 strain is involved in drug tolerance and confers protection from cell death under multiple

  10. 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

  11. The ABC of Biofilm Drug Tolerance: the MerR-Like Regulator BrlR Is an Activator of ABC Transport Systems, with PA1874-77 Contributing to the Tolerance of Pseudomonas aeruginosa Biofilms to Tobramycin.

    Science.gov (United States)

    Poudyal, Bandita; Sauer, Karin

    2018-02-01

    A hallmark of biofilms is their tolerance to killing by antimicrobial agents. In Pseudomonas aeruginosa , biofilm drug tolerance requires the c-di-GMP-responsive MerR transcriptional regulator BrlR. However, the mechanism by which BrlR mediates biofilm drug tolerance has not been elucidated. Here, we demonstrate that BrlR activates the expression of at least 7 ABC transport systems, including the PA1874-PA1875-PA1876-PA1877 (PA1874-77) operon, with chromatin immunoprecipitation and DNA binding assays confirming BrlR binding to the promoter region of PA1874-77. Insertional inactivation of the 7 ABC transport systems rendered P. aeruginosa PAO1 biofilms susceptible to tobramycin or norfloxacin. Susceptibility was linked to drug accumulation, with BrlR contributing to norfloxacin accumulation in a manner dependent on multidrug efflux pumps and the PA1874-77 ABC transport system. Inactivation of the respective ABC transport system, furthermore, eliminated the recalcitrance of biofilms to killing by tobramycin but not norfloxacin, indicating that drug accumulation is not linked to biofilm drug tolerance. Our findings indicate for the first time that BrlR, a MerR-type transcriptional activator, activates genes encoding several ABC transport systems, in addition to multiple multidrug efflux pump genes. Moreover, our data confirm a BrlR target contributing to drug tolerance, likely countering the prevailing dogma that biofilm tolerance arises from a multiplicity of factors. Copyright © 2018 American Society for Microbiology.

  12. L-form transformation phenomenon in Mycobacterium tuberculosis associated with drug tolerance to ethambutol

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    Georgi Slavchev

    2016-01-01

    Full Text Available Objective/background: Cell wall-deficient bacterial forms (L-forms may occur along with resistance to factors that trigger their appearance. It is of interest to study the relationship between the L-form transformation of Mycobacterium tuberculosis and the exhibition of drug tolerance to ethambutol (EMB, an inhibitor of cell wall synthesis. Methods: L-form variant was produced from a sensitive EMB strain of M. Tuberculosis through a cryogenic stress treatment protocol and was subsequently cultivated in Middlebrook 7H9 semisolid medium, containing EMB in a minimal inhibitory concentration of 2 mg/L. Susceptibility to EMB of the parental strain and its L-form variant was evaluated phenotypically and using polymerase chain reaction-restriction fragment length polymorphism assay targeting a mutation in the embB306 gene fragment. Results: In contrast to the sensitivity to EMB of the parental strain, its L-form variant showed phenotypic resistance to high concentrations of EMB (16 mg/L, but the mutation in embB306 was not found. Electron microscopy observation of the L-form variant showed a heterogenic population of bacteria, with different degrees of cell wall deficiency, as well as cells of protoplastic type without cell walls. Of special interest were the observed capsule-like structures around the L-form cells and the biofilm-like matrix produced by the L-form population. Conclusion: We suggest that the expression of phenotypic resistance to EMB in M. Tuberculosis can be associated with alterations or loss of cell walls in L-form bacteria, respectively, which results in a lack of a specific target for EMB action. In addition, production of capsule-like structures and biofilm matrix by L-forms could contribute to their resistance and survival in the presence of antibacterial agents.

  13. 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)

  14. 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

  15. Antihypertensive and organ-protective effects of benazepril.

    Science.gov (United States)

    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.

  16. 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.

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

    DEFF Research Database (Denmark)

    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...

  18. 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.

  19. 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 ...

  20. Induced tolerance to nebulized colistin after severe reaction to the drug.

    Science.gov (United States)

    Domínguez-Ortega, J; Manteiga, E; Abad-Schilling, C; Juretzcke, M A; Sánchez-Rubio, J; Kindelan, C

    2007-01-01

    Daily nebulized colistin therapy has been used as maintenance therapy for patients with chronic Pseudomonas aeruginosa infection and in treatment protocols aimed at eradicating early P aeruginosa infection. Colistin-induced nephrotoxicity and mild neurotoxic effects have been described but hypersensitivity reactions are rare. However, bronchial constriction has been reported associated with the inhalation of the antibiotic. We report the case of a 63-year-old man who had been diagnosed with bronchiectasis and bronchopleural fistula and who developed severe bronchospasm when using nebulized colistin. A skin prick test (80 mg/mL) with colistin was performed and was negative. An intradermal test was not performed due to its possible irritant effect. As our patient suffered from a tobramycin-resistant P aeruginosa infection, we started a procedure to induce tolerance to 80 mg colistin (8 mg, 16 mg, 24 mg, 32 mg, 40 mg, 80 mg) nebulized in 30-minutes-intervals. No changes in forced expiratory volume in 1 second values were observed and the patient continues on treatment twice daily after the tolerance induction with no new episodes of bronchospasm. We report the first successful procedure to induce tolerance to colistin after escalating doses of inhaled colistin.

  1. 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

  2. ANTIHYPERTENSIVE THERAPY AND CLIMACTERIC DISORDERS IN POSTMENOPAUSAL WOMEN

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    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.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Clinical pharmacokinetics of Icotinib, an anti-cancer drug: evaluation of dose proportionality, food effect, and tolerability in healthy subjects.

    Science.gov (United States)

    Liu, Dongyang; Jiang, Ji; Zhang, Li; Tan, Fenlai; Wang, Yingxiang; Zhang, Don; Hu, Pei

    2014-04-01

    Icotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, has proved effectiveness in xenografted nude mice. Purpose of the present studies was to investigate tolerability and pharmacokinetics of Icotinib in healthy subjects for the first time, including dose proportionality, food effect, and tolerability. Two studies were conducted in total of 22 healthy subjects: a randomized, two-Latin-square crossover, dose proportional study (n = 12) and a randomized two-way crossover food-effect study (n = 10). Plasma concentration of Icotinib reached peak at a median Tmax of 0.75-3.5 h after single dose and then declined with a mean t1/2β of 6.02-7.83 h. Over the dose range of 100-600 mg, AUC values were proportional to dose and Cmax showed a slight saturation when dose increases. Only 0.2 % of the dose was excreted through kidney in unchanged Icotinib. After dosing 400 mg of Icotinib with high-fat and high-calorie meal, mean Cmax and AUC were significantly increased by 59 and 79 %, respectively. Three subjects experienced four adverse events (rash, increase in AST and ALT, and external injury). Rash and increased levels of AST and ALT were considered as drug-related. No serious adverse events were reported. The current work demonstrated that Icotinib was well tolerated in healthy male subjects (n = 22) over the dose range of 100-600 mg with or without food. Icotinib exposure, expressed in AUC, was proportionally increased with dose over the above dose range. Food intake significantly increased the absorption and exposure of Icotinib in healthy subjects.

  6. 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.

  7. Reversible antibiotic tolerance induced in Staphylococcus aureus by concurrent drug exposure

    DEFF Research Database (Denmark)

    Haaber, Jakob Krause; Friberg, Cathrine; McCreary, Mark

    2015-01-01

    UNLABELLED: Resistance of Staphylococcus aureus to beta-lactam antibiotics has led to increasing use of the glycopeptide antibiotic vancomycin as a life-saving treatment for major S. aureus infections. Coinfection by an unrelated bacterial species may necessitate concurrent treatment with a second...... antibiotic that targets the coinfecting pathogen. While investigating factors that affect bacterial antibiotic sensitivity, we discovered that susceptibility of S. aureus to vancomycin is reduced by concurrent exposure to colistin, a cationic peptide antimicrobial employed to treat infections by Gram......-negative pathogens. We show that colistin-induced vancomycin tolerance persists only as long as the inducer is present and is accompanied by gene expression changes similar to those resulting from mutations that produce stably inherited reduction of vancomycin sensitivity (vancomycin-intermediate S. aureus [VISA...

  8. An ETP model (exclusion-tolerance-progression for multi drug resistance

    Directory of Open Access Journals (Sweden)

    Kannan Subburaj

    2005-04-01

    Full Text Available Abstract Background It is known that sensitivity or resistance of tumor cells to a given chemotherapeutic agent is an acquired characteristic(s, depending on the heterogeneity of the tumor mass subjected to the treatment. The clinical success of a chemotherapeutic regimen depends on the ratio of sensitive to resistant cell populations. Results Based on findings from clinical and experimental studies, a unifying model is proposed to delineate the potential mechanism by which tumor cells progress towards multi drug resistance, resulting in failure of chemotherapy. Conclusion It is suggested that the evolution of multi drug resistance is a developmentally orchestrated event. Identifying stage-specific time windows during this process would help to identify valid therapeutic targets for the effective elimination of malignancy.

  9. Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation.

    Science.gov (United States)

    Wilby, J; Kainth, A; Hawkins, N; Epstein, D; McIntosh, H; McDaid, C; Mason, A; Golder, S; O'Meara, S; Sculpher, M; Drummond, M; Forbes, C

    2005-04-01

    To examine the clinical effectiveness, tolerability and cost-effectiveness of gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), tiagabine (TGB), topiramate (TPM) and vigabatrin (VGB) for epilepsy in adults. Electronic databases. Internet resources. Pharmaceutical company submissions. Selected studies were screened and quality assessed. Separate analyses assessed clinical effectiveness, serious, rare and long-term adverse events and cost-effectiveness. An integrated economic analysis incorporating information on costs and effects of newer and older antiepileptic drugs (AEDs) was performed to give direct comparisons of long-term costs and benefits. A total of 212 studies were included in the review. All included systematic reviews were Cochrane reviews and of good quality. The quality of randomised controlled trials (RCTs) was variable. Assessment was hampered by poor reporting of methods of randomisation, allocation concealment and blinding. Few of the non-randomised studies were of good quality. The main weakness of the economic evaluations was inappropriate use of the cost-minimisation design. The included systematic reviews reported that newer AEDs were effective as adjunctive therapy compared to placebo. For newer versus older drugs, data were available for all three monotherapy AEDs, although data for OXC and TPM were limited. There was limited, poor-quality evidence of a significant improvement in cognitive function with LTG and OXC compared with older AEDs. However, there were no consistent statistically significant differences in other clinical outcomes, including proportion of seizure-free patients. No studies assessed effectiveness of AEDs in people with intellectual disabilities or in pregnant women. There was very little evidence to assess the effectiveness of AEDs in the elderly; no significant differences were found between LTG and carbamazepine monotherapy. Sixty-seven RCTs compared adjunctive therapy with placebo, older

  10. [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.

  11. The Yin and Yang of SagS: Distinct Residues in the HmsP Domain of SagS Independently Regulate Biofilm Formation and Biofilm Drug Tolerance

    Science.gov (United States)

    Dingemans, Jozef; Poudyal, Bandita

    2018-01-01

    ABSTRACT The formation of inherently drug-tolerant biofilms by the opportunistic pathogen Pseudomonas aeruginosa requires the sensor-regulator hybrid SagS, with ΔsagS biofilms being unstructured and exhibiting increased antimicrobial susceptibility. Recent findings indicated SagS to function as a switch to control biofilm formation and drug tolerance independently. Moreover, findings suggested the periplasmic sensory HmsP domain of SagS is likely to be the control point in the regulation of biofilm formation and biofilm cells transitioning to a drug-tolerant state. We thus asked whether specific amino acid residues present in the HmsP domain contribute to the switch function of SagS. HmsP domain residues were therefore subjected to alanine replacement mutagenesis to identify substitutions that block the sensory function(s) of SagS, which is apparent by attached cells being unable to develop mature biofilms and/or prevent transition to an antimicrobial-resistant state. Mutant analyses revealed 32 residues that only contribute to blocking one sensory function. Moreover, amino acid residues affecting attachment and subsequent biofilm formation but not biofilm tolerance also impaired histidine kinase signaling via BfiS. In contrast, residues affecting biofilm drug tolerance but not attachment and subsequent biofilm formation negatively impacted BrlR transcription factor levels. Structure prediction suggested the two sets of residues affecting sensory functions are located in distinct areas that were previously described as being involved in ligand binding interactions. Taken together, these studies identify the molecular basis for the dual regulatory function of SagS. IMPORTANCE The membrane-bound sensory protein SagS plays a pivotal role in P. aeruginosa biofilm formation and biofilm cells gaining their heightened resistance to antimicrobial agents, with SagS being the control point at which both pathways diverge. Here, we demonstrate for the first time that the two

  12. [Drug tolerance and PFGE molecular typing of Salmonella paratyphi A isolated in Dengfeng, Henan province, 2009-2015].

    Science.gov (United States)

    Zhao, J Y; Zhang, S Y; Mu, Y J; Zhang, B F; Xia, S L; Huang, X Y; Xu, B L

    2016-05-01

    To investigate the drug tolerance and PFGE patterns of Salmonella(S.)paratyphi A strains isolated from sentinel hospitals in Dengfeng, Henan province, during 2009-2015. Venous blood samples were collected from paratyphoid patients and cultured in double phase blood culture bottle. Suspicious strains were identified and used for Salomonella. O antigen and H1/2 phase flagellum-induced serum agglutination test with API20E biochemical systems and SSI Salmonella typing sera. According to Salmonella molecular typing and K-B drug susceptibility testing method published by PulseNet China bacterial infectious disease monitoring network and USA Clinical and Laboratory Standards Institute, we analyzed the drug susceptibility and PFGE molecule characteristics of S. paratyphi A strains isolated from the patients. A total of 126 strains of S. paratyphi A were isolated from 248 blood samples, the antigen modes of them were 1, 2, 12:a:-. The resistance rate of 126 strains of S. paratyphi A was 83.3% to ampicillin; 29.4% to ceftazidime, 31.2% to cefotaxime, 17.5% to cefepime; 62.6% to nalidixic acid; 19.3% to ciprofloxacin, 26.4% to norfloxacin; 22.8% to gentamicin, 47.9% to streptomycin; 19.2% to chloramphenicol, 24.2% to methicillin benzyl ammonium, 58.6% to compound sulfamethoxazole and 46.7% to tetracycline. The 126 strains of S. paratyphi A had different levels of resistance to 8 kinds of antibiotics, 109 strains were multidrug resistant(86.5%), 9 strains were resistant to 2-3 kinds of antibiotics(7.1%), 76 strains were resistant to 5-8 kinds of antibiotics(60.3%), 17 strains were resistant to 9-10 kinds of antibiotics(13.5%), 7 strains were resistant to 11-12 kinds of antibiotics(5.6%). The 126 strains of S. paratyphi A were divided into 14 molecular patterns by digestion with XbaⅠand pulsed field gel electrophoresis. The antibiotics resistance to third generation cephalosporin(CAZ, CTX), one generation and three generation of quinolones(NAL, CIP, NOR)and aminoglycosides

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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...

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

    Directory of Open Access Journals (Sweden)

    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

  16. Clinical perspectives on the influence of drug formulation on patient tolerability and use of commonly prescribed antidepressants in major depressive disorder

    Directory of Open Access Journals (Sweden)

    Matthew A Fuller

    2013-01-01

    Full Text Available The purpose of this review is to summarize the formulation options for currently available antidepressants, and discuss examples of the influence that formulation may have on the pharmacologic and clinical profiles of the medications. A review of current literature suggests that differences in drug-delivery technologies can lead to variations in the pharmacokinetic and pharmacodynamic profiles of generic and branded drugs, despite generic drugs being required to meet bioequivalence standards compared with their branded counterparts. These differences may influence the effectiveness and tolerability of treatment. Recent reports have highlighted the need for individualized treatment regimens and careful assessment of tolerability and efficacy when switching patients from brand to generic formulations. There is a growing body of evidence indicating that differences in formulation can substantially impact drug pharmacokinetics and pharmacodynamics, which in turn, can affect drug effects. The clinical impact of these differences remains unclear. Further research is needed to clarify the influence of antidepressant formulations on treatment adherence, patient preference, and quality of life, and how this impacts clinical practice with regard to brand versus generic treatment selection.

  17. Antihypertensive Drug Prescribing in a Tertiary Hospital in Eastern ...

    African Journals Online (AJOL)

    HP

    hypertensive patients (> 18 years) visiting a referral hospital in Enugu, southeastern Nigeria between. June and July .... Class of hypertension by blood pressure measurement ..... beneficial effects in secondary prevention of cardiovascular ...

  18. Antihypertensive Drugs and the Sexually Active Hypertensive Male ...

    African Journals Online (AJOL)

    Background: Erectile dysfunction (ED) has made the initiations of therapy and continued therapy increasingly problematic in the management of the hypertensive male. There are reports suggesting beneficial effects of angiotensin II antagonists on sexual function. The effects of losartan on ED in Nigerian hypertensive men ...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  2. 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...

  3. 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.

  4. 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....

  5. Antihypertensive Action of Allantoin in Animals

    Directory of Open Access Journals (Sweden)

    Mei-Fen Chen

    2014-01-01

    Full Text Available The agonists of imidazoline I-1 receptors (I-1R are widely used to lower blood pressure. It has been indicated that guanidinium derivatives show an ability to activate imidazoline receptors. Also, allantoin has a chemical stricture similar to guanidinium derivatives. Thus, it is of special interest to characterize the effect of allantoin on I-1R. In conscious male spontaneous hypertensive rats (SHRs, mean blood pressure (MBP was recorded using the tail-cuff method. Furthermore, the hemodynamic analyses in catheterized rats were applied to measure the actions of allantoin in vivo. Allantoin decreased blood pressures in SHRs at 30 minutes, as the most effective time. Also, this antihypertensive action was shown in a dose-dependent manner from SHRs treated with allantoin. Moreover, in anesthetized rats, allantoin inhibited cardiac contractility and heart rate as showing in hemodynamic dP/dt max significantly. Also, the peripheral blood flow was markedly increased by allantoin. Both actions were diminished by efaroxan at the dose sufficient to block I-1R. Thus, we suggest that allantoin, as I-1R agonist, has the potential to develop as a new therapeutic agent for hypertension in the future.

  6. Antihypertensive potential of bioactive hydrolysate from edible bird's nest

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  8. Overcoming drug-tolerant cancer cell subpopulations showing AXL activation and epithelial–mesenchymal transition is critical in conquering ALK-positive lung cancer

    Science.gov (United States)

    Nakamichi, Shinji; Seike, Masahiro; Miyanaga, Akihiko; Chiba, Mika; Zou, Fenfei; Takahashi, Akiko; Ishikawa, Arimi; Kunugi, Shinobu; Noro, Rintaro; Kubota, Kaoru; Gemma, Akihiko

    2018-01-01

    Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) induce a dramatic response in non–small cell lung cancer (NSCLC) patients with the ALK fusion gene. However, acquired resistance to ALK-TKIs remains an inevitable problem. In this study, we aimed to discover novel therapeutic targets to conquer ALK-positive lung cancer. We established three types of ALK-TKI (crizotinib, alectinib and ceritinib)-resistant H2228 NSCLC cell lines by high exposure and stepwise methods. We found these cells showed a loss of ALK signaling, overexpressed AXL with epithelial-mesenchymal transition (EMT), and had cancer stem cell-like (CSC) properties, suggesting drug-tolerant cancer cell subpopulations. Similarly, we demonstrated that TGF-β1 treated H2228 cells also showed AXL overexpression with EMT features and ALK-TKI resistance. The AXL inhibitor, R428, or HSP90 inhibitor, ganetespib, were effective in reversing ALK-TKI resistance and EMT changes in both ALK-TKI-resistant and TGF-β1-exposed H2228 cells. Tumor volumes of xenograft mice implanted with established H2228-ceritinib-resistant (H2228-CER) cells were significantly reduced after treatment with ganetespib, or ganetespib in combination with ceritinib. Some ALK-positive NSCLC patients with AXL overexpression showed a poorer response to crizotinib therapy than patients with a low expression of AXL. ALK signaling-independent AXL overexpressed in drug-tolerant cancer cell subpopulations with EMT and CSC features may be commonly involved commonly involved in intrinsic and acquired resistance to ALK-TKIs. This suggests AXL and HSP90 inhibitors may be promising therapeutic drugs to overcome drug-tolerant cancer cell subpopulations in ALK-positive NSCLC patients for the reason that ALK-positive NSCLC cells do not live through ALK-TKI therapy. PMID:29930762

  9. 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.

  10. Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

    Science.gov (United States)

    Lilius, T O; Jokinen, V; Neuvonen, M S; Niemi, M; Kalso, E A; Rauhala, P V

    2015-01-01

    Background and Purpose The effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal. Experimental Approach Morphine minipumps (6 mg·day–1) induced tolerance during 5 days in Sprague–Dawley rats, after which s.c. ketamine (10 mg·kg–1) was administered. Tail flick, hot plate and rotarod tests were used for behavioural testing. Serum levels and whole tissue brain and liver concentrations of morphine, morphine-3-glucuronide, ketamine and norketamine were measured using HPLC-tandem mass spectrometry. Key Results In morphine-naïve rats, ketamine caused no antinociception whereas in morphine-tolerant rats there was significant antinociception (57% maximum possible effect in the tail flick test 90 min after administration) lasting up to 150 min. In the brain of morphine-tolerant ketamine-treated rats, the morphine, ketamine and norketamine concentrations were 2.1-, 1.4- and 3.4-fold, respectively, compared with the rats treated with morphine or ketamine only. In the liver of morphine-tolerant ketamine-treated rats, ketamine concentration was sixfold compared with morphine-naïve rats. After a 2 day morphine withdrawal period, smaller but parallel concentration changes were observed. In acute coadministration, ketamine increased the brain morphine concentration by 20%, but no increase in ketamine concentrations or increased antinociception was observed. Conclusions and Implications The ability of ketamine to induce antinociception in rats made tolerant to morphine may also be due to increased brain concentrations of morphine, ketamine and norketamine. The relevance of these findings needs to be assessed in humans. PMID:25297798

  11. 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 ...

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

    Science.gov (United States)

    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

  13. 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

    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

  14. 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

  15. Impaired glucose tolerance in first-episode drug-naïve patients with schizophrenia: relationships with clinical phenotypes and cognitive deficits.

    Science.gov (United States)

    Chen, D C; Du, X D; Yin, G Z; Yang, K B; Nie, Y; Wang, N; Li, Y L; Xiu, M H; He, S C; Yang, F D; Cho, R Y; Kosten, T R; Soares, J C; Zhao, J P; Zhang, X Y

    2016-11-01

    Schizophrenia patients have a higher prevalence of type 2 diabetes mellitus with impaired glucose tolerance (IGT) than normals. We examined the relationship between IGT and clinical phenotypes or cognitive deficits in first-episode, drug-naïve (FEDN) Han Chinese patients with schizophrenia. A total of 175 in-patients were compared with 31 healthy controls on anthropometric measures and fasting plasma levels of glucose, insulin and lipids. They were also compared using a 75 g oral glucose tolerance test and the homeostasis model assessment of insulin resistance (HOMA-IR). Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Of the patients, 24.5% had IGT compared with none of the controls, and they also had significantly higher levels of fasting blood glucose and 2-h glucose after an oral glucose load, and were more insulin resistant. Compared with those patients with normal glucose tolerance, the IGT patients were older, had a later age of onset, higher waist or hip circumference and body mass index, higher levels of low-density lipoprotein and triglycerides and higher insulin resistance. Furthermore, IGT patients had higher PANSS total and negative symptom subscale scores, but no greater cognitive impairment except on the emotional intelligence index of the MCCB. IGT occurs with greater frequency in FEDN schizophrenia, and shows association with demographic and anthropometric parameters, as well as with clinical symptoms but minimally with cognitive impairment during the early course of the disorder.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  18. Selected Alkylating Agents Can Overcome Drug Tolerance of G0-like Tumor Cells and Eradicate BRCA1-Deficient Mammary Tumors in Mice.

    Science.gov (United States)

    Pajic, Marina; Blatter, Sohvi; Guyader, Charlotte; Gonggrijp, Maaike; Kersbergen, Ariena; Küçükosmanoğlu, Aslι; Sol, Wendy; Drost, Rinske; Jonkers, Jos; Borst, Piet; Rottenberg, Sven

    2017-11-15

    Purpose: We aimed to characterize and target drug-tolerant BRCA1-deficient tumor cells that cause residual disease and subsequent tumor relapse. Experimental Design: We studied responses to various mono- and bifunctional alkylating agents in a genetically engineered mouse model for BRCA1/p53 -mutant breast cancer. Because of the large intragenic deletion of the Brca1 gene, no restoration of BRCA1 function is possible, and therefore, no BRCA1-dependent acquired resistance occurs. To characterize the cell-cycle stage from which Brca1 -/- ;p53 -/- mammary tumors arise after cisplatin treatment, we introduced the fluorescent ubiquitination-based cell-cycle indicator (FUCCI) construct into the tumor cells. Results: Despite repeated sensitivity to the MTD of platinum drugs, the Brca1 -mutated mammary tumors are not eradicated, not even by a frequent dosing schedule. We show that relapse comes from single-nucleated cells delaying entry into the S-phase. Such slowly cycling cells, which are present within the drug-naïve tumors, are enriched in tumor remnants. Using the FUCCI construct, we identified nonfluorescent G 0 -like cells as the population most tolerant to platinum drugs. Intriguingly, these cells are more sensitive to the DNA-crosslinking agent nimustine, resulting in an increased number of multinucleated cells that lack clonogenicity. This is consistent with our in vivo finding that the nimustine MTD, among several alkylating agents, is the most effective in eradicating Brca1 -mutated mouse mammary tumors. Conclusions: Our data show that targeting G 0 -like cells is crucial for the eradication of BRCA1/p53-deficient tumor cells. This can be achieved with selected alkylating agents such as nimustine. Clin Cancer Res; 23(22); 7020-33. ©2017 AACR . ©2017 American Association for Cancer Research.

  19. Tolerância a agente curarizante provocada pela administração repetida da droga Tolerance to curarizing drug induced by chronic administration: an experimental study

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Zanini

    1974-03-01

    effective dose of DMT was determined by a "third part blind" when a 80% block was attained. When only 10 high frequency stimuli were applied to the nerve, a significant difference (p<0.05 in response was observed: Group I, 46.50 ± 20.00 g+; Group II, 55.25 ± 11.33 g+; Group III, 37.25 ± 10.77 g+; Group IV, 37.00 ± 12.74 g+. Significant differences in muscular force were also observed with sustained tetanus: Group I, 79.00 ± 16.21 g+; Group II, 76.75 ± 15.23 g+; Group III, 59.12 ± 17.38 g+; Group IV, 61.62 ± 14.74 g. Significant higher doses of curare i.v. were necessary in the group injected daily with the highest dose of curare than in any other group (p < 0.01: Group I, 3.62 ± 1.17 mcg/kg; Group II, 3.69 ± 1.21 mcg/kg; Group III, 4.01 ± 0.80 mcg/kg; Group IV, 5.48 ± 1.40. These results show that chronic administration of curare leads to physical weakness and hyposensitivity to the drug, thus suggesting that although the existence of a curarizing drug in the human blood may in fact contribute for the muscular weakness of the myasthenic patient, the blood curare does not play a major role in the pathogenesis of the syndrome since the myasthenic patient is highly sensitive to the injection of any curare.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. The therapeutic advantage of combination antihypertensive drug therapy using amlodipine and irbesartan in hypertensive patients: Analysis of the post-marketing survey data from PARTNER (Practical combination therapy of Amlodin and angiotensin II Receptor blocker; safety and efficacy in patients with hypertension) study.

    Science.gov (United States)

    Ishimitsu, Toshihiko; Fukuda, Hirofumi; Uchida, Masako; Ishibashi, Kazushi; Sato, Fusako; Nukui, Kazuhiko; Nagao, Munehiko

    2015-01-01

    Two-thirds of hypertensive patients need a combination antihypertensive therapy to achieve the target blood pressure (BP). The PARTNER (Practical combination therapy of Amlodin and angiotensin II Receptor blocker; Safety and efficacy in paTieNts with hypERtension) study is a prospective specific clinical use survey examining the efficacy and safety of 12-week treatment with amlodipine (AML) and Angiotensin II Receptor Blocker (ARB) in 5900 hypertensive patients. The current analysis was performed as to the BP control, adverse reactions, and the effects on laboratory data in patients treated with the combination of AML and irbesartan (IRB), namely the patients added AML to already taking IRB (AML add-on group, n = 1202) and the patients added IRB to AML (IRB add-on group, n = 1050). Both study groups showed distinct decreases in office BP at 4 week (p 7 mg/dl. The incidence of adverse reactions was as few as 1.11% and there were no severe adverse reactions which hampered the continuation of combination therapy. In conclusion, combination antihypertensive therapy with AML and IRB effectively lowers BP without particular safety problems, reduces serum uric acid especially in patients with hyperuricemia and exhibits renoprotective effects in patients with chronic kidney disease.

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

    Science.gov (United States)

    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.

  3. 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

  4. 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 ...

  5. 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 ...

  6. Invited review: Fermented milk as antihypertensive functional food.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  12. 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.

  13. Antihypertensive Properties of Plant-Based Prebiotics

    Science.gov (United States)

    Yeo, Siok-Koon; Ooi, Lay-Gaik; Lim, Ting-Jin; Liong, Min-Tze

    2009-01-01

    Hypertension is one of the major risk factors for cardiovascular disease. Although various drugs for its treatment have been synthesized, the occurring side effects have generated the need for natural interventions for the treatment and prevention of hypertension. Dietary intervention such as the administration of prebiotics has been seen as a highly acceptable approach. Prebiotics are indigestible food ingredients that bypass digestion and reach the lower gut as substrates for indigenous microflora. Most of the prebiotics used as food adjuncts, such as inulin, fructooligosaccharides, dietary fiber and gums, are derived from plants. Experimental evidence from recent studies has suggested that prebiotics are capable of reducing and preventing hypertension. This paper will discuss some of the mechanisms involved, the evidence generated from both in-vitro experiments and in-vivo trials and some controversial findings that are raised. PMID:20111692

  14. 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.

  15. ANTIHYPERTENSIVE AND ANTIOXIDATIVE EFFECTS OF CARVEDILOL AND METOPROLOL IN HYPERTENSIVE PATIENTS WITH OVERWEIGHT/OBESITY

    Directory of Open Access Journals (Sweden)

    V. A. Nevzorova

    2010-01-01

    Full Text Available Aim. To evaluate an efficacy of the 24-week antihypertensive therapy based on the carvedilol or metoprolol and its influence on markers of blood oxidative status in hypertensive patients with overweight/obesity.Material and methods. The observation data of 20 hypertensive patients (aged 40-65 y.o. with overweight/obesity were analyzed. Blood pressure (BP dynamics at each visit and a rate of target BP achievement were evaluated. Blood oxidative status was evaluated by plasma malondialdehyde (MDA level and erythrocyte superoxide dismutase (SOD activity. Therapy safety was evaluated by adverse events registration.Results. Significant reduction in both systolic and diastolic BP compared with baseline values was found. BP targets were achieved in all patients in both groups. The therapy based on carvedilol had a greater effect on blood oxidative status in comparison with metoprolol therapy. Plasma MDA level reduced from 7.03 [6.49;7.41] to 3.23 [2.88;3.57] μM/l (p<0.05 vs from 6.95 [6.51;7.39] to 6.08 [5.46;6.71] μM/l, respectively, and erythrocyte SOD activity increased from 27,89 [25.29;30.49] to 40.18 [35.89;44.45]% (p<0.05 vs from 28.41 [25.18;31.64] to 33.45 [30.65;36.23]%, respectively.Conclusion. The high antihypertensive efficacy, positive effect on blood oxidative status and well tolerability of therapy based on carvedilol in everyday clinical practice is presented.

  16. 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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

  19. 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.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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

  3. 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.

  4. 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.

  5. Comparison of the Local Tolerability to 5 Long-acting Drug Nanosuspensions with Different Stabilizing Excipients, Following a Single Intramuscular Administration in the Rat.

    Science.gov (United States)

    Chamanza, Ronnie; Darville, Nicolas; van Heerden, Marjolein; De Jonghe, Sandra

    2018-01-01

    To investigate the effects of common nanosuspension-stabilizing excipients on the nature and temporal evolution of histopathological changes at intramuscular (i.m.) administration sites, 5 groups of 39 male rats per group received a single injection of 1 of the 5 analogous crystalline drug nanosuspensions containing 200 mg/ml of an antiviral compound with particle sizes of ±200 nm and identical vehicle compositions, except for the type of nanosuspension stabilizer. The investigated stabilizers were poloxamer 338, poloxamer 407, d-α-tocopherol polyethylene glycol 1,000-succinate (TPGS), polysorbate 80, and polysorbate 80 combined with egg phosphatidylglycerol. Histopathology and immunohistochemistry revealed progressive inflammatory changes at the i.m. administration sites and the draining lymph nodes that differed according to the time point of sacrifice and the type of stabilizer. Although the overall time course of inflammatory changes was similar across the groups, differences in the nature, severity, and timing of the inflammatory response were observed between animals injected with poloxamer- or TPGS-containing nanosuspensions and those injected with formulations containing polysorbate 80. A more severe and prolonged active inflammatory phase, the presence of multinucleate giant cells, prolonged macrophage infiltration of the formulation depot, and more persistent histiocytic infiltrates in the lymph nodes were observed in the polysorbate 80-containing nanosuspension groups. Such vehicle-mediated effects could influence the overall tolerability profile of long-acting nanosuspensions.

  6. Evaluation of a Low-Threshold/High-Tolerance Methadone Maintenance Treatment Clinic in Saint John, New Brunswick, Canada: One Year Retention Rate and Illicit Drug Use

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    Timothy K. S. Christie

    2013-01-01

    Full Text Available Objective. To report the one-year retention rate and the prevalence of illicit opioid use and cocaine use in the Low-Threshold/High-Tolerance (LTHT methadone maintenance treatment (MMT clinic located in Saint John, New Brunswick, Canada. Methods. A description of the LTHT MMT clinic is provided. The one-year retention rate was determined by collecting data on patients who enrolled in the LTHT MMT clinic between August 04, 2009 and August 04, 2010. The prevalence of illicit drug use was determined using a randomly selected retrospective cohort of 84 participants. For each participant the results of six consecutive urine tests for the most recent three months were compared to the results of the first six consecutive urine tests after program entry. Results. The one-year retention rate was 95%, 67% of the cohort achieved abstinence from illicit opioids and an additional 13% abstained from cocaine use. Conclusion. The novel feature of the LTHT MMT clinic is that patients are not denied methadone because of lack of ancillary services. Traditional comprehensive MMT programs invest the majority of financial resources in ancillary services that support the biopsychosocial model, whereas the LTHT approach utilizes a medical model and directs resources at medical management.

  7. 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.

  8. Prognostic value of microalbuminuria during antihypertensive treatment in essential hypertension.

    Science.gov (United States)

    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.

  9. 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.

  10. 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

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

    Science.gov (United States)

    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

  12. 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.

  13. 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.

  14. 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...

  15. 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.

  16. EVALUATIN OF ANTIHYPERTENSIVE ACTIVITY OF SONCHUS ASPER L. IN RATS.

    Science.gov (United States)

    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.

  17. [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

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

    Science.gov (United States)

    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

  19. Patient adherence to antihypertensive therapy and its individual psychological factors

    Directory of Open Access Journals (Sweden)

    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

  20. Assessment of maximum tolerated dose of a new herbal drug, Semelil (ANGIPARSTM in patients with diabetic foot ulcer: A Phase I clinical trial

    Directory of Open Access Journals (Sweden)

    Heshmat R

    2008-04-01

    Full Text Available Background and the purpose of the study: In many cases of diabetic foot ulcer (DFU management, wound healing is incomplete, and wound closure and epithelial junctional integrity are rarely achieved. Our aim was to evaluate the maximum tolerated dose (MTD and dose-limiting toxicity (DLT of Semelil (ANGIPARSTM, a new herbal compound for wound treatment in a Phase I clinical trial.Methods: In this open label study, six male diabetic patients with a mean age of 57±7.6 years were treated with escalating intravenous doses of Semelil, which started at 2 cc/day to 13.5 cc/day for 28 days. Patients were assessed with a full physical exam; variables which analyzed included age, past history of diabetes and its duration, blood pressure, body temperature, weight, characteristics of DFU, Na, K, liver function test, Complete Blood Count and Differential(CBC & diff, serum amylase, HbA1c, PT, PTT, proteinuria, hematuria, and side effects were recorded. All the measurements were taken at the beginning of treatment, the end of week 2 and week 4. We also evaluated Semelil's side effects at the end of weeks 4 and 8 after ending therapy.Results and major conclusions: Up to the drug dose of 10 cc/day foot ulcer dramatically improved. We did not observe any clinical or laboratory side effects at this or lower dose levels in diabetic patients. With daily dose of 13.5 cc of Semelil we observed phlebitis at the infusion site, which was the only side effect. Therefore, in this study we determined the MTD of Semelil at 10 cc/day, and the only DLT was phlebitis in injection vein. The recommended dose of Semelil I.V. administration for Phase II studies was 4 cc/day.

  1. SAFETY AND TOLERABILITY OF ANTIEPILEPTIC DRUGS AT WOMEN WITH EPILEPSY (DATA OF SVT. LUKA’S INSTITUTE OF CHILD NEUROLOGY AND EPILEPSY

    Directory of Open Access Journals (Sweden)

    K. Yu. Мukhin

    2015-01-01

    Full Text Available Women with epilepsy are referred to the special risk group due to the development of side effects of antiepileptic drugs (АED. Women’s neuroendocrinal disorders can be caused by the disease itself-epilepsy, as well as by the undertaken therapy. We have carried out a retrospective research in order to assess the safety and the tolerance of different AED at young girls and women of reproductive age. Was analyzed the data base of patients of Svt. Luka’s Institute of Child Neurology and Epilepsy, comprising all patients, who have been monitored in the period between 2000 and 2014 inclusive at the age between 15–40 years (n = 301. The research included patients, with different diagnosed forms of focal or generalized epilepsy, who were taking AED both during mono and polytherapy. Were analyzed all cases of neuroendocrinal, especially reproductive disorders, including the considerable gain of weight, menstrual disorder, sterility at AED background. Also was analyzed the result of all registered pregnancies at women with epilepsy (at the background of the antiepileptic therapy, as well as without treatment during pregnancy. The retrospective data analysis has revealed 51 сase (17 % in the group under review of expressed neuroendocrinal, reproductive and cosmetic side effects (including the menstrual disorder: dysmenorrhea, opsomenorrhea, amenorrhea, anovulatory cycles, sterility, unfavorable pregnancy outcomes, as well as cosmetic endocrinal side effects: obesity, hirsutism, hair loss. Most patients have got such combined side effects. Our research results show, that in most cases the pregnancy at women with epilepsy ends by birth of a healthy child, the pregnancy outcome depends on many factors, it also differs according to applied AED. Valproic acid drugs show the highest teratogenic risk. Also at the back ground of the therapy with valproic acid have been registered most cases of neuroendocrinal reproductive diseases at women

  2. 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

    Directory of Open Access Journals (Sweden)

    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%.

  3. 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.

  4. Efficacy and tolerability of urate-lowering drugs in gout : a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol

    NARCIS (Netherlands)

    Reinders, Mattheus; van Roon, E.N.; Jansen, T.L.; Delsing, J.; Griep, E.N.; Hoekstra, M.; van de Laar, M.F.; Brouwers, J.R.

    Objectives: To investigate the efficacy and tolerability of allopurinol as the first-choice antihyperuricaemic treatment for gout, and compare the efficacy and tolerability of benzbromarone and probenecid as second-choice treatment. Methods: Prospective, multicentre, open-label, two-stage randomised

  5. Mechanisms underlying the antihypertensive properties of Urtica dioica.

    Science.gov (United States)

    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.

  6. Crafting tolerance

    DEFF Research Database (Denmark)

    Kirchner, Antje; Freitag, Markus; Rapp, Carolin

    2011-01-01

    Ongoing changes in social structures, orientation, and value systems confront us with the growing necessity to address and understand transforming patterns of tolerance as well as specific aspects, such as social tolerance. Based on hierarchical analyses of the latest World Values Survey (2005......–08) and national statistics for 28 countries, we assess both individual and contextual aspects that influence an individual's perception of different social groupings. Using a social tolerance index that captures personal attitudes toward these groupings, we present an institutional theory of social tolerance. Our...

  7. 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.

  8. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Adherence to antihypertensive treatment and its determinants among urban slum dwellers in Kolkata, India.

    Science.gov (United States)

    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.

  11. Critical appraisal of the differential effects of antihypertensive agents on arterial stiffness

    Directory of Open Access Journals (Sweden)

    Francesca Kum

    2010-06-01

    Full Text Available Francesca Kum, Janaka KarallieddeUnit for Metabolic Medicine, Cardiovascular Division, Kings College-Waterloo Campus, King’s College London, United KingdomAbstract: Increased central arterial stiffness, involving accelerated vascular ageing of the aorta, is a powerful and independent risk factor for early mortality and provides prognostic information above and beyond traditional risk factors for cardiovascular disease (CVD. Central arterial stiffness is an important determinant of pulse pressure; therefore, any pathological increase may result in left ventricular hypertrophy and impaired coronary perfusion. Central artery stiffness can be assessed noninvasively by measurement of aortic pulse wave velocity, which is the gold standard for measurement of arterial stiffness. Earlier, it was believed that changes in arterial stiffness, which are primarily influenced by long-term pressure-dependent structural changes, may be slowed but not reversed by pharmacotherapy. Recent studies with drugs that inhibit the renin–angiotensin–aldosterone system, advanced glycation end products crosslink breakers, and endothelin antagonists suggest that blood pressure (BP-independent reduction and reversal of arterial stiffness are feasible. We review the recent literature on the differential effect of antihypertensive agents either as monotherapy or combination therapy on arterial stiffness. Arterial stiffness is an emerging therapeutic target for CVD risk reduction; however, further clinical trials are required to confirm whether BP-independent changes in arterial stiffness directly translate to a reduction in CVD events.Keywords: aortic pulse wave velocity, augmentation index, blood pressure, renin–angiotensin–aldosterone system

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

    Science.gov (United States)

    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.

  13. Interactions of renin-angiotensin system gene polymorphisms and antihypertensive effect of benazepril in Chinese population.

    Science.gov (United States)

    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.

  14. 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.

  15. COMPARATIVE EFFICАCY AND TOLERABILITY OF MONOTHERAPY WITH DEPAKINE CHRONOSPHERE, DRUGS OF CARBAMAZEPINE GROUP WITH EXTENDED RELEASE AND OXCARBAZEPINE IN SYMPTOMATIC AND CRYPTOGENIC FOCAL EPILEPSY (SVT. LUKA’S INSTITUTE OF CHILD NEUROLOGY AND EPILEPSY

    Directory of Open Access Journals (Sweden)

    K. Yu. Mukhin

    2015-01-01

    Full Text Available Research on comparative efficаcy and tolerability of monotherapy with Depakine chronosphere, drugs of Carbamazepine group with extended release and oxcarbazepine in symptomatic and cryptogenic focal epilepsy has been conducted at Svt. Luka’s Institute of Child Neurology and Epilepsy (ICNE (Moscow. This retrospective study covers a random sample of patients treated in ICNE in the period from December 1, 2013 to September 1, 2014.  The study included 131 patients aged 1 to 18 years with symptomatic and cryptogenic focal epilepsy receiving treatment with one of the study drugs in monotherapy: group 1 – monotherapy with Depakine chronosphere (n = 56; group 2 – monotherapy with drugs of carbamazepine group with extended release (n = 55; group 3 – monotherapy with oxcarbazepine (trileptal (n = 20. The obtained results allow us to conclude that the effectiveness of Depakin chronosphere, carbamazepine with extended release and oxcarbazepine in monotherapy of symptomatic and cryptogenic focal epilepsy was comparable (statistically significant differences in efficacy were not found. However, carbamazepine was awarded the highest frequency of seizures aggravation. Drugs showed approximately same tolerability (statistically significant differences in tolerability were not found. However, withdrawal of the drug due to side effects was the rarest in Depakine (3.5 %, and withdrawal due to intolerance was higher in carbamazepine and oxcarbazepine (5 and 10 % respectively. Depakinum and oxcarbazepine had the best results in the blocking of pathological activity on the electroencephalogram, whereas carbamazepine was clearly inferior to them. In this regard, complete clinical-electroencephalographic remission (lasting 12 months or more was achieved under treatment of Depakine chromosphere in 21.5 % of cases, oxcarbazepi on therapy for 12 months was similar in all study drugs. Considering that the objective of epilepsy treatment is to achieve complete

  16. 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

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

    Science.gov (United States)

    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

  18. 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...

  19. 21 CFR 570.18 - Tolerances for related food additives.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Tolerances for related food additives. 570.18 Section 570.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES General Provisions § 570.18 Tolerances...

  20. Om tolerance

    DEFF Research Database (Denmark)

    Huggler, Jørgen

    2007-01-01

    Begrebet tolerance og dets betydninger diskuteres med henblik på en tydeliggørelse af begrebets forbindelse med stat, religion, ytringsfrihed, skeptisk erkendelsesteori, antropologi og pædagogik.......Begrebet tolerance og dets betydninger diskuteres med henblik på en tydeliggørelse af begrebets forbindelse med stat, religion, ytringsfrihed, skeptisk erkendelsesteori, antropologi og pædagogik....

  1. Combined in vivo and in vitro approach for the characterization of penicillin-specific polyclonal lymphocyte reactivity: tolerance tests with safe penicillins instead of challenge with culprit drugs.

    Science.gov (United States)

    Sachs, B; Al Masaoudi, T; Merk, H F; Erdmann, S

    2004-10-01

    Amino-penicillins are a major cause of delayed-type reactions to penicillins. The aim of this study was to establish a diagnostic approach for the characterization of the individual penicillin-specific polyclonal lymphocyte reactivity in order to detect side chain-specific sensitization to amino-penicillins. Patients can then be advised to undergo a tolerance test with safe penicillins instead of provocation with culprit penicillins for confirmation of penicillin allergy. We investigated penicillin-specific polyclonal lymphocyte reactivity in nine patients with delayed-type reactions to amino-penicillins by a combined in vivo (patch, prick and intracutaneous tests with delayed readings) and in vitro (lymphocyte transformation test, LTT) approach. A combination of LTT and skin tests improved the sensitivity for the characterization of penicillin-specific polyclonal lymphocyte reactivity and allowed the detection of three different patterns of lymphocyte reactivity. Four patients showed a side chain-specific sensitization to amino-penicillins in vivo and in vitro and were advised to undergo tolerance tests with safe penicillins. Two patients agreed and were exposed to parenteral benzyl-penicillin and oral phenoxymethyl-penicillin which they tolerated without complications. These data suggest that a combined in vivo and in vitro approach is helpful for the detection of side chain-specific sensitization to amino-penicillins. Patients with such sensitization are very likely to tolerate safe penicillins, thereby expanding their therapeutic options when antibiotic treatment is required.

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

    Science.gov (United States)

    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.

  3. Antihypertensive and cardioprotective effects of pumpkin seed oil.

    Science.gov (United States)

    El-Mosallamy, Aliaa E M K; Sleem, Amany A; Abdel-Salam, Omar M E; Shaffie, Nermeen; Kenawy, Sanaa A

    2012-02-01

    Pumpkin seed oil is a natural product commonly used in folk medicine for treatment of prostatic hypertrophy. In the present study, the effects of treatment with pumpkin seed oil on hypertension induced by the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME) (50 mg /kg/day) in rats were studied and compared with those of the calcium channel blocker amlodipine. Pumpkin seed oil (40 or 100 mg/kg), amlodipine (0.9 mg/kg), or vehicle (control) was given once daily orally for 6 weeks. Arterial blood pressure (BP), heart rate, electrocardiogram (ECG) changes, levels of serum nitric oxide (NO) (the concentrations of nitrite/nitrate), plasma malondialdehyde (MDA), blood glutathione, and erythrocytic superoxide dismutase activity were measured. Histopathological examination of heart and aorta was conducted as well. L-NAME administration resulted in a significant increase in BP starting from the second week. Pumpkin seed oil or amlodipine treatment significantly reduced the elevation in BP by L-NAME and normalized the L-NAME-induced ECG changes-namely, prolongation of the RR interval, increased P wave duration, and ST elevation. Both treatments significantly decreased the elevated levels of MDA and reversed the decreased levels of NO metabolites to near normal values compared with the L-NAME-treated group. Amlodipine also significantly increased blood glutathione content compared with normal (but not L-NAME-treated) rats. Pumpkin seed oil as well as amlodipine treatment protected against pathological alterations in heart and aorta induced by L-NAME. In conclusion, this study has shown that pumpkin seed oil exhibits an antihypertensive and cardioprotective effects through a mechanism that may involve generation of NO.

  4. 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.

  5. Choosing antihypertensive treatment for a South African population

    African Journals Online (AJOL)

    failure (third-generation beta blockers) and a prior myocardial infarction. ACE inhibitors. ACE inhibitors are first-line therapy in all patients who have heart failure or ... alpha blocker may be preferred in older men with symptoms of prostatism. Drug dosing and drug frequency. The steepest part of the dose response curve is ...

  6. Towards Tolerance

    NARCIS (Netherlands)

    Lisette Kuyper; Jurjen Iedema; Saskia Keuzenkamp

    2013-01-01

    Across Europe, public attitudes towards lesbian, gay and bisexual (LGB) individuals range from broad tolerance to widespread rejection. Attitudes towards homosexuality are more than mere individual opinions, but form part of the social and political structures which foster or hinder the equality

  7. Intolerant tolerance.

    Science.gov (United States)

    Khushf, G

    1994-04-01

    The Hyde Amendment and Roman Catholic attempts to put restrictions on Title X funding have been criticized for being intolerant. However, such criticism fails to appreciate that there are two competing notions of tolerance, one focusing on the limits of state force and accepting pluralism as unavoidable, and the other focusing on the limits of knowledge and advancing pluralism as a good. These two types of tolerance, illustrated in the writings of John Locke and J.S. Mill, each involve an intolerance. In a pluralistic context where the free exercise of religion is respected, John Locke's account of tolerance is preferable. However, it (in a reconstructed form) leads to a minimal state. Positive entitlements to benefits like artificial contraception or nontherapeutic abortions can legitimately be resisted, because an intolerance has already been shown with respect to those that consider the benefit immoral, since their resources have been coopted by taxation to advance an end that is contrary to their own. There is a sliding scale from tolerance (viewed as forbearance) to the affirmation of communal integrity, and this scale maps on to the continuum from negative to positive rights.

  8. Long-term organ protection by doxazosin and/or quinapril as antihypertensive therapy.

    Science.gov (United States)

    Gallego-Delgado, Julio; Lazaro, Alberto; Gomez-Garre, Dulcenombre; Osende, Julio I; Gonzalez-Rubio, Maria L; Herraiz, Marta; Manzarbeitia, Félix; Fortes, José; Fernandez-Cruz, Arturo; Egido, Jesús

    2006-01-01

    Even with optimal blood pressure control, organ protection may also depend on the selected therapeutic regime. Angiotensin-converting enzyme inhibitors have been shown to provide excellent organ protection in hypertension, and may show dose-dependent protective effects. Adrenergic alpha blockers have been associated with an increased rate of heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and Vasodilator-Heart Failure Trial (V-HeFT). This has been related to a proapoptotic effect of this drug in cardiomyocytes. Our purpose is to compare the heart and renal protection of a high quinapril dose, with a combined low quinapril dose plus doxazosin, in an animal model of chronic hypertension. Uninephrectomized spontaneously hypertensive 12-week-old rats were treated for 36 weeks with either quinapril or a combination of doxazosin plus a low quinapril dose. Tight blood pressure control was achieved with both treatments. Renal and cardiac protection was assessed by different parameters, and cardiac apoptosis was evaluated by active caspase-3, apoptotic protein and heat shock protein levels. Untreated hypertensive and normotensive rats were included as controls. Both treatments showed significant heart and renal protection compared with untreated animals. Both therapeutic regimes showed similar protection in renal and cardiac pathology, coronary media fibrosis, myocardial apoptosis and cardiac index. Proteinuria and left ventricular hypertrophy regression were significantly lower in the quinapril group compared with the combined treatment group. Blood pressure control with a high quinapril dose provided higher organ protection than a combined therapy with a lower quinapril dose. This effect was not due to a deleterious effect of doxazosin.

  9. The cancer drug Dasatinib increases PGC-1α in adipose tissue but has adverse effects on glucose tolerance in obese mice

    DEFF Research Database (Denmark)

    Sylow, Lykke; Long, Jonathan; Lokurkar, Isha A

    2016-01-01

    Dasatinib (Sprycel) is a tyrosine kinase inhibitor approved for treatment of chronic myeloid leukemia (CML). In this study we identify dasatinib as a potent inducer of PGC-1α mRNA. Dasatinib increased PGC-1α mRNA expression up to 6-fold in 3T3-F442A adipocytes, primary adipocytes, and epididymal ......, dasatinib significantly impaired glucose tolerance in obese, but not lean mice. As far as we are aware, this is the first study to show that dasatinib regulates PGC-1α and causes glucose intolerance in obese mice. This should be considered in the treatment of CML....

  10. Drugs in breast milk.

    Science.gov (United States)

    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.

  11. Plasmodium falciparum in vitro continuous culture conditions: A comparison of parasite susceptibility and tolerance to anti-malarial drugs throughout the asexual intra-erythrocytic life cycle.

    Science.gov (United States)

    Duffy, Sandra; Avery, Vicky M

    2017-12-01

    The continuous culture of Plasmodium falciparum is often seen as a means to an end, that end being to probe the biology of the parasite in question, and ultimately for many in the malaria drug discovery arena, to identify means of killing the parasite in order to treat malaria. In vitro continuous culture of Plasmodium falciparum is a fundamental requirement when undertaking malaria research where the primary objectives utilise viable parasites of a desired lifecycle stage. This investigation, and resulting data, compared the impact culturing Plasmodium falciparum long term (4 months) in different environmental conditions had on experimental outcomes and thus conclusions. The example presented here focused specifically on the effect culture conditions had on the in vitro tolerance of Plasmodium falciparum to standard anti-malarial drugs, including artemisinin and lumefantrine. Historical data from an independent experiment for 3D7-ALB (5% O 2 ) was also compared with that obtained from this study. We concluded that parasites cultured for several months in media supplemented with a serum substitute such as Albumax II ® or within hyperoxic conditions (21% O 2 ), demonstrate highly variable responses to artemisinin and lumefantrine but not all anti-malarial drugs, when compared to those cultured in human serum in combination with Albumax II ® under normoxic conditions (5% O 2 ) for the parasite. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Alcohol Ataxia Tolerance: Extinction Cues, Spontaneous Recovery, and Relapse

    OpenAIRE

    Brooks, Douglas C.

    2005-01-01

    This article reviews ethanol ataxic tolerance experiments with rats that investigate spontaneous recovery after extinction and how extinction-related cues reduce this recovery. Tolerance to the effects of many drugs including ethanol is partly the result of Pavlovian conditioning. Tolerance to the ataxic (and other) effects of ethanol depends critically upon the circumstances in which the drug is administered. Tolerance shows other characteristics common in Pavlovian conditioning, e.g.,. it c...

  13. Tolerance to and cross tolerance between ethanol and nicotine.

    Science.gov (United States)

    Collins, A C; Burch, J B; de Fiebre, C M; Marks, M J

    1988-02-01

    Female DBA mice were subjected to one of four treatments: ethanol-containing or control diets, nicotine (0.2, 1.0, 5.0 mg/kg/hr) infusion or saline infusion. After removal from the liquid diets or cessation of infusion, the animals were challenged with an acute dose of ethanol or nicotine. Chronic ethanol-fed mice were tolerant to the effects of ethanol on body temperature and open field activity and were cross tolerant to the effects of nicotine on body temperature and heart rate. Nicotine infused animals were tolerant to the effects of nicotine on body temperature and rotarod performance and were cross tolerant to the effects of ethanol on body temperature. Ethanol-induced sleep time was decreased in chronic ethanol- but not chronic nicotine-treated mice. Chronic drug treatment did not alter the elimination rate of either drug. Chronic ethanol treatment did not alter the number or affinity of brain nicotinic receptors whereas chronic nicotine treatment elicited an increase in the number of [3H]-nicotine binding sites. Tolerance and cross tolerance between ethanol and nicotine is discussed in terms of potential effects on desensitization of brain nicotinic receptors.

  14. 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

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Salt Tolerance

    OpenAIRE

    Xiong, Liming; Zhu, Jian-Kang

    2002-01-01

    Studying salt stress is an important means to the understanding of plant ion homeostasis and osmo-balance. Salt stress research also benefits agriculture because soil salinity significantly limits plant productivity on agricultural lands. Decades of physiological and molecular studies have generated a large body of literature regarding potential salt tolerance determinants. Recent advances in applying molecular genetic analysis and genomics tools in the model plant Arabidopsis thaliana are sh...

  18. 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.

  19. 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....

  20. Pavlovian conditioning analysis of morphine tolerance.

    Science.gov (United States)

    Siegel, S

    1978-01-01

    It has been demonstrated that many conditional responses to a variety of drugs are opposite in direction to the unconditional effects of the drug, and the conditioning analysis of morphine tolerance emphasizes the fact that subjects with a history of morphine administration display morphine-compensatory conditional responses when confronted with the usual administration procedure but without the drug. Thus, when the drug is presented in the context of the usual administration cues, these conditional morphine-compensatory responses would be expected to attenuate the drug-induced unconditional responses, thereby decreasing the observed response to the drug. Research has been summarized which supports this compensatory conditioning model of tolerance by demonstrating that the display of tolerance is specific to the environment in which the drug has been previously administered. Further evidence supporting this theory of tolerance has been provided by studies establishing that extinction, partial reinforcement, and latent inhibition--non-pharmacological manipulations known to be effective in generally affecting the display of conditional responses--similarly affect the display of morphine tolerance. Additional research has suggested many parallels between learning and morphine tolerance: Both processes exhibit great retention, both are disrupted by electroconvulsive shock and frontal cortical stimulation, both are retarded by inhibitors of protein synthesis, and both are facilitated by antagonists of these metabolic inhibitors.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. An open-label, multicenter, flexible dose study to evaluate the efficacy and safety of Viagra (sildenafil citrate) in Korean men with erectile dysfunction and arterial hypertension who are taking antihypertensive agents.

    Science.gov (United States)

    Park, Hyun Jun; Park, Nam Cheol; Shim, Hong Bang; Park, Jong Kwan; Lee, Sung Won; Park, Kwangsung; Kim, Sae Woong; Moon, Ki Hak; Lee, Dong Hyeon; Yoon, Sang Jin

    2008-10-01

    Erectile dysfunction (ED) is common among men taking antihypertensive agents to control blood pressure. We evaluated the efficacy and safety of sildenafil citrate in men with ED taking antihypertensive agents. A total of 198 male subjects, aged 20 years and older were enrolled. This study was conducted for 10 weeks as an open-label, multicenter and flexible dose trial with a 2-week screening period and an 8-week treatment phase. Subjects were asked to complete Event Log Worksheets, as well as the International Index of Erectile Function (IIEF) and the Global Efficacy Assessment Questions (GEAQ) questionnaires during the study period. The average age among the 167 subjects who completed the study was 55.8 (31.7 to 77.1). The scores for questions 3 and 4 of IIEF improved from 2.3 and 1.8 at baseline to 3.7 and 3.4 at week 4 and 3.8 and 3.4 at week 8, respectively. There were 86.3% of the patients reported improved erectile function at week 8; 88.3% of the patients reported improved ability to achieve sexual intercourse at week 8. There were no significant differences observed in the responses to questions 3 and 4 of IIEF and GEAQ by the number of antihypertensive agents taken. The adverse events were facial flushing (20.1%), headache (11.7%), palpitation (5.0%), rhinitis (2.8%), URI (2.8%), dizziness (2.2%), dyspnea (2.2%), and nausea (1.7%). Sildenafil citrate is an effective treatment for ED; it is safe and well tolerated by patients with ED taking multiple antihypertensive agents for arterial hypertension.

  3. A systematic study of the effect of low pH acid treatment on anti-drug antibodies specific for a domain antibody therapeutic: Impact on drug tolerance, assay sensitivity and post-validation method assessment of ADA in clinical serum samples.

    Science.gov (United States)

    Kavita, Uma; Duo, Jia; Crawford, Sean M; Liu, Rong; Valcin, Joan; Gleason, Carol; Dong, Huijin; Gadkari, Snaehal; Dodge, Robert W; Pillutla, Renuka C; DeSilva, Binodh S

    2017-09-01

    We developed a homogeneous bridging anti-drug antibody (ADA) assay on an electro chemiluminescent immunoassay (ECLIA) platform to support the immunogenicity evaluation of a dimeric domain antibody (dAb) therapeutic in clinical studies. During method development we evaluated the impact of different types of acid at various pH levels on polyclonal and monoclonal ADA controls of differing affinities and on/off rates. The data shows for the first time that acids of different pH can have a differential effect on ADA of various affinities and this in turn impacts assay sensitivity and drug tolerance as defined by these surrogate controls. Acid treatment led to a reduction in signal of intermediate and low affinity ADA, but not high affinity or polyclonal ADA. We also found that acid pretreatment is a requisite for dissociation of drug bound high affinity ADA, but not for low affinity ADA-drug complexes. Although we were unable to identify an acid that would allow a 100% retrieval of ADA signal post-treatment, use of glycine pH3.0 enabled the detection of low, intermediate and high affinity antibodies (Abs) to various extents. Following optimization, the ADA assay method was validated for clinical sample analysis. Consistencies within various parameters of the clinical data such as dose dependent increases in ADA rates and titers were observed, indicating a reliable ADA method. Pre- and post-treatment ADA negative or positive clinical samples without detectable drug were reanalyzed in the absence of acid treatment or presence of added exogenous drug respectively to further assess the effectiveness of the final acid treatment procedure. The overall ADA results indicate that assay conditions developed and validated based on surrogate controls sufficed to provide a reliable clinical data set. The effect of low pH acid treatment on possible pre-existing ADA or soluble multimeric target in normal human serum was also evaluated, and preliminary data indicate that acid type and

  4. Micropropagation and in vitro flowering of Rauvolfia tetraphylla; a potent source of anti-hypertension drugs.

    Science.gov (United States)

    Sarma, D; Sarma, S; Baruah, A

    1999-04-01

    A simple protocol for in vitro mass multiplication of Rauvolfia tetraphylla (Apocynaceae) has been developed. The endophytic microflora was controlled by adopting integrated measures. Multiple shoot development was achieved on MS + Kin (0.1-0.2 mg/l) + BAP (0.4-0.5 mg/l) media. Rooting from in vitro shoots occurred on NAA containing media. In vitro flowering was induced in shoot multiplication media.

  5. A rapid method for the determination of some antihypertensive and antipyretic drugs by thermometric titrimetry.

    Science.gov (United States)

    Abbasi, U M; Chand, F; Bhanger, M I; Memon, S A

    1986-02-01

    A simple and rapid method is described for the direct thermometric determination of milligram amounts of methyl dopa, propranolol hydrochloride, 1-phenyl-3-methylpyrazolone (MPP) and 2,3-dimethyl-1-phenylpyrazol-5-one (phenazone) in the presence of excipients. The compounds are reacted with N'-bromosuccinimide and the heat of reaction is used to determine the end-point of the titration. The time required is approximately 2 min, and the accuracy is analytically acceptable.

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

    OpenAIRE

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

    2016-01-01

    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 < 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 ph...

  7. 75 FR 69353 - Isoxaben; Pesticide Tolerances

    Science.gov (United States)

    2010-11-12

    ...; and pistachio. Dow AgroSciences requested these tolerances under the Federal Food, Drug, and Cosmetic... 0.01 ppm; and nut, tree, group 14 and pistachio at 0.03 ppm. That notice referenced a summary of the... the data supporting the petition, EPA has reduced the tolerances for nut, tree, group 14 and pistachio...

  8. Infectious Tolerance

    OpenAIRE

    Jonuleit, Helmut; Schmitt, Edgar; Kakirman, Hacer; Stassen, Michael; Knop, Jürgen; Enk, Alexander H.

    2002-01-01

    Regulatory CD4+CD25+ T cells (Treg) are mandatory for maintaining immunologic self-tolerance. We demonstrate that the cell-cell contact–mediated suppression of conventional CD4+ T cells by human CD25+ Treg cells is fixation resistant, independent from membrane-bound TGF-β but requires activation and protein synthesis of CD25+ Treg cells. Coactivation of CD25+ Treg cells with Treg cell–depleted CD4+ T cells results in anergized CD4+ T cells that in turn inhibit the activation of conventional, ...

  9. 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.

    Science.gov (United States)

    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.

  10. Impact of overweight and obesity on cardiac benefit of antihypertensive treatment

    DEFF Research Database (Denmark)

    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...

  11. Time course of the antiproteinuric and antihypertensive effects of direct renin inhibition in type 2 diabetes

    DEFF Research Database (Denmark)

    Persson, F; Rossing, P; Schjoedt, K J

    2008-01-01

    Inhibition of renin with an active site inhibitor, aliskiren, lowers blood pressure (BP) in diabetic patients. Here, we studied the time course of the antihypertensive and antiproteinuric effect of renin inhibition in 15 patients with type 2 diabetes and elevated urinary albumin/creatinine ratios...

  12. Blood Pressure Variability and Outcome in Patients with Acute Nonlobar Intracerebral Hemorrhage following Intensive Antihypertensive Treatment

    Directory of Open Access Journals (Sweden)

    Jin Pyeong Jeon

    2018-01-01

    Conclusions: The MAC of SBP is associated with hematoma growth, and SD and COV are correlated with 3-month poor outcome in patients with supratentorial nonlobar ICH. Therefore, sustained SBP control, with a reduction in SBP variability is essential to reinforce the beneficial effect of intensive antihypertensive treatment.

  13. 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

  14. Infectious Tolerance

    Science.gov (United States)

    Jonuleit, Helmut; Schmitt, Edgar; Kakirman, Hacer; Stassen, Michael; Knop, Jürgen; Enk, Alexander H.

    2002-01-01

    Regulatory CD4+CD25+ T cells (Treg) are mandatory for maintaining immunologic self-tolerance. We demonstrate that the cell-cell contact–mediated suppression of conventional CD4+ T cells by human CD25+ Treg cells is fixation resistant, independent from membrane-bound TGF-β but requires activation and protein synthesis of CD25+ Treg cells. Coactivation of CD25+ Treg cells with Treg cell–depleted CD4+ T cells results in anergized CD4+ T cells that in turn inhibit the activation of conventional, freshly isolated CD4+ T helper (Th) cells. This infectious suppressive activity, transferred from CD25+ Treg cells via cell contact, is cell contact–independent and partially mediated by soluble transforming growth factor (TGF)-β. The induction of suppressive properties in conventional CD4+ Th cells represents a mechanism underlying the phenomenon of infectious tolerance. This explains previously published conflicting data on the role of TGF-β in CD25+ Treg cell–induced immunosuppression. PMID:12119350

  15. 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.

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

    Science.gov (United States)

    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.

  17. A retention-time-shift-tolerant background subtraction and noise reduction algorithm (BgS-NoRA) for extraction of drug metabolites in liquid chromatography/mass spectrometry data from biological matrices.

    Science.gov (United States)

    Zhu, Peijuan; Ding, Wei; Tong, Wei; Ghosal, Anima; Alton, Kevin; Chowdhury, Swapan

    2009-06-01

    A retention-time-shift-tolerant background subtraction and noise reduction algorithm (BgS-NoRA) is implemented using the statistical programming language R to remove non-drug-related ion signals from accurate mass liquid chromatography/mass spectrometry (LC/MS) data. The background-subtraction part of the algorithm is similar to a previously published procedure (Zhang H and Yang Y. J. Mass Spectrom. 2008, 43: 1181-1190). The noise reduction algorithm (NoRA) is an add-on feature to help further clean up the residual matrix ion noises after background subtraction. It functions by removing ion signals that are not consistent across many adjacent scans. The effectiveness of BgS-NoRA was examined in biological matrices by spiking blank plasma extract, bile and urine with diclofenac and ibuprofen that have been pre-metabolized by microsomal incubation. Efficient removal of background ions permitted the detection of drug-related ions in in vivo samples (plasma, bile, urine and feces) obtained from rats orally dosed with (14)C-loratadine with minimal interference. Results from these experiments demonstrate that BgS-NoRA is more effective in removing analyte-unrelated ions than background subtraction alone. NoRA is shown to be particularly effective in the early retention region for urine samples and middle retention region for bile samples, where the matrix ion signals still dominate the total ion chromatograms (TICs) after background subtraction. In most cases, the TICs after BgS-NoRA are in excellent qualitative correlation to the radiochromatograms. BgS-NoRA will be a very useful tool in metabolite detection and identification work, especially in first-in-human (FIH) studies and multiple dose toxicology studies where non-radio-labeled drugs are administered. Data from these types of studies are critical to meet the latest FDA guidance on Metabolite in Safety Testing (MIST). Copyright (c) 2009 John Wiley & Sons, Ltd.

  18. In vivo antihypertensive and antidyslipidemic effects of the crude extracts and fractions of Moringa stenopetala (Baker f. Cufod. leaves in rats.

    Directory of Open Access Journals (Sweden)

    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.

  19. COMPARISON OF EFFICACY AND TOLERABILITY OF ORIGINAL AND GENERIC DRUGS OF SIMVASTATIN IN PATIENTS WITH HYPERLIPIDAEMIA AND HIGH RISK OF ISCHEMIC HEART DISEASE COMPLICATIONS

    Directory of Open Access Journals (Sweden)

    S. N. Tolpygina

    2008-01-01

    Full Text Available Aim. To assess efficacy and safety of generic simvastatin, Simvahexal, in comparison with original drug of simvastatin, Zocor, in patients with hyperlipidaemia in short-term study.Material and methods. 30 patients (19 men and 11 women, 64,0±1,8 y.o. with low density lipoprotein (LDL cholesterol ≥3,0 mmol/l and high cardiovascular risk were involved into the study. During 5 weeks before study including patients kept the hypolipidaemic diet and did not receive any hypolipidaemic drug. 28 patients completed study, 2 patients drop out: one patient because of nettle rash on Zocor therapy, another one – because of personal reason. Efficacy was assessed by dynamic of lipid profile and a number of patients who reached target level of LDL cholesterol (<3 mmol/l. Safety was assessed by side effect rate registration. Patients were randomized in 2 groups (G1 and G2: G1 patients (n=15 received Zocor 20 mg/day during 6 weeks, G2 patients (n=15 – Simvahexal 20 mg/day. After 6 weeks of therapy G1 patients were switched from Zocor to Simvahexal, G2 patients did not change their therapy. Simvahexal dose was increased to 30 mg/day, if the target level of LDL cholesterol had not been reached after first 6 weeks of therapy.Results. After switching therapy from Zocor to Simvahexal 11 patients increased the dose to 30 mg/day, 3 patients kept the dose of 20 mg/day, 1 patient drop out. At the beginning of the study 15 patients received Simvahexal 20 mg/day, after 6 weeks the dose was increased to 30 mg/day in 8 patients, 7 patients kept the dose of 20 mg/day. After 6 weeks of therapy with Zocor 20 mg/day levels of the total cholesterol (TC and LDL cholesterol reduced on 25,2% and 33,6% (p<0,001, respectively. Next 6 weeks of therapy with Simvahexal in the average dose of 27,7 mg/day this reduction reached to 30,9% and 39,9% (p<0,001, respectively. After 6 weeks of therapy with Simvahexal 20mg/day levels of the TC and LDL cholesterol reduced on 28,2%and 38%(p<0

  20. Economic evaluation for first-line anti-hypertensive medicines: applications for the Philippines

    Directory of Open Access Journals (Sweden)

    Geroy Lester Sam Araneta

    2012-12-01

    Full Text Available Abstract Background Medicines to control hypertension, a leading cause of morbidity and mortality, are a major component of health expenditures in the Philippines. This study aims to review economic studies for first line anti-hypertensive medical treatment without co-morbidities; and discuss practical, informational and policy implications on the use of economic evaluation in the Philippines. Methods A systematic literature review was performed using the following databases: MEDLINE, EMBASE, BIOSIS, PubMed, The Cochrane Library, Health Economics Evaluations Database (HEED and the Centre for Reviews and Dissemination – NHS NICE. Six existing economic analytical frameworks were reviewed and one framework for critical appraisal was developed. Results Out of 1336 searched articles, 12 fulfilled the inclusion criteria. The studies were summarized according to their background characteristics (year, journal, intervention and comparators, objective/study question, target audience, economic study type, study population, setting and country and source of funding/conflict of interest and technical characteristics (perspective, time horizon, methodology/modeling, search strategy for parameters, costs, effectiveness measures, discounting, assumptions and biases, results, cost-effectiveness ratio, endpoints, sensitivity analysis, generalizability, strengths and limitations, conclusions, implications and feasibility and recommendations. The studies represented different countries, perspectives and stakeholders. Conclusions Diuretics were the most cost-effective drug class for first-line treatment of hypertension without co-morbidities. Although the Philippine Health Insurance Corporation may apply the recommendations given in previous studies (i.e. to subsidize diuretics, ACE inhibitors and calcium channel blockers, it is uncertain how much public funding is justified. There is an information gap on clinical data (transition probabilities, relative risks

  1. EFFICACY OF COMBINED ANTIHYPERTENSIVE THERAPY IN ACHIEVEMENT OF TARGET BLOOD PRESSURE IN DIABETIC PATIENTS

    Directory of Open Access Journals (Sweden)

    O. A. Koshel'skaya

    2012-01-01

    Full Text Available Aim. To evaluate the efficacy of long-term combined antihypertensive therapy (AHT based on renin-angiotensin-aldosterone system (RAAS blockers, indapamide and calcium channel blocker (CCB in hypertensive patients with diabetes mellitus (DM in accordance with target blood pressure (BP <130/80 mm Hg achievement rate, dynamics of 24-hour BP profile, metabolic indices, and local stiffness of the main arteries. Besides, to study the effects of the CCB addition to dual therapy on these parameters. Material and methods. Patients (16 men, 31 women, 57.2±6.6 years old with arterial hypertension degrees 1–3 and mild to moderate DM type 2 were included into the study. The patients were treated with perindopril (5–10 mg/day or valsartan (80–160 mg/day in combination with indapamide SR (1.5 mg/day and amlodipine (5–10 mg/day. Examination included office BP measurement and ambulatory BP monitoring (ABPM, common carotid arteries sonarography , evaluation of serum levels of potassium, creatinine, uric acid, glucose metabolism and lipid profile parameters, calculation of insulin resistance index (HOMA at baseline and after 30–32 weeks of treatment. Results. Target BP was achieved in 86.7% of patients. Evenly reduction of day and night BP without reflex tachycardia and hypotension episodes was observed. Office BP decreased from 149.5±12.0/90.0±8.3 to 125.0±7.6/76.8±4.9 mm Hg (p<0.05 and average daily BP (ABPM decreased to 120.1±10.0/71.7±6.9 mmHg. Three drugs were needed to achieve target BP in baseline systolic BP >150 mm Hg (office or >134 mmHg (ABPM. Marked beneficial effect on the morphological and functional characteristics of the vascular wall and its elastic properties, improvement of glycemic control, tissue insulin sensitivity and lipids profile were found. These effects were associated mainly with amlodipine inclusion into the therapy. Conclusion. The combined AHT based on RAAS blockers, indapamide SR and CCB provides achievement of

  2. EFFICACY OF COMBINED ANTIHYPERTENSIVE THERAPY IN ACHIEVEMENT OF TARGET BLOOD PRESSURE IN DIABETIC PATIENTS

    Directory of Open Access Journals (Sweden)

    O. A. Koshel'skaya

    2015-12-01

    Full Text Available Aim. To evaluate the efficacy of long-term combined antihypertensive therapy (AHT based on renin-angiotensin-aldosterone system (RAAS blockers, indapamide and calcium channel blocker (CCB in hypertensive patients with diabetes mellitus (DM in accordance with target blood pressure (BP <130/80 mm Hg achievement rate, dynamics of 24-hour BP profile, metabolic indices, and local stiffness of the main arteries. Besides, to study the effects of the CCB addition to dual therapy on these parameters. Material and methods. Patients (16 men, 31 women, 57.2±6.6 years old with arterial hypertension degrees 1–3 and mild to moderate DM type 2 were included into the study. The patients were treated with perindopril (5–10 mg/day or valsartan (80–160 mg/day in combination with indapamide SR (1.5 mg/day and amlodipine (5–10 mg/day. Examination included office BP measurement and ambulatory BP monitoring (ABPM, common carotid arteries sonarography , evaluation of serum levels of potassium, creatinine, uric acid, glucose metabolism and lipid profile parameters, calculation of insulin resistance index (HOMA at baseline and after 30–32 weeks of treatment. Results. Target BP was achieved in 86.7% of patients. Evenly reduction of day and night BP without reflex tachycardia and hypotension episodes was observed. Office BP decreased from 149.5±12.0/90.0±8.3 to 125.0±7.6/76.8±4.9 mm Hg (p<0.05 and average daily BP (ABPM decreased to 120.1±10.0/71.7±6.9 mmHg. Three drugs were needed to achieve target BP in baseline systolic BP >150 mm Hg (office or >134 mmHg (ABPM. Marked beneficial effect on the morphological and functional characteristics of the vascular wall and its elastic properties, improvement of glycemic control, tissue insulin sensitivity and lipids profile were found. These effects were associated mainly with amlodipine inclusion into the therapy. Conclusion. The combined AHT based on RAAS blockers, indapamide SR and CCB provides achievement of

  3. Use of angiotensin II receptor blockers alone and in combination with other drugs: a large clinical experience trial

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    Matthew R Weir

    2001-03-01

    Full Text Available Angiotensin II (Ang II receptor blockers are the newest class of antihypertensive drugs to be developed. No large-scale clinical trials have been performed to evaluate their efficacy alone, or in combination with other drugs. A large-scale, eight week, open-label, non-placebo-controlled, single-arm trial evaluated the efficacy, tolerability and dose-response of candesartan cilexetil, 16—32 mg once-daily, either as monotherapy or as part of combination therapy, in a diverse hypertensive population in actual practice settings. 6465 patients with high blood pressure, of whom 52% were female and 16% African American, with a mean age of 58 years, were included. 5446 patients had essential hypertension and 1014 patients had isolated systolic hypertension. In order to be included in this study, patients had either untreated or uncontrolled hypertension (systolic blood pressure (SBP 140—179 mmHg and/or diastolic blood pressure (DBP 90—109 mmHg inclusive at baseline, despite a variety of other antihypertensive drugs. Of the 5156 patients with essential hypertension and at least one post baseline efficacy measurement, the mean pretreatment blood pressure (BP was 156/97 mmHg. Candesartan cilexetil monotherapy reduced mean SBP/DBP by 18.0/12.2 mmHg. Similarly, in the 964 patients with isolated systolic hypertension and at least one post baseline efficacy measurement, candesartan cilexetil monotherapy reduced SBP/DBP from 158/81 by 16.5/4.5 mmHg. Candesartan cilexetil was similarly effective when employed as add-on therapy. When added to baseline antihypertensive medication in 51% of the patients with essential hypertension not achieving BP control, additional reduction in BP was achieved regardless of the background therapy, including diuretics (17.8/11.7 mmHg calcium antagonists (16.6/11.2 mmHg, beta-blockers (16.5/10.4 mmHg, angiotensin-converting enzyme inhibitors (ACE-I (15.3/10.0 mmHg, and alpha blockers (16.4/10.4 mmHg. Likewise, when

  4. 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

  5. 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

    Directory of Open Access Journals (Sweden)

    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

  6. Drugs and drug policy in the Netherlands

    NARCIS (Netherlands)

    Leuw, Ed.

    1991-01-01

    The Dutch parliament enacted the revised Opium Act in 1976. This penal law is part of the Dutch drug policy framework that includes tolerance for nonconforming lifestyles, risk reduction in regard to the harmful health and social consequences of drug taking, and penal measures directed against

  7. The Cost-effectiveness of Sequences of Biological Disease-modifying Antirheumatic Drug Treatment in England for Patients with Rheumatoid Arthritis Who Can Tolerate Methotrexate.

    Science.gov (United States)

    Stevenson, Matt D; Wailoo, Allan J; Tosh, Jonathan C; Hernandez-Alava, Monica; Gibson, Laura A; Stevens, John W; Archer, Rachel J; Simpson, Emma L; Hock, Emma S; Young, Adam; Scott, David L

    2017-07-01

    To ascertain whether strategies of treatment with a biological disease-modifying antirheumatic drug (bDMARD) are cost-effective in an English setting. Results are presented for those patients with moderate to severe rheumatoid arthritis (RA) and those with severe RA. An economic model to assess the cost-effectiveness of 7 bDMARD was developed. A systematic literature review and network metaanalysis was undertaken to establish relative clinical effectiveness. The results were used to populate the model, together with estimates of Health Assessment Questionnaire (HAQ) score following European League Against Rheumatism response; annual costs, and utility, per HAQ band; trajectory of HAQ for patients taking bDMARD; and trajectory of HAQ for patients using nonbiologic therapy (NBT). Results were presented as those associated with the strategy with the median cost-effectiveness. Supplementary analyses were undertaken assessing the change in cost-effectiveness when only patients with the most severe prognoses taking NBT were provided with bDMARD treatment. The costs per quality-adjusted life-year (QALY) values were compared with reported thresholds from the UK National Institute for Health and Care Excellence of £20,000 to £30,000 (US$24,700 to US$37,000). In the primary analyses, the cost per QALY of a bDMARD strategy was £41,600 for patients with severe RA and £51,100 for those with moderate to severe RA. Under the supplementary analyses, the cost per QALY fell to £25,300 for those with severe RA and to £28,500 for those with moderate to severe RA. The cost-effectiveness of bDMARD in RA in England is questionable and only meets current accepted levels in subsets of patients with the worst prognoses.

  8. Repressive Tolerance

    DEFF Research Database (Denmark)

    Pedersen, Morten Jarlbæk

    2017-01-01

    Consultation of organised interests and others when drafting laws is often seen as an important source of both input and output legitimacy. But whereas the input side of the equation stems from the very process of listening to societal actors, output legitimacy can only be strengthened if consult......Consultation of organised interests and others when drafting laws is often seen as an important source of both input and output legitimacy. But whereas the input side of the equation stems from the very process of listening to societal actors, output legitimacy can only be strengthened...... a substantial effect on the substance of laws – shows that there is a great difference in the amenability of different branches of government but that, in general, authorities do not listen much despite a very strong consultation institution and tradition. A suggestion for an explanation could be pointing...... to an administrative culture of repressive tolerance of organised interests: authorities listen but only reacts in a very limited sense. This bears in it the risk of jeopardising the knowledge transfer from societal actors to administrative ditto thus harming the consultation institutions’ potential for strengthening...

  9. Comparison of metoprolol as hydrochlorothiazide and antihypertensive agents.

    Science.gov (United States)

    Pedersen, O L

    1976-01-01

    A crossover comparison of metoprolol and hydrochlorothiazide has been performed in 20 patients with mild hypertension. Both drugs caused almost identical statistically significant reduction in blood pressure of about 20 mm Hg systolic and 15 mm Hg diastolic. The side effects during active therapy were few and mild, but 5 patients experienced subjective symptoms during the first few days following abrupt withdrawal of metoprolol, namely general malaise, palpitations, headache, sweating and tremor. The symptoms were more pronounced in the standing position and disappeared at once on resumption of beta-blocker therapy, or gradually over 5 - 7 days when placebo tablets were given. In 11 of the 20 patients hydrochlorothiazide produced subnormal serum potassium levels and potassium supplements were given. The serum uric acid level was also significantly increased during hydrochlorothiazide treatment.

  10. 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...

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  13. 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.

  14. 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

  15. Development and evaluation of novel antihypertensive orodispersible tablets.

    Science.gov (United States)

    Khan, Hafeez Ullah; Hanif, Muhammad; Sarfraz, Rai M; Maheen, Safirah; Afzal, Samina; Sher, Muhammad; Afzal, Khurram; Mahmood, Asif; Shamim, Ayesha

    2017-09-01

    Objective of present study was to enhance patient compliance in pediatrics and geriatrics patients of Hypertension. To achieve this target, innovative orodispersible tablets of atenolol and atorvastatin was developed to produce instant action by rapidly disintegrating into oral cavity. Three different techniques like direct compression, effervescent and sublimation methods were used to prepare these tablets (Five batches of tablets by each method) by using two superdisintegrants like Sodium starch glycolate and pregelatinized starch alone and in combination. Pre-formulation studies including rheological analysis (Bulk density, tapped density, Angle of repose, Carr's compressibility index, Hausner's ratio), compatibility studies such as Fourier transform infrared spectrophotometry (FTIR) and Differential scanning colorimetry (DSC), Post-compression and stability studies were also performed. Finally, results were statistically evaluated by the applying one way ANOVA test and mean. It was concluded that the formulation F8 containing Sodium starch glycolate 2% and pregelatinized starch 6% found best regarding disintegration time, wetting volume, wetting time, release studies etc. The order in which drug release was quicker is Pregelatinized starch plus Sodium starch glycolate > Pregelatinized starch > Sodium starch glycolate (primojel). It was concluded that sublimation method was the best among three methods used for orodispersible tablets formulations.

  16. Drug development in neuropsychopharmacology.

    Science.gov (United States)

    Fritze, Jürgen

    2008-03-01

    Personalized medicine is still in its infancy concerning drug development in neuropsychopharmacology. Adequate biomarkers with clinical relevance to drug response and/or tolerability and safety largely remain to be identified. Possibly, this kind of personalized medicine will first gain clinical relevance in the dementias. The clinical relevance of the genotyping of drug-metabolizing enzymes as suggested by drug licensing authorities for the pharmacokinetic evaluation of medicinal products needs to be proven in sound clinical trials.

  17. 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.

  18. 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.

  19. What are the ideal properties for functional food peptides with antihypertensive effect? A computational peptidology approach.

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Factors affecting compliance to antihypertensive treatment among adults in a tertiary care hospital in Mumbai

    Directory of Open Access Journals (Sweden)

    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.

  2. Pavlovian control of cross-tolerance between pentobarbital and ethanol.

    Science.gov (United States)

    Cappell, H; Roach, C; Poulos, C X

    1981-01-01

    Tolerance to several effects of a number of drugs has been shown to depend on Pavlovian conditioning processes. Experiment I extended the compensatory conditioning model (Siegel 1975) to tolerance to the hypothermic effect of pentobarbital (30 mg/kg). In Experiment I, rats that acquired hypothermic tolerance in one environment did not display tolerance when tested in an environment not previously associated with drug administration. In Experiment II, rats were made tolerant to the hypothermic effect of pentobarbital (30 mg/kg) and tested for cross-tolerance to ethanol (2.5 g/kg). Cross-tolerance was observed, but it was significantly reduced if the test was in an environment different from the one in which tolerance to pentobarbital was originally acquired. Thus, the compensatory conditioning model accounts for at least part of the tolerance and cross-tolerance to the thermic effects of alcohol and pentobarbital. The physiological processes in the CNS underlying tolerance and cross-tolerance for these drugs, therefore, are controlled by associative processes.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

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

    Science.gov (United States)

    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.

  6. AN OPEN-LABEL MULTICENTER OBSERVATIONAL STUDY OF THE EFFICACY, TOLERABILITY, AND SAFETY OF THE NONSTEROIDAL ANTI-INFLAMMATORY DRUG AMTOLMETIN GUACIL IN PATIENTS WITH KNEE OSTEOARTHRITIS AND DYSPEPSIA

    Directory of Open Access Journals (Sweden)

    E. S. Tsvetkova

    2016-01-01

    Full Text Available Objective: to investigate the efficacy and tolerability of amtolmetin guacil (AMG; Niselat®, Dr. Reddy's Laboratories Ltd, India versus previous therapy with nonsteroidal anti-inflammatory drugs (NSAIDs in patients with knee osteoarthritis (OA and signs of dyspepsia.Subjects and methods. The open-label observational study included 220 patients aged 30–65 years who suffered from knee OA and intense pain during NSAID intake and had symptoms of dyspepsia in the absence of contraindications to the use of AMG. Among the comorbidities that generally occurred in 68% of the patients, there was a preponderance of hypertension (42%, lower extremity varicose veins (6.4%, and diabetes mellitus (6%. Treatment efficacy was evaluated using three domains of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, by also taking into account pain intensity and general health assessment on the visual analogue scale. A Severity of Dyspepsia Assessment (SODA scale was used to rate dyspepsia.Results and discussion. AMG had a marked analgesic effect confirmed by 40% or more pain reduction that occurred in 72.5% of the patients. The high analgesic effect of AMG was confirmed by a statistically significant (p <0.001 reduction in the WOMAC index (pain and stiffness and by an increase in functional activity. There was a significant decrease in painless and painful signs of dyspepsia, as well as positive changes in the measures “overall assessment of dyspepsia severity” (p < 0.001 and “satisfaction with treatment”. Overall assessment of AMG tolerability was only positive: excellent (33%, good (56%, and satisfactory (11%. There were no serious adverse events (AE. AE were graded as moderate and mild in 8 and 82% of cases, respectively. AE were recorded in 7.7% of the patients. Conclusion. The findings suggest that AMG offers good prospects for knee OA treatment.

  7. 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.

    Science.gov (United States)

    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

  8. 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.

  9. 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.

  10. Job Strain and Casual Blood Pressure Distribution: Looking beyond the Adjusted Mean and Taking Gender, Age, and Use of Antihypertensives into Account. Results from ELSA-Brasil

    Science.gov (United States)

    Juvanhol, Leidjaira Lopes; Melo, Enirtes Caetano Prates; Carvalho, Marilia Sá; Chor, Dóra; Mill, José Geraldo; Griep, Rosane Härter

    2017-01-01

    Methodological issues are pointed to as the main sources of inconsistencies in studies about the association between job strain and blood pressure (BP)/hypertension. Our aim was to analyze the relationship between job strain and the whole BP distribution, as well as potential differences by gender, age, and use of antihypertensives. Additionally, we addressed issues relating to the operationalization of the exposure and outcome variables that influence the study of their inter-relations. We evaluated the baseline date of 12,038 participants enrolled in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) (2008–2010), a multicenter cohort study of 35–74-year-old civil servants. Job strain was assessed by the Demand-Control-Support Questionnaire. The distribution of casual BP by categories of job strain was compared by a combination of exploratory techniques. Participants were classified into three subgroups (normotensives, medicated hypertensives, and unmedicated hypertensives), and analyses were stratified by gender and age. The relationship between job strain and casual BP varied along the whole outcome distribution. Hypertensive participants had greater differences in casual BP by job strain category, especially medicated hypertensives. Differences in casual BP were also greater for systolic than for diastolic BP and for older participants. No differences were encountered by gender. The exclusion of participants susceptible to misclassification for the exposure and outcome variables increased the differences observed between the categories of low and high job strain. In conclusion, the relationship between job strain and casual BP varied along the whole outcome distribution and by use of antihypertensive drugs, age, and BP parameter evaluated. Misclassification for exposure and outcome variables should be considered in analyses of this topic. PMID:28441727

  11. Teaching Tolerance? Associational Diversity and Tolerance Formation

    DEFF Research Database (Denmark)

    Rapp, Carolin; Freitag, Markus

    2015-01-01

    , a closer look is taken at how associational diversity relates to the formation of tolerance and the importance of associations as schools of tolerance are evaluated. The main theoretical argument follows contact theory, wherein regular and enduring contact in diverse settings reduces prejudice and thereby...

  12. Antihypertensive and vasorelaxant effects of aqueous extract of Artemisia campestris L. from Eastern Morocco.

    Science.gov (United States)

    Dib, Ikram; Tits, Monique; Angenot, Luc; Wauters, Jean Noel; Assaidi, Asmae; Mekhfi, Hassane; Aziz, Mohammed; Bnouham, Mohammed; Legssyer, Abdelkhaleq; Frederich, Michel; Ziyyat, Abderrahim

    2017-07-12

    Artemisia campestris L. (Asteraceae) has many traditional uses, among which treatment of diabetes and hypertension. This study was conducted in order to confirm the antihypertensive and hypotensive effects of A. campestris L. aqueous extract (AcAE) and to explore the underlying mechanism of action of its vasorelaxant effect, besides the acute toxicity. Also, the chemical composition of AcAE was investigated. the chemical content of AcAE was determined by using HPLC and NMR techniques. The antihypertensive effect was assessed indirectly by tail-cuff method on L-NAME induced hypertensive rats, while the hypotensive action was monitored intravenously by invasive method on normotensive rats. The vasorelaxant effect and vascular mechanism of action were studied in the presence of antagonists and blockers on aorta isolated from normotensive rats. On the other side, the acute toxicity was studied by oral feeding of extract to the mice. The global phytochemical profile of AcAE reveals the presence of several polyphenols as main components. A. campestris L. infusion was characterized by mono- and di-cinnamoyl compounds, with 3,5-dicaffeoylquinic (isochlorogenic A) acid being the main compound, followed by 5-caffeoylquinic (chlorogenic) acid. Vicenin-2 (apigenin 6,8-di-C-glucoside) appeared to be the most abundant compound among flavonoids. The daily treatment with AcAE at 150mg/kg/day prevented the installation of hypertension on L-NAME hypertensive rats, and reduced SBP from 172mmHg up to 144mmHg. At the dose 40mg/kg, AcAE provoked reduction of systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP), without affecting the heart rate. Also, AcAE (10 -2 -2mg/ml) relaxed the precontracted aorta by 95.8±1.3%. The denudation and preincubation of aorta with atropine, calmidazolium, L-NAME, hydroxycobalamin, ODQ, 8-RP-Br-PET-cGMP, thapsigargin and verapamil attenuated the vasorelaxant response, while the pre-treatment with 4-AP, TEA, glibenclamide and BaCl 2 did not

  13. Lactose tolerance tests

    Science.gov (United States)

    Hydrogen breath test for lactose tolerance ... Two common methods include: Lactose tolerance blood test Hydrogen breath test The hydrogen breath test is the preferred method. It measures the amount of hydrogen ...

  14. Pharmacokinetic, pharmacodynamic, and antihypertensive effects of the neprilysin inhibitor LCZ-696: sacubitril/valsartan.

    Science.gov (United States)

    Chrysant, Steven G

    2017-07-01

    LCZ-696, sacubitril/valsartan, is a dual-acting molecule consisting of the angiotensin II (Ang II) receptor blocker valsartan and the neprilysin (neutral endopeptidase) inhibitor AHU-377 with significant beneficial effects in patients with hypertension and heart failure (HF). Several recent studies have demonstrated a higher effectiveness of LCZ-696 compared to valsartan in the treatment of hypertension and HF. The rationale for the development and the Food and Drug Administration approval of LCZ-696 was based on the concept of an additive effect of the Ang II receptor blocker valsartan and the neutral endopeptidase (neprilysin) inhibitor AHU-377 for the treatment of hypertension and HF. The synergism from these drugs arises from the vasodilating effects of valsartan through its blockade of Ang II type 1 receptor and the action of natriuretic peptides atrial natriuretic peptide and B-type natriuretic peptide (BNP) by preventing their catabolism with neprilysin resulting in increase of cyclic guanosine monophosphate. This action of neprilysin is associated with increased natriuresis, diuresis, and systemic vasodilation, since these peptides have been shown to have potent diuretic, natriuretic, and vasodilating effects. In addition, it reduces the levels of N terminal pro-BNP. Therefore, administration of LCZ-696 results in significant reduction of wall stress from pressure and volume overload of the left ventricle as demonstrated by the reduction of N terminal pro-BNP, both significant constituents of hypertension and HF, and it is safe, well tolerated and is almost free of cough and angioedema. Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

    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...

  17. Short communication: Assessing antihypertensive activity in native and model Queso Fresco cheeses.

    Science.gov (United States)

    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.

  18. Nutraceutical Value of Black Cherry Prunus serotina Ehrh. Fruits: Antioxidant and Antihypertensive Properties

    Directory of Open Access Journals (Sweden)

    Francisco J. Luna-Vázquez

    2013-11-01

    Full Text Available In Mexico black cherry (Prunus serotina Ehrh. fruits are consumed fresh, dried or prepared in jam. Considering the evidence that has linked intake of fruits and vegetables rich in polyphenols to cardiovascular risk reduction, the aim of this study was to characterize the phenolic profile of black cherry fruits and to determine their antioxidant, vasorelaxant and antihypertensive effects. The proximate composition and mineral contents of these fruits were also assessed. Black cherry fruits possess a high content of phenolic compounds and display a significant antioxidant capacity. High-performance liquid chromatography/mass spectrometric analysis indicated that hyperoside, anthocyanins and chlorogenic acid were the main phenolic compounds found in these fruits. The black cherry aqueous extract elicited a concentration-dependent relaxation of aortic rings and induced a significant reduction on systolic blood pressure in L-NAME induced hypertensive rats after four weeks of treatment. Proximate analysis showed that black cherry fruits have high sugar, protein, and potassium contents. The results derived from this study indicate that black cherry fruits contain phenolic compounds which elicit significant antioxidant and antihypertensive effects. These findings suggest that these fruits might be considered as functional foods useful for the prevention and treatment of cardiovascular diseases.

  19. Antihypertensive Effects of Roselle-Olive Combination in L-NAME-Induced Hypertensive Rats.

    Science.gov (United States)

    Abdel-Rahman, Rehab F; Hessin, Alyaa F; Abdelbaset, Marwan; Ogaly, Hanan A; Abd-Elsalam, Reham M; Hassan, Salah M

    2017-01-01

    This study aimed to evaluate the antihypertensive efficacy of a new combination therapy of Hibiscus sabdariffa and Olea europaea extracts (2 : 1; Roselle-Olive), using N(G)-nitro-L-arginine-methyl ester- (L-NAME-) induced hypertensive model. Rats received L-NAME (50 mg/kg/day, orally) for 4 weeks. Concurrent treatment with Roselle-Olive (500, 250, and 125 mg/kg/day for 4 weeks) resulted in a dose-dependent decrease in both systolic and diastolic blood pressure, reversed the L-NAME-induced suppression in serum nitric oxide (NO), and improved liver and kidney markers, lipid profile, and oxidative status. Furthermore, Roselle-Olive significantly lowered the elevated angiotensin-converting enzyme activity (ACE) and showed a marked genoprotective effect against oxidative DNA damage in hypertensive rats. Roselle-Olive ameliorated kidney and heart lesions and reduced aortic media thickness. Real-time PCR and immunohistochemistry showed an enhanced endothelial nitric oxide synthase (eNOS) gene and protein expression in both heart and kidney of Roselle-Olive-treated rats. To conclude, our data revealed that Roselle-Olive is an effective combination in which H. sabdariffa and O. europaea synergistically act to control hypertension. These effects are likely to be mediated by antioxidant and genoprotective actions, ACE inhibition, and eNOS upregulation by Roselle-Olive constituents. These findings provide evidences that Roselle-Olive combination affords efficient antihypertensive effect with a broad end-organ protective influence.

  20. Evaluation of the Possible Mechanisms of Antihypertensive Activity of Loranthus micranthus: An African Mistletoe

    Directory of Open Access Journals (Sweden)

    Bamidele A. Iwalokun

    2011-01-01

    Full Text Available Loranthus micranthus (LM, also called African mistletoe is a major Nigerian Loranthaceae plant used traditionally to treat hypertension. The methanolic leaf extract of the plant (LMME has been shown to elicit anti-hypertensive activity in rats but mechanism remains unclear. This study was undertaken to study the effect of LM on pressor-induced contraction of rat aorta smooth muscles and serum lipid profiles in mice. The LMME was partitioned to produce n-butanol (NBF-LMME, chloroform (CF-LMME, ethyl acetate (EAF-LMME and water (WF-LMME fractions. The median effective concentrations and maximum relaxation of the fractions were determined against epinephrine and KCl pre-contracted rat aorta ring model. Serum lipid profiles and nitric oxide (NO were determined spectrophotometrically in mice administered per orally 250 mg/kg b.w. of each fraction for 21 days. Data were analyzed statistically. NBF-LMME elicited the highest dose-dependent inhibitory effect on rat aorta pre-contracted with norepinephrine and KCl, followed in decreasing order by WF-LMME > CF-LMME > EAF-LMME. Similar order of activity was observed in the ability of these fractions to inhibit elevation in artherogenic lipids, raise serum nitric oxide and reduce cardiac arginase in mice. We conclude the anti-hypertensive activity of L. micranthus involve anti-artherogenic events, vasorelaxation, cardiac arginase reduction and NO elevation.

  1. Evaluation of antihyperglycemia and antihypertension potential of native Peruvian fruits using in vitro models.

    Science.gov (United States)

    Pinto, Marcia Da Silva; Ranilla, Lena Galvez; Apostolidis, Emmanouil; Lajolo, Franco Maria; Genovese, Maria Inés; Shetty, Kalidas

    2009-04-01

    Local food diversity and traditional crops are essential for cost-effective management of the global epidemic of type 2 diabetes and associated complications of hypertension. Water and 12% ethanol extracts of native Peruvian fruits such as Lucuma (Pouteria lucuma), Pacae (Inga feuille), Papayita arequipeña (Carica pubescens), Capuli (Prunus capuli), Aguaymanto (Physalis peruviana), and Algarrobo (Prosopis pallida) were evaluated for total phenolics, antioxidant activity based on 2, 2-diphenyl-1-picrylhydrazyl radical scavenging assay, and functionality such as in vitro inhibition of alpha-amylase, alpha-glucosidase, and angiotensin I-converting enzyme (ACE) relevant for potential management of hyperglycemia and hypertension linked to type 2 diabetes. The total phenolic content ranged from 3.2 (Aguaymanto) to 11.4 (Lucuma fruit) mg/g of sample dry weight. A significant positive correlation was found between total phenolic content and antioxidant activity for the ethanolic extracts. No phenolic compound was detected in Lucuma (fruit and powder) and Pacae. Aqueous extracts from Lucuma and Algarrobo had the highest alpha-glucosidase inhibitory activities. Papayita arequipeña and Algarrobo had significant ACE inhibitory activities reflecting antihypertensive potential. These in vitro results point to the excellent potential of Peruvian fruits for food-based strategies for complementing effective antidiabetes and antihypertension solutions based on further animal and clinical studies.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Effectiveness and tolerability of second-line treatment with vildagliptin versus other oral drugs for type 2 diabetes in a real-world setting in the Middle East: results from the EDGE study.

    Science.gov (United States)

    Saab, Charles; Al-Saber, Feryal A; Haddad, Jihad; Jallo, Mahir Khalil; Steitieh, Habib; Bader, Giovanni; Ibrahim, Mohamed

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is a chronic progressive disease that requires treatment intensification with antihyperglycemic agents due to progressive deterioration of β-cell function. A large observational study of 45,868 patients with T2DM across 27 countries (EDGE) assessed the effectiveness and safety of vildagliptin as add-on to other oral antidiabetic drugs (OADs) versus other comparator OAD combinations. Here, we present results from the Middle East countries (Bahrain, Jordan, Kuwait, Lebanon, Oman, Palestine, and the United Arab Emirates). Patients inadequately controlled with OAD monotherapy were eligible after the add-on treatment was chosen by the physician based on clinical judgment and patient need. Patients were assigned to either vildagliptin or comparator OADs (sulfonylureas, thiazolidinediones, glinides, α-glucosidase inhibitors, or metformin, except incretin-based therapies) based on the add-on therapy. The primary endpoint was the proportion of patients achieving a glycated hemoglobin (HbA1c) reduction of >0.3% without peripheral edema, hypoglycemia, discontinuation due to a gastrointestinal event, or weight gain≥5%. One of the secondary endpoints was the proportion of patients achieving HbA1cvildagliptin and 2,267 received other OADs. Overall, the mean (±standard deviation) age at baseline was 52.1±10.2 years, mean HbA1c was 8.5%±1.3%, and mean T2DM duration was 4.2±4.0 years. The proportion of patients achieving the primary (76.1% versus 61.6%, Pvildagliptin than with the comparator OADs. The unadjusted odds ratios for the primary and secondary endpoints were 1.98 (95% confidence interval 1.75-2.25) and 2.8 (95% confidence interval 2.5-3.2), respectively, in favor of vildagliptin. Vildagliptin achieved a numerically greater reduction in HbA1c (1.7%) from baseline versus comparator OADs (1.4%). The overall incidence of adverse events was comparable between studied cohorts. In real life, treatment with vildagliptin was associated with

  4. Recognition and Toleration

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2010-01-01

    Recognition and toleration are ways of relating to the diversity characteristic of multicultural societies. The article concerns the possible meanings of toleration and recognition, and the conflict that is often claimed to exist between these two approaches to diversity. Different forms...... or interpretations of recognition and toleration are considered, confusing and problematic uses of the terms are noted, and the compatibility of toleration and recognition is discussed. The article argues that there is a range of legitimate and importantly different conceptions of both toleration and recognition...

  5. Fault Tolerant Feedback Control

    DEFF Research Database (Denmark)

    Stoustrup, Jakob; Niemann, H.

    2001-01-01

    An architecture for fault tolerant feedback controllers based on the Youla parameterization is suggested. It is shown that the Youla parameterization will give a residual vector directly in connection with the fault diagnosis part of the fault tolerant feedback controller. It turns out...... that there is a separation be-tween the feedback controller and the fault tolerant part. The closed loop feedback properties are handled by the nominal feedback controller and the fault tolerant part is handled by the design of the Youla parameter. The design of the fault tolerant part will not affect the design...... of the nominal feedback con-troller....

  6. Effectiveness and tolerability of second-line treatment with vildagliptin versus other oral drugs for type 2 diabetes in a real-world setting in the Middle East: results from the EDGE study

    Directory of Open Access Journals (Sweden)

    Saab C

    2015-02-01

    assessed. Results: Of the 4,780 patients enrolled in the Middle East, 2,513 received vildagliptin and 2,267 received other OADs. Overall, the mean (± standard deviation age at baseline was 52.1±10.2 years, mean HbA1c was 8.5%±1.3%, and mean T2DM duration was 4.2±4.0 years. The proportion of patients achieving the primary (76.1% versus 61.6%, P<0.0001 and secondary (54.8% versus 29.9%, P<0.0001 endpoints was higher with vildagliptin than with the comparator OADs. The unadjusted odds ratios for the primary and secondary endpoints were 1.98 (95% confidence interval 1.75–2.25 and 2.8 (95% confidence interval 2.5–3.2, respectively, in favor of vildagliptin. Vildagliptin achieved a numerically greater reduction in HbA1c (1.7% from baseline versus comparator OADs (1.4%. The overall incidence of adverse events was comparable between studied cohorts. Conclusion: In real life, treatment with vildagliptin was associated with a higher proportion of patients with T2DM achieving better glycemic control without tolerability issues in the Middle East. Keywords: dipeptidyl peptidase-4, Middle East, oral antidiabetic drugs, real world, type 2 diabetes mellitus, vildagliptin

  7. Mechanical tolerance stackup and analysis

    CERN Document Server

    Fischer, Bryan R

    2004-01-01

    BackgroundDimensioning and TolerancingTolerance Format and Decimal PlacesConverting Plus/Minus Dimensions and Tolerances into Equal Bilaterally Toleranced DimensionsVariation and Sources of VariationTolerance AnalysisWorst-case Tolerance StackupsStatistical Tolerance StackupsGeometric Dimensioning and Tolerancing (GD&T)Converting Plus/Minus Tolerancing to Positional Tolerancing and Projected Tolerance ZonesDiametral and Radial Tolerance StackupsSpecifying Material Condition Modifiers and Their Effect on Tolerance Stackups The Tolerance Stackup SketchThe Tolerance Stackup Report FormTolerance S

  8. 76 FR 70890 - Fenamidone; Pesticide Tolerances

    Science.gov (United States)

    2011-11-16

    .... Bayer Crop Science requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA... Bayer CropScience, 2 T.W. Alexander Dr., Research Triangle Park, NC 27709. The petition requested that... Bayer CropScience, the registrant, which is available in the docket, http://www.regulations.gov . There...

  9. 77 FR 41284 - Azoxystrobin; Pesticide Tolerances

    Science.gov (United States)

    2012-07-13

    ... Rice, straw 12 Rice, wild, grain 5.0 Sapodilla 2.0 Sapote, black 2.0 Sapote, mamey 2.0 Sapote, white 2... Crop Protection requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA...%; peppers, 15%; pistachios, 15%; potatoes, 35%; prunes, 2.5%; pumpkins, 20%; raspberries, 5%; rice, 35...

  10. 77 FR 8746 - Indoxacarb; Pesticide Tolerances

    Science.gov (United States)

    2012-02-15

    ... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 180 [EPA-HQ-OPP-2011-0578; FRL-9336-7] Indoxacarb... regulation establishes tolerances for residues of indoxacarb in or on egg, poultry fat, poultry meat, and... under the Federal Food, Drug, and Cosmetic Act (FFDCA). DATES: This regulation is effective February 15...

  11. 78 FR 32146 - Triforine; Pesticide Tolerances

    Science.gov (United States)

    2013-05-29

    ... America Holding Corporation requested these tolerances under the Federal Food, Drug, and Cosmetic Act... in the liver and hematopoietic system following repeated oral dosing, and the dog is the most... UFA = 10x mg/kg/day. (dog) UFH = 10x cPAD = 0.22 mg/kg/ LOAEL = 120 mg/kg/day, based on FQPA SF = 1x...

  12. 78 FR 46274 - Pyroxasulfone; Pesticide Tolerances

    Science.gov (United States)

    2013-07-31

    .... requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA). DATES: This regulation is... pyroxasulfone in mice, rats, and dogs produced a variety of adverse effects in several target organs. Effects... indicators), neurotoxicity characterized by axonal/myelin degeneration in the sciatic nerve (dog, mouse, and...

  13. 77 FR 13502 - Pyriofenone; Pesticide Tolerances

    Science.gov (United States)

    2012-03-07

    ... and grape, raisin. ISK BioSciences Corporation requested these tolerances under the Federal Food, Drug... maternal body weight gain and food consumption. There was no evidence of neurotoxicity and a developmental... pregnancy in a developmental toxicity study are assumed to be attributable to a single exposure and thus...

  14. Marketed nonsteroidal anti-inflammatory agents, antihypertensives, and human immunodeficiency virus protease inhibitors: as-yet-unused weapons of the oncologists’ arsenal

    Directory of Open Access Journals (Sweden)

    Papanagnou P

    2015-05-01

    Full Text Available Panagiota Papanagnou,1 Panagiotis Baltopoulos,2 Maria Tsironi1 1Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Sparta, 2Department of Sports Medicine and Biology of Physical Activity, Faculty of Physical Education and Sport Science, National and Kapodistrian University of Athens, Athens, Greece Abstract: Experimental data indicate that several pharmacological agents that have long been used for the management of various diseases unrelated to cancer exhibit profound in vitro and in vivo anticancer activity. This is of major clinical importance, since it would possibly aid in reassessing the therapeutic use of currently used agents for which clinicians already have experience. Further, this would obviate the time-consuming process required for the development and the approval of novel antineoplastic drugs. Herein, both pre-clinical and clinical data concerning the antineoplastic function of distinct commercially available pharmacological agents that are not currently used in the field of oncology, ie, nonsteroidal anti-inflammatory drugs, antihypertensive agents, and anti-human immunodeficiency virus agents inhibiting viral protease, are reviewed. The aim is to provide integrated information regarding not only the molecular basis of the antitumor function of these agents but also the applicability of the reevaluation of their therapeutic range in the clinical setting. Keywords: repositioning, tumorigenesis, pleiotropy, exploitation

  15. 21 CFR 170.18 - Tolerances for related food additives.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Tolerances for related food additives. 170.18... (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES General Provisions § 170.18 Tolerances for related food additives. (a) Food additives that cause similar or related pharmacological effects will be...

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

    Science.gov (United States)

    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.

  17. Effectiveness and tolerability of fixed-dose combination enalapril plus nitrendipine in hypertensive patients: results of the 3-month observational, post-marketing, multicentre, prospective CENIT study.

    Science.gov (United States)

    Sierra, Alejandro de la; Roca-Cusachs, Alejandro; Redón, Josep; Marín, Rafael; Luque, Manuel; Figuera, Mariano de la; Garcia-Garcia, Margarida; Falkon, Liliana

    2009-01-01

    Monotherapy with any class of antihypertensive drug effectively controls blood pressure (BP) in only about 50% of patients. Consequently, the majority of patients with hypertension require combined therapy with two or more medications. This study aimed to evaluate the effectiveness (systolic BP [SBP]/diastolic BP [DBP] control) and tolerability of the fixed-dose combination enalapril/nitrendipine 10 mg/20 mg administered as a single daily dose in hypertensive patients. This was a post-authorization, multicentre, prospective, observational study conducted in primary care with a 3-month follow-up. Patients throughout Spain with uncontrolled hypertension (> or =140/90 mmHg for patients without diabetes mellitus, or > or =130/85 mmHg for patients with diabetes) on monotherapy or with any combination other than enalapril + nitrendipine, or who were unable to tolerate their previous antihypertensive therapy, were recruited. Change from previous to study treatment was according to usual clinical practice. BP was measured once after 5 minutes of rest in the sitting position. Therapeutic response was defined as follows: 'controlled' meant controlled BP ( or =20 mmHg and in DBP of > or =10 mmHg. The main laboratory test parameters were documented at baseline and after 3 months. Patients aged >65 years, with diabetes, with isolated systolic hypertension (ISH; SBP > or =140 mmHg for patients without diabetes, SBP > or =130 mmHg for patients with diabetes) and who were obese (body mass index [BMI] > or =30 kg/m2) were analysed separately. Of 6537 patients included, 5010 and 6354 patients were assessed in effectiveness and tolerability analyses, respectively. In the tolerability analysis population, there were 3023 men (47.6%) and 3321 women (52.4%). The mean (+/- SD) age of the tolerability analysis group was 62.8 (+/- 10.7) years. A total of 71.1% of the patients presented at least one clinical cardiovascular risk factor other than hypertension, with the most frequent being

  18. Identification of validated questionnaires to measure adherence to pharmacological antihypertensive treatments

    Directory of Open Access Journals (Sweden)

    Pérez-Escamilla B

    2015-04-01

    Full Text Available Beatriz Pérez-Escamilla,1 Lucía Franco-Trigo,1 Joanna C Moullin,2 Fernando Martínez-Martínez,1 José P García-Corpas1 1Academic Centre in Pharmaceutical Care, Faculty of Pharmacy, University of Granada, Granada, Spain; 2Graduate School of Health, Faculty of Pharmacy, University of Technology Sydney, Sydney, NSW, Australia 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

  19. Assessment of cholecalciferol and antihypertensive therapy concominant use in people with arterial hypertension

    Directory of Open Access Journals (Sweden)

    L.V. Yankouskaya

    2017-04-01

    Full Text Available Background. The purpose of the study was to assess the effect of cholecalciferol intake at a daily dose of 2,000 IU on the serum level of 25(ОНD total and blood pressure (BP against the background of antihypertensive therapy in people with arterial hypertension(AH stage II. Materials and methods. We performed a prospective, single-center study of 115 individuals with AH stage II (91 females and 24 males, mean age 50.7 ± 7.1 years. The duration of the follow-up period averaged 15.8 ± 1.8 months (from 12 to 18 months. The patients were receiving antihypertensive therapy according to the European guidelines: angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists — losartan, or diuretics (hydrochlorothiazide or indapamide as a part of combination therapy, or calcium antagonists — amlodipine, or beta-adrenergic blockers, or their combination. Every second patient was recommended to take vitamin D in the form of cholecalciferol at a dose of 2000 IU/d daily. All subjects were performed full blood count, clinical urine examination, measure of fasting blood sugar, serum urea, serum creatinine, office systolic and diastolic blood pressure, anthropometric data, electrocardiography. Serum level of total vitamin D was determined using immunoenzymatic assay. Statistical analysis was done by using software package STATISTICA 10.0 (SN AXAR207F394425FA-Q. Results. It was found that intake of diuretics (hydrochlorothiazide at a dose of 12.5–25.0 mg or indapamide 1.5 mg as part of combination antihypertensive therapy influenced the dynamics of serum 25(OHD (F = 5.35; p = 0.02 and its level (F = 11.8; p = 0.0009. Dynamic SBP value was highest (–27.4 ± 17.9 in the group receiving a diuretic and cholecalciferol, which was significantly (p < 0.001 different from the comparison group. In the same group, we established a correlation relationship between dynamic SBP and length of cholecalciferol intake (R = 0.42; p = 0.023. A

  20. Antihypertensive activities of the aqueous extract of Kalanchoe pinnata (Crassulaceae) in high salt-loaded rats.

    Science.gov (United States)

    Bopda, Orelien Sylvain Mtopi; Longo, Frida; Bella, Thierry Ndzana; Edzah, Protais Marcellin Ohandja; Taïwe, Germain Sotoing; Bilanda, Danielle Claude; Tom, Esther Ngo Lemba; Kamtchouing, Pierre; Dimo, Theophile

    2014-04-28

    The leaves of Kalanchoe pinnata (Crassulaceae) are used in Cameroon folk medicine to manage many diseases such as cardiovascular dysfunctions. In this work, we aimed to evaluate the activities of aqueous leaf extract of Kalanchoe pinnata on the blood pressure of normotensive rat (NTR) and salt hypertensive rats (SHR), as well as its antioxidant properties. Hypertension was induced in rats by oral administration of 18% NaCl for 4 weeks. For the preventive study, three groups of rats received 18% NaCl solution and the plant extract at 25 mg/kg/day, 50 mg/kg/day or 100 mg/kg/day by gavage. Two positive control groups received 18% NaCl solution and either spironolactone (0.71 mg/kg/day) or eupressyl (0.86 mg/kg/day) by gavage for 4 weeks. At the end of this experimental period, systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and heart rate (HR) were measured by the invasive method. Some oxidative stress biomarkers (reduced glutathione (GSH), superoxide dismutase (SOD), nitric monoxide (NO) were evaluated in heart, aorta, liver and kidney. NO level was indirectly evaluated by measuring nitrite concentration. Kalanchoe pinnata extract prevented significantly the increase of systolic and diastolic arterial pressures in high salt-loaded rats (SHR). In SHR, concomitant administration of Kalanchoe pinnata at 25, 50 and 100 mg/kg/day significantly prevented the increase in blood pressure by 32%, 24% and 47% (for SAP); 35%, 33% and 56% (for DAP), respectively. No significant change was recorded in heart rate of those rats. The plant extract improved antioxidant status in various organs, but more potently in aorta. Thus, antioxidant and modulatory effects of Kalanchoe pinnata at the vasculature might be of preponderant contribution to its overall antihypertensive activity. The work demonstrated that the concomitant administration of high-salt and the aqueous extract of Kalanchoe pinnata elicits prevention of salt-induced hypertension in rat. This

  1. Labetalol Versus Nifedipine as Antihypertensive Treatment for Chronic Hypertension in Pregnancy: A Randomized Controlled Trial.

    Science.gov (United States)

    Webster, Louise M; Myers, Jenny E; Nelson-Piercy, Catherine; Harding, Kate; Cruickshank, J Kennedy; Watt-Coote, Ingrid; Khalil, Asma; Wiesender, Cornelia; Seed, Paul T; Chappell, Lucy C

    2017-11-01

    Data from randomized controlled trials to guide antihypertensive agent choice for chronic hypertension in pregnancy are limited; this study aimed to compare labetalol and nifedipine, additionally assessing the impact of ethnicity on treatment efficacy. Pregnant women with chronic hypertension (12 +0 -27 +6 weeks' gestation) were enrolled at 4 UK centers (August 2014 to October 2015). Open-label first-line antihypertensive treatment was randomly assigned: labetalol- (200-1800 mg/d) or nifedipine-modified release (20-80 mg/d). Analysis included 112 women (98%) who completed the study (labetalol n=55, nifedipine n=57). Maximum blood pressure after randomization was 161/101 mm Hg with labetalol versus 163/105 mm Hg with nifedipine (mean difference systolic: 1.2 mm Hg [-4.9 to 7.2 mm Hg], diastolic: 3.3 mm Hg [-0.6 to 7.3 mm Hg]). Mean blood pressure was 134/84 mm Hg with labetalol and 134/85 mm Hg with nifedipine (mean difference systolic: 0.3 mm Hg [-2.8 to 3.4 mm Hg], and diastolic: -1.9 mm Hg [-4.1 to 0.3 mm Hg]). Nifedipine use was associated with a 7.4-mm Hg reduction (-14.4 to -0.4 mm Hg) in central aortic pressure, measured by pulse wave analysis. No difference in treatment effect was observed in black women (n=63), but a mean 4 mm Hg reduction (-6.6 to -0.8 mm Hg; P =0.015) in brachial diastolic blood pressure was observed with labetalol compared with nifedipine in non-black women (n=49). Labetalol and nifedipine control mean blood pressure to target in pregnant women with chronic hypertension. This study provides support for a larger definitive trial scrutinizing the benefits and side effects of first-line antihypertensive treatment. URL: https://www.isrctn.com. Unique identifier: ISRCTN40973936. © 2017 American Heart Association, Inc.

  2. Identification of validated questionnaires to measure adherence to pharmacological antihypertensive treatments

    Science.gov (United States)

    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

  3. 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.

  4. Reduced albuminuria during early and aggressive antihypertensive treatment of insulin-dependent diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Andersen, A R; Smidt, U M

    1981-01-01

    nephropathy. Mean age of the patients was 30 yr. All patients had a diastolic blood pressure greater than or equal to 95 mm Hg. Metoprolol, hydralazine, and furosemide or thiazide were used as antihypertensives. During the 12-mo treatment period, BP decreased from 151/104 to 133/85 mm Hg (P less than 0...

  5. Reduction in albuminuria predicts a beneficial effect on diminishing the progression of human diabetic nephropathy during antihypertensive treatment

    DEFF Research Database (Denmark)

    Rossing, P; Hommel, E; Smidt, U M

    1994-01-01

    Diabetic nephropathy is the main cause of increased mortality and morbidity in IDDM patients. The effect of antihypertensive treatment on the progression of the nephropathy is highly variable. The aim of this study was to evaluate putative predictors of the progression in diabetic nephropathy dur...

  6. Acute and long-term effect of antihypertensive treatment on exercise-induced albuminuria in incipient diabetic nephropathy

    DEFF Research Database (Denmark)

    Christensen, Cramer; Mogensen, C E

    1986-01-01

    The aim of the study was to clarify whether antihypertensive treatment could affect the systolic blood pressure (SBP) and urinary albumin excretion (UAE) in diabetics during exercise (450 kpm/min, followed by 600 kpm/min, 20 min each). Young male insulin-dependent diabetics with normal UAE (n = 9...

  7. Antihypertensive mechanisms of chronic captopril (CPT) or N-Acetylcysteine (NAC) treatment in L-NAME hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Dobešová, Zdenka; Zicha, Josef; Pecháňová, Olga; Kuneš, Jaroslav

    2005-01-01

    Roč. 46, č. 4 (2005), s. 912-913 ISSN 0194-911X. [Annual Meeting of the European Council for Cardiovascular Research (ECCR) /10./. 14.10.2005-16.10.2005, La Colle sur Loup] R&D Projects: GA MZd(CZ) NR7786 Keywords : antihypertensive mechanism * captopril * N-Acetylcysteine * L-NAME hypertension Subject RIV: ED - Physiology

  8. Toleration out of respect?

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2013-01-01

    Under conditions of pluralism different cultures, interests or values can come into conflict, which raises the problem of how to secure peaceful co-existence. The idea of toleration historically emerged as an answer to this problem. Recently Rainer Forst has argued that toleration should not just...... be based on a modus vivendi designed to secure peaceful co-existence, but should be based on moral reasons. Forst therefore advances what he calls the ‘respect conception’ of toleration as an in itself morally desirable type of relationship, which is furthermore the only conception of toleration...... that avoids various so-called ‘paradoxes of toleration’. The paper first examines whether Forst’s respect conception can be applied descriptively to distinguish between actual patterns of behaviour and classify different acts of toleration. Then the focus is shifted to toleration out of respect as a normative...

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

  11. Hypertension, antihypertensive medication and risk of renal carcinoma in California Seventh-Day Adventists.

    Science.gov (United States)

    Fraser, G E; Phillips, R L; Beeson, W L

    1990-12-01

    A longitudinal study of 34 198 non-Hispanic white California Seventh-day Adventists identified incident cases of renal carcinoma over six years of follow-up. The use of antihypertensive medications and self-reported hypertension had estimated age-sex adjusted incidence rate ratios of 4.51 and 2.90 respectively. These were relatively unchanged by stratifying on additional variables that may have been confounders. Cases diagnosed later during the follow-up period had the strongest association with hypertension, making the alternative explanation that the cancer may have caused the hypertension less likely. Being married in 1976 (amongst females at least) was also associated with a marked elevation of risk. Point estimates of effect suggested that frequent (greater than or equal to 3 week) consumption of fruit (RR = 0.21) and salad vegetables (RR = 0.34) may be protective for this cancer, although the 95% confidence interval did not quite exclude the null value.

  12. Tolerance in Drosophila

    OpenAIRE

    Atkinson, Nigel S.

    2009-01-01

    The set of genes that underlie ethanol tolerance (inducible resistance) are likely to overlap with the set of genes responsible for ethanol addiction. Whereas addiction is difficult to recognize in simple model systems, behavioral tolerance is readily identifiable and can be induced in large populations of animals. Thus, tolerance lends itself to analysis in model systems with powerful genetics. Drosophila melanogaster has been used by a variety of laboratories for the identification of genes...

  13. Antihypertensive Effects of Roselle-Olive Combination in L-NAME-Induced Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Rehab F. Abdel-Rahman

    2017-01-01

    Full Text Available This study aimed to evaluate the antihypertensive efficacy of a new combination therapy of Hibiscus sabdariffa and Olea europaea extracts (2 : 1; Roselle-Olive, using N(G-nitro-L-arginine-methyl ester- (L-NAME- induced hypertensive model. Rats received L-NAME (50 mg/kg/day, orally for 4 weeks. Concurrent treatment with Roselle-Olive (500, 250, and 125 mg/kg/day for 4 weeks resulted in a dose-dependent decrease in both systolic and diastolic blood pressure, reversed the L-NAME-induced suppression in serum nitric oxide (NO, and improved liver and kidney markers, lipid profile, and oxidative status. Furthermore, Roselle-Olive significantly lowered the elevated angiotensin-converting enzyme activity (ACE and showed a marked genoprotective effect against oxidative DNA damage in hypertensive rats. Roselle-Olive ameliorated kidney and heart lesions and reduced aortic media thickness. Real-time PCR and immunohistochemistry showed an enhanced endothelial nitric oxide synthase (eNOS gene and protein expression in both heart and kidney of Roselle-Olive-treated rats. To conclude, our data revealed that Roselle-Olive is an effective combination in which H. sabdariffa and O. europaea synergistically act to control hypertension. These effects are likely to be mediated by antioxidant and genoprotective actions, ACE inhibition, and eNOS upregulation by Roselle-Olive constituents. These findings provide evidences that Roselle-Olive combination affords efficient antihypertensive effect with a broad end-organ protective influence.

  14. Antihypertensive and cardioprotective effects of the dipeptide isoleucine-tryptophan and whey protein hydrolysate.

    Science.gov (United States)

    Martin, M; Kopaliani, I; Jannasch, A; Mund, C; Todorov, V; Henle, T; Deussen, A

    2015-12-01

    Angiotensin-converting enzyme inhibitors are treatment of choice in hypertensive patients. Clinically used inhibitors exhibit a structural similarity to naturally occurring peptides. This study evaluated antihypertensive and cardioprotective effects of ACE-inhibiting peptides derived from food proteins in spontaneously hypertensive rats. Isoleucine-tryptophan (in vitro IC50 for ACE = 0.7 μm), a whey protein hydrolysate containing an augmented fraction of isoleucine-tryptophan, or captopril was given to spontaneously hypertensive rats (n = 60) over 14 weeks. Two further groups, receiving either no supplement (Placebo) or intact whey protein, served as controls. Systolic blood pressure age-dependently increased in the Placebo group, whereas the blood pressure rise was effectively blunted by isoleucine-tryptophan, whey protein hydrolysate and captopril (-42 ± 3, -38 ± 5, -55 ± 4 mm Hg vs. Placebo). At study end, myocardial mass was lower in isoleucine-tryptophan and captopril groups but only partially in the hydrolysate group. Coronary flow reserve (1 μm adenosine) was improved in isoleucine-tryptophan and captopril groups. Plasma ACE activity was significantly decreased in isoleucine-tryptophan, hydrolysate and captopril groups, but in aortic tissue only after isoleucine-tryptophan or captopril treatment. This was associated with lowered expression and activity of matrix metalloproteinase-2. Following isoleucine-tryptophan and captopril treatments, gene expression of renin was significantly increased indicating an active feedback within renin-angiotensin system. Whey protein hydrolysate and isoleucine-tryptophan powerfully inhibit plasma ACE resulting in antihypertensive effects. Moreover, isoleucine-tryptophan blunts tissue ACE activity, reduces matrix metalloproteinase-2 activity and improves coronary flow reserve. Thus, whey protein hydrolysate and particularly isoleucine-tryptophan may serve as innovative food additives with the goal of attenuating

  15. REFRACTORY HYPERTENSION: EVIDENCE OF HEIGHTENED SYMPATHETIC ACTIVITY AS A CAUSE OF ANTIHYPERTENSIVE TREATMENT FAILURE

    Science.gov (United States)

    Dudenbostel, Tanja; Acelajado, Maria C.; Pisoni, Roberto; Li, Peng; Oparil, Suzanne; Calhoun, David A.

    2015-01-01

    Refractory hypertension is an extreme phenotype of treatment failure defined as uncontrolled blood pressure (BP) in spite of ≥5 classes of antihypertensive agents, including chlorthalidone and a mineralocorticoid receptor antagonist. A prospective evaluation of possible mechanisms of refractory hypertension has not been done. The goal of this study was to test for evidence of heightened sympathetic tone as indicated by 24-hr urinary (U-) normetanephrine levels, clinic and ambulatory heart rate (HR), HR variability (HRV), arterial stiffness as indexed by pulse wave velocity (PWV), and systemic vascular resistance (SVR) compared to patients with controlled resistant hypertension. Forty-four consecutive patients, 15 with refractory and 29 with controlled resistant hypertension, were evaluated prospectively. Refractory hypertensive patients were younger (48±13.3 vs. 56.5±14.1 years, p=0.038) and more likely female (80.0 vs 51.9 %, p=0.047) compared to patients with controlled resistant hypertension. They also had higher U-normetanephrine levels (464.4±250.2 vs. 309.8±147.6 μg/24h, p=0.03), higher clinic HR (77.8±7.7 vs. 68.8±7.6 bpm, p=0.001) and 24-hr ambulatory HR (77.8±7.7 vs 68.8±7.6, p=0.0018), higher PWV (11.8±2.2 vs. 9.4±1.5 m/s, p=0.009), reduced HRV (4.48 vs. 6.11, p=0.03), and higher SVR (3795±1753 vs. 2382±349 dyne·sec·cm5·m2, p=0.008). These findings are consistent with heightened sympathetic tone being a major contributor to antihypertensive treatment failure and highlight the need for effective sympatholytic therapies in patients with refractory hypertension. PMID:25987662

  16. Phytochemical and in vitro and in vivo biological investigation on the antihypertensive activity of mango leaves (Mangifera indica L.).

    Science.gov (United States)

    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

  17. 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.

  18. Role of adenosine receptors in caffeine tolerance

    Energy Technology Data Exchange (ETDEWEB)

    Holtzman, S.G.; Mante, S.; Minneman, K.P. (Emory Univ. School of Medicine, Atlanta, GA (USA))

    1991-01-01

    Caffeine is a competitive antagonist at adenosine receptors. Receptor up-regulation during chronic drug treatment has been proposed to be the mechanism of tolerance to the behavioral stimulant effects of caffeine. This study reassessed the role of adenosine receptors in caffeine tolerance. Separate groups of rats were given scheduled access to drinking bottles containing plain tap water or a 0.1% solution of caffeine. Daily drug intake averaged 60-75 mg/kg and resulted in complete tolerance to caffeine-induced stimulation of locomotor activity, which could not be surmounted by increasing the dose of caffeine. 5'-N-ethylcarboxamidoadenosine (0.001-1.0 mg/kg) dose dependently decreased the locomotor activity of caffeine-tolerant rats and their water-treated controls but was 8-fold more potent in the latter group. Caffeine (1.0-10 mg/kg) injected concurrently with 5-N-ethylcarboxamidoadenosine antagonized the decreases in locomotor activity comparably in both groups. Apparent pA2 values for tolerant and control rats also were comparable: 5.05 and 5.11. Thus, the adenosine-antagonist activity of caffeine was undiminished in tolerant rats. The effects of chronic caffeine administration on parameters of adenosine receptor binding and function were measured in cerebral cortex. There were no differences between brain tissue from control and caffeine-treated rats in number and affinity of adenosine binding sites or in receptor-mediated increases (A2 adenosine receptor) and decreases (A1 adenosine receptor) in cAMP accumulation. These results are consistent with theoretical arguments that changes in receptor density should not affect the potency of a competitive antagonist. Experimental evidence and theoretical considerations indicate that up-regulation of adenosine receptors is not the mechanism of tolerance to caffeine-induced stimulation of locomotor activity.

  19. Role of adenosine receptors in caffeine tolerance

    International Nuclear Information System (INIS)

    Holtzman, S.G.; Mante, S.; Minneman, K.P.

    1991-01-01

    Caffeine is a competitive antagonist at adenosine receptors. Receptor up-regulation during chronic drug treatment has been proposed to be the mechanism of tolerance to the behavioral stimulant effects of caffeine. This study reassessed the role of adenosine receptors in caffeine tolerance. Separate groups of rats were given scheduled access to drinking bottles containing plain tap water or a 0.1% solution of caffeine. Daily drug intake averaged 60-75 mg/kg and resulted in complete tolerance to caffeine-induced stimulation of locomotor activity, which could not be surmounted by increasing the dose of caffeine. 5'-N-ethylcarboxamidoadenosine (0.001-1.0 mg/kg) dose dependently decreased the locomotor activity of caffeine-tolerant rats and their water-treated controls but was 8-fold more potent in the latter group. Caffeine (1.0-10 mg/kg) injected concurrently with 5-N-ethylcarboxamidoadenosine antagonized the decreases in locomotor activity comparably in both groups. Apparent pA2 values for tolerant and control rats also were comparable: 5.05 and 5.11. Thus, the adenosine-antagonist activity of caffeine was undiminished in tolerant rats. The effects of chronic caffeine administration on parameters of adenosine receptor binding and function were measured in cerebral cortex. There were no differences between brain tissue from control and caffeine-treated rats in number and affinity of adenosine binding sites or in receptor-mediated increases (A2 adenosine receptor) and decreases (A1 adenosine receptor) in cAMP accumulation. These results are consistent with theoretical arguments that changes in receptor density should not affect the potency of a competitive antagonist. Experimental evidence and theoretical considerations indicate that up-regulation of adenosine receptors is not the mechanism of tolerance to caffeine-induced stimulation of locomotor activity

  20. The time course of ethanol tolerance: associative learning

    Directory of Open Access Journals (Sweden)

    J.L.O. Bueno

    2007-11-01

    Full Text Available The effect of different contextual stimuli on different ethanol-induced internal states was investigated during the time course of both the hypothermic effect of the drug and of drug tolerance. Minimitters were surgically implanted in 16 Wistar rats to assess changes in their body temperature under the effect of ethanol. Rat groups were submitted to ethanol or saline trials every other day. The animals were divided into two groups, one receiving a constant dose (CD of ethanol injected intraperitoneally, and the other receiving increasing doses (ID during the 10 training sessions. During the ethanol training sessions, conditioned stimuli A (tone and B (buzzer were presented at "state +" (35 min after drug injection and "state -" (170 min after drug injection, respectively. Conditioned stimuli C (bip and D (white noise were presented at moments equivalent to stimuli A and B, respectively, but during the saline training sessions. All stimuli lasted 15 min. The CD group, but not the ID group, developed tolerance to the hypothermic effect of ethanol. Stimulus A (associated with drug "state +" induced hyperthermia with saline injection in the ID group. Stimulus B (associated with drug "state -" reduced ethanol tolerance in the CD group and modulated the hypothermic effect of the drug in the ID group. These results indicate that contextual stimuli acquire modulatory conditioned properties that are associated with the time course of both the action of the drug and the development of drug tolerance.

  1. Haloperidol Disrupts Opioid-Antinociceptive Tolerance and Physical Dependence

    Science.gov (United States)

    Yang, Cheng; Chen, Yan; Tang, Lei

    2011-01-01

    Previous studies from our laboratory and others have implicated a critical role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in opioid tolerance and dependence. Translational research targeting the CaMKII pathway is challenging, if not impossible, because of a lack of selective inhibitors. We discovered in a preliminary study that haloperidol, a butyrophenone antipsychotic drug, inhibited CaMKII, which led us to hypothesize that haloperidol can attenuate opioid tolerance and dependence by inhibiting CaMKII. The hypothesis was tested in two rodent models of opioid tolerance and dependence. Pretreatment with haloperidol (0.2–1.0 mg/kg i.p.) prevented the development of morphine tolerance and dependence in a dose-dependent manner. Short-term treatment with haloperidol (0.06–0.60 mg/kg i.p.) dose-dependently reversed the established morphine-antinociceptive tolerance and physical dependence. Correlating with behavioral effects, pretreatment or short-term treatment with haloperidol dose-dependently inhibited morphine-induced up-regulation of supraspinal and spinal CaMKIIα activity. Moreover, haloperidol given orally was also effective in attenuating morphine-induced CaMKIIα activity, antinociceptive tolerance, and physical dependence. Taken together, these data suggest that haloperidol attenuates opioid tolerance and dependence by suppressing CaMKII activity. Because haloperidol is a clinically used drug that can be taken orally, we propose that the drug may be of use in attenuating opioid tolerance and dependence. PMID:21436292

  2. TRX-4 (TolerRx Inc).

    Science.gov (United States)

    Brown, William M

    2006-04-01

    TolerRx Inc, under license from BTG plc, is developing TRX-4, an anti-CD3 humanized monoclonal antibody for the potential treatment of type 1 diabetes and psoriasis. Phase II trials of the therapeutic antibody in type 1 diabetes have been completed and the company is planning a pivotal phase III trial for this indication. TolerRx is also enrolling psoriasis patients in a phase Ib clinical study of TRX-4. TRX-4 has been awarded Orphan Drug status for recent-onset type 1 diabetes.

  3. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...

  4. Compromise and Toleration

    DEFF Research Database (Denmark)

    Rostbøll, Christian F.

    Political compromise is akin to toleration, since both consist of an "agreement to disagree." Compromise and toleration also share a predicament of being regarded as ambiguous virtues that require of us to accept something we actually regard as wrong. However, we misunderstand the nature, justifi...... in compromise are more stringent than those for being tolerated. Still, the limits of compromise cannot be drawn to narrowly if it is to remain its value as a form of agreement that respects and embodies the differences of opinion in society.......Political compromise is akin to toleration, since both consist of an "agreement to disagree." Compromise and toleration also share a predicament of being regarded as ambiguous virtues that require of us to accept something we actually regard as wrong. However, we misunderstand the nature......, justification, and limits of compromise if we see it merely as a matter of toleration. While toleration is mainly a matter of accepting citizens' equal right to co-existence as subjects to law, political compromise includes the parties in making law – it makes them co-authors of law. Toleration entails...

  5. Tolerances in micro manufacturing

    DEFF Research Database (Denmark)

    Hansen, Hans Nørgaard; Zhang, Yang; Islam, Aminul

    This paper describes a method for analysis of tolerances in micro manufacturing. It proposes a mapping oftolerances to dimensions and compares this with current available international standards. The analysisdocuments that tolerances are not scaled down as the absolute dimension. In practice...

  6. Fault tolerant computing systems

    International Nuclear Information System (INIS)

    Randell, B.

    1981-01-01

    Fault tolerance involves the provision of strategies for error detection damage assessment, fault treatment and error recovery. A survey is given of the different sorts of strategies used in highly reliable computing systems, together with an outline of recent research on the problems of providing fault tolerance in parallel and distributed computing systems. (orig.)

  7. Toleration out of respect?

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2014-01-01

    be based on a modus vivendi designed to secure peaceful co-existence, but should be based on moral reasons. Forst therefore advances what he calls the ‘respect conception’ of toleration as an in itself morally desirable type of relationship, which is furthermore the only conception of toleration...

  8. Recognition and Toleration

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2010-01-01

    Recognition and toleration are ways of relating to the diversity characteristic of multicultural societies. The article concerns the possible meanings of toleration and recognition, and the conflict that is often claimed to exist between these two approaches to diversity. Different forms or inter...

  9. Student-on-Student Harassment and Zero Tolerance: Achieving a Delicate Balance

    Science.gov (United States)

    Essex, Nathan L.

    2009-01-01

    Zero tolerance policy. Most school districts have a zero tolerance policy in place for drug use, weapons on campus, sexual harassment, or all of the above. At their very core, zero tolerance policies make schools safer. However, a one-size-fits-all approach does not work well in all situations involving student misconduct. This article outlines…

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

    Directory of Open Access Journals (Sweden)

    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

  11. Remember Tolerance Differently

    DEFF Research Database (Denmark)

    Tønder, Lars

    2012-01-01

    This essay questions the linear conception of history which often accompanies the way contemporary democratic theory tends to disavow tolerance's discontinuities and remainders. In the spirit of Foucault's genealogy of descent, the idea is to develop a new sense of tolerance's history, not by inv......This essay questions the linear conception of history which often accompanies the way contemporary democratic theory tends to disavow tolerance's discontinuities and remainders. In the spirit of Foucault's genealogy of descent, the idea is to develop a new sense of tolerance's history......, not by invoking a critique external to contemporary democratic theory, but by witnessing the history of tolerance paraliptically, with an eye to what it obscures and yet presupposes....

  12. 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...

  13. Antihypertensive treatment and control according to gender, education, country of birth and psychiatric disorder: the Swedish Primary Care Cardiovascular Database (SPCCD).

    Science.gov (United States)

    Ljungman, C; Kahan, T; Schiöler, L; Hjerpe, P; Wettermark, B; Boström, K B; Manhem, K

    2015-06-01

    The reasons why women and men are treated with different antihypertensive drugs are not clear. Whether socioeconomic factors influence prescription patterns and blood pressure control differently in women and men has not been investigated. This cross-sectional study performed in a cohort of hypertensive patients from the Swedish Primary Care Cardiovascular Database (SPCCD) examined the influence of educational level, country of birth, gender and concomitant psychiatric disorder on prescription pattern and blood pressure control in 40,825 hypertensive patients. Men were more often than women treated with calcium channel blocker and angiotensin-converting enzyme inhibitor (ACEI), irrespective of education, country of birth and psychiatric disorder. Educational level influenced the prescription pattern to some extent, where the gender differences were reduced in patients with a higher educational level. In women, but not in men, high educational level and concomitant psychiatric disorder were associated with a higher proportion reaching target blood pressure. The predominant use of ACEI and calcium channel blockers in men is not influenced by educational level, country of birth or psychiatric disorder. Thus other explanations must be considered such as gender differences in side effects. Educational level seems to have a greater impact on reaching target blood pressure in women compared with men.

  14. 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

  15. 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.

  16. A Multirelational Account of Toleration

    DEFF Research Database (Denmark)

    Ferretti, Maria Paola; Lægaard, Sune

    2013-01-01

    Toleration classically denotes a relation between two agents that is characterised by three components: objection, power, and acceptance overriding the objection. Against recent claims that classical toleration is not applicable in liberal democracies and that toleration must therefore either be ...

  17. Chronic and acute effects of different antihypertensive drugs on femoral artery relaxations of L-NAME hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Sládková, M.; Kojšová, S.; Jendeková, L.; Pecháňová, Olga

    2007-01-01

    Roč. 56, Suppl.2 (2007), S85-S91 ISSN 0862-8408 Grant - others:VEGA(SK) 2/6148/26; VEGA(SK) 1/3429/06; -(SK) APVV-0586-06 Institutional research plan: CEZ:AV0Z50110509 Keywords : L-NAME induced hypertension * indapamide * hydrochlorothiazide * captopril Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.505, year: 2007

  18. Clinical Perspective on Antihypertensive Drug Treatment in Adults With Grade 1 Hypertension and Low-to-Moderate Cardiovascular Risk

    DEFF Research Database (Denmark)

    Morales Salinas, Alberto; Coca, Antonio; Olsen, Michael H.

    2017-01-01

    Hypertension is a leading risk factor for disease burden globally. An unresolved question is whether grade 1 hypertension (140-159/90-99. mm. Hg) with low (cardiovascular mortality <1% at 10 years) to moderate (cardiovascular mortality ≥1% and <5% at 10 years) absolute total cardiovascular risk (...

  19. Interaction by known beta cell loci on the association of antihypertensive drug therapies with hyperglycemia in the Framingham Offspring Study

    OpenAIRE

    Miguel y Yanes, José María de

    2013-01-01

    Antecedentes: Los polimorfismos de nucleótido simple (SNPs) comunes asociados a función de célula beta y la hipertensión o su tratamiento podrían interaccionar con la variación en el tiempo en la glucosa en ayunas (ΔGA) o la aparición de diabetes mellitus tipo 2 (DM-2). Métodos: Agrupamos datos de 3.471 participantes del Estudio Descendencia de Framingham en 6 períodos de ~4 años (15.852 personas-examen; edad media 52 años, 54% mujeres). Definimos tres exposiciones de hipertensión: 1) hiperte...

  20. Ionic Liquid Crystals Modifier for Selective Determination of Terazosin Antihypertensive Drug in Presence of Common Interference Compounds

    Directory of Open Access Journals (Sweden)

    Nada F. Atta

    2017-01-01

    Full Text Available Electrochemical sensor was fabricated based on carbon paste electrode modified with an ionic liquid crystal ILC (2-chloro-1,3-dimethyl-imidazolidinium hexafluorophosphate in presence of sodium dodecyl sulfate for the selective electrochemical determination of Terazosin (TZ in presence of common interference compounds. The electrode performance was compared in presence of other ionic liquids ILs (1-Butyl-4-methyl pyridinium tetrafluoroborate and (1-n-Hexyl-3-methyl imidazolium tetrafluoroborate. Ultrasensitive determination of Terazosin HCl at the ILC modified electrode in the linear dynamic ranges of 0.002 to 0.09 μmol·L−1 and 0.2 to 30 μmol·L−1 with correlation coefficients 0.996 and 0.995 and LODs 1.69 × 10−11 mol·L−1 and 6.43 × 10−9 mol·L−1, respectively, were obtained. Selective determination of TZ in presence of uric acid and ascorbic acid and simultaneous determination of binary mixtures of TZ/dopamine, TZ/paracetamol and TZ/Morphine were also determined successfully using the modified sensor.

  1. Determination of antihypertensive drug moexipril hydrochloride based on the enhancement effect of sodium dodecyl sulfate at carbon paste electrode.

    Science.gov (United States)

    Attia, Ali K

    2010-04-15

    Herein, an electrochemical differential pulse voltammetric method was developed for the determination of moexipril hydrochloride based on the enhancement effect of sodium dodecyl sulfate. The oxidation process has been carried out in Britton-Robinson buffer. Moexipril hydrochloride exhibits a well-defined irreversible oxidation peak over the entire pH range (2-11). The peak current varied linearly over the range from 4.0 x 10(-7) to 5.2 x 10(-6) mol L(-1). The limits of detection and quantification were 6.87 x 10(-8) mol L(-1) and 2.29 x 10(-7) mol L(-1), respectively. The recovery was found in the range from 99.65% to 100.76%. The relative standard deviation was found in the range from 0.429% to 0.845%. The proposed method possesses high sensitivity, accuracy and rapid response. Finally, this method was successfully used to determine moexipril hydrochloride in tablets. (c) 2009 Elsevier B.V. All rights reserved.

  2. Drug Policy: the "Dutch Model"

    NARCIS (Netherlands)

    van Ooijen-Houben, M.M.J.; Kleemans, E.R.

    2015-01-01

    Dutch drug policy, once considered pragmatic and lenient and rooted in a generally tolerant attitude toward drug use, has slowly but surely shifted from a primarily public health focus to an increasing focus on law enforcement. The "coffee shop" policy and the policy toward MDMA/ecstasy are

  3. Validation of an abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9 among patients on antihypertensive medications

    Directory of Open Access Journals (Sweden)

    Desrosiers Marie-Pierre

    2009-04-01

    Full Text Available Abstract Background The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM Version 1.4 is a reliable and valid instrument to assess patients' satisfaction with medication, providing scores on four scales – side effects, effectiveness, convenience and global satisfaction. In naturalistic studies, administering the TSQM with the side effects domain could provoke the physician to assess the presence or absence of adverse events in a way that is clinically atypical, carrying the potential to interfere with routine medical care. As a result, an abbreviated 9-item TSQM (TSQM-9, derived from the TSQM Version 1.4 but without the five items of the side effects domain was created. In this study, an interactive voice response system (IVRS-administered TSQM-9 was psychometrically evaluated among patients taking antihypertensive medication. Methods A total of 3,387 subjects were invited to participate in the study from an online panel who self-reported taking a prescribed antihypertensive medication. The subjects were asked to complete the IVRS-administered TSQM-9 at the start of the study, along with the modified Morisky scale, and again within 7 to 14 days. Standard psychometric analyses were conducted; including Cronbach's alpha, intraclass correlation coefficients, structural equation modeling, Spearman correlation coefficients and analysis of covariance (ANCOVA. Results A total of 396 subjects completed all the study procedures. Approximately 50% subjects were male with a good racial/ethnic mix: 58.3% white, 18.9% black, 17.7% Hispanic and 5.1% either Asian or other. There was evidence of construct validity of the TSQM-9 based on the structural equation modeling findings of the observed data fitting the Decisional Balance Model of Treatment Satisfaction even without the side effects domain. TSQM-9 domains had high internal consistency as evident from Cronbach's alpha values of 0.84 and greater. TSQM-9 domains also demonstrated good test

  4. Mechanism of antihypertensive effect of Mucuna pruriens L. seed extract and its isolated compounds.

    Science.gov (United States)

    Khan, Mohammad Yaseen; Kumar, Vimal

    2017-06-21

    Background In the search of safe and effective lead molecules from natural sources, Mucuna pruriens (MP) L. (Fabaceae) seeds were utilized for exploring the antihypertensive potential. Traditionally, it is used as diuretic and hypotensive. Methods Bioassay-guided fractions were utilized for the isolation of active compounds by column chromatography. IC50 value, enzyme kinetics and inhibition mechanism were determined. In vivo time and dose-dependent hypotensive study followed by changes in mean arterial pressure (MAP) induced by angiotensin I (3 nmol/kg), angiotensin II (3 nmol/kg), and bradykinin (10 nmol/kg) in anesthetized rats was done. Plasma and tissue angiotensin I-converting enzyme (ACE) activities were also determined. Results Phytochemical analysis by spectroscopic techniques revealed the presence of known compounds like genistein, ursolic acid and L-DOPA from the ethyl acetate and water fraction, respectively. In vitro study revealed MP ethyl acetate (MPEA) fraction and genistein as the most active fraction (IC50 156.45 µg/mL) and compound (IC50 253.81 µM), respectively. Lineweaver-Burk plots revealed a non-competitive mode of inhibition. ACE protein precipitation was the suggested mechanism for inhibition. The extract showed a time- and dose-dependent decrease in MAP. Genistein was able to dose-dependently reduce the MAP, up to 53±1.5 mmHg (40 mg/kg, i.v.). As compared to control, it showed a dose-dependent decrease in plasma ACE activity of 40.61 % and 54.76 % at 10 mg/kg and 20 mg/kg, respectively. It also decreased the ACE activity in the aorta (107.67nM/ml min at 10 mg, p<0.001; 95.33nM/ml min at 20 mg p<0.001). Captopril was used as a standard for various in vitro and in vivo assays. Conclusions The study revealed the antihypertensive potential of MP seed compounds via ACE inhibition.

  5. Antihypertensive combination therapy in primary care offices: results of a cross-sectional survey in Switzerland

    Directory of Open Access Journals (Sweden)

    Roas S

    2014-12-01

    Full Text Available Susanne Roas,1 Felix Bernhart,2 Michael Schwarz,3 Walter Kaiser,4 Georg Noll5 1Department of Internal Medicine, University Hospital, Zurich, 2Private Practice, Biberist, 3Ambulatorium Wiesendamm, Basel, 4Healthworld (Schweiz AG, Steinhausen, 5HerzKlinik Hirslanden, Zurich, Switzerland Background: Most hypertensive patients need more than one substance to reach their target blood pressure (BP. Several clinical studies indicate the high efficacy of antihypertensive combinations, and recent guidelines recommend them in some situations even as initial therapies. In general practice they seem widespread, but only limited data are available on their effectiveness under the conditions of everyday life. The objectives of this survey among Swiss primary care physicians treating hypertensive patients were: to know the frequency of application of different treatment modalities (monotherapies, free individual combinations, single-pill combinations; to see whether there are relationships between prescribed treatment modalities and patient characteristics, especially age, treatment duration, and comorbidities; and to determine the response rate (percentage of patients reaching target BP of different treatment modalities under the conditions of daily practice. Methods: This cross-sectional, observational survey among 228 randomly chosen Swiss primary care physicians analyzed data for 3,888 consecutive hypertensive patients collected at one single consultation. Results: In this survey, 31.9% of patients received monotherapy, 41.2% two substances, 20.9% three substances, and 4.7% more than three substances. By combination mode, 34.9% took free individual combinations and 30.0% took fixed-dose single-pill combinations. Combinations were more frequently given to older patients with a long history of hypertension and/or comorbidities. In total, 67.8% of patients achieved their BP target according to their physician's judgment. When compared, single

  6. Engineering antigen-specific immunological tolerance.

    Energy Technology Data Exchange (ETDEWEB)

    Kontos, Stephan; Grimm, Alizee J.; Hubbell, Jeffrey A.

    2015-05-01

    Unwanted immunity develops in response to many protein drugs, in autoimmunity, in allergy, and in transplantation. Approaches to induce immunological tolerance aim to either prevent these responses or reverse them after they have already taken place. We present here recent developments in approaches, based on engineered peptides, proteins and biomaterials, that harness mechanisms of peripheral tolerance both prophylactically and therapeutically to induce antigenspecific immunological tolerance. These mechanisms are based on responses of B and T lymphocytes to other cells in their immune environment that result in cellular deletion or ignorance to particular antigens, or in development of active immune regulatory responses. Several of these approaches are moving toward clinical development, and some are already in early stages of clinical testing.

  7. Potential drug-drug and drug-disease interactions in well-functioning community-dwelling older adults.

    Science.gov (United States)

    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

  8. COMPARATIVE CONTROLLED STUDY OF ANTIHYPERTENSIVE EFFICACY AND SAFETY OF CARVEDILOL IN PATIENTS WITH HYPERTENSION AND OBESITY OR DIABETES 2 TYPE (BASED ON RESULTS OF MULTICENTER TRIAL ACCORD

    Directory of Open Access Journals (Sweden)

    Yu. V. Yu.V. Lukina

    2009-01-01

    Full Text Available Aim. To study efficacy and safety of beta-blocker with vasodilating properties carvedilol (Acridilole, Akrihin, Russia as a part of the combined therapy of patients with arterial hypertension (HT and diabetes mellitus 2 type (DM2 and/or obesity.Material and methods. 592 patients: 176 men (29,7% and 416 women (70,3% with HT were examined. 194 patients had D2 and 398 patients had obesity. Patients were randomized for carvedilol therapy (n=291 or control group (n=301. Carvedilol was prescribed additionally to current therapy in dose of 6,25 mg BID, in 2 weeks the dose was increased to 12,5 mg BID if it was necessary. Blood pressure (BP and heart rate, number of angina attacks were registered at visits. ECG, laboratory analysis (plasma lipide profile, serum glucose, glycolised haemoglobin, serum K+ and Na+, evaluation of depression and anxiety status (according to special questionnaires were performed on the first and the last visits.Results. 582 patients completed the study. 7 patients dropped out from carvedilol group and 3 patients - from control group. The levels of systolic BP (SBP and diastolic BP (DBP were decreased during study, more significantly in carvedilol group (р<0,0001. SBP decreased on 24,8 mm Hg in patients of carvedilol group and on 21,4 mm Hg in patients of control group. DBP decreased on 12,5 mm Hg and 11 mm Hg respectively. Angina attacks were registered less often in patients of carvedilol group (р=0,001. Serum glucose and lipid spectrum did not change in both groups. Depression level decreased in patients receiving carvedilol. 17 side effects were registered in carvedilol group and 15 - in control group (р=0,575Conclusion. High antihypertensive efficacy of carvedilol is confirmed in hypertensive patients with DM2 and/or obesity. Good tolerability and metabolic neutrality of carvedilol is also observed.

  9. COMPARATIVE CONTROLLED STUDY OF ANTIHYPERTENSIVE EFFICACY AND SAFETY OF CARVEDILOL IN PATIENTS WITH HYPERTENSION AND OBESITY OR DIABETES 2 TYPE (BASED ON RESULTS OF MULTICENTER TRIAL ACCORD

    Directory of Open Access Journals (Sweden)

    Yu. V. Yu.V. Lukina

    2016-01-01

    Full Text Available Aim. To study efficacy and safety of beta-blocker with vasodilating properties carvedilol (Acridilole, Akrihin, Russia as a part of the combined therapy of patients with arterial hypertension (HT and diabetes mellitus 2 type (DM2 and/or obesity.Material and methods. 592 patients: 176 men (29,7% and 416 women (70,3% with HT were examined. 194 patients had D2 and 398 patients had obesity. Patients were randomized for carvedilol therapy (n=291 or control group (n=301. Carvedilol was prescribed additionally to current therapy in dose of 6,25 mg BID, in 2 weeks the dose was increased to 12,5 mg BID if it was necessary. Blood pressure (BP and heart rate, number of angina attacks were registered at visits. ECG, laboratory analysis (plasma lipide profile, serum glucose, glycolised haemoglobin, serum K+ and Na+, evaluation of depression and anxiety status (according to special questionnaires were performed on the first and the last visits.Results. 582 patients completed the study. 7 patients dropped out from carvedilol group and 3 patients - from control group. The levels of systolic BP (SBP and diastolic BP (DBP were decreased during study, more significantly in carvedilol group (р<0,0001. SBP decreased on 24,8 mm Hg in patients of carvedilol group and on 21,4 mm Hg in patients of control group. DBP decreased on 12,5 mm Hg and 11 mm Hg respectively. Angina attacks were registered less often in patients of carvedilol group (р=0,001. Serum glucose and lipid spectrum did not change in both groups. Depression level decreased in patients receiving carvedilol. 17 side effects were registered in carvedilol group and 15 - in control group (р=0,575Conclusion. High antihypertensive efficacy of carvedilol is confirmed in hypertensive patients with DM2 and/or obesity. Good tolerability and metabolic neutrality of carvedilol is also observed.

  10. State of a large vessels and microcirculation - a new target for antihypertensive therapy in patients with hypertension and type 2 diabetes

    Directory of Open Access Journals (Sweden)

    M. E. Statsenko

    2016-01-01

    Full Text Available Aim. To evaluate the effect of 12 weeks of complex therapy with the fixed combination of enalapril and indapamide on indicators of vascular stiffness of large arteries and parameters of skin microcirculation (MC in patients with arterial hypertension (HT and diabetes mellitus (DM type 2.Material and methods. 30 patients with HT stage II-III in combination with DM type 2 aged 40-70 years were included into the study. The fixed combination of enalapril and indapamide in addition to lipid-lowering and hypoglycemic therapy was prescribed to all patients. Elastic properties of large arteries were assessed by analyzing the pulse wave velocity (PWV and the calculation of the index of aortic stiffness (IAS. Skin MC and level of glycated hemoglobin (HbA1c were also determined.Results. After the 12-week treatment all patients reached the target values of blood pressure (BP. Office systolic and diastolic BP levels decreased by 18.8 and 13.1% (p<0.05 for both, respectively. The treatment did not have a negative effect on glucose metabolism – HbA1C concentration decreased by 2.7%. PWV in the vessels of elastic and muscular types decreased by 10.8 and 10.1% (p<0.05 for both, respectively, and IAS decreased by 27.4% (p<0.05. Significant growth in factor myogenic regulation of MC and reduction in bypass indicator by 21.8% were found.Conclusion. Combined therapy with the inclusion of a fixed combination of enalapril and indapamide for 12 weeks had a high antihypertensive efficacy and good tolerability in patients with HT and DM type 2. Treatment significantly reduced the vascular stiffness of large arteries and improved the MC indices in these patients.

  11. 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...

  12. A comparison of the development of tolerance to ethanol and cross-tolerance to nicotine after chronic ethanol treatment in long- and short-sleep mice.

    Science.gov (United States)

    de Fiebre, C M; Collins, A C

    1993-09-01

    Previous studies have shown that inbred mouse strains differ in the development of tolerance to both nicotine and ethanol, indicating that genetic factors regulate tolerance development. Those mouse strains that are most sensitive to an acute challenge dose of either drug develop the most tolerance to that drug. The ethanol-sensitive long-sleep (LS) mice are more sensitive to several behavioral and physiological effects of nicotine than are the ethanol-resistant short-sleep (SS) mice. The experiments reported here assessed whether the LS and SS mice develop tolerance to ethanol after chronic treatment with ethanol-containing liquid diets and whether cross-tolerance to nicotine also developed. Tolerance and cross-tolerance were measured by assessing the effects of acute challenge doses of drug on Y-maze crossing and rearing activities, heart rate and body temperature. The LS mice developed tolerance to ethanol's effects on three of the four measures and were cross-tolerant to nicotine on all of the measures. In contrast, the SS mice developed tolerance to ethanol for only two of the measures, but failed to develop cross-tolerance to any action of nicotine. These findings support the hypothesis that ethanol and nicotine share sites of action and that common genes regulate responses to these two drugs. Evidence suggests that tolerance to nicotine may be related to an up-regulation of brain nicotinic receptors, at least in some inbred mouse strains, but chronic ethanol treatment did not reproducibly change either [3H]nicotine or alpha-[125I]bungarotoxin binding. Therefore, other mechanisms must underlie the tolerance and cross-tolerance that was seen.

  13. Vasorelaxing and antihypertensive activities of synthesized peptides derived from computer-aided simulation of pepsin hydrolysis of yam dioscorin

    OpenAIRE

    Lin, Yin-Shiou; Lu, Yeh-Lin; Wang, Guei-Jane; Liang, Hong-Jen; Hou, Wen-Chi

    2014-01-01

    Background We reported that yam dioscorin and its peptic hydrolysates exhibited ACE inhibition and antihypertensive effects on SHRs, however, the active peptides are not really isolated until now. Using ACE inhibitory screenings, two penta-peptides, KTCGY and KRIHF, were selected for ex vivo and in vivo experiments. Results KTCGY, KRIHF, and captopril were shown to have similar vasodilating effects against phenylephrine (PE)-induced tensions in rat endothelium-dependent thoracic aortic rings,...

  14. Continuing or Temporarily Stopping Prestroke Antihypertensive Medication in Acute Stroke:An Individual Patient Data Meta-Analysis

    OpenAIRE

    Woodhouse, Lisa J.; Manning, Lisa; Potter, John F.; Berge, Eivind; Sprigg, Nikola; Wardlaw, Joanna; Lees, Kennedy R.; Bath, Philip M.; Robinson, Thompson G.; , Blood Pressure in Acute Stroke Collaboration (BASC)

    2017-01-01

    Over 50% of patients are already taking blood pressure-lowering therapy on hospital admission for acute stroke. An individual patient data meta-analysis from randomized controlled trials was undertaken to determine the effect of continuation versus temporarily stopping pre-existing antihypertensive medication in acute stroke. Key databases were searched for trials against the following inclusion criteria: randomized design; stroke onset ≤48 hours; investigating the effect of continuation vers...

  15. The apolipoprotein E epsilon4-allele and antihypertensive treatment are associated with increased risk of cerebral MRI white matter hyperintensities

    DEFF Research Database (Denmark)

    Høgh, P; Garde, Ellen; Mortensen, Erik Lykke

    2007-01-01

    ) in a community-based sample of elderly subjects. MATERIALS AND METHODS: From a cohort of 976 subjects born in 1914, APOE genotype was determined and MRI examinations were carried out in 75 subjects. WMH were rated using a standard semi-quantitative method. ANOVA and regression analyses were conducted to explore...... the relative importance of the potential risk factors. RESULTS: APOE genotype and antihypertensive treatment were significantly associated with severity of total WMH load (P Pharmaceutical treatment for arterial...

  16. The Antihypertensive Effects of Hydroalcoholic Extract of Allium Eriophyllum Leaves on Rats with Simultaneous Type 2 Diabetes and Renal Hypertension

    Directory of Open Access Journals (Sweden)

    Masoud Mozafari

    2015-03-01

    Full Text Available Background: Some species of Allium family are known to have antihypertensive, anti-diabetic, and lipid lowering effects. Objectives: This study aimed to examine the possible mechanisms of antihypertensive, anti-diabetic, and anti-lipid activities of Allium eriophyllum which grows in Fars province, Iran in a rat model of simultaneous type 2 diabetes and renal hypertension. Materials and Methods: This study was conducted on six groups of male Spargue-Dawley rats each containing 8 - 10 animals, including a sham-control, a diabetic, a renal hypertensive, and three simultaneously hypertensive–diabetic groups receiving vehicle or 30 or 100 mg/kg/day hydroalcoholic extract of Allium eriophyllum. Four weeks after induction of diabetes, renal hypertension was induced and the animals started receiving the vehicle or extract for the subsequent four weeks. Afterwards, blood pressure, fasting blood sugar, serum cholesterol, triglyceride, and markers of oxidative stress were measured, and isolated studies were performed on aortic rings. Results: Systolic blood pressure, heart rate, fasting blood sugar, maximal response, and effective concentrations 50 (EC50 of phenylephrine and acetylcholine of the hypertensive-diabetic group receiving vehicle were significantly higher compared to those of the sham-control group, and treatment with the extract led to a significant reduction in these variables. Moreover, serum superoxide dismutase and glutathione reductase and maximal response of acetylcholine were significantly lower in the hypertensive-diabetic group receiving vehicle in comparison to the sham-control group, and treatment with the extract significantly reduced these variables. Conclusions: The present study findings indicated that antihypertensive, anti-diabetic, and anti-lipid effects of the extract might be partly due to its antioxidant mechanism. It was also revealed that its antihypertensive effects may be additionally mediated by improving the release

  17. Drug Facts

    Medline Plus

    Full Text Available ... Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use and Other People Drug Use and Families Drug Use and Kids Drug Use and Unborn ...

  18. Drug Facts

    Medline Plus

    Full Text Available ... Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, ... Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug Use and Kids ...

  19. Drug Facts

    Medline Plus

    Full Text Available ... People Drug Use and Families Drug Use and Kids Drug Use and Unborn Children Drug Use and ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used ...

  20. State, religion and toleration

    DEFF Research Database (Denmark)

    Huggler, Jørgen

    2009-01-01

    Contribution to Religion and State - From separation to cooperation? Legal-philosophical reflections for a de-secularized world. (IVR Cracow Special Workshop). Eds. Bart. C. Labuschagne & Ari M. Solon. Abstract: Toleration is indeed a complex phenomenon. A discussion of the concept will have...... to underline not only the broadmindedness and liberty of individuals or of groups, but also the relevant distinctions and arguments in political philosophy, epistemology, philosophy of religion and philosophical anthropology and their connection with educational issues. Through a discussion of these relations......, the essay argues three theses: (1) Toleration is not reducible to an ethics of spiritual freedom. (2) Toleration is not neutral to fanatism. (3) Toleration involves esteem for the person....

  1. 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.

  2. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial.

    Science.gov (United States)

    Townsend, Raymond R; Mahfoud, Felix; Kandzari, David E; Kario, Kazuomi; Pocock, Stuart; Weber, Michael A; Ewen, Sebastian; Tsioufis, Konstantinos; Tousoulis, Dimitrios; Sharp, Andrew S P; Watkinson, Anthony F; Schmieder, Roland E; Schmid, Axel; Choi, James W; East, Cara; Walton, Anthony; Hopper, Ingrid; Cohen, Debbie L; Wilensky, Robert; Lee, David P; Ma, Adrian; Devireddy, Chandan M; Lea, Janice P; Lurz, Philipp C; Fengler, Karl; Davies, Justin; Chapman, Neil; Cohen, Sidney A; DeBruin, Vanessa; Fahy, Martin; Jones, Denise E; Rothman, Martin; Böhm, Michael

    2017-11-11

    Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; prenal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP -5·0 mm Hg (95% CI -9·9 to -0·2; p=0·0414), 24-h DBP -4·4 mm Hg (-7·2 to -1·6; p=0·0024), office SBP -7·7 mm Hg (-14·0

  3. A Theory of Tolerance

    OpenAIRE

    Corneo, Giacomo; Jeanne, Olivier

    2006-01-01

    We develop an economic theory of tolerance where styles of behaviour are invested with symbolic value. Value systems are endogenous and taught by parents to their children. In conjunction with actual behaviour, value systems determine the esteem enjoyed by individuals. Intolerant individuals have all symbolic value invested in a single style of behaviour, whereas tolerant people have diversified values. The proposed model identifies a link between the unpredictability of children's lifestyles...

  4. Antioxidant and Antihypertensive Potential of Protein Fractions from Flour and Milk Substitutes from Canary Seeds (Phalaris canariensis L.).

    Science.gov (United States)

    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.

  5. A risk stratification model for antihypertensive medication non-adherence among Chinese immigrants

    Directory of Open Access Journals (Sweden)

    Wen-Wen Li

    2016-12-01

    Full Text Available The purpose of this study was to establish a risk stratification model for identifying Chinese immigrants at risk for non-adherence to antihypertensive medications. Questionnaires were self-administered to 200 Chinese immigrants in San Francisco, USA. Questionnaires included demographics, culture factors (e.g., Perceived Susceptibility in General, Perceived Benefits of Western Medication, Perceived Benefits of Chinese Herbs, and Health-Related Social Support, and medications adherence. Participants' mean age was 70.6 (±10.3 years. Three stratification factors were identified for non-adherence: Lower Perceived Susceptibility in General, lower Perceived Benefit of Western Medications, and longer Length of Stay in the United States. The probability of non-adherence was 77%, 62%, and 57% for lower perceived susceptibility, longer stay in the United States, and lower perceived benefits of Western medications, respectively. A combination of lower perceived susceptibility and lower perceived benefits of medication predicted 81% non-adherence and lower perceived susceptibility with longer stay in the United States predicted at 84%. All three factors combined predicted nearly 90%. Patients with all three factors had the highest risk for non-adherence. The second priority groups are patients with lower perceived susceptibility and those with lower perceived susceptibility combined with any of the other two factors. In the clinical setting, these three groups are a high priority for education on the importance of medication adherence.

  6. Predictive factor and antihypertensive usage of tyrosine kinase inhibitor-induced hypertension in kidney cancer patients

    Science.gov (United States)

    IZUMI, KOUJI; ITAI, SHINGO; TAKAHASHI, YOSHIKO; MAOLAKE, AERKEN; NAMIKI, MIKIO

    2014-01-01

    Hypertension (HT) is the common adverse event associated with vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKI). The present study was performed to identify the predictive factors of TKI-induced HT and to determine the classes of antihypertensive agents (AHTA) that demonstrate optimal efficacy against this type of HT. The charts of 50 cases of patients that had received VEGFR-TKI treatment were retrospectively examined. The association between patient background and TKI-induced HT, and the effect of administering AHTA were analyzed. High systolic blood pressure at baseline was identified to be a predictive factor for HT. In addition, there was no difference observed between calcium channel blockers (CCBs) and angiotensin receptor II blockers (ARBs) as first-line AHTA for the control of HT. The findings of the present study may aid with predicting the onset of TKI-induced HT, as well as for its management via the primary use of either CCBs or ARBs. PMID:24959266

  7. Home blood pressure monitoring and self-titration of antihypertensive medications: Proposed patient selection criteria.

    Science.gov (United States)

    Hill, James R

    2016-05-01

    Recent studies have demonstrated that home blood pressure monitoring (HBPM), coupled with self-titration of medications is a viable intervention to control hypertension. There are currently no established criteria to evaluate patients for inclusion in such a program. The purpose of this discussion is to propose criteria for determining if a patient is appropriate to participate in a program of HBPM and self-titration. Inclusion criteria for two self-titration trials were examined, and additional factors in clinical practice were identified and discussed. Additional selection criteria were proposed to support the decision to enroll a patient in an antihypertensive self-titration program. Inclusion criteria from self-titration trials provide a reasonable starting point for choosing appropriate patients in clinical practice, but additional research is necessary. Adaptation of these criteria and consideration of the identified factors can be used to develop decision support instruments. Such instruments should be evaluated for effectiveness and reliability prior to use in clinical practice. HBPM combined with self-titration is an effective patient-centered approach for hypertension management. Decision support instruments to determine appropriate patients are necessary for safe and effective use in clinical practice. ©2015 American Association of Nurse Practitioners.

  8. Honey Supplementation in Spontaneously Hypertensive Rats Elicits Antihypertensive Effect via Amelioration of Renal Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Omotayo O. Erejuwa

    2012-01-01

    Full Text Available Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP in spontaneously hypertensive rats (SHR. It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2 and glutathione S-transferase (GST were significantly downregulated while total antioxidant status (TAS and activities of GST and catalase (CAT were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR.

  9. BPP-5a produces a potent and long-lasting NO-dependent antihypertensive effect.

    Science.gov (United States)

    Ianzer, Danielle; Xavier, Carlos Henrique; Fraga, Fabiana Costa; Lautner, Roberto Queiroga; Guerreiro, Juliano Rodrigo; Machado, Leonor Tapias; Mendes, Elizabeth Pereira; de Camargo, Andônio Carlos Martins; Santos, Robson Augusto Souza

    2011-12-01

    The bradykinin potentiating peptides (BPPs) are oligopeptides found in different animal venoms. BPPs isolated from Bothrops jararaca venom were the first natural inhibitors described for somatic angiotensin I-converting enzyme (ACE). They were used in the structural modeling for captopril development, a classical ACE inhibitor widely used to treat human hypertension. We evaluated the effect of BPP-5a on cardiovascular parameters of conscious Wistar (WTs) and spontaneously hypertensive rats (SHRs). In SHR, BPP-5a showed potent cardiovascular effects, at doses ranging from 0.47 to 710 nmol/kg. The maximal changes in mean arterial pressure (MAP) and heart rate (HR) were found at the dose of 2.37 nmol/kg (Δ MAP: -38 ± 4 mmHg, p BPP-5a upon argininosuccinate synthetase and B(1), B(2), AT(1), AT(2) or Mas receptors. Ex vivo assays showed that BPP-5a induced endothelium-dependent vasorelaxation in isolated aortic rings of SHRs and WTs. Although the BPP-5a is considered an ACE inhibitor, our results indicate that its antihypertensive effect is exerted via a unique target, a nitric-oxide-dependent mechanism.

  10. Characterization of Imidazoline Receptors in Blood Vessels for the Development of Antihypertensive Agents

    Directory of Open Access Journals (Sweden)

    Mei-Fen Chen

    2014-01-01

    Full Text Available It has been indicated that activation of peripheral imidazoline I2-receptor (I-2R may reduce the blood pressure in spontaneously hypertensive rats (SHRs. Also, guanidinium derivatives show the ability to activate imidazoline receptors. Thus, it is of special interest to characterize the I-2R using guanidinium derivatives in blood vessels for development of antihypertensive agent(s. Six guanidinium derivatives including agmatine, amiloride, aminoguanidine, allantoin, canavanine, and metformin were applied in this study. Western blot analysis was used for detecting the expression of imidazoline receptor in tissues of Wistar rats. The isometric tension of aortic rings isolated from male rats was also estimated. The expression of imidazoline receptor on rat aorta was identified. However, guanidinium derivatives for detection of aortic relaxation were not observed except agmatine and amiloride which induced a marked relaxation in isolated aortic rings precontracted with phenylephrine or KCl. Both relaxations induced by agmatine and amiloride were attenuated by glibenclamide at concentration enough to block ATP-sensitive potassium (KATP channels. Meanwhile, only agmatine-induced relaxation was abolished by BU224, a selective antagonist of imidazoline I2-receptors. Taken together, we suggest that agmatine can induce vascular relaxation through activation of peripheral imidazoline I2-receptor to open KATP channels. Thus, agmatine-like compound has the potential to develop as a new therapeutic agent for hypertension in the future.

  11. Pharmacological basis for the empirical use of Eugenia uniflora L. (Myrtaceae) as antihypertensive.

    Science.gov (United States)

    Consolini, A E; Baldini, O A; Amat, A G

    1999-07-01

    The rational basis for the use of Eugenia uniflora L. (Myrtaceae) as antihypertensive in Northeastern Argentina was assessed in normotensive rats. Intraperitoneal administration of the aqueous crude extract (ACE) decreased blood pressure (BP) of normotensive rats dose-dependently until 47.1 +/- 8.2% of control. The effective-dose 50 was 3.1 +/- 0.4 mg dried leaves/kg (d.l./kg) (yielding of ACE: 17% w/w). To determine the origin of hypotensive activity. Alpha-adrenergic antagonistic and vasorelaxant ACE activities were tested. The dose-response curve for phenylephrine on BP was inhibited non-competitively until 80% of its maximal effect (at 8 mg d.l. ACE/kg). Perfusion pressure (PP) of rat hindquarters (previously vasoconstricted by high-K+) was decreased by ACE in a concentration-dependent manner until -32.3 +/- 11.5% of tonic contraction at 1.2 g d.l. ACE/100 ml. In addition, A.C.E demonstrated diuretic activity at a dose (120 mg d.l./kg) higher than the hypotensive one. It was almost as potent as amiloride, but while amiloride induced loss of Na+ and saving of K+, ACE induced decrease in Na+ excretion. The results suggest that the empirical use of Eugenia uniflora L. (Myrtaceae) is mostly due to a hypotensive effect mediated by a direct vasodilating activity, and to a weak diuretic effect that could be related to an increase in renal blood flow.

  12. Essential Oil Composition, Antioxidant, Antidiabetic and Antihypertensive Properties of Two Afromomum Species.

    Science.gov (United States)

    Adefegha, Stephen Adeniyi; Olasehinde, Tosin Abiola; Oboh, Ganiyu

    2017-01-01

    This study was designed to assess the antioxidant, antidiabetic and antihypertensive effects of essential oils from A. melegueta and A. danielli seeds. The essential oils were extracted via hydrodistillation, dried with anhydrous Na 2 SO 4 and characterized using gas chromatography-mass spectrometry (GC-MS). Antioxidant properties and inhibition of some pro-oxidant induced lipid peroxidation in rats' pancreas and heart homogenates were also determined. The results revealed that eugenol, eucalyptol, α-terpineol, α-caryophyllene and β-caryophyllene were the most abundant components in A. melegueta and A. danielli seeds. The essential oils inhibited α-amylase, α-glucosidase and angiotensin-I-converting enzyme in vitro. A.melegueta oil showed a higher α-amylase and α- glucosidase inhibitory activities with EC 50 values of 139.00 µL/mL and 91.83 µL/mL respectively than A. danielli. However, A. danielli oil (EC 50 = 48.73 µL/mL) showed the highest ACE inhibitory acivity. The highest NO radical scavenging ability was observed in A. melegueta oil while A. danielli had the highest OH radical scavenging and Fe 2+ - chelating ability. Furthermore, both essential oils inhibited SNP and Fe 2+ - induced lipid peroxidation in rats' pancreas and heart respectively in a dose dependent manner. This study reveals the biochemical principle by which essential oils from A. danielli and A.melegueta seed elicits their therapeutic effects on type-2 diabetes and hypertension.

  13. [Correlation of angiotensin-converting enzyme 2 gene polymorphism with antihypertensive effects of benazepril].

    Science.gov (United States)

    Chen, Qing; Tang, Xun; Yu, Can-qing; Chen, Da-fang; Tian, Jun; Cao, Yang; Fan, Wen-yi; Cao, Wei-hua; Zhan, Si-yan; Lv, Jun; Guo, Xiao-xia; Li, Li-ming; Hu, Yong-hua

    2010-06-18

    To explore the correlation of rs2106809 from angiotensin-converting enzyme 2 gene with antihypertensive effects of benazepril, as well as its interactions with polymorphisms of angiotensinogen(AGT) and angiotensin II type 1 receptor(AGTR1) gene. Correlation between rs2106809 and blood pressure reduction was estimated based on a field trail with 1 831 hypertensive patients using benazepril for 2 weeks. Generalized multifactor dimensionality reduction (GMDR) was used to explore the interactions of rs2106809 and 8 single nucleotide polymorphisms (SNPs) of AGTR1 gene and 3 SNPs of AGT gene. rs2106809 was found to be associated with reduction in systolic blood pressure and pulse pressure in women, as well as pulse pressure reduction in men. T allele carriers presented more blood pressure reduction (1.4, 1.3 and 0.9 mmHg/T allele respectively). Gene-gene interactions involving rs2106809 were found in systolic blood pressure reduction of men, and the response to benazepril of non-sensitive genotypes carriers was 8.2 (95% confidence interval: 6.6-9.7) mmHg, lower than that of sensitive genotypes carriers. rs2106809 might act as an independent influencing factor or component of gene-gene interaction in blood pressure reducing effects of benazepril.

  14. Nephrogenic factors of resistance to antihypertensive treatment in patients with essential hypertension

    Directory of Open Access Journals (Sweden)

    N. V. Teplova

    2015-01-01

    Full Text Available Aim. To study the prevalence of renal and renovascular disorders in the development and progression of primary arterial hypertension (HT resistant to combination antihypertensive therapy (AHT in cardiac and therapeutic patients of general hospital.Material and methods. 286 patients with essential HT stages 1-3, including 105 patients with stages 2-3 with the signs of treatment resistance were included into the study. All patients were treated with personalized AHT in accordance with current guidelines for the management of HT. Laboratory and instrumental assessment of a functional status of kidneys was performed.Results. A group of patients with resistant HT made 36.7% of the total number of examined patients. The most significant distinction in patients with resistant HT was a high incidence of changes in renal vessels and infrarenal aorta. Deformation of the abdominal aorta (9.7%, renal arteries tortuosity (7.3%, vasourethral conflict (4.8% were detected in this group significantly more often.Conclusion. Congenital and acquired lesions of renal arteries are detected several times more often in patients with resistant essential HT.

  15. Nephrogenic factors of resistance to antihypertensive treatment in patients with essential hypertension

    Directory of Open Access Journals (Sweden)

    N. V. Teplova

    2015-12-01

    Full Text Available Aim. To study the prevalence of renal and renovascular disorders in the development and progression of primary arterial hypertension (HT resistant to combination antihypertensive therapy (AHT in cardiac and therapeutic patients of general hospital.Material and methods. 286 patients with essential HT stages 1-3, including 105 patients with stages 2-3 with the signs of treatment resistance were included into the study. All patients were treated with personalized AHT in accordance with current guidelines for the management of HT. Laboratory and instrumental assessment of a functional status of kidneys was performed.Results. A group of patients with resistant HT made 36.7% of the total number of examined patients. The most significant distinction in patients with resistant HT was a high incidence of changes in renal vessels and infrarenal aorta. Deformation of the abdominal aorta (9.7%, renal arteries tortuosity (7.3%, vasourethral conflict (4.8% were detected in this group significantly more often.Conclusion. Congenital and acquired lesions of renal arteries are detected several times more often in patients with resistant essential HT.

  16. Electronic monitoring of patient adherence to oral antihypertensive medical treatment: a systematic review.

    Science.gov (United States)

    Christensen, Arne; Osterberg, Lars G; Hansen, Ebba Holme

    2009-08-01

    Poor patient adherence is often the reason for suboptimal blood pressure control. Electronic monitoring is one method of assessing adherence. The aim was to systematically review the literature on electronic monitoring of patient adherence to self-administered oral antihypertensive medications. We searched the Pubmed, Embase, Cinahl and Psychinfo databases and websites of suppliers of electronic monitoring devices. The quality of the studies was assessed according to the quality criteria proposed by Haynes et al. Sixty-two articles were included; three met the criteria proposed by Haynes et al. and nine reported the use of electronic adherence monitoring for feedback interventions. Adherence rates were generally high, whereas average study quality was low with a recent tendency towards improved quality. One study detected investigator fraud based on electronic monitoring data. Use of electronic monitoring of patient adherence according to the quality criteria proposed by Haynes et al. has been rather limited during the past two decades. Electronic monitoring has mainly been used as a measurement tool, but it seems to have the potential to significantly improve blood pressure control as well and should be used more widely.

  17. Sulfasalazine efficacy and tolerability in rheumatic diseases

    Directory of Open Access Journals (Sweden)

    V. V. Badokin

    2005-01-01

    Full Text Available Sulfasalazine is one of the main disease modifying drugs for the treatment of chronic inflammatory joint and spine diseases. The article describes mechanism of action of sulfasalazine and its main metabolites. Detailed information about anti-inflammatory and immunosuppressive action of the drug is presented. Results of many studies of sulfasalazine efficacy in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and reactive arthritis are discussed from the evidence based medicine point of view. Data on sulfasalazine tolerability and safety are presented with separate discussion of hypersensitivity and dose-dependent adverse reactions so as their treatment and prophylaxis.

  18. Targeting phenotypically tolerant Mycobacterium tuberculosis

    Science.gov (United States)

    Gold, Ben; Nathan, Carl

    2016-01-01

    While the immune system is credited with averting tuberculosis in billions of individuals exposed to Mycobacterium tuberculosis, the immune system is also culpable for tempering the ability of antibiotics to deliver swift and durable cure of disease. In individuals afflicted with tuberculosis, host immunity produces diverse microenvironmental niches that support suboptimal growth, or complete growth arrest, of M. tuberculosis. The physiological state of nonreplication in bacteria is associated with phenotypic drug tolerance. Many of these host microenvironments, when modeled in vitro by carbon starvation, complete nutrient starvation, stationary phase, acidic pH, reactive nitrogen intermediates, hypoxia, biofilms, and withholding streptomycin from the streptomycin-addicted strain SS18b, render M. tuberculosis profoundly tolerant to many of the antibiotics that are given to tuberculosis patients in a clinical setting. Targeting nonreplicating persisters is anticipated to reduce the duration of antibiotic treatment and rate of post-treatment relapse. Some promising drugs to treat tuberculosis, such as rifampicin and bedaquiline, only kill nonreplicating M. tuberculosis in vitro at concentrations far greater than their minimal inhibitory concentrations against replicating bacilli. There is an urgent demand to identify which of the currently used antibiotics, and which of the molecules in academic and corporate screening collections, have potent bactericidal action on nonreplicating M. tuberculosis. With this goal, we review methods of high throughput screening to target nonreplicating M. tuberculosis and methods to progress candidate molecules. A classification based on structures and putative targets of molecules that have been reported to kill nonreplicating M. tuberculosis revealed a rich diversity in pharmacophores. However, few of these compounds were tested under conditions that would exclude the impact of adsorbed compound acting during the recovery phase of

  19. Availability, cost, and prescription patterns of antihypertensive medications in primary health care in China: a nationwide cross-sectional survey.

    Science.gov (United States)

    Su, Meng; Zhang, Qiuli; Bai, Xueke; Wu, Chaoqun; Li, Yetong; Mossialos, Elias; Mensah, George A; Masoudi, Frederick A; Lu, Jiapeng; Li, Xi; Salas-Vega, Sebastian; Zhang, Anwen; Lu, Yuan; Nasir, Khurram; Krumholz, Harlan M; Jiang, Lixin

    2017-12-09

    Around 200 million adults in China have hypertension, but few are treated or achieve adequate control of their blood pressure. Available and affordable medications are important for successfully controlling hypertension, but little is known about current patterns of access to, and use of, antihypertensive medications in Chinese primary health care. We used data from a nationwide cross-sectional survey (the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project primary health care survey), which was undertaken between November, 2016 and May, 2017, to assess the availability, cost, and prescription patterns of 62 antihypertensive medications at primary health-care sites across 31 Chinese provinces. We surveyed 203 community health centres, 401 community health stations, 284 township health centres, and 2474 village clinics to assess variation in availability, cost, and prescription by economic region and type of site. We also assessed the use of high-value medications, defined as guideline-recommended and low-cost. We also examined the association of medication cost with availability and prescription patterns. Our study sample included 3362 primary health-care sites and around 1 million people (613 638 people at 2758 rural sites and 478 393 people at 604 urban sites). Of the 3362 sites, 8·1% (95% CI 7·2-9·1) stocked no antihypertensive medications and 33·8% (32·2-35·4) stocked all four classes that were routinely used. Village clinics and sites in the western region of China had the lowest availability. Only 32·7% (32·2-33·3) of all sites stocked high-value medications, and few high-value medications were prescribed (11·2% [10·9-11·6] of all prescription records). High-cost medications were more likely to be prescribed than low-cost alternatives. China has marked deficiencies in the availability, cost, and prescription of antihypertensive medications. High-value medications are not preferentially used. Future efforts to

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Antihypertension and anti-cardiovascular remodeling by phenylalanine in spontaneously hypertensive rats: effectiveness and mechanisms.

    Science.gov (United States)

    Zhao, G; Li, Z; Gu, T

    2001-03-01

    To investigate mechanisms of anti-hypertension and anti-cardiovascular remodeling by phenylalanine (phe) in spontaneously hypertensive rats (SHRs). The comparison of blood pressure (BP) increment with the ages and cardiovascular changes of SHRs was made between the 3% phe-intervented group (SHR-phe) and the control SHRs group. Detection of the structural changes with the VIDAS digital vedio-frequency processing technique and light and electron microscopy were made. The cell growth and proliferation of cultured smooth muscle cells (CSMCs) of the thoracic aortas or myocardial fibroblasts were evaluated by measuring the 3H-thymidine counts per minute (cpm) incorporated into the new synthesized desoxyribonucleic acid (DNA) and determining the cell number with the crystal violet stain technique. The Ca2+ influx was measured in counts/min of 45CaCl2 after incubating it with 5 different concentrations of phenylalanine and the intracellular [Ca2+]i by Fura-II/Am indicator. The total messenger ribonucleic acid (mRNA) of the myocardium was extracted and Northern blot analysis was performed with the probe collagen alpha 2 (I) cDNA. The tyrosine hydroxylase (TH) activity was measured by high-performance liquid chromatography (HPLC) with electrochemical detector after having reacted with its substrate tyrosine and other reagents. The catecholamine contents in brain homogenat were detected by HPLC method. The comparison of pharmacokinetics of phenylalanine among SHR-phe, SHRs and control Wistar Kyoto (WKY) rats was made after intravenous injection of 3H-L-phe (1 ml/kg) by PK-GRAPH Program for kinetic calculation. The 3H-L-phe uptake by CSMCs after incubating for definite intervals was also detected and compared. Phenylalanine could prevent the increase of BP with ages and the heart weight (heart/body weight index). The aortic media thickness and the collagen content in the myocardium were decreased significantly in SHR-phe. Whereas the dearranged cardiovascular structure was

  2. Use of hematopoietic cell transplants to achieve tolerance in patients with solid organ transplants

    OpenAIRE

    Strober, Samuel

    2016-01-01

    The goals of tolerance in patients with solid organ transplants are to eliminate the lifelong need for immunosuppressive (IS) drugs and to prevent graft loss due to rejection or drug toxicity. Tolerance with complete withdrawal of IS drugs has been achieved in recipients of HLA-matched and mismatched living donor kidney transplants in 3 medical centers using hematopoietic cell transplants to establish mixed or complete chimerism.

  3. Use of hematopoietic cell transplants to achieve tolerance in patients with solid organ transplants.

    Science.gov (United States)

    Strober, Samuel

    2016-03-24

    The goals of tolerance in patients with solid organ transplants are to eliminate the lifelong need for immunosuppressive (IS) drugs and to prevent graft loss due to rejection or drug toxicity. Tolerance with complete withdrawal of IS drugs has been achieved in recipients of HLA-matched and mismatched living donor kidney transplants in 3 medical centers using hematopoietic cell transplants to establish mixed or complete chimerism. © 2016 by The American Society of Hematology.

  4. The antihypertensive effect of orally administered nifedipine-loaded nanoparticles in spontaneously hypertensive rats.

    Science.gov (United States)

    Kim, Y I; Fluckiger, L; Hoffman, M; Lartaud-Idjouadiene, I; Atkinson, J; Maincent, P

    1997-02-01

    1. The therapeutic use of nifedipine is limited by the rapidity of the onset of its action and its short biological half-life. In order to produce a form devoid of these disadvantages we made nanoparticles of nifedipine from three different polymers, poly-epsilon-caprolactone (PCL), polylactic and glycolic acid (1:1) copolymers (PLAGA), and Eudragit RL/RS (Eudragit). Nifedipine in polyethylene glycol 400 (PEG) solution was used as a control. 2. The average diameters of the nanoparticles ranged from 0.12 to 0.21 micron; the encapsulation ratio was 82% to 88%. 3. In spontaneously hypertensive rats (SHR), the initial rapid fall in systolic arterial blood pressure following oral administration of nifedipine in PEG solution (from 193 +/- 3 to 102 +/- 2 mmHg) was not seen following administration of the same dose in Eudragit nanoparticles (from 189 +/- 2 to 156 +/- 2 mmHg); with PCL and PLAGA nanoparticles the initial fall in blood pressure was significantly reduced (nadirs PCL 124 +/- 2 and PLAGA 113 +/- 2 mmHg). Ten hours following administration, blood pressure in rats administered the nifedipine/PEG preparation had returned to normal (183 +/- 3 mmHg) whereas that of animals given nifedipine in nanoparticles (PCL 170 +/- 3, PLAGA 168 +/- 2, Eudragit 160 +/- 3 mmHg) was still significantly reduced. 4. All of the nanoparticle dosage forms decreased Cmax and increased Tmax and the mean residence time (MRT) values. Relative bioavailability was significantly increased with Eudragit nanoparticles compared to the nifedipine/PEG solution. 5. There was an inverse linear correlation between the fall in blood pressure and plasma nifedipine concentration with all preparations. 6. The nanoparticle nifedipine preparations represent sustained release forms with increased bioavailability, a less pronounced initial antihypertensive effect and a long-lasting action.

  5. Diuretics, first-line antihypertensive agents: are they always safe in the elderly?

    Science.gov (United States)

    Diaconu, Camelia C; Balaceanu, Alice; Bartos, Daniela

    2014-01-01

    Diuretics are frequently recommended as antihypertensive agents. Some of the main side effects of diuretic therapy are hypokalaemia and hyponatremia. The objective of the study was to describe the frequency of hyponatremia in a group of elderly hypertensive patients treated with diuretics. The study included 202 elderly hypertensive patients (over 65 years old), treated with diuretics at least 4 weeks before hospitalization, consecutivly admitted in the Internal Medicine Clinic of the Clinical Emergency Hospital of Bucharest during a period of 4 months. The distribution by sex: 103 (52.28%) men and 94 (47.71%) women. The mean age of the patients was 72 ± 8 years. Incidence of hyponatremia was 24.87% (49 patients) in the whole group. From the 49 hyponatremic patients, 31 (63.26%) were women and 18 (36.73%) men. The distribution by age of hypertensive hyponatremic female patients was: between 65-70 years old--4 patients (12.90%), between 70-75 years old--7 patients (22.58%), over 75 years old--20 patients (64.51%). The distribution by age of hypertensive hyponatremic male patients was: between 65-70 years old--3 patients (16.66%), between 70-75 years old--2 patients(11.11%), over 75 years old--13 patients (72.22%). Most of the patients affected (73.46%) used a thiazide-type diuretic, the other 26.54% being on loop diuretics. Elderly hypertensive patients were more likely to develop hyponatremia after age 75. Female patients had a higher frequency of hyponatremia than male patients. The main cause of hyponatremia in patients treated with diuretics was thiazide.

  6. Isolation and structural analysis of antihypertensive peptides that exist naturally in Gouda cheese.

    Science.gov (United States)

    Saito, T; Nakamura, T; Kitazawa, H; Kawai, Y; Itoh, T

    2000-07-01

    Seven kinds of ripened cheeses (8-mo-aged and 24-mo-aged Gouda, Emmental, Blue, Camembert, Edam, and Havarti) were homogenized with distilled water, and water-soluble peptides were prepared by C-18 hydrophobic chromatography. The inhibitory activity to angiotensin I-converting enzyme and decrease in the systolic blood pressure in spontaneously hypertensive rats were measured before and after oral administration of each peptide sample. The strongest depressive effect in the systolic blood pressure (-24.7 mm Hg) and intensive inhibitory activity to angiotensin I-converting enzyme (75.7%) were detected in the peptides from 8-mo-aged Gouda cheese. Four peptides were isolated by HPLC with reverse-phase and gel filtration modes. Their chemical structures and origins, clarified by combination analyses of protein sequencing, amino acid composition, and mass spectrometry, were as follows: peptide A, Arg-Pro-Lys-His-Pro-Ile-Lys-His-Gln [alpha(s1)-casein (CN), B-8P; f 1-9]; peptide B, Arg-Pro-Lys-His-Pro-Ile-Lys-His-Gln-Gly-Leu-Pro-Gln (alpha(s1)-CN, B-8P; f 1-13); peptide F, Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro-Asn (beta-CN, A2-5P; f 60-68); and peptide G, Met-Pro-Phe-Pro-Lys-Tyr-Pro-Val-Gln-Pro-Phe (beta-CN, A2-5P; f 109-119). Peptides A and F, which were chemically synthesized, showed potent angiotensin I-converting enzyme inhibitory activity with little antihypertensive effects.

  7. Antihypertensive effects of continuous oral administration of nattokinase and its fragments in spontaneously hypertensive rats.

    Science.gov (United States)

    Fujita, Mitsugu; Ohnishi, Katsunori; Takaoka, Shinsaku; Ogasawara, Kazuya; Fukuyama, Ryo; Nakamuta, Hiromichi

    2011-01-01

    To determine whether the antihypertensive effect of nattokinase is associated with the protease activity of this enzyme, we compared nattokinase with the fragments derived from nattokinase, which possessed no protease activity, in terms of the effect on hypertension in spontaneously hypertensive rats (SHR). In the continuous oral administration test, the groups were given a basic diet alone (control), the basic diet containing nattokinase (0.2, 2.6 mg/g diet) or the basic diet containing the fragments derived from nattokinase (0.2, 0.6 mg/g diet). The group fed the basic diet containing high-dosage nattokinase (2.6 mg/g diet) showed significant reductions in systolic blood pressure (SBP), diastolic blood pressure (DBP) and plasma fibrinogen level, compared with control group and no influence on activities of renin and angiotensin-converting enzyme (ACE, EC 3.4.15.1), and plasma angiotensin II level in the renin-angiotensin system. The treatment of the basic diet containing high-dosage fragments (0.6 mg/g diet) significantly decreased SBP, DBP and plasma angiotensin II level in plasma but the treatment did not influence on plasma fibrinogen level. These results suggest that nattokinase and its fragments are different from each other in the mechanism to reduce hypertension. Nattokinase, retained its protease activity after absorbance across the intestines, may decrease blood pressure through cleavage of fibrinogen in plasma. The fragments, which absorbed as nattokinase-degradation products, prevents the elevation of plasma angiotensin II level to suppress hypertension.

  8. Escaping the tolerance trap

    International Nuclear Information System (INIS)

    Hammoudeh, S.; Madan, V.

    1994-01-01

    In order to examine the implications of the weakening of OPEC's responsiveness in adjusting its production levels, this paper explicitly incorporates rigidity in the quantity adjustment mechanism, thereby extending previous research which assumed smooth quantity adjustments. The rigidity is manifested in a tolerance range for the discrepancy between the declared target price and that of the market. This environment gives rise to a 'tolerance trap' which impedes the convergence process and inevitably brings the market to a standstill before its reaches the targeted price and revenue objectives. OPEC's reaction to the standstill has important implications for the achievement of the target-based equilibrium and for the potential collapse of the market price. This paper examines OPEC's policy options in the tolerance trap and reveals that the optional policy in order to break this impasse and move closer to the equilibrium point is gradually to reduce output and not to flood the market. (Author)

  9. Drug Facts

    Medline Plus

    Full Text Available ... Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used Drugs in the Past Drug Use ... Videos Information About Drugs Alcohol ...

  10. Drug Allergy

    Science.gov (United States)

    ... Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days or ... you take the drug. Drugs commonly linked to allergies Although any drug can cause an allergic reaction, ...

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

    Science.gov (United States)

    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.

  12. Fault tolerant linear actuator

    Science.gov (United States)

    Tesar, Delbert

    2004-09-14

    In varying embodiments, the fault tolerant linear actuator of the present invention is a new and improved linear actuator with fault tolerance and positional control that may incorporate velocity summing, force summing, or a combination of the two. In one embodiment, the invention offers a velocity summing arrangement with a differential gear between two prime movers driving a cage, which then drives a linear spindle screw transmission. Other embodiments feature two prime movers driving separate linear spindle screw transmissions, one internal and one external, in a totally concentric and compact integrated module.

  13. Inequality, Tolerance, and Growth

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    This paper argues for the importance of individuals' tolerance of inequality for economic growth. By using the political ideology of governments as a measure of revealed tolerance of inequality, the paper shows that controlling for ideology improves the accuracy with which the effects of inequality...... are measured. Results show that inequality reduces growth but more so in societies where people perceive it as being relatively unfair. Further results indicate that legal quality and social trust are likely transmission channels for the effects of inequality....

  14. Inequality, Tolerance, and Growth

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    2004-01-01

    This paper argues for the importance of individuals' tolerance of inequality for economic growth. By using the political ideology of governments as a measure of revealed tolerance of inequality, the paper shows that controlling for ideology improves the accuracy with which the effects of inequality...... are measured. Results show that inequality reduces growth but more so in societies where people perceive it as being relatively unfair. Further results indicate that legal quality and social trust are likely transmission channels for the effects of inequality....

  15. Reversal of oxycodone and hydrocodone tolerance by diazepam.

    Science.gov (United States)

    Gonek, Maciej; Akbarali, Hamid I; Henderson, Graeme; Dewey, William L

    2017-11-01

    The Centers for Disease Control has declared opioid abuse to be an epidemic. Overdose deaths are largely assumed to be the result of excessive opioid consumption. In many of these cases, however, opioid abusers are often polydrug abusers. Benzodiazepines are one of the most commonly co-abused substances and pose a significant risk to opioid users. In 2016, the FDA required boxed warnings - the FDA's strongest warning - for prescription opioid analgesics and benzodiazepines about the serious risks associated with using these medications at the same time. The point of our studies was to evaluate the interactions between these two classes of drugs. We investigated whether diazepam adds to the depressant effects of opioids or do they alter the levels of tolerance to opioids. In the present study, we have found that the antinociceptive tolerance that developed to repeated administration of oxycodone was reversed by an acute dose of diazepam. Antinociceptive tolerance to hydrocodone was also reversed by acute injection of diazepam; however, a fourfold higher dose of diazepam was required when compared to reversal of oxycodone-induced tolerance. These doses of diazepam did not potentiate the acute antinociceptive effect of either opioid. The same dose of diazepam that reversed oxycodone antinociceptive tolerance also reversed oxycodone locomotor tolerance while having no potentiating effects. These studies show that diazepam does not potentiate the acute effect of prescription opioids but reverses the tolerance developed after chronic administration of the drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial.

    Science.gov (United States)

    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

    (53 patients in each group, intention-to-treat population) and 101 analysed because of patients with missing endpoints (48 in the renal denervation group, 53 in the control group, modified intention-to-treat population). The mean change in daytime ambulatory systolic blood pressure at 6 months was -15·8 mm Hg (95% CI -19·7 to -11·9) in the renal denervation group and -9·9 mm Hg (-13·6 to -6·2) in the group receiving SSAHT alone, a baseline-adjusted difference of -5·9 mm Hg (-11·3 to -0·5; p=0·0329). The number of antihypertensive drugs and drug-adherence at 6 months were similar between the two groups. Three minor renal denervation-related adverse events were noted (lumbar pain in two patients and mild groin haematoma in one patient). A mild and similar decrease in estimated glomerular filtration rate from baseline to 6 months was observed in both groups. In patients with well defined resistant hypertension, renal denervation plus an SSAHT decreases ambulatory blood pressure more than the same SSAHT alone at 6 months. This additional blood pressure lowering effect may contribute to a reduction in cardiovascular morbidity if maintained in the long term after renal denervation. French Ministry of Health. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Toleration, Groups, and Multiculturalism

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2014-01-01

    have the ability to interfere with the group’s activities, an object of dislike or disapproval, an agent enjoying non-interference or a moral patient. This means that 'toleration of groups' can mean quite different things depending on the exact meaning of 'group' in relation to each component...

  18. Fault Tolerant Control Systems

    DEFF Research Database (Denmark)

    Bøgh, S. A.

    This thesis considered the development of fault tolerant control systems. The focus was on the category of automated processes that do not necessarily comprise a high number of identical sensors and actuators to maintain safe operation, but still have a potential for improving immunity to component...

  19. Toleration and its enemies

    DEFF Research Database (Denmark)

    Jarvad, Ib Martin

    2010-01-01

    After a presentation of the development of freedom of expression in Danish constitutional law, to freedom of the press in European human rights law - the Jersild case- to a right to mock and ridicule other faiths in recent Danish practice, the essay of Locke on toleration is examined, its...

  20. A little toleration, please

    Science.gov (United States)

    McKnight, C.

    2000-01-01

    Value pluralism does not imply relativism or subjectivism about values. What it does is allow respect for an at least limited toleration of values with which one may profoundly disagree. Thus a doctor can respect the autonomy of a patient whose values he does not share. Key Words: Pluralism • multiculturalism • relativism • subjectivism • patient autonomy PMID:11129842

  1. Antihypertensive medication adherence in chronic type B aortic dissection is an important consideration in the management debate.

    Science.gov (United States)

    Martin, Guy; Patel, Nandesh; Grant, Yasmin; Jenkins, Michael; Gibbs, Richard; Bicknell, Colin

    2018-03-31

    Early aortic stenting in chronic type B aortic dissection (TBAD) may lead to long-term benefit, although the optimal treatment strategy is hotly debated. A robust comparison to outcomes seen in medically managed patients is challenging as the rate of antihypertensive medication adherence is unknown. The aims of this study were therefore to identify the rate of antihypertensive medication adherence and predictors of adherence in TBAD. This was a cross-sectional mixed methods study of patients with TBAD. Medication adherence was assessed by the eight-item Morisky Medication Adherence Scale together with an assessment of demographic, behavioral, and psychological variables and disease-specific knowledge. There were 47 patients (mean age, 59 years; 81% male) who were recruited from a tertiary vascular unit. The mean total number of medications taken was 5.8 (2-14), and the mean number of antihypertensive medications was 1.9 (1-6). Of the 47 patients, 20 (43%) reported high levels of medication adherence, 17 (36%) reported moderate adherence, and 10 (21%) reported low adherence. Previous aortic surgery was associated with higher levels of adherence (β = 0.332; P = .03), as was taking a greater number of medications (β = 0.332; P = .026), perceived benefit from treatment (β = 0.486; P debate; one cannot robustly compare two strategies when half of a treatment group may not be receiving the stated intervention. To develop an evidence-based treatment strategy for TBAD, we must take into account the direct and indirect effects of medical therapy and thoracic endovascular aortic repair. Further work to improve medication adherence and to understand its impact on disease progression is vital to inform the debate and to deliver the best outcomes for patients. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  2. Influence of antihypertensive therapy, sodium intake and the concentration of potassium in plasma on concentration of aldosterone and plasma renin activity

    Directory of Open Access Journals (Sweden)

    Lalić Tijana

    2013-01-01

    Full Text Available Introduction: Primary aldosteronism (PA is a group of disorders which are characterized by inadequate and non-suppressible production of aldosterone. The prevalence of PA is increasing in hypertensive population. The golden standard of screening for primary aldosteronism, determination of aldosterone/plasma renin activity (ARR, is influenced by numerous exogenous and endogenous factors. Testing cannot always be conducted under optimal conditions. Objective: To determine influence of antihypertensive drugs and concentrations of potassium and sodium in blood and urine on values of aldosterone and plasma renin activity. Methods: In this retrospective study, we analyzed medical reports of patients admitted to Department of thyroid gland disease in the period from 2009 to 2011, with increased risk for primary aldosteronism. Body weight and height, sodium and potassium in serum and urine, plasma aldosterone concentrations and plasma renin activity, data on medicines and comorbidity were analyzed in all patients. In processing data, statistical methods descriptive analysis, Student T test and univariate linear regression were applied. Result: Of 137 patients, there were more patients with resistant hypertension (53,28% than with adrenal tumors (46,72%. Most patients used calcium channel blockers. Treatment with alpha blockers and calcium channel blockers does not influence ARR. Beta blockers and ACE inhibitors can influence ARR and diuretics and vasodilatators have definite influence. Diabetes mellitus can have higher risk of false negative results. Urine sodium excretion is significantly correlated with plasma aldosteron and serum potassium. Plasma aldosteron and PRA are significantly correlated with concentrations of electrolites in urine. Conclusion: Increased prevalence of primary aldosteronism necessitates need for accurate and better diagnostics.

  3. Deconstructing tolerance with clobazam

    Science.gov (United States)

    Wechsler, Robert T.; Sankar, Raman; Montouris, Georgia D.; White, H. Steve; Cloyd, James C.; Kane, Mary Clare; Peng, Guangbin; Tworek, David M.; Shen, Vivienne; Isojarvi, Jouko

    2016-01-01

    Objective: To evaluate potential development of tolerance to adjunctive clobazam in patients with Lennox-Gastaut syndrome. Methods: Eligible patients enrolled in open-label extension study OV-1004, which continued until clobazam was commercially available in the United States or for a maximum of 2 years outside the United States. Enrolled patients started at 0.5 mg·kg−1·d−1 clobazam, not to exceed 40 mg/d. After 48 hours, dosages could be adjusted up to 2.0 mg·kg−1·d−1 (maximum 80 mg/d) on the basis of efficacy and tolerability. Post hoc analyses evaluated mean dosages and drop-seizure rates for the first 2 years of the open-label extension based on responder categories and baseline seizure quartiles in OV-1012. Individual patient listings were reviewed for dosage increases ≥40% and increasing seizure rates. Results: Data from 200 patients were included. For patients free of drop seizures, there was no notable change in dosage over 24 months. For responder groups still exhibiting drop seizures, dosages were increased. Weekly drop-seizure rates for 100% and ≥75% responders demonstrated a consistent response over time. Few patients had a dosage increase ≥40% associated with an increase in seizure rates. Conclusions: Two-year findings suggest that the majority of patients do not develop tolerance to the antiseizure actions of clobazam. Observed dosage increases may reflect best efforts to achieve seizure freedom. It is possible that the clinical development of tolerance to clobazam has been overstated. ClinicalTrials.gov identifier: NCT00518713 and NCT01160770. Classification of evidence: This study provides Class III evidence that the majority of patients do not develop tolerance to clobazam over 2 years of treatment. PMID:27683846

  4. Impact of Empagliflozin on Blood Pressure in Patients With Type 2 Diabetes Mellitus and Hypertension by Background Antihypertensive Medication.

    Science.gov (United States)

    Mancia, Giuseppe; Cannon, Christopher P; Tikkanen, Ilkka; Zeller, Cordula; Ley, Ludwin; Woerle, Hans J; Broedl, Uli C; Johansen, Odd Erik

    2016-12-01

    In the EMPA-REG BP trial, empagliflozin 10 mg and 25 mg once daily reduced glycohemoglobin, blood pressure (BP), and weight versus placebo in patients with type 2 diabetes mellitus and hypertension. Patients received placebo (n=271), empagliflozin 10 mg (n=276), or empagliflozin 25 mg (n=276) for 12 weeks (n=full analysis set). This present analysis investigated changes from baseline to week 12 in mean 24-hour systolic BP (SBP) and diastolic BP (DBP) in patients receiving 0, 1, or ≥2 antihypertensive medications and patients receiving/not receiving diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Compared with placebo, empagliflozin 10 mg and 25 mg reduced mean 24-hour SBP/DBP in patients receiving 0 (10 mg: -3.89/-2.58 mm Hg; 25 mg: -3.77/-2.45 mm Hg), 1 (10 mg: -4.74/-1.97 mm Hg; 25 mg: -4.27/-1.81 mm Hg), or ≥2 (10 mg: -2.36/-0.68 mm Hg; 25 mg: -4.17/-1.54 mm Hg) antihypertensives. The effect of empagliflozin was not significantly different between subgroups by number of antihypertensives for changes in SBP (interaction P value 0.448) or DBP (interaction P value 0.498). Empagliflozin reduced 24-hour mean SBP/DBP irrespective of diuretic or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, with no significant difference between subgroups by use/no use of diuretics (interaction P values 0.380 [systolic]; 0.240 [diastolic]) or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (interaction P values 0.900 [systolic]; 0.359 [diastolic]). In conclusion, in patients with type 2 diabetes mellitus and hypertension, empagliflozin for 12 weeks reduced SBP and DBP versus placebo, irrespective of the number of antihypertensives and use of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. URL: https://clinicaltrials.gov. Unique identifier: NCT01370005. © 2016 American Heart Association, Inc.

  5. Characteristics Associated With Antihypertensive Treatment and Blood Pressure Control: A Population-Based Follow-Up Study in Peru.

    Science.gov (United States)

    Zavala-Loayza, J Alfredo; Benziger, Catherine Pastorius; Cárdenas, María Kathia; Carrillo-Larco, Rodrigo M; Bernabé-Ortiz, Antonio; Gilman, Robert H; Checkley, William; Miranda, J Jaime

    2016-03-01

    Over one-quarter of the world's adult population has hypertension, yet achieving adequate treatment or control targets remains a challenge. This study sought to identify, longitudinally, characteristics associated with antihypertensive treatment and blood pressure (BP) control among individuals with hypertension. Data from individuals enrolled in the population-based CRONICAS Cohort Study (adults ≥35 years, living in 4 different rural/urban and coastal/high-altitude Peruvian settings) with hypertension at baseline were used. Antihypertensive treatment and BP control were assessed at baseline and at 15 months. Multinomial logistic regressions were used to estimate relative risk ratios (RRR) and 95% confidence intervals (95% CI) of factors associated with antihypertensive treatment and BP control at follow-up. At baseline, among 717 individuals with hypertension (53% women, mean age 61.5 ± 12.4 years), 28% were unaware of their hypertension status, 30% were aware but untreated, 16% were treated but uncontrolled, and 26% were treated and controlled. At follow-up, 89% of unaware and 82% of untreated individuals persisted untreated, and only 58% of controlled individuals remained controlled. Positive predictors of receiving treatment and being controlled at follow-up included age (RRR: 0.81; 95% CI: 0.73 to 0.91 for every 5 years) and family history of a chronic disease (RRR: 0.53; 95% CI: 0.31 to 0.92 vs. no history); whereas Puno rural site (RRR: 16.51; 95% CI: 1.90 to 143.56 vs. Lima) and male sex (RRR: 2.59; 95% CI: 1.54 to 4.36) were risk factors. Systolic BP at baseline (RRR: 1.27; 95% CI: 1.16 to 1.39 for every 5 mm Hg) and male sex (RRR: 1.75, 95% CI: 1.02 to 2.98) were risk factors for being treated but uncontrolled at follow-up. Large gaps in treatment of hypertension were observed. Targeting specific populations such as men, younger individuals, or those without family history of disease may increase coverage of antihypertensive treatment. Also, targeting

  6. Justification of a dose of diuretics in antihypertensive treatment of patients with essential hypertension stage II-III

    OpenAIRE

    Plesh, I. A.; Boreyko, L. D.; Slyvka, N. O.; Kshanovska, G. I.

    2017-01-01

    "Pressor natriuresis" coefficient in  ratio of daily urinary sodium excretion (ENadob) by means of  electrometric method using ionselective electrodes (SINO - 005) to average of median arterial pressure (MAPdob) a day  and character of circadian rhytm, by the method of daily monitoring of blood pressure (hardware «Solvaig») to optimize the dose of a diuretic in combined antihypertensive treatment was determened іn 65 patients with essential  hypertension (EH II-III stage and 26 control (normo...

  7. The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients.

    Science.gov (United States)

    Massart, Annick; Pallier, Annaïck; Pascual, Julio; Viklicky, Ondrej; Budde, Klemens; Spasovski, Goce; Klinger, Marian; Sever, Mehmet Sukru; Sørensen, Søren Schwartz; Hadaya, Karine; Oberbauer, Rainer; Dudley, Christopher; De Fijter, Johan W; Yussim, Alexander; Hazzan, Marc; Wekerle, Thomas; Berglund, David; De Biase, Consuelo; Pérez-Sáez, María José; Mühlfeld, Anja; Orlando, Giuseppe; Clemente, Katia; Lai, Quirino; Pisani, Francesco; Kandus, Aljosa; Baas, Marije; Bemelman, Frederike; Ponikvar, Jadranka Buturovic; Mazouz, Hakim; Stratta, Piero; Subra, Jean-François; Villemain, Florence; Hoitsma, Andries; Braun, Laura; Cantarell, Maria Carmen; Colak, Hulya; Courtney, Aisling; Frasca, Giovanni Maria; Howse, Matthew; Naesens, Maarten; Reischig, Tomas; Serón, Daniel; Seyahi, Nurhan; Tugmen, Cem; Alonso Hernandez, Angel; Beňa, Luboslav; Biancone, Luigi; Cuna, Vania; Díaz-Corte, Carmen; Dufay, Alexandre; Gaasbeek, André; Garnier, Arnaud; Gatault, Philippe; Gentil Govantes, Miguel Angel; Glowacki, François; Gross, Oliver; Hurault de Ligny, Bruno; Huynh-Do, Uyen; Janbon, Bénédicte; Jiménez Del Cerro, Luis Antonio; Keller, Frieder; La Manna, Gaetano; Lauzurica, Ricardo; Le Monies De Sagazan, Hervé; Thaiss, Friedrich; Legendre, Christophe; Martin, Séverine; Moal, Marie-Christine; Noël, Christian; Pillebout, Evangeline; Piredda, Gian Benedetto; Puga, Ana Ramírez; Sulowicz, Wladyslaw; Tuglular, Serhan; Prokopova, Michaela; Chesneau, Mélanie; Le Moine, Alain; Guérif, Pierrick; Soulillou, Jean-Paul; Abramowicz, Marc; Giral, Magali; Racapé, Judith; Maggiore, Umberto; Brouard, Sophie; Abramowicz, Daniel

    2016-06-01

    Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency. One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still operationally tolerant. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively. In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  8. Antihypertensive therapy: nocturnal dippers and nondippers. Do we treat them differently?

    Directory of Open Access Journals (Sweden)

    Mahabala C

    2013-03-01

    Full Text Available Chakrapani Mahabala,1 Padmanabha Kamath,2 Unnikrishnan Bhaskaran,3 Narasimha D Pai,2 Aparna U Pai41Department of Medicine, Kasturba Medical College, Manipal University, Mangalore, Karnataka State, India; 2Department of Cardiology, Kasturba Medical College, Manipal University, Mangalore, Karnataka State, India; 3Department of Community Medicine, Kasturba Medical College, Manipal University, Mangalore, Karnataka State, India; 4Department of Radiodiagnosis, Vivekananda Institute of Medical Sciences, Kolkata, West Bengal State, IndiaAbstract: Hypertension is a major independent risk factor for cardiovascular diseases. Management of hypertension is generally based on office blood pressure since it is easy to determine. Since casual blood pressure readings in the office are influenced by various factors, they do not represent basal blood pressure. Dipping of the blood pressure in the night is a normal physiological change that can be blunted by cardiovascular risk factors and the severity of hypertension. Nondipping pattern is associated with disease severity, left ventricular hypertrophy, increased proteinuria, secondary forms of hypertension, increased insulin resistance, and increased fibrinogen level. Long-term observational studies have documented increased cardiovascular events in patients with nondipping patterns. Nocturnal dipping can be improved by administering the antihypertensive medications in the night. Long-term clinical trials have shown that cardiovascular events can be reduced by achieving better dipping patterns by administering medications during the night. Identifying the dipping pattern is useful for decisions to investigate for secondary causes, initiating treatment, necessity of chronotherapy, withdrawal or reduction of unnecessary medications, and monitoring after treatment initiation. Use of this concept at the primary care level has been limited because 24-hour ambulatory blood pressure monitoring has been the only method

  9. Adherence to Treatment, Safety, Tolerance, and Effectiveness of Perindopril/Amlodipine Fixed-Dose Combination in Greek Patients with Hypertension and Stable Coronary Artery Disease: A Pan-Hellenic Prospective Observational Study of Daily Clinical Practice.

    Science.gov (United States)

    Liakos, Charalampos I; Papadopoulos, Dimitrios P; Kotsis, Vasilios T

    2017-10-01

    Initiation of antihypertensive therapy with a two-drug fixed-dose combination (FDC) in a single tablet may be recommended in patients at high risk of cardiovascular events to improve adherence and effectiveness. Preferred combinations include an angiotensin-converting enzyme inhibitor with a dihydropyridine calcium antagonist. This study assessed adherence to and the safety, tolerance, and effectiveness of the perindopril/amlodipine FDC in Greek patients with hypertension and stable coronary artery disease (CAD) over a 4-month period. A total of 1907 patients with hypertension and CAD (59.1% males) who had recently (≤2 weeks) commenced treatment with the perindopril/amlodipine FDC (5/5, 5/10, 10/5, or 10/10 mg) were studied at baseline and at 1 and 4 months. Adherence to treatment was assessed with the Morisky Medication-taking Adherence Scale (MMAS). Seven patients (0.4%) did not attend the scheduled visits. In total, 1607 (84.6%) patients received a constant treatment dose throughout the study. High adherence (MMAS score = 0) was reported by 1592 (83.6%), 1628 (85.7%), and 1477 (77.7%) patients at the second and the third visit and at both visits, respectively. Adverse reactions were reported by only 13 (0.7%) patients, were all minor, and did not result in treatment discontinuation. Office blood pressure (BP) was significantly decreased at the third visit (130.8 ± 8.4/78.2 ± 6.4 mmHg) compared with baseline (156.5 ± 15.0/89.9 ± 9.6 mmHg; p < 0.001), regardless of previous antihypertensive treatment. Patients with grade 1, 2, and 3 hypertension at baseline showed a reduction in BP of 19.3/9.4, 31.5/13.5, and 47.8/22.2 mmHg, respectively (p < 0.001). Uncontrolled hypertension (≥140/90 mmHg) was notably reduced from 90.3% at baseline to 18.5% at the third visit. The perindopril/amlodipine FDC is characterized by high adherence and effectiveness, regardless of previous treatment. Degree of BP reduction was related to baseline BP levels

  10. Alcohol-induced histone acetylation reveals a gene network involved in alcohol tolerance.

    Directory of Open Access Journals (Sweden)

    Alfredo Ghezzi

    Full Text Available Sustained or repeated exposure to sedating drugs, such as alcohol, triggers homeostatic adaptations in the brain that lead to the development of drug tolerance and dependence. These adaptations involve long-term changes in the transcription of drug-responsive genes as well as an epigenetic restructuring of chromosomal regions that is thought to signal and maintain the altered transcriptional state. Alcohol-induced epigenetic changes have been shown to be important in the long-term adaptation that leads to alcohol tolerance and dependence endophenotypes. A major constraint impeding progress is that alcohol produces a surfeit of changes in gene expression, most of which may not make any meaningful contribution to the ethanol response under study. Here we used a novel genomic epigenetic approach to find genes relevant for functional alcohol tolerance by exploiting the commonalities of two chemically distinct alcohols. In Drosophila melanogaster, ethanol and benzyl alcohol induce mutual cross-tolerance, indicating that they share a common mechanism for producing tolerance. We surveyed the genome-wide changes in histone acetylation that occur in response to these drugs. Each drug induces modifications in a large number of genes. The genes that respond similarly to either treatment, however, represent a subgroup enriched for genes important for the common tolerance response. Genes were functionally tested for behavioral tolerance to the sedative effects of ethanol and benzyl alcohol using mutant and inducible RNAi stocks. We identified a network of genes that are essential for the development of tolerance to sedation by alcohol.

  11. Chrono pharmacotherapy: A pulsatile Drug Delivery

    Directory of Open Access Journals (Sweden)

    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.

  12. 21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

    Science.gov (United States)

    2010-04-01

    ... a food additive, may be established to define a level of contamination at which a food may be... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

  13. 21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

    Science.gov (United States)

    2010-04-01

    ... a food additive, may be established to define a level of contamination at which a food may be... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

  14. Tolerability and safety aspects of mirtazapine.

    Science.gov (United States)

    Nutt, David J

    2002-06-01

    The tolerability and safety profile of the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine reflects its unique pharmacological profile. The 5-HT(2) blocking effect contributes towards its anxiolytic effects and benefits on sleep, as well as preventing the sexual dysfunction that may occur with non-specific stimulation of the serotonin system by drugs such as the selective serotonin reuptake inhibitors (SSRIs). In addition, 5-HT(3) blockade by mirtazapine helps to prevent nausea and vomiting. Weight gain is the most commonly reported side-effect of mirtazapine, although there is evidence to suggest that this is not a significant problem during long-term treatment. In conclusion, mirtazapine has a good tolerability and safety profile that demonstrates several benefits over other antidepressants. Copyright 2002 John Wiley & Sons, Ltd.

  15. Drug Safety

    Science.gov (United States)

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  16. Drug Abuse

    Science.gov (United States)

    ... Cocaine Heroin Inhalants Marijuana Prescription drugs, including opioids Drug abuse also plays a role in many major social problems, such as drugged driving, violence, stress, and child abuse. Drug abuse can lead to ...

  17. Drug Facts

    Medline Plus

    Full Text Available ... Use and Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  18. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Kids Drug Use and Unborn Children Drug Use and Your Health Other Effects on ... Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids ...

  19. Club Drugs

    Science.gov (United States)

    ... uses. Other uses of these drugs are abuse. Club drugs are also sometimes used as "date rape" drugs, to make someone unable to say no to or fight back against sexual assault. Abusing these drugs can ...

  20. Heat tolerance in wheat

    DEFF Research Database (Denmark)

    Sharma, Dew Kumari

    As a consequence of global climate change, heat stress together with other abiotic stresses will remain an important determinant of future food security. Wheat (Triticum aestivum L.) is the third most important crop of the world feeding one third of the world population. Being a crop of temperate...... climate, wheat is sensitive to heat stress. We need to understand how our crops will perform in these changing climatic conditions and how we can develop varieties, which are more tolerant. The PhD study focussed on understanding heat tolerance in wheat with a combined approach of plant physiology...... and quantitative genetics in particular, plant phenotyping based quantitative trait loci (QTL) discovery for a physiological trait under heat stress. Chlorophyll a fluorescence trait, Fv/Fm was used as a phenotyping tool, as it reflects the effect of heat stress on maximum photochemical efficiency of photosystem...

  1. Socially-Tolerable Discrimination

    OpenAIRE

    Amegashie, J. Atsu

    2008-01-01

    History is replete with overt discrimination on the basis of race, gender, age, citizenship, ethnicity, marital status, academic performance, health status, volume of market transactions, religion, sexual orientation, etc. However, these forms of discrimination are not equally tolerable. For example, discrimination based on immutable or prohibitively unalterable characteristics such as race, gender, or ethnicity is much less acceptable. Why? I develop a simple rent-seeking model of conflict w...

  2. A Critical Review of the Drug/Performance Literature. Volume II.

    Science.gov (United States)

    1979-12-01

    Cannabis Drug Tolerance Drugs and Stress Amphetamine Depressants Drug Users Ethanol Behavior Drug Abuse Drug Withdrawal Hallucinogens Cannabinoids Drug...Therapeutics Clin Tox Clinical Toxicology Couw Psychopharm Communications in Psychopharmacology Comp Psychiat Comprehensive Psychiatry Current Ther Res Current...European Journal of Toxicology Exp Neurol Experimental Neurology EEG Clin Neurophys EEG Clinical Neurophysiology EEG J EEG Journal Ger Med German Medicine

  3. Transplantation tolerance after total lymphoid irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Strober, S.; Slavin, S.; Fuks, Z.; Kaplan, H.S.; Gottlieb, M.; Bieber, C.; Hoppe, R.T.; Grumet, F.C.

    1979-03-01

    We have presented an animal model of tissue transplantation tolerance using the unusual effects of TLI on the immune system. The application of TLI to bone marrow and whole-organ transplantation in humans merits further study, since TLI offers several advantages over presently used therapeutic modalities. Current regimens used to prepare patients for marrow transplantation are lethal in the absence of allogeneic marrow engraftment, and marrow donors are restricted to HLA-matched siblings due to the danger of GHVD. On the other hand, TLI is a nonlethal procedure that has been used successfully in animals to transplant allogeneic marrow from unmatched donors without the development of GHVD. Thus, TLI might allow for marrow transplantation in all patients with a single sibling, whereas conventional procedures are feasible in only one of four such cases (probability of finding a single HLA-matched sibling). In addition, the induction of transplantation tolerance with TLI would obviate the requirement for the use of maintenance immunosuppressive drugs after whole-organ transplantation. Systemic infections associated with the use of these drugs currently account for the majority of deaths in heart transplant patients. Serious infectious complications associated with TLI are rare; thus this therapeutic regimen may offer considerable improvement in the long-term survival of organ graft recipients as compared to that presently obtained with immunosuppressive drugs.

  4. Vasorelaxant activity of extracts obtained from Apium graveolens:Possible source for vasorelaxant molecules isolation with potential antihypertensive effect

    Institute of Scientific and Technical Information of China (English)

    Vergara-Galicia Jorge; Jimenez-Ramirez Luis ngel; Tun-Suarez Adrin; Aguirre-Crespo Francisco; Salazar-Gmez Anuar; Estrada-Soto Samuel; Sierra-Ovando ngel; Hernandez-Nuez Emmanuel

    2013-01-01

    Objective:To investigate the vasorelaxant effect of organic extracts from Apium graveolens (A. graveolens) which is a part of a group of plants subjected to pharmacological and phytochemical study with the purpose of offering it as an ideal source for obtaining lead compounds for designing new therapeutic agents with potential vasorelaxant and antihypertensive effects. Methods:An ex vivo method was employed to assess the vasorelaxant activity. This consisted of using rat aortic rings with and without endothelium precontracted with norepinephrine. Results:All extracts caused concentration-dependent relaxation in precontracted aortic rings with and without endothelium;the most active extracts were Dichloromethane and Ethyl Acetate extracts from A. graveolens. These results suggested that secondary metabolites responsible for the vasorelaxant activity belong to a group of compounds of medium polarity. Also, our evidence showed that effect induced by dichloromethane and ethyl acetate extracts from A. graveolens is mediated probably by calcium antagonism. Conclusions: A. graveolens represents an ideal source for obtaining lead compounds for designing new therapeutic agents with potential vasorelaxant and antihypertensive effects.

  5. Social adversity experience and blood pressure control following antihypertensive medication use in a community sample of older adults.

    Science.gov (United States)

    Wainwright, Nicholas W J; Levy, Sheldon; Pico, Jose; Luben, Robert N; Surtees, Paul G; Khaw, Kay-Tee

    2014-06-01

    Psychosocial stress is a risk factor for hypertension and has been shown to affect response to treatment for psychiatric illnesses. We investigate the relationship between a history of social adversity experience and blood pressure control following antihypertensive medication use. A total of 1,186 participants selected from the European Prospective Investigation into Cancer-Norfolk study (531 men and 655 women, aged 42 to 80 years) had attended two health checks at which blood pressure measurements were taken; were taking antihypertensive medication at the second, but not the first health check; and had completed a questionnaire assessment of their social and psychological circumstances which included details of traumatic experiences in childhood and of adverse life events, long-term difficulties, and perceived stress in adulthood. Experience of recent loss events in adulthood was associated with a smaller reduction in systolic blood pressure after starting hypertension treatment (β = 1.78, 95 % confidence interval 0.15-3.40, per life event), independently of age, sex, preexisting health conditions, cigarette smoking history, alcohol consumption, physical activity, and obesity. Results from this study suggest that stress caused by recent losses may be associated with reduced effectiveness of treatment for hypertension. Subject to replication, these findings may help determine the specific physiological mechanisms by which medication treatment effectiveness is affected by stress.

  6. Evaluation of the antihypertensive properties of yellow passion fruit pulp (Passiflora edulis Sims f. flavicarpa Deg.) in spontaneously hypertensive rats.

    Science.gov (United States)

    Konta, Eliziane Mieko; Almeida, Mara Ribeiro; do Amaral, Cátia Lira; Darin, Joana Darc Castania; de Rosso, Veridiana V; Mercadante, Adriana Zerlotti; Antunes, Lusânia Maria Greggi; Bianchi, Maria Lourdes Pires

    2014-01-01

    Various species of the genus Passiflora have been extensively used in traditional medicine as sedatives, anxiolytics, diuretics and analgesics. In the present study, after the identification and quantification of phytochemical compounds from yellow passion fruit pulp by liquid chromatography-photodiode array-mass spectrometry (HPLC-PDA-MS/MS), its antihypertensive effect was investigated on spontaneously hypertensive rats. Additionally, the renal function, evaluated by kidney/body weight, serum creatinine, proteinuria, urinary flow, reduced glutathione (GSH) levels and thiobarbituric acid-reactive substances (TBARS) and mutagenicity in bone marrow cells were assessed to evaluate the safety of passion fruit consumption. Yellow passion fruit pulp (5, 6 or 8 g/kg b.w.) was administered by gavage once a day for 5 consecutive days. HLPC-PDA-MS/MS analysis revealed that yellow passion fruit pulp contains phenolic compounds, ascorbic acid, carotenoids and flavonoids. The highest dose of passion fruit pulp significantly reduced the systolic blood pressure, increased the GSH levels and decreased TBARS. There were no changes in renal function parameters or the frequency of micronuclei in bone marrow cells. In conclusion, the antihypertensive effect of yellow passion fruit pulp, at least in part, might be due to the enhancement of the antioxidant status. The exact mechanisms responsible by this effect need further investigation. Copyright © 2013 John Wiley & Sons, Ltd.

  7. Vasorelaxing and antihypertensive activities of synthesized peptides derived from computer-aided simulation of pepsin hydrolysis of yam dioscorin.

    Science.gov (United States)

    Lin, Yin-Shiou; Lu, Yeh-Lin; Wang, Guei-Jane; Liang, Hong-Jen; Hou, Wen-Chi

    2014-12-01

    We reported that yam dioscorin and its peptic hydrolysates exhibited ACE inhibition and antihypertensive effects on SHRs, however, the active peptides are not really isolated until now. Using ACE inhibitory screenings, two penta-peptides, KTCGY and KRIHF, were selected for ex vivo and in vivo experiments. KTCGY, KRIHF, and captopril were shown to have similar vasodilating effects against phenylephrine (PE)-induced tensions in rat endothelium-dependent thoracic aortic rings, however, KTCGYKTCGY (two-repeated KTCGY) and TCGYTCGY (two-repeated TCGY) were showed endothelium-independent vasodilating effects against PE-induced tensions. KTCGY, KRIHF (10 or 20 mg/kg), and captopril (10 mg/kg) were used to evaluate antihypertensive activity during 24-h after a single oral administration to spontaneously hypertensive rats (SHRs). The KTCGY and KRIHF showed significantly different and reduced the systolic blood pressure of SHRs compared to the blank. These results suggest that KTCGY and KRIHF may contribute important roles in yam dioscorin for regulating blood pressure in vivo.

  8. Serum Metabolomics Study Based on LC-MS and Antihypertensive Effect of Uncaria on Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Ana Liu

    2018-01-01

    Full Text Available Our previous studies have shown that Uncaria has an important role in lowering blood pressure, but its intervention mechanism has not been clarified completely in the metabolic level. Therefore, in this study, a combination method of HPLC-TOF/MS-based metabolomics and multivariate statistical analyses was employed to explore the mechanism and evaluate the antihypertensive effect of Uncaria. Serum samples were analyzed and identified by HPLC-TOF/MS, while the acquired data was further processed by partial least squares discriminant analysis (PLS-DA and orthogonal partial least squares discriminant analysis (OPLS-DA to discover the perturbed metabolites. A clear cluster among the different groups was obtained, and 7 significantly changed potential biomarkers were screened out. These biomarkers were mainly associated with lipid metabolism (dihydroceramide, ceramide, PC, LysoPC, and TXA2 and vitamin and amino acids metabolism (nicotinamide riboside, 5-HTP. The result indicated that Uncaria could decrease the blood pressure effectively, partially by regulating the above biomarkers and metabolic pathways. Analyzing and verifying the specific biomarkers, further understanding of the therapeutic mechanism and antihypertensive effect of Uncaria was acquired. Metabolomics provided a new insight into estimate of the therapeutic effect and dissection of the potential mechanisms of traditional Chinese medicine (TCM in treating hypertension.

  9. Tissue distribution in mice of BPP 10c, a potent proline-rich anti-hypertensive peptide of Bothrops jararaca.

    Science.gov (United States)

    Silva, Carlos A; Portaro, Fernanda C V; Fernandes, Beatriz L; Ianzer, Danielle A; Guerreiro, Juliano R; Gomes, Claudiana L; Konno, Katsuhiro; Serrano, Solange M T; Nascimento, Nanci; Camargo, Antonio C M

    2008-03-15

    The snake venom proline-rich peptide BPP 10c is an active somatic angiotensin-converting enzyme (sACE) inhibitors. Recently we demonstrated that the anti-hypertensive effect of BPP 10c is not related to the inhibition of sACE alone, thus suggesting that this enzyme is not its only target for blood pressure reduction. In the present work, a biodistribution study in Swiss mice of [(125)I]-BPP 10c in the absence or in the presence of a saturating concentration of captopril, a selective active-site inhibitor of sACE, demonstrated that: (1) [(125)I]-BPP 10c was present in several organs and the renal absorption was significantly high; (2) [(125)I]-BPP 10c showed a clear preference for the kidney, maintaining a high concentration in this organ in the presence of captopril for at least 3h; (3) The residual amount of [(125)I]-BPP 10c in the kidney of animals simultaneously treated with captopril suggest that the peptide can interact with other targets different from sACE in this organ. We also showed that Cy3-labeled BPP 10c was internalized by human embryonic kidney cells (HEK-293T). Taken together, these results suggest that sACE inhibition by captopril affects the tissue distribution of [(125)I]-BPP 10c and that the anti-hypertensive effects of BPP 10c are not only dependent on sACE inhibition.

  10. Williams syndrome predisposes to vascular stiffness modified by antihypertensive use and copy number changes in NCF1.

    Science.gov (United States)

    Kozel, Beth A; Danback, Joshua R; Waxler, Jessica L; Knutsen, Russell H; de Las Fuentes, Lisa; Reusz, Gyorgy S; Kis, Eva; Bhatt, Ami B; Pober, Barbara R

    2014-01-01

    Williams syndrome is caused by the deletion of 26 to 28 genes, including elastin, on human chromosome 7. Elastin insufficiency leads to the cardiovascular hallmarks of this condition, namely focal stenosis and hypertension. Extrapolation from the Eln(+/-) mouse suggests that affected people may also have stiff vasculature, a risk factor for stroke, myocardial infarction, and cardiac death. NCF1, one of the variably deleted Williams genes, is a component of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex and is involved in the generation of oxidative stress, making it an interesting candidate modifier for vascular stiffness. Using a case-control design, vascular stiffness was evaluated by pulse wave velocity in 77 Williams cases and matched controls. Cases had stiffer conducting vessels than controls (PWilliams syndrome. Pulse wave velocity increased with age at comparable rates in cases and controls, and although the degree of vascular stiffness varied, it was seen in both hypertensive and normotensive Williams participants. Use of antihypertensive medication and extension of the Williams deletion to include NCF1 were associated with protection from vascular stiffness. These findings demonstrate that vascular stiffness is a primary vascular phenotype in Williams syndrome and that treatment with antihypertensives or agents inhibiting oxidative stress may be important in managing patients with this condition, potentially even those who are not overtly hypertensive.

  11. Chemical study, antioxidant, anti-hypertensive, and cytotoxic/cytoprotective activities of Centaurea cyanus L. petals aqueous extract.

    Science.gov (United States)

    Escher, Graziela Bragueto; Santos, Jânio Sousa; Rosso, Neiva Deliberali; Marques, Mariza Boscacci; Azevedo, Luciana; do Carmo, Mariana Araújo Vieira; Daguer, Heitor; Molognoni, Luciano; Prado-Silva, Leonardo do; Sant'Ana, Anderson Souza; da Silva, Marcia Cristina; Granato, Daniel

    2018-05-19

    This study aimed to optimise the experimental conditions of extraction of the phytochemical compounds and functional properties of Centaurea cyanus petals. The following parameters were determined: the chemical composition (LC-ESI-MS/MS), the effects of pH on the stability and antioxidant activity of anthocyanins, the inhibition of lipid peroxidation, antioxidant activity, anti-hemolytic activity, antimicrobial, anti-hypertensive, and cytotoxic/cytoprotective effect, and the measurements of intracellular reactive oxygen species. Results showed that the temperature and time influenced (p ≤ 0.05) the content of flavonoids, anthocyanins, and FRAP. Only the temperature influenced the total phenolic content, non-anthocyanin flavonoids, and antioxidant activity (DPPH). The statistical approach made it possible to obtain the optimised experimental extraction conditions to increase the level of bioactive compounds. Chlorogenic, caffeic, ferulic, and p-coumaric acids, isoquercitrin, and coumarin were identified as the major compounds in the optimised extract. The optimised extract presented anti-hemolytic and anti-hypertensive activity in vitro, in addition to showing stability and reversibility of anthocyanins and antioxidant activity with pH variation. The C. cyanus extract exhibited high IC 50 and GI 50 (>900 μg/mL) values for all cell lines, meaning low cytotoxicity. Based on the stress oxidative assay, the extract exhibited pro-oxidant action (10-100 μg/mL) but did not cause damage or cell death. Copyright © 2018. Published by Elsevier Ltd.

  12. Drug-induced gingival enlargement: Series of cases

    Directory of Open Access Journals (Sweden)

    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.

  13. 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 normotensiv