Effects Of Antihypertensive Medications Research Articles

Comparison of angiotensin II receptor blockers: impact of missed doses of candesartan cilexetil and losartan in systemic hypertension

Blood pressure remains poorly controlled in the hypertensive population due in large part to low or unsatisfactory patient compliance. Clinical studies that incorporate an intentionally missed dose have been designed to evaluate the impact of poor patient compliance on the effectiveness of antihypertensive medications. In these studies, ambulatory blood pressure monitoring is continued throughout the dosing interval and beyond in order to determine when systolic and diastolic blood pressure increase into the hypertensive range. In an 8-week, randomized, double-blind, placebo-controlled trial in patients with mild-to-moderate hypertension, the antihypertensive effects of candesartan cilexetil 16 mg were maintained after a missed dose, whereas systolic and diastolic blood pressure increased toward baseline levels after a missed dose of losartan 100 mg. Candesartan cilexetil provided a significantly greater reduction in sitting systolic (p = 0.004) and diastolic blood pressure (p = 0.008) than losartan when measured 48 hours after the last dose. Moreover, the homogeneity of antihypertensive effects was greater after candesartan cilexetil than losartan based on calculation of the smoothness index from ambulatory systolic and diastolic measurements during the first 24-hour period after dosing and during the 12-hour period after the missed dose. These results demonstrate that missing or delaying a dose of candesartan cilexetil has less impact on antihypertensive efficacy than missing or delaying a dose of losartan.

Subjective Sleep Quality during Treatment with Two Different Antihypertensive Medications

Objective: Only a few studies have addressed the effect of antihypertensive medication on the quality of sleep and sleep apnoea. Therefore, we evaluated the subjective sleep quality of hypertensive patients using self-administered questionnaires (in particular factors reflecting sleep apnoea and snoring) when treated with either metoprolol, a β-blocking agent, or isradipine, a calcium antagonist.

Ambulatory blood pressure monitoring. Application to clinical medicine and antihypertension medication trials.

The wide use of ABPM has resulted in greater appreciation of the circadian time structure of BP variability and its clinical relevance. It is now recognized that the day-night change in BP results from an interplay of circadian rhythms in neurohumoral mechanisms coupled with temporal patterns in physical activity and mental load. The composite effect and balance of these endogenous and exogenous cyclic phenomena give rise to elevated BP during diurnal activity and reduced BP during nighttime repose in both normotension and uncomplicated essential hypertension. The balance is frequently disturbed in complicated and secondary forms of hypertension causing gross alteration of the 24-hour BP profile. ABPM also reveals the efficiency of antihypertensive treatment throughout the 24 hours and as a function of drug administration time. The pharmacokinetics and/or pharmacodynamics of antihypertensive medications have been demonstrated to vary with ingestion time. Such time-dependencies arise from circadian rhythms in BP and underlying mechanisms. The effect of antihypertensive medications is not simply superimposed upon endogenous bioperiodicities. Rhythms in neurohumoral mechanisms of BP control may modulate treatment effect. Certain aspects of the shape of the 24-hour BP profile, such as the magnitude of the morning surge and nocturnal decrease, have been implicated as determinants of morbid and mortal cardiovascular events. One large clinical multicenter investigation, known as the CONVINCE (Controlled Onset Verapamil Investigation of Clinical Endpoints) trial, is aimed at assessing the impact (cardiovascular morbidity and mortality) of verapamil chronotherapy over standard diuretic or beta anatagonist treatment in hypertensive patients with at least one risk factor of coronary heart disease. ABPM will help ascertain to what extent depression of the morning surge in BP relates to reduction in cardiac morbidity and mortality in this as well as other such trials. In any event, the importance of ABPM and the indices derived from its application are just beginning to be appreciated and explored.

Stroke incidence with hypertension and ischemic heart disease in Rochester, Minnesota.

The primary contribution to increased incidence rates for ischemic stroke in Rochester, Minnesota, for the 1980 to 1984 time period in the age groups from 55 to 84 years was from those persons in the population with ischemic heart disease. The rate and pattern of the decline in incidence rates of ischemic stroke in hypertensive individuals and in nonhypertensive individuals were quite similar, showing no demonstrable population effect of antihypertensive medication. These observations emphasize that there must be some, as yet unidentified, factor that is important in the decline of stroke incidence.

Renal effects of antihypertensive medications: an overview.

A variety of antihypertensive agents are available for management of elevated arterial pressure. Although these agents all effectively lower arterial pressure, they have somewhat diverse renal hemodynamic profiles. This report reviews the various similarities and differences in renal hemodynamic profiles among the different antihypertensive agents.

Renal toxicity of the nonsteroidal anti-inflammatory drugs.

NSAIDs pose little threat of renal insult in normal, healthy persons at therapeutic dosages. However, NSAID administration to susceptible persons may cause decrements in renal plasma flow and glomerular filtration rate within hours. Such acute noxious renal effects are mediated by products of arachidonic acid metabolism. Precipitous decrements in glomerular filtration and renal ischemia, manifested by increased serum creatinine and urea nitrogen, are possible. However, these effects are usually fully reversible with prompt discontinuation of the offending NSAID. Risk factors for the development of these acute renal effects are known. Acute interstitial nephritis with or without nephrotic syndrome is a rare form of renal toxicity that typically occurs between 2-18 months of use. Renal impairment may be so severe as to require temporary hemodialysis; however, renal function usually returns to normal upon discontinuation of the NSAID. The mechanism of acute interstitial nephritis is presumed to be of allergic origin but could also be caused by a reactive metabolite. Fenoprofen use appears to be associated with a much higher risk for its development. In contrast to the acute effects of NSAIDs, irreversible, analgesic-associated nephropathy manifested by papillary necrosis and chronic interstitial nephritis may occur following months to years of high doses of analgesic mixtures. The mechanism by which combination analgesics produce this form of renal injury is unknown and could be either a result of medullary ischemia or a direct effect of a reactive metabolite. An important issue to be resolved is the relationship between the acute, reversible, prostaglandin-mediated renal effects of the NSAIDs and chronic, irreversible destruction, if such a relationship exists. Theoretically, continual or repeated decrements in renal function in patients with predisposing risk factors could cause or contribute to progressive deterioration in renal function. Elevations in blood pressure or interference with the effects of antihypertensive medications could theoretically also contribute to long-term renal deterioration. In addition to renal syndromes caused by NSAIDs that result in renal impairment, other transient effects on electrolyte and water metabolism may also occur. Reduced secretion of sodium may result in formation of edema, exacerbation of heart failure, or increased blood pressure. Hyporeninemic-hypoaldosteronism may produce hyperkalemia. Finally, reduced excretion of water has rarely caused hyponatremia. It has been suggested that NSAIDs may be renoprotective in patients with nephrotic syndrome. Others have suggested that sulindac is "renal-sparing" because of a unique metabolic pathway that supposedly limits the exposure of the kidney to the active sulfide metabolite.(ABSTRACT TRUNCATED AT 400 WORDS)

Longitudinal prediction of adult blood pressure from juvenile blood pressure levels.

The link between blood pressure measured at juvenile ages (3-18 years) and subsequent adult ages (30 and 50 years) was investigated in a community-based longitudinal study conducted in the San Francisco Bay Area from 1928 to the present. The original sample of 550 persons decreased 61 percent by age 50 years, leaving only 211 persons in the cohort. Blood pressure was measured annually up to age 18 years and each decade thereafter, providing a unique opportunity to link childhood and adult blood pressures over periods of up to 50 years. Juvenile blood pressure measured from age 6 years onward was a positive predictor of blood pressure at age 30 years. Blood pressure measured at age 50 years was predicted best by juvenile pressures measured at early school age and early puberty. The juvenile-adult blood pressure association was partly explained by controlling for smoking and parental history of cardiovascular disease, but was not explained by controlling for juvenile height or body mass. It was stronger in children from blue collar families. The reported correlations probably represent an underestimation of the true strength of the association because of a greater loss to follow-up among subjects with higher blood pressure and the effects of antihypertensive medication in adulthood.

The Effects of Antihypertensive Medications on the Physiological Response to Maximal Exercise Testing

The Effects of Antihypertensive Medications on the Physiological Response to Maximal Exercise Testing

The Effects of Antihypertensive Medications on the Physiological Response to Maximal Exercise Testing

This study compared the effects of clinically prescribed doses of cilazapril, nifedipine, and atenolol on maximal exercise performance in physically active subjects. In a double-blind crossover trial, 10 healthy male volunteers performed progressive aerobic exercise to exhaustion for determination of maximal oxygen consumption (VO2 max), after single dose ingestion of cilazapril, nifedipine, atenolol, and placebo. Measurements were made at exhaustion and at a single submaximal workload (250 W). Exercise time to exhaustion and peak workload were decreased by all agents (p less than 0.05 vs. placebo), but VO2 max was decreased by atenolol only (p less than 0.05 vs. placebo). Although both atenolol and cilazapril decreased the maximum systolic blood pressure, the peak heart rate was decreased only by atenolol (p less than 0.001 vs. placebo). Whereas submaximal oxygen consumption, minute ventilation, and blood lactate concentrations were not different between groups, ratings of perceived exertion were increased during submaximal exercise by atenolol and cilazapril (p less than 0.05 vs. placebo). Cilazapril, nifedipine, and atenolol all impaired exercise performance and increased ratings of perceived exertion during submaximal exercise without altering rates of oxygen consumption or blood lactate accumulation. Maximal exercise performance was impaired to a greater extent by atenolol than by nifedipine or cilazapril. This study suggests that either angiotensin-converting enzyme inhibitors or calcium-channel antagonists might be preferable for the management of hypertension in athletic patients as they have a lesser effect on exercise performance, at least in healthy individuals.

167. Effect of antihypertensive medication on endurance exercise capacity in sporting hypertensive patients

167. Effect of antihypertensive medication on endurance exercise capacity in sporting hypertensive patients

Assessing the Effects of Antihypertensive Medication on Cerebral Blood Flow: Demonstration in Internal Carotid Artery Occlusion

Dynamic cerebral blood flow (CBF) studies using acetazolamide or hypercapnia as a vasodilatory challenge have attempted to evaluate intracranial hemodynamics. We report two patients with asymptomatic internal carotid artery occlusion in whom the vasodilatory stimulus was a single oral dose of antihypertensive medication (prazosin hydrochloride or enalapril maleate). In both patients, changes in regional CBF occurred that were larger than those seen in nine normal controls. One patient experienced an improvement in regional CBF with a reduction in probe pair asymmetry. In the other patient, who had bilateral carotid artery disease, a decrease in regional CBF in all 16 probes (mean decrease 12 percent) and an accentuation of the predose asymmetry were observed. Both patients remained asymptomatic throughout the study. Assessing these effects on cerebral circulation may help identify patients at risk for iatrogenic focal cerebral ischemia and provide information regarding the functional status of the cerebral vasculature.

167. Effect of antihypertensive medication on endurance exercise capacity in sporting hypertensive patients

167. Effect of antihypertensive medication on endurance exercise capacity in sporting hypertensive patients

Mechanical factors in large artery disease and antihypertensive drugs

Hypertension may induce early alterations in large arteries by 2 mechanical stresses: one related to intravascular pressure, the other to blood flow dynamics. Distending pressure force acts in a circumferential direction, inducing decreased arterial distensibility. Arterial distensibility can be evaluated in humans by measurement of arterial compliance and pulse-wave velocity. It is well established that in chronic hypertension age and elevated pressure act together to increase arterial rigidity. Blood flow dynamics induce frictional forces in the endothelial surfaces of arteries. These forces, expressed by shear stress, are proportional to the viscosity of the blood and to the velocity gradient at the arterial wall. Measurement of blood viscosity and evaluation of velocity profile in the brachial arteries of hypertensive subjects have shown a reduction in wall shear rate and stress despite the elevation in blood viscosity. Several studies have shown that drug therapy that successfully reduces blood pressure does not necessarily improve arterial compliance. In contrast, few data are available on the effects of antihypertensive medication on arterial wall shear in humans. Arterial compliance and wall shear stress are 2 main therapeutic targets of potential importance in the physiopharmacologic approach to the effects of hypertension on atherogenesis.

Hypertensive black men and women. Quality of life and effects of antihypertensive medications. Black Hypertension Quality of Life Multicenter Trial Group

A multicenter, randomized double-blind clinical trial was conducted among 306 black men and women with mild to moderate hypertension to determine effects of atenolol, captopril, and verapamil SR on measures of quality of life. Patients were randomly assigned to a stable or forced-dose titration sequence. After an 8-week treatment period, the rate of withdrawal from treatment because of adverse effects was low and did not differ by drug treatment group or titration level. Patients taking verapamil SR showed a significantly greater reduction in mean blood pressures than patients treated with atenolol or captopril. Along with absence of worsening on any quality of life total scale scores examined over the treatment period, we found either improvement or no change in the total scale scores for all three treatment groups. Among both male and female patients, comparisons between drug treatment groups showed no differences in degree of change on the total scale scores. In comparisons within each treatment group, improvement in scores of male patients after 8 weeks appeared among those taking atenolol in general well-being and physical symptoms reduction; among male patients taking captopril in general well-being, physical symptoms, and sexual performance; and among male patients receiving verapamil SR in scores in irritability, sleep, and the Digit Span test. Improvement in scores among female patients taking atenolol was found in scores on general well-being, physical symptoms, and sleep; among women taking captopril on general well-being, physical symptoms, and irritability; and among women taking verapamil SR on general well-being. Patients in all treatment groups improved on measures of visuomotor functioning. The research shows that with the three newer generation antihypertensive medications studied, blood pressure control was achieved during the treatment period without negative effects on quality of life scales, along with findings of improvement on some measures. Given the special clinical features of hypertension in black patients, the study underlines as well the potential and utility of systematic tracking of measures of quality of life, while monitoring blood pressures in this patient population.

Antihypertensive Therapy and Coronary Prevention

Antihypertensive therapy reduces cardiovascular risk in patients with malignant hypertension, but has not yet been shown to reduce risk in patients with mild to moderate hypertension. The lack of significant coronary prevention in the latter group, in large-scale trials, may have resulted from methodologic problems, statistical limitations, the adverse effects of antihypertensive medications, or failure to recognize the prognostic importance of concomitant regression of left ventricular hypertrophy. To date, primary prevention studies have focused on the use of beta-blockers and diuretics, both of which may have adverse metabolic effects and neither of which is capable of modifying left ventricular hypertrophy. Future research should be directed toward evaluating coronary prevention in patients with nonmalignant hypertension who have been treated with newer agents, such as calcium channel blockers and angiotensin-converting enzyme inhibitors, each of which has been shown to regress left ventricular hypertrophy and not to have adverse metabolic effects.

The effect of antihypertensive medications on exercise performance

This review describes the effects of antihypertensive drugs on the performance of aerobic exercise. All available antihypertensive drugs lower blood pressure both at rest and decrease the rate of increase during exercise. However, they differ in their effects on exercise performance. The ideal antihypertensive agent should not have significant depressant effects on the myocardium, should not promote arrhythmias, should preserve the distribution of blood flow to exercising muscle, and should not interfere with substrate utilization. Diuretics, one of the most commonly prescribed class of antihypertensives, have few deleterious effects on exercise performance but have adverse metabolic effects; beta blockers have many adverse effects on exercise performance. Agents which have the least potential for adverse effects on exercise performance and metabolic effects are the converting enzyme inhibitors, calcium channel blockers, and alpha blockers, and central alpha agonists. The literature concerning each of these drugs is reviewed and recommendations are made for prescribing for the hypertensive who wishes to engage in vigorous exercise.

Evaluation of the cerebral effects of antihypertensive medication.

Evaluation of the cerebral effects of antihypertensive medication.

HYPERTENSIVES HAVE HIGHER "WELL-BEING" SCORES WITH CAPTOPRIL.

To determine the effects of antihypertensive medications on quality of life, investigators conducted a randomized, double-blind trial in 626 men with mild to moderate hypertension. Subjects received either captopril, methyldopa, or propranolol for 24 weeks. General …

Effect of antihypertensive medications on physical work capacity

Effect of antihypertensive medications on physical work capacity

Effects of antihypertensive medication on the cardiovascular response to ketamine in rats.

The effects of hydralazine, clonidine, propranolol and methyldopa medications on the cardiovascular response to ketamine anaesthesia were studied in spontaneously hypertensive (SH) rats. Except in propranolol- and methyldopa-treated animals, blood pressure was increased by ketamine in all groups. The heart rate was increased only in the normotensive control rats, whereas it was reduced in both the unmedicated and all of the medicated SH rats. Plasma renin activity under ketamine anaesthesia was markedly higher in normotensive control rats than in any of the SH groups. The pressor responses to dopamine and metaraminol were not altered by propranolol medication, but hydralazine suppressed these responses, while they were markedly intensified by clonidine and methyldopa treatment. Similarly, small additional doses of ketamine caused a pressor response only in clonidine- and methyldopa-treated animals, whereas in the other groups the response was depressive. The tolerance to haemorrhagic shock during ketamine anaesthesia was notably improved by hydralazine and methyldopa medication, but impaired by propranolol treatment. The results suggest that, with special reference to shock tolerance, hydralazine and methyldopa, and to a lesser extent also clonidine, have a favourable effect on the circulation under ketamine anaesthesia, whereas the action of beta-blockade may be harmful.