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Antihypertensive Drugs (antihypertensive + drug)
Terms modified by Antihypertensive Drugs Selected AbstractsPharmacodynamics of S-2150, a Simultaneous Calcium-blocking and ,1 -Inhibiting Antihypertensive Drug, in RatsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2000TORU ISHIBASHI The in-vivo pharmacodynamics of S-2150, a newly developed dual-blocking type antihypertensive drug, was evaluated following intravenous infusion to rats. Previous in-vitro studies showed that the drug has two distinct mechanisms of antihypertensive effect,calcium-channel blocking activity and ,1 -adrenoceptor antagonism,which could be explained by a combination of two different pharmacodynamic models. The present in-vivo study showed that S-2150 also displays a complex pharmacodynamic profile (as measured by the decrease in mean blood pressure), which could be described by a combination of two sigmoid Emax models independently connected with the central compartment and the effect compartment. These results suggested that the dual-blocking mechanism of S-2150, which has been observed in in-vitro experiments, was also evaluated by the pharmacodynamic analysis of in-vivo experimental data. [source] Antihypertensive Drugs and New-Onset Diabetes: A Retrospective Longitudinal Cohort StudyCARDIOVASCULAR THERAPEUTICS, Issue 3 2009Gwo-Ping Jong Antihypertensive drugs have been linked to new-onset diabetes (NOD); however, data on the effect of these drugs on the development of NOD in hypertensive patients has not been well determined. We aimed to investigate the association between antihypertensive drugs and NOD. This was a retrospective cohort study performed using data from claim forms provided to the central region branch of the Bureau of National Health Insurance in Taiwan from January 2002 to December 2007. Prescriptions for antihypertensive drugs before the index date were retrieved from a prescription database. We estimated the odds ratios (ORs) of NOD associated with antihypertensive drug use; nondiabetic subjects served as the reference group. A total of 4233 NOD cases were identified in 24,688 hypertensive patients during the study period. The risk of NOD after adjusting for sex and age was higher among users of diuretics (OR = 1.10, 95% confidence interval [CI]= 1.01,1.20), beta-blockers (BBS; OR = 1.12, 95% CI = 1.04,1.21), and calcium channel blockers (CCBs; OR = 1.10, 95% CI = 1.02,1.18) than among nonusers. Patients who take angiotensin-converting enzyme (ACE) inhibitors (OR = 0.92, 95% CI = 0.84,1.00), angiotensin receptor blockers (ARB; OR = 0.90, 95% CI = 0.81,0.98), or alpha-blockers (OR = 0.88, 95% CI = 0.80,0.98) are at a lower risk of developing NOD than nonusers. Vasodilators were not associated with the risk of NOD. The results of this study suggest that hypertensive patients who take ACE inhibitors, ARBs, or alpha-blockers are at a lower risk of NOD. Diuretics, BBs, and CCBs were associated with a significant increase in the risk of NOD. [source] Population pharmacokinetics of ketanserin in pre-eclamptic patients and its association with antihypertensive responseFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2005Lidwien M. Hanff Abstract Ketanserin is an antihypertensive drug that is increasingly being used parenterally in the treatment of pre-eclampsia. Because of lack of efficacy in a substantial part of our pre-eclamptic patients, we determined the plasma concentrations of ketanserin in 51 pre-eclamptic patients. Population pharmacokinetic parameters were assessed using the iterative two-stage Bayesian population procedure. The influence of individual pharmacokinetic parameters on antihypertensive response, expressed as the attainment of a diastolic blood pressure ,90 mmHg using ketanserin treatment, was analysed. Almost all plasma concentrations of ketanserin were in or above the therapeutic range. The individual pharmacokinetics of ketanserin in pre-eclamptic patients showed an accurate fit using a three-compartment model. The pharmacokinetic parameters in our pre-eclamptic population were a metabolic clearance (Clm) of 37.9 ± 10.86 L/h and volume of distribution (V1) of 0.544 ± 0.188 L/kg, which is comparable with data from healthy volunteers. Despite a considerable inter-individual variation, no correlation was found between differences in pharmacokinetic parameters and antihypertensive response. We conclude that therapeutic plasma levels can be obtained in pre-eclamptic patients with a fixed dosage schedule of ketanserin and differences in antihypertensive responses within a pre-eclamptic population cannot be attributed to pharmacokinetic differences. [source] Duplex Doppler sonography of transplant renal artery stenosisJOURNAL OF CLINICAL ULTRASOUND, Issue 3 2003Ruth Helena de Morais MD Abstract Purpose The aim of this study was to evaluate the accuracy of duplex Doppler sonography in diagnosing transplant renal artery stenosis (TRAS) and to determine which parameter is the most reliable for making that diagnosis. Methods Over a 3-year period, we sonographically evaluated patients who were referred for investigation of possible TRAS. We investigated the following parameters: peak systolic velocity (PSV) in the external iliac and renal arteries, acceleration time and acceleration in the intrarenal arteries, acceleration time in the renal artery, resistance index, and the ratio of the PSVs in the renal and external iliac arteries. We also used MR angiography and digital subtraction arteriography to verify the degree of stenosis. After the evaluations, the patients were classified into 2 groups, 1 with and the other without significant stenosis (> 50% narrowing of the lumen) on digital subtraction arteriography. We also included a control group of patients who had undergone renal transplantation at least 6 months before, had had a good course after transplantation, had a diastolic blood pressure of 90 mm Hg or less, and were taking a maximum of 1 antihypertensive drug. Results Our study population consisted of 22 patients suspected to have TRAS (10 without and 12 with confirmed significant stenosis) and 19 control patients. We found statistically significant differences between the mean values of these 3 groups except for the PSV in the iliac artery and the resistance index in the intrarenal arteries. The most accurate parameters to use in diagnosing TRAS were an acceleration time of 0.1 second or higher in the renal and intrarenal arteries, a PSV of greater than 200 cm/second in the renal artery, and a ratio of PSVs in the renal and external iliac arteries of greater than 1.8. Conclusions Duplex Doppler sonography is an excellent method for screening patients suspected to have TRAS and can help select which of those patients should undergo digital subtraction arteriography. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:135,141, 2003 [source] Pharmacodynamics of S-2150, a Simultaneous Calcium-blocking and ,1 -Inhibiting Antihypertensive Drug, in RatsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2000TORU ISHIBASHI The in-vivo pharmacodynamics of S-2150, a newly developed dual-blocking type antihypertensive drug, was evaluated following intravenous infusion to rats. Previous in-vitro studies showed that the drug has two distinct mechanisms of antihypertensive effect,calcium-channel blocking activity and ,1 -adrenoceptor antagonism,which could be explained by a combination of two different pharmacodynamic models. The present in-vivo study showed that S-2150 also displays a complex pharmacodynamic profile (as measured by the decrease in mean blood pressure), which could be described by a combination of two sigmoid Emax models independently connected with the central compartment and the effect compartment. These results suggested that the dual-blocking mechanism of S-2150, which has been observed in in-vitro experiments, was also evaluated by the pharmacodynamic analysis of in-vivo experimental data. [source] Antihypertensive drug therapy and the risk of lower extremity amputations in pharmacologically treated type 2 diabetes patients,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 3 2004Joëlle A. Erkens PharmD Abstract Purpose The objective of this study was to determine the association between different antihypertensive drug therapies and lower extremity amputations (LEAs) in type 2 diabetes patients. Methods Data were obtained from the PHARMO Record Linkage System comprising pharmacy records and data on hospitalisations for all 450,000 residents of eight Dutch cities. In a nested case-control study among 12,140 type 2 diabetes patients who used antihypertensive drugs, 26 cases with a first LEA and 94 controls without a LEA matched on age, sex and calendar time were identified. Logistic regression was used to estimate the relative risk of LEA and to adjust for potential confounding factors. Results Among type 2 diabetes patients who used antihypertensive drugs, subjects who used thiazide diuretics, alone or in combination, had a higher risk of LEA compared to subjects who used Angiotensin Converting Enzyme (ACE) inhibitor monotherapy (crude odds ratio (OR): 6.11 [95% confidence interval (CI): 1.32,28.27]). The use of thiazide diuretics was also associated with an increased risk of LEA when compared to the use of any non-thiazide antihypertensive drug (adjusted OR: 7.04 [1.10,45.30]). The increased risk of LEA associated with the use of thiazides compared to the use of non-thiazides depended on the duration of use (adjusted OR,365 days, 4.82 [0.61,38.34] and adjusted OR>365 days, 26.16 [1.02,674.02], p -trend,=,0.01). Conclusions Treatment with thiazide diuretics compared to treatment with other antihypertensive drugs was associated with excess amputations in type 2 diabetes patients. Due to several limitations of this study, our findings do not preclude the use of thiazides in type 2 diabetes mellitus patients as yet. Copyright © 2004 John Wiley & Sons, Ltd. [source] Practical pharmacovigilance analysis strategiesPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2003A. Lawrence Gould Abstract Purpose To compare two recently proposed Bayesian methods for quantitative pharmacovigilance with respect to assumptions and results, and to describe some practical strategies for their use. Methods The two methods were expressed in common terms to simplify identifying similarities and differences, some extensions to both methods were provided, and the empirical Bayes method was applied to accumulated experience on a new antihypertensive drug to elucidate the pattern of adverse-event reporting. Both methods use the logarithm of the proportional risk ratio as the basic metric for association. Results The two methods provide similar numerical results for frequently reported events, but not necessarily when few events are reported. Using a lower 5% quantile of the posterior distribution gives some assurance that potential signals are unlikely to be noise. The calculations indicated that most potential adverse event,drug associations that were well-recognized after 6 years of use could be identified within the first year, that most of the associations identified in the first year persisted over time. Other insights into the pattern of event reporting were also noted. Conclusion Both methods can provide useful early signals of potential drug,event associations that subsequently can be the focus of detailed evaluation by skilled clinicians and epidemiologists. Copyright © 2002 John Wiley & Sons, Ltd. [source] Treatment of isolated systolic hypertension in diabetes mellitus type 2DIABETES OBESITY & METABOLISM, Issue 4 2006Ingrid Os Age-related arterial stiffness is more pronounced in diabetics compared to non-diabetics, which could explain the prevalence of isolated systolic hypertension (ISH, systolic blood pressure ,140 mmHg and diastolic blood pressure <90 mmHg) being approximately twice that of the general population without diabetes. Large-scale interventional outcome trials have also shown that diabetics usually have higher pulse pressure and higher systolic blood pressure than non-diabetics. Advanced glycation end-product formation has been implicated in vascular and cardiac complications of diabetes including loss of arterial elasticity, suggesting possibilities for new therapeutic options. With increasing age, there is a shift to from diastolic to systolic blood pressure and pulse pressure as predictors of cardiovascular disease. This may affect drug treatment as different antihypertensive drugs may have differential effects on arterial stiffness that can be dissociated from their effects on blood pressure. While thiazide diuretics are associated with little or no change in arterial stiffness despite a robust antihypertensive effect, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and calcium-channel blockers have been shown to reduce arterial stiffness. However, combination therapy is nearly always necessary to obtain adequate blood pressure control in diabetics. There are no randomized controlled trials looking specifically at treatment of ISH in diabetics. Recommendations regarding treatment of ISH in diabetes mellitus type 2 are based on extrapolation from studies in non-diabetics, post-hoc analyses and prespecified subgroup analysis in large-scale studies, and metaanalysis. These analyses have clearly demonstrated that blood pressure lowering in ISH confers improved prognosis and reduced cardiovascular and renal outcomes in both diabetics and non-diabetics. [source] Risk factor control in patients with Type 2 diabetes and coronary heart disease: findings from the Swedish National Diabetes Register (NDR)DIABETIC MEDICINE, Issue 1 2009S. Gudbjörnsdottir Abstract Aims Patients with Type 2 diabetes and coronary heart disease (CHD) are infrequently treated to risk factor targets in current guidelines. We aimed to examine risk factor management and control levels in a large sample of patients with Type 2 diabetes with CHD. Methods This was an observational study of 1612 patients with first incidence of CHD before 2002, and of 4570 patients with first incidence of CHD before 2005, from the Swedish National Diabetes Register (NDR). Results In patients with CHD 1,2 years before follow-up, the achievement of cardiovascular risk factor targets (follow-up 2002/follow-up 2005) was: HbA1c < 7%, 47%/54% (P < 0.01); blood pressure , 130/80 mmHg, 31%/40% (P < 0.001); total cholesterol < 4.5 mmol/l, 47%/60% (P < 0.001); and low-density lipoprotein-cholesterol < 2.5 mmol/l, 49%/65% (P < 0.001). Use of medication: antihypertensives, 90%/94% (P < 0.01); lipid-lowering drugs, 75%/86% (P < 0.001); and aspirin, 85%/89% (P < 0.05). A high prevalence of adverse lifestyle characteristics prevailed (2002/2005): overweight [body mass index (BMI) , 25 kg/m2], 86%/85%; obesity (BMI , 30 kg/m2), 41%/42%; smokers in age group < 65 years, 16,23%/18,19%; as well as waist circumference , 102 cm (men) or , 88 cm (women), 68% in 2005. Conclusions Patients with a combination of Type 2 diabetes and CHD showed an increased use of lipid-lowering drugs over time, corresponding to improving blood lipid levels. A discrepancy existed between the prevalent use of antihypertensive drugs and the low proportion reaching blood pressure targets. Regretfully, a high prevalence of adverse lifestyle characteristics prevailed. Evidence-based therapy with professional lifestyle intervention and drugs seems urgent for improved quality of secondary prevention in these patients. [source] Pharmacogenetics of antihypertensive treatmentDRUG DEVELOPMENT RESEARCH, Issue 3 2004Donna K. Arnett Abstract Hypertension is a common disorder associated with increased cardiovascular morbidity and mortality. Unfortunately, in the United States, only about one third of those who are aware of their hypertensive status successfully control their blood pressure. One reason for this is the variable and unpredictable response individuals have to pharmacologic treatment. Clinicians often resort to a trial-and-error approach to match patients with effective drug treatment. It is the goal of hypertension pharmacogenetics to apply knowledge of genetic predictors of treatment response to drugs that lower blood pressure and to translate this knowledge into clinical practice. To date, more than 30 studies have investigated associations between specific genetic polymorphisms and response to particular antihypertensive drugs. Angiotensin-converting enzyme inhibitors have been most frequently studied, followed by diuretics, beta-blockers, angiotensin II blockers, adrenergic alpha-agonists, and calcium channel blockers. Renin,angiotensin,aldosterone system genes have been the most widely studied, with the angiotensin-converting enzyme I/D variant being typed in about one third of all hypertension pharmacogenetic studies to date. In a number of cases, significant and potentially promising associations between genes and drug treatments have been reported. However, taken in sum, the literature suggests that the path from gene-drug-outcome association studies to clinically useful knowledge may be neither short nor direct. In the future, carefully designed studies must acknowledge that hypertension is caused by multiple genes and environmental factors that act in concert. These considerations, along with a better understanding of the complexities of the biology of hypertension, open the next set of opportunities for hypertension pharmacogenetics research. Drug Dev. Res. 62:191,199, 2004. © 2004 Wiley-Liss, Inc. [source] Effects of six antihypertensive drugs on blood pressure and hypothalamic GABA content in spontaneously hypertensive ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2001Ying Guan In order to investigate the effects of antihypertensive drugs on blood pressure and ,-amino butyric acid (GABA) content in the hypothalamus and the possible relationship between blood pressure decrease and GABA content changes, blood pressure and GABA contents after chronic (20 weeks) treatments of nitrendipine, atenolol, captopril, hydrochlorothiazide, dihydralazine and prazosin were studied in spontaneously-hypertensive rats (SHR). The acute and subacute (1 week) effects of nitrendipine on GABA contents was also observed in SHR. It was found that 20 week treatments with six different antihypertensive agents produced a decrease in systolic blood pressure and an increase in GABA content. The blood pressure level was significantly correlated with GABA content in the hypothalamus, but not with that in the cortex. Acute treatment with a single dose of nitrendipine, did not alter GABA content. Bicuculline, a GABA receptor antagonist, did not attenuate the hypotensive effect of nitrendipine. In conclusion, chronic treatments by different antihypertensive agents produced an increase of hypothalamic GABA content and a decrease of blood pressure. The increase of GABA content induced by nitrendipine seems likely to be secondary to blood pressure decrease. [source] Optimal treatment of hypertension in the elderly: A Korean perspectiveGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 1 2008Kwang-Il Kim With the progression of the aging population, common diseases of the elderly have become the center of attention in most developed countries. Hypertension is one of the most common morbid conditions in the elderly and has a great impact on their health status because it is the main risk factor of cardiovascular and cerebrovascular diseases. However, a considerable amount of uncertainty remains regarding hypertension in the elderly, such as the benefits of hypertension control in oldest-old populations, the optimal level of blood pressure control, and the efficacy of antihypertensive drugs for the prevention of cognitive dysfunction. While there are many controversial issues concerning the optimal management of hypertension in the elderly, the number of elderly hypertensive patients that require treatment is expected to increase due to the aging population. As a result, knowledge regarding the mechanisms of hypertension in the elderly and specific consideration in managing hypertensive elderly patients are needed to improve the clinical outcome. Furthermore, new therapeutic interventions that are aimed at attenuating age-related vascular changes should be investigated, because hypertension in the elderly, especially isolated systolic hypertension has specific characteristics of increased arterial stiffness in most cases. [source] Interdialytic blood pressure obtained by ambulatory blood pressure measurement and left ventricular structure in hypertensive hemodialysis patientsHEMODIALYSIS INTERNATIONAL, Issue 3 2008Siddig MOMINADAM Abstract Unlike in subjects with normal renal function, the relationship between hypertension and cardiovascular morbidity and mortality in dialysis patients is still being debated. In order to clarify this issue, we performed 44-hour ambulatory blood pressure measurements (ABPM) during the interdialytic period in a group of 164 hypertensive patients, the blood pressure (BP) control based on conventional antihypertensive strategy previously, on chronic hemodialysis treatment in the Mediterranean region of Turkey. These results were then compared with their echocardiographic data. This is a cross-sectional analysis. The mean ABPM during 44 hours was close to the manually measured predialysis value, but there was a gradual increase in the ABPM values in the interdialytic period. When divided into a group with mild or no left ventricular hypertrophy (LVH) (45 patients) and severe LVH (119 patients), the latter had significantly higher BP levels in all separate periods, while the difference in predialysis BP was not significant. Patients with severe LVH had larger left atrium and left ventricular diameters, and consumed more antihypertensive drugs. Systolic BP during the night before dialysis showed the strongest relation to LVH, but interdialytic weight gain was also independently related to LVH. Yet, 56% of the patients with systolic BP <135 had severe LVH. There is not only an association between BP and presence of LVH, but it is shown that volume expansion is also an important independent determinant of LVH. This may explain the difficulty in identifying hypertension as a cardiac risk factor in these patients. [source] Revisiting Autonomic Dysfunction in End-Stage Renal Disease PatientsHEMODIALYSIS INTERNATIONAL, Issue 3 2003Jocemir R. Lugon Background:,Autonomic dysfunction is frequent in end-stage renal disease (ESRD) patients, but both the relative involvement of the parasympathetic and sympathetic branches and the role of antihypertensive drugs in this setting are still controversial. The present study addressed these issues employing a battery of standard noninvasive cardiovascular autonomic tests. Methods:,Sympathetic (S) function was evaluated by responses of both systolic blood pressure (BP) to passive tilting and diastolic BP to handgrip; parasympathetic (P) function, through the respiratory sinus arrhythmia test and the heart rate response to the 4-s unloaded exercise test. Additional tests influenced by both branches of the autonomic system (P + S) were accomplished by the assessment of heart rate response to the Valsalva maneuver, handgrip, and tilting. Results:,Studied subjects belonged to one of the three groups: ESRD patients not requiring BP medications (n = 11; 8 men, 3 women); ESRD patients receiving antihypertensive therapy (n = 36; 21 men, 15 women); and apparently healthy controls (n = 15; 10 men, 5 women). When the variables grouped according to the branch of the autonomic nervous system predominantly probed were analyzed, only the frequency of impaired sympathetic autonomic responses was higher in ESRD patients not receiving BP drugs compared to controls (55 vs. 23%, P = 0.040). In contrast, when ESRD patients receiving BP drugs were compared to controls, the differences became significant in S, P, and P + S tests (46 vs. 23%, P = 0.045; 22 vs. 3%, P = 0.020; and 34 vs. 13%, P = 0.010, respectively). With the criterion of more than one positive finding in any of the variables examined for diagnosing autonomic dysfunction, the prevalence of autonomic dysfunction was 20% in controls, 64% in ESRD patients not receiving BP drugs (P = 0.005 vs. controls), and 67% in ESRD patients receiving BP drugs (P = 0.043 vs. controls). Conclusions:,ESRD continues to be associated with a high prevalence of autonomic dysfunction. ESRD patients receiving BP drugs were found to have detectable impairment in the entire autonomic system in contrast to those not receiving BP drugs in whom inadequate responses were restricted to the sympathetic branch. [source] Short Daily Dialysis (SDHD) Efficacy : Pilot Multicentric Study with Nine Patients from MadridHEMODIALYSIS INTERNATIONAL, Issue 1 2003G. Barril Interest in quotidian (daily) hemodialysis (HD) seems to be growing. Clinical data consistently showed improved quality of life, better control of blood pressure, less need for medications including erythropoietin (EPO) and better nutrition. We evaluate the SDHD efficacy in 9 patients in conventional HD (3 weekly sesions/4 hours), mean age 57,78 years range (33,75), 6 males and 3 females who needed increased dialysis efficiency by different medical indications: 5 cases with hypertensive miocardiopathy and severe LVH, 2 of them with EFLV 26% and 27%. 2 cases with ischemic cardiopathy symptoms, one of them with anger and restless dysnea with a non resvascularizable coronary lesion, and other with cardiac insufficiency episodes requiring hospitalization once a month. 1 patient with big body surface area and elevated phosphorus levels although without control, with conventional three times/week HD. 1 patient indication was made by 12 years on HD with multiple vascular accesses failed needing a Tessio cathéter being into infradialysis regimen for his malnutrition status. The schedule in all of them was 6 days per week sessions between 2.15 hrs till 3 hours depending of body surface area to obtain a weekly kt/v nearest to 4. HD session were realized in the Hospital (4 pts) or in satellite unit (5 pts) due to the characteristics of the patients. The time remaining in this schedule was between 5 months to 2 years and 9 months. All the patients showed clinical improvement, subjective and objective, since the first weeks of starting SDHD. Sleep symptoms were the first to improve. All patients showing good coping with this HD alternative. Blood pressure levels were controlled without need for antihypertensive drugs, although the dry weight increased significantly in all cases. Albumin serum levels increased as nutrition parameter, controlling also the osteodystrophy and phosphorus. In a patient the EFLV was normalized from 6 months (26%,50%) improving in other. Two patients could be included in Tx waiting list. Again, anemia improved and decreasing EPO was required. No vascular access (autologous AVF) malfunction was detected in relation to daily procedure. Conclusion: Our pilot experience shows a clinical and biochemical improvement in the patients and quality of life as well. Prospective studies to demonstrate the financial benefits of these modalities are needed. [source] Withdrawal syndrome following cessation of antihypertensive drug therapyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2005G. N. Karachalios Summary In this study, a review of the available information concerning abrupt withdrawal of antihypertensive drug therapy is presented. Abrupt withdrawal of these drugs can produce a syndrome of sympathetic overactivity that includes nervousness, tachycardia, headache, agitation and nausea 36,72 h after cessation of the drug. A withdrawal syndrome may occur after discontinuation of almost all types of antihypertensive drugs, but mostly occurs with clonidine, ,-blockers, methyldopa and guanabenz. Less commonly can produce a rapid increase of the blood pressure to pre-treatment levels or above, or both and/or myocardial ischaemia. Although the exact incidence of the syndrome is not known, it appears to be rare, at least in patients receiving standard doses of the above antihypertensive drugs. The best treatment is prevention. In this study regarding the withdrawal syndrome that follows cessation of antihypertensive drugs therapy, a reference to the abrupt discontinuation of the main categories of antihypertensive drugs is also attempted. [source] Non-prescription medicine use by outpatients of a hospital in north-central Trinidad living with hypertension, and the potential clinical risksINTERNATIONAL JOURNAL OF PHARMACY PRACTICE, Issue 5 2008Miss Rian Extavour Assistant Lecturer, principal investigator Objective To describe the reported use of non-prescription medicines (NPMs) and the reported frequency of use by outpatients living with hypertension; to identify potential drug-drug and drug-disease interactions between reported NPMs and either antihypertensives prescribed or hypertension. Setting Adult outpatient clinics of the Eric Williams Medical Sciences Complex Adult Hospital in Trinidad. Method Outpatients were interviewed about their use of NPMs using a structured instrument. Chi-squared test or Fisher's exact test was used to test for associations between NPM use and selected variables: age group, gender, education level, number of prescribed medicines, use of prescribed medicines and the presence of comorbidities. Combinations of NPMs and antihypertensive drugs or hypertension itself that may lead to undesirable interactions were identified. Key findings One hundred and fifty-five clients were interviewed (mean age 61 years; 46% men; 56% of East Indian descent). Of these, 82% were living with a cardiac condition and 60% with diabetes mellitus. In addition, 92% reported using NPMs to treat minor illnesses. Analgesic use was reported by 81%. Some 66% reported using paracetamol, 54% reported antitussives, 48% antacids, 47% antihistamines and 39% said they used sympathomimetic drugs. The majority (98%) of NPMs were used only when needed. Sixty per cent had at least one combination a with risk of interaction with NPMs and hypertension or antihypertensive medicines: 16% had risk of interactions between enalapril (or captopril) and antacids, 13% between angiotensin-converting enzyme (ACE) inhibitors and non-steroidal anti-inflammatory drugs (NSAIDs), 12% between beta-blockers and NSAIDs and 12% between thiazide diuretics and NSAIDs. Thirty-nine per cent had a drug-disease interaction risk due to sympathomimetic drugs and 26% had one due to NSAID use. Conclusion Based on self-reports, outpatients living with hypertension in north-central Trinidad use NPMs when needed to treat minor illnesses, mainly paracetamol for pain. Non-prescription-antihypertensive interactions may arise due to ACE inhibitor/antacid combinations and NPM-hypertension interactions may result from use of sympathomimetics. Interactions may also arise as a result of the use of NPMs containing NSAIDs and sodium. [source] Meeting the Challenge to Improve the Treatment of Hypertension in BlacksJOURNAL OF CLINICAL HYPERTENSION, Issue 6 2003Antonio Alberto Lopes MD Hypertension is more prevalent and severe in African descendent populations living outside Africa than in any other population. Given this greater burden of hypertension in blacks, it is increasingly necessary to refine strategies to prevent the disorder as well as improve its treatment and control. This review assesses results from clinical trials on lifestyle and pharmacologic interventions to identify which approaches most effectively prevent adverse hypertension-related outcomes in African descendent populations. The Dietary Approaches to Stop Hypertension (DASH) study provided evidence that a carefully controlled diet rich in fruits, vegetables, low-fat dairy foods, and reduced in saturated fat, total fat, and cholesterol (i.e., the DASH diet) reduces blood pressure in blacks and is well accepted. The combination of the DASH diet with reduction in dietary sodium below 100 mmol/d may provide a reduction in blood pressure beyond that reached by the DASH diet alone. Physical exercise and interventions to reduce psychological stress may also reduce blood pressure in blacks. Strong evidence from numerous studies is a compelling argument for continuing to recommend diuretics and , blockers as first-line antihypertensive therapy for persons of all races. Some new studies also favor angiotensin-converting enzyme inhibitors as first-line antihypertensive drugs. The African American Study of Kidney Disease and Hypertension provided evidence that an angiotensin-converting enzyme inhibitor-based treatment program is more beneficial than calcium channel blockers and , blockers in reducing the progression of renal failure in blacks with hypertensive nephropathy. Studies in patients with diabetes have also shown evidence that both angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists are more effective than other classes of antihypertensives in reducing adverse renal events. Studies to evaluate the effects of the new antihypertensives in improving outcomes in blacks living outside the United States are needed. [source] Queen Mary Utilization of Antihypertensive Drugs Study: side-effects of antihypertensive drugsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2005B. M. Y. Cheung PhD FRCP Summary Background and objective:, Effective prevention of cardiovascular events in hypertensive patients requires good control of blood pressure. Side-effects of antihypertensive drugs affect tolerability and compliance. Accordingly, we surveyed side-effects in the hypertension outpatient clinic. Methods:, A total of 228 patients (109 men, 119 women) were interviewed in April,May 2004 in the Queen Mary Utilization of Antihypertensive Drugs Study. Results:, The percentage of patients receiving no drug (life-style modification), one, two, three and over three drugs were 3, 30, 40, 22 and 6% respectively. The proportion of patients taking calcium channel blockers, , -blockers (BB), angiotensin-converting enzyme inhibitors, thiazide diuretics, , -blockers and angiotensin receptor blockers were 65, 64, 33, 24, 4 and 7% respectively. Blood pressure on treatment was 144 ± 21/82 ± 11 mmHg. Among patients on antihypertensive drug therapy, 34% reported adverse effects: dizziness (9%), ankle swelling (7%), headache (5%), fatigue (4%), chest discomfort (3%) and cough (3%). Fewer patients on BBs reported side-effects (OR 0·46, P = 0·008). The likelihood of experiencing side-effects was unrelated to sex, age, weight, BMI, years of treatment, number of drugs used, heart rate on treatment or compliance. Conclusions:, To achieve good blood pressure control, multiple drugs are used. Thiazides are underused whereas BBs are popular. The popularity of the latter may be related to its tolerability. [source] Cardioprotection with beta-blockers: myths, facts and Pascal's wagerJOURNAL OF INTERNAL MEDICINE, Issue 3 2009F. H. Messerli Abstract. Beta-blockers were documented to reduce reinfarction rate more than 3 decades ago and subsequently touted as being cardioprotective for a broad spectrum of cardiovascular indications such as hypertension, diabetes, angina, atrial fibrillation as well as perioperatively in patients undergoing surgery. However, despite lowering blood pressure, beta-blockers have never shown to reduce morbidity and mortality in uncomplicated hypertension. Also, beta-blockers do not prevent heart failure in hypertension any better than any other antihypertensive drug class. Beta-blockers have been shown to increase the risk on new onset diabetes. When compared with nondiuretic antihypertensive drugs, beta-blockers increase all-cause mortality by 8% and stroke by 30% in patients with new onset diabetes. Beta-blockers are useful for rate control in patients with chronic atrial fibrillation but do not help restore sinus rhythm or have antifibrillatory effects in the atria. Beta-blockers provide symptomatic relief in patients with chronic stable angina but do not reduce the risk of myocardial infarction. Adverse effects of beta-blockers are common including fatigue, dizziness, depression and sexual dysfunction. However, beta-blockers remain a cornerstone in the management of patients having suffered a myocardial infarction and for patients with heart failure. Thus, recent evidence argues against universal cardioprotective properties of beta-blockers but attest to their usefulness for specific cardiovascular indications. [source] The Frequency Of Arterial Hypertension Versus Orthostatic Hypotension In Diabetic PatientsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2000C Ionescu-Tîrgoviste Aim: The aim of this study was to assess the relationship between supine high blood pressure and orthostatic hypotension both in Type 1 (T1DM) and Type 2 (T2DM) diabetic patients. Patients and Methods: Our study included 321 T2DM patients (153 M/168 F; mean age 62.3 (14.2 yr; duration of disease 12.1 (7.6 yr) and 116 T1DM patients (65 M/51 F; mean age 39.7 (9.2 yr; duration of diabetes 11.9 (8.1 yr). Patients with orthostatic hypotension were divided into 3 groups: A , without symptoms; B , mild/moderate symptoms (short and tolerable dizziness when standing); C , severe symptoms (persistent and disabling dizziness or even fainting in upright position). Results: Arterial hypertension was registered in 67.6% of T2DM patients (217 from 321 cases) and in 50.0% of T1DM patients (58 from 116 cases). Orthostatic hypotension (defined as a decrease in systolic blood pressure (30 mm Hg)) was encountered in 64.5% in T2DM patients (207 out of 321 cases) and in 60.3% of T1DM patients (70 out of 116 cases). From 207 T2DM patients with orthostatic hypotension, 105 were in Group A (50.7%), 89 in Group B (42.99%) and 13 in Group C (6.28%), while from 70 T1DM patients with orthostatic hypotension 14 were in Group A (20.0%), 51 in Group B (72.8%) and 5 in Group C (7.14%). An association of supine arterial hypertension with orthostatic hypotension was registered in 96 (29.9%) T2DM patients (68 of them receiving antihypertensive treatment) and in 25 (21.5%) T1DM patients (19 of which were on antihypertensive treatment). From the 18 patients with severe orthostatic hypotension (13 T2DM and 5 T1DM), supine arterial hypertension was registered in 5 cases (3 T2DM and 2 T1DM). In 4 of these 5 cases, patients were receiving antihypertensive treatment. Discontinuation of this treatment led to a decrease in the intensity of clinical signs of orthostatic hypotension in 4 out of 5 cases. An improvement of clinical symptoms of orthostatic hypotension was recorded in about 1/3 of hypertensive patients after discontinuation or just lowering of the dose of antihypertensive drugs (26 out of 87 cases). Conclusion: An association between hypertension and orthostatic hypotension is frequent both in T1DM and in T2DM, rising in difficulties for treatment. The treatment of hypertension in diabetic patients should take into account the possible orthostatic hypotension induced by some of the antihypertensive drugs. [source] Imidazoline binding sites and their ligands: An overview of the different chemical structuresMEDICINAL RESEARCH REVIEWS, Issue 5 2004Christophe Dardonville Abstract Since Bousquet et al. discovered the imidazoline binding sites (IBS) two decades ago, when they realized that the antihypertensive drug clonidine interacts not only with the ,2 -adrenenoceptors (,2 -AR) but also with a distinct imidazoline preferring binding site, these receptors have been paid a great deal of attention. At least two subtypes, I1 and I2, have been characterised based on their binding affinity for different radioligands, but their structures still remain unknown. The pharmacological profile of these IBSs has been the objective of several and very thorough reviews. However, a medicinal chemistry overview of the different IBS ligands prepared to date has never been attempted. In this study, we attempt to compile all the different chemical structures reported to date as IBS ligands and classify them in function of their chemical structure and binding affinity for the different IBS subtypes. Thus, we comment on the different endogenous IBS ligands known as well as the drugs described to interact with the I1 -IBS which have found application as antihypertensive drugs. Then, we review those compounds described in the literature to interact with the I2 -IBS, classifying them by their chemical families (imidazolines, guanidines, 2-aminoimidazolines, ,-carbolines). Finally, some conclusions are drawn. © 2004 Wiley Periodicals, Inc. Med Res Rev, 24, No. 5, 639,661, 2004 [source] Antihypertensive drug therapy and the risk of lower extremity amputations in pharmacologically treated type 2 diabetes patients,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 3 2004Joëlle A. Erkens PharmD Abstract Purpose The objective of this study was to determine the association between different antihypertensive drug therapies and lower extremity amputations (LEAs) in type 2 diabetes patients. Methods Data were obtained from the PHARMO Record Linkage System comprising pharmacy records and data on hospitalisations for all 450,000 residents of eight Dutch cities. In a nested case-control study among 12,140 type 2 diabetes patients who used antihypertensive drugs, 26 cases with a first LEA and 94 controls without a LEA matched on age, sex and calendar time were identified. Logistic regression was used to estimate the relative risk of LEA and to adjust for potential confounding factors. Results Among type 2 diabetes patients who used antihypertensive drugs, subjects who used thiazide diuretics, alone or in combination, had a higher risk of LEA compared to subjects who used Angiotensin Converting Enzyme (ACE) inhibitor monotherapy (crude odds ratio (OR): 6.11 [95% confidence interval (CI): 1.32,28.27]). The use of thiazide diuretics was also associated with an increased risk of LEA when compared to the use of any non-thiazide antihypertensive drug (adjusted OR: 7.04 [1.10,45.30]). The increased risk of LEA associated with the use of thiazides compared to the use of non-thiazides depended on the duration of use (adjusted OR,365 days, 4.82 [0.61,38.34] and adjusted OR>365 days, 26.16 [1.02,674.02], p -trend,=,0.01). Conclusions Treatment with thiazide diuretics compared to treatment with other antihypertensive drugs was associated with excess amputations in type 2 diabetes patients. Due to several limitations of this study, our findings do not preclude the use of thiazides in type 2 diabetes mellitus patients as yet. Copyright © 2004 John Wiley & Sons, Ltd. [source] Agreement between patient self-report and a Veterans Affairs national pharmacy database for identifying recent exposures to antibioticsPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2003Joshua P. Metlay MD Abstract Purpose The dramatic rise in antibiotic drug resistance among community pathogens has stimulated interest in the epidemiological relationship between antibiotic exposure and drug resistance. In assessing the strength of this relationship, studies are hampered by the lack of data on the accuracy of subject self-report of antibiotic exposure. The authors compared self-report with pharmacy dispensing data to determine the accuracy of self-reported antibiotic exposure. Methods The study design was a cross-sectional survey of veterans seen at the Philadelphia Veterans Affairs (VA) Medical Center in 1999 and 2000. Subjects reported exposures to antibiotics, antihypertensive drugs and nonsteroidal anti-inflammatory drugs through a structured telephone interview. The instrument included open-ended questions, condition-specific prompts and drug-specific prompts. Subject responses were linked to a national VA pharmacy database that served as the reference standard for evaluating self-reported exposures. Results The authors found that the sensitivity of self-report of antibiotic exposure increased with increasing use of prompts. A comprehensive assessment of antibiotic exposure identified 73% of antibiotic exposures, compared to 73% of antihypertensive drug exposures and 92% of nonsteroidal anti-inflammatory drug exposures. Conclusions Assessment of antibiotic exposure appears to be comparable to assessment of other chronic and episodic drugs. Multistep assessment of exposure improves the sensitivity of assessment. Copyright © 2002 John Wiley & Sons, Ltd. [source] Latest news and product developmentsPRESCRIBER, Issue 5 2007Article first published online: 16 MAY 200 OFT wants PPRS reform The Office of Fair Trading (www.oft.gov.uk) says reform of the Pharmaceutical Price Regulatory Scheme (PPRS) would allow the NHS to re- invest £500 million in drugs it needs. Its investigation of the 50- year-old PPRS concludes that the scheme does not reflect the therapeutic value of drugs and, while providing a financial safety net for the industry, it mitigates against innovation. The OFT believes drugs should be priced according to their therapeutic value based on their cost effectiveness. Analyses would be fast- tracked for new drugs or, if there are insufficient data, a risk-sharing scheme should be adopted. The ABPI insists that its medicines offer the NHS value for money and believes the OFT's proposal for drug- by-drug pricing would delay access to new medicines. Switching saves money and is problem free Switching to cheaper alternatives within a drug class does not affect the quality of care and offers substantial savings, say UK researchers (Int J Clin Pract 2007;61:15-23). They switched selected patients from atorvastatin (Lipitor) to simvastatin and from losartan (Cozaar) to candesartan (Amias). Exclusion criteria included previous unsuccessful use, poor control of lipids or blood pressure, contraindications and potential drug interactions. In 70 patients switched to simvastatin, there was no change in mean total cholesterol after four months; one patient reverted to atorvastatin due to adverse effects. Of 115 switched to candesartan, seven reverted to losartan; in the remainder, blood pressure was slightly reduced after four months. The switch was not associated with adverse effects. Savings for the year 2005/06 were estimated at £12 716 for statins and £13 374 for antihypertensive drugs. Scotland gets donepezil for mild to moderate AD The Scottish Medicines Consortium (www.scottish medicines.org.uk) has approved the use of orodispersible donepezil (Aricept Evess) for the treatment of mild to moderate Alzheimer's disease in NHS Scotland. The decision conflicts with NICE advice that the drug is not appropriate for patients with mild disease. The SMC has not approved rimonabant (Acomplia) as adjunctive treatment for obese patients. Adherence threatens anticoagulation Patients find it difficult to adhere to anticoagulant treatment ,significantly impairing the quality of anticoagulation, US investigators have shown (Arch Intern Med 2007;167:229-35). Using electronic containers to monitor dose adherence over 32 weeks in 136 patients, they found that 92 per cent opened the container at least once too often or too little and one-third missed 20 per cent of scheduled openings. Patients with less than 20 per cent adherence were twice as likely to be undercoagulated compared with adherent patients. Those with overadherence were overcoagulated. Hypo risk greatest with glibenclamide Glibenclamide is associated with a significantly greater risk of hypoglycaemic events than other secretagogues, a new systematic review has concluded (Diabetes Care 2007;30:389-94). The review of 21 randomised trials found that the risk of experiencing at least one hypoglycaemic event was 52 per cent greater with glibenclamide compared with other secretagogues and 83 per cent greater than with other sulphonylureas. In three comparative trials with insulin, there was no significant difference in the risk of hypoglycaemia (though this could not be excluded) but only insulin was associated with weight gain. Glibenclamide was not associated with significantly increased risks of cardiovascular events, weight gain or death. Few major hypoglycaemic events were reported in these trials. Drug groups implicated in ADR admissions Four classes of drugs account for half of hospital admissions for adverse reactions, according to a new systematic review (Br J Clin Pharmacol 2007;63:136-47). Antiplatelet agents (16 per cent of admissions), diuretics (16 per cent), NSAIDs (11 per cent) and anticoagulants (8 per cent) were implicated in drug- related admissions according to a review of nine studies. Analysis of five studies also showed that adherence problems were associated with one-third of drug-related admissions. The authors suggest that focussing resources in these areas could substantially reduce admissions. Value of pharmacist MUR questioned Pharmacist medicines use review (MUR) for older patients does not reduce hospital readmission and is not cost effective by current standards, according to a study from Norfolk (Pharmacoeconomics 2007;25:171-80). A total of 872 patients aged over 80 who had been admitted as an emergency and discharged taking two or more drugs were randomised to MUR by a pharmacist or usual care. The pharmacist visited twice, providing education, removing out-of-date drugs and checking for adverse effects, interactions and the need for compliance aids. After six months, the admissions rate was not reduced among patients who received MUR and quality of life was not significantly improved. The estimated cost per QALY gained was £54 454 , above the conventional threshold for cost effectiveness of £30 000. MHRA review of LABAs The MHRA has clarified which aspects of long-acting beta-agonists (LABAs) are being addressed in its current review. This full review of salmeterol (Serevent) and formoterol, following advice issued in December last year, will consider recent research, whether the two agents differ significantly, dose-response relationships, the effect of concurrent treatment with inhaled steroid and how they are used in practice. Manufacturers have been asked to provide data by the end of March. Interventions for weight gain in schizophrenia There is not enough evidence to support the use of drugs to reduce weight gain associated with schizophrenia, a new Cochrane review has found (Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD005148. DOI: 10.1002/14651858. CD005148.pub2). Noting a lack of adequate trials, the review found that cognitive/behavioural interventions effectively prevented weight gain by a mean of 3.4kg and reduced established weight gain by a mean of 1.7kg. Drugs prevented weight gain by about 1.2kg. Switching anti-TNFs An analysis of a UK rheumatoid arthritis (RA) registry has shown that patients who stop treatment with their first anti-TNF agent should be switched to a second (Arthr Rheum 2007;56:13-20). Every UK patient with RA who receives an anti-TNF agent is included in the British Society for Rheumatology Biologics Register. Analysis of this database identified 6739 patients who started treatment, of whom 841 stopped within 15 months due to lack of efficacy and 1023 due to toxicity. Of these, 503 and 353 respectively were switched to another anti- TNF agent. Overall, 73 per cent of patients remained on their second drug by the end of follow-up, but patients were two to three times more likely to stop their second treatment for the same reason they discontinued their first. Copyright © 2007 Wiley Interface Ltd [source] ORIGINAL RESEARCH,ENDOCRINOLOGY: Pulse Pressure, an Index of Arterial Stiffness, Is Associated with Androgen Deficiency and Impaired Penile Blood Flow in Men with EDTHE JOURNAL OF SEXUAL MEDICINE, Issue 1 2009Giovanni Corona MD ABSTRACT Introduction., Pulse pressure (PP; i.e., the arithmetic difference between systolic and diastolic blood pressure) reflects arterial stiffness and has been suggested to be an independent cardiovascular risk factor. Aim., The aim of the present study is to asses the possible contribution of PP to arteriogenic erectile dysfunction (ED) and ED-associated hypogonadism. Methods., A consecutive series of 1,093 (mean age 52.1 ± 13.0 years) male patients with ED and without a previous history of hypertension or not taking any antihypertensive drugs were investigated. Main Outcome Measures., Several hormonal and biochemical parameters were studied, along with structured interview on erectile dysfunction (SIEDY), ANDROTEST structured interviews, and penile Doppler ultrasound. Results., Subjects with higher PP quartiles showed worse erectile function and higher prevalence of arteriogenic ED even after adjustment for confounding factors. Furthermore, sex hormone binding globulin-unbound testosterone levels declined as a function of PP quartiles. Accordingly, the prevalence of overt hypogonadism (calculated free testosterone < 180 pmol/L or free testosterone < 37 pmol/L) increased as a function of PP quartiles (17.% vs. 39.7%, and 30.8% vs. 58.6% for the first vs. fourth quartile, respectively, for calculated free testosterone and free testosterone; all P < 0.0001 for trend). This association was confirmed even after adjustment for confounders (Adjusted [Adj]) r = 0.090 and 0.095 for calculated free testosterone < 180 pmol/L and free testosterone < 37 pmol/L, respectively; all P < 0.05). Conclusions., PP is an easy method to estimate and quantify patient arterial stiffness. We demonstrated here for the first time that elevated PP is associated with arteriogenic ED and male hypogonadism. The calculation of PP should became more and more familiar in the clinical practice of health care professionals involved in sexual medicine. Corona G, Mannucci E, Lotti F, Fisher AD, Bandini E, Balercia G, Forti G, and Maggi M. Pulse pressure, an index of arterial stiffness, is associated with androgen deficiency and impaired penile blood flow in men with ED. J Sex Med 2009;6:285,293. [source] Perception of risk of adverse drug reactions by medical students: influence of a 1 year pharmacological courseBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2007G. Durrieu What is already known about this subject ,,Previous studies have pointed out the question of effective training and information for health professionals on adverse drug reactions (ADRs). ,,This lack of training is known to induce inadequate use of drugs and noncompliance of patients. What this study adds ,,Our study was the first to evaluate the perceived risk of ADRs among young medical students and to investigate the impact of university pharmacology courses on their perception of this risk. ,,The aim of our study was not to assess a definite level of perception of risk for the different drug classes but to determine whether the perceived risk of ADRs differs after attending pharmacology courses. ,,Our results show that the pharmacological training allows young medical students to be aware of potentially serious ADRs, especially related to drugs considered as relatively safe, such as NSAIDs and aspirin. Aims To investigate how adverse drug reactions (ADRs) to several classes of drugs are perceived by young medical students before and after a 1 year pharmacology course. Methods The whole cohort of 92 medical students (63 females and 29 males) was questioned during their third year. A visual analogue scale was used to define a score (ranging from 0 to 10) of perceived risk of ADRs associated with each drug class before and at the end of the pharmacological training period. Results Before the pharmacology course, hypnotics were ranked as the most dangerous drugs by the medical students, followed by antidepressants and anticoagulants. Contraceptive pills were listed in the last position. After pharmacological training, antidepressants moved into the first position, followed by anticoagulants and hypnotics. When all different drug classes were taken as a whole, the mean (±SD) of median scores of the perceived risk were 4.8 (±1.3) before and 5.8 (±1.5) at the end of the pharmacology course (P < 0.0001). Except for antidiabetics, antihypertensive drugs, tranquillizers, corticosteroids and hypnotics, the perceived risk significantly increased after the pharmacology course for the other drugs. The highest increases were observed for contraceptive pills (+104%, P < 0.01), NSAIDs (+86%, P < 0.01) and aspirin (+56%, P < 0.01). Conclusions Pharmacological training allows young medical students to be aware of potentially serious ADRs associated with drugs, in particular with drugs considered relatively safe (such as NSAIDs and aspirin) by nonhealth professionals. [source] Pharmacogenetic interactions of three candidate gene polymorphisms with ACE-inhibitors or ,-blockers and the risk of atherosclerosisBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2007H. Schelleman What is already known about this subject ,,To our knowledge, there are no prior studies which investigate whether there is a drug,gene interaction between the three genes involved in the renin,angiotensin system and ACE-inhibitor therapy or ,-blocker therapy with these subclinical measurements of atherosclerosis. ,,Some studies have found an effect on blood pressure or stroke/myocardial infarction, although the results are not conclusive. What this study adds ,,The results do not indicate the presence of a strong drug,gene interaction between the use of ACE-inhibitors or ,-blockers and the ACE insertion/deletion, AGT M235T or AGTR1573C/T polymorphism on the overall risk of atherosclerosis. Aims To investigate whether the angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen M235T or angiotensin II receptor type 1 573C/T polymorphism modify the risk of atherosclerosis associated with ,-blocker or ACE-inhibitor therapy. Methods Data were used from the Rotterdam Study, a population-based prospective cohort study in the Netherlands, which started in 1990 and included 7983 subjects of , 55 years. In this study, 2216 subjects with hypertension were included. Three subclinical measurements were used for atherosclerosis, i.e. peripheral arterial disease, carotid atherosclerosis and aortic atherosclerosis. The interaction between antihypertensive drugs and genetic polymorphisms on the risk of atherosclerosis was determined with binary logistic regression analysis. Results The risk of aortic atherosclerosis associated with long-term (,4 years) ,-blocker treatment compared with no use of ,-blockers was higher in subjects with the TT genotype than in subjects with the MM genotype of the AGT gene [synergy index (SI) = 3.36; 95% confidence interval (CI) 1.14, 9.97]. The risk of carotid atherosclerosis associated with long-term ACE-inhibitor treatment compared with no use of ACE-inhibitors was lower in subjects with the TT genotype than in subjects with the MM genotype of the AGT gene (SI = 0.20; 95% CI 0.04, 0.95). Conclusion Overall, the risk of atherosclerosis in hypertensives taking a ,-blocker or ACE-inhibitor-based regimen was not strongly modified by any of the three candidate gene polymorphisms. [source] Increased baroreflex sensitivity and heart rate variability in migraine patientsACTA NEUROLOGICA SCANDINAVICA, Issue 6 2009K. B. Nilsen Objectives,,, We investigated whether spontaneous baroreflex sensitivity and heart rate variability (HRV) are different in migraine patients compared to healthy controls. Material and methods,,, Sixteen female migraine patients without aura aged 18,30 years and 14 age-matched healthy female controls were included. Continuous finger blood pressure and ECG were measured supine during paced breathing in the laboratory. Continuous finger blood pressure was measured the following 24-h period. Spontaneous baroreflex sensitivity (time-domain cross correlation baroreflex sensitivity) as well as HRV parameters were calculated. Results,,, Spontaneous baroreflex sensitivity measured in the 24-h period was increased in patients (20.6 ms/mmHg) compared to controls (15.7 ms/mmHg, P = 0.031). HRV parameters were increased during paced breathing in patients (P < 0.045). Conclusions,,, The results suggest that central hypersensitivity in migraine also includes cardiovascular reactivity and may be important for the understanding of the mechanisms for the effect of antihypertensive drugs for migraine prophylaxis. [source] Antihypertensive Drugs and New-Onset Diabetes: A Retrospective Longitudinal Cohort StudyCARDIOVASCULAR THERAPEUTICS, Issue 3 2009Gwo-Ping Jong Antihypertensive drugs have been linked to new-onset diabetes (NOD); however, data on the effect of these drugs on the development of NOD in hypertensive patients has not been well determined. We aimed to investigate the association between antihypertensive drugs and NOD. This was a retrospective cohort study performed using data from claim forms provided to the central region branch of the Bureau of National Health Insurance in Taiwan from January 2002 to December 2007. Prescriptions for antihypertensive drugs before the index date were retrieved from a prescription database. We estimated the odds ratios (ORs) of NOD associated with antihypertensive drug use; nondiabetic subjects served as the reference group. A total of 4233 NOD cases were identified in 24,688 hypertensive patients during the study period. The risk of NOD after adjusting for sex and age was higher among users of diuretics (OR = 1.10, 95% confidence interval [CI]= 1.01,1.20), beta-blockers (BBS; OR = 1.12, 95% CI = 1.04,1.21), and calcium channel blockers (CCBs; OR = 1.10, 95% CI = 1.02,1.18) than among nonusers. Patients who take angiotensin-converting enzyme (ACE) inhibitors (OR = 0.92, 95% CI = 0.84,1.00), angiotensin receptor blockers (ARB; OR = 0.90, 95% CI = 0.81,0.98), or alpha-blockers (OR = 0.88, 95% CI = 0.80,0.98) are at a lower risk of developing NOD than nonusers. Vasodilators were not associated with the risk of NOD. The results of this study suggest that hypertensive patients who take ACE inhibitors, ARBs, or alpha-blockers are at a lower risk of NOD. Diuretics, BBs, and CCBs were associated with a significant increase in the risk of NOD. [source] |