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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent reports have confirmed that some slow calcium channel inhibitors have useful antihypertensive properties because they produce dilatation of the peripheral arterioles without reflex tachycardia. Verapamil is such a drug, but its clinical role in the management of hypertension is not clear. An open crossover trial was performed to compare the 24-hour profiles of blood pressure reduction after long-term therapy with a standard beta-adrenoceptor blocker, propranolol, and verapamil. Nineteen patients were studied by continuous ambulatory intraarterial recording and the order of drug administration was determined by random allocation. The drugs were administered 2 times a day and titrated according to casual clinic pressures (propranolol, 40 to 240 mg 2 times a day; verapamil, 120 to 240 mg 2 times a day). Mean hourly blood pressure and heart rate values were obtained over a 24-hour cycle and the responses to isometric and dynamic exercise were also examined. The drugs produced a uniform and comparable reduction in blood pressure throughout the day, together with a reduction in heart rate, which was greater with propranolol. Comparable effects were also seen on the pressor responses to exercise. Both drugs were equally well tolerated and caused no patient withdrawals. Thus, oral verapamil given 2 times a day shows a degree of efficacy similar to that of propranolol and provides 24-hour blood pressure control. This slow calcium channel inhibitor was well tolerated and may be used as initial therapy for hypertension.
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PMID:Twice-daily verapamil for hypertension: a comparison with propranolol. 351 19

We compared verapamil and propranolol hydrochloride for monotherapy of hypertension. Verapamil lowered blood pressure (BP) more effectively than propranolol in black and white patients. Verapamil was equally effective in blacks and whites, whereas propranolol was more effective in whites. Heart rate was reduced by 6.0 beats per minute by verapamil, and by 13.6 beats per minute by propranolol. In blacks, verapamil lowered systolic BP 16.9 vs 8.1 mm Hg for propranolol; verapamil reduced diastolic BP 12.8 vs 8.6 mm Hg for propranolol. In whites, verapamil lowered systolic BP 19.0 vs 12.7 mm Hg for propranolol; verapamil reduced diastolic BP 16.7 vs 12.3 mm Hg for propranolol. Increases in systolic BP were observed in 22% and 3.4% of patients receiving propranolol and verapamil, respectively. The PR interval was increased from 163.5 to 174.9 ms for verapamil vs 160.3 to 164.4 ms for propranolol. Constipation (15%) and headaches (10%) were most frequent complaints for verapamil vs fatigue (18%) and dizziness (7%) for propranolol. Changes in blood biochemistry values were of small magnitude. We conclude that verapamil monotherapy is a safe and effective means of achieving BP control in patients with essential hypertension.
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PMID:A comparison of verapamil and propranolol for the initial treatment of hypertension. Racial differences in response. 353 60

The calcium antagonists diltiazem, nifedipine and verapamil are widely used in the treatment of coronary heart disease, arterial hypertension, certain supraventricular tachyarrhythmias and obstructive hypertrophic cardiomyopathy. During recent years their pharmacokinetic properties and metabolism have been studied in more detail. Although these 3 calcium antagonists exhibit great diversity in chemical structure, they exhibit common pharmacokinetic properties. These drugs are extensively metabolised and only traces of unchanged drugs are eliminated in urine. Their systemic plasma clearances are high and dependent on liver blood flow. Therefore, their bioavailabilities (diltiazem 40 to 50%; nifedipine 40 to 50%; verapamil 10 to 30%) are low despite almost complete absorption following oral administration. During long term treatment, oral clearance decreases and bioavailability increases due to saturation of hepatic first-pass metabolism. Pronounced intra- and inter-individual variations in clearance and bioavailability are observed. In patients with liver cirrhosis the various pharmacokinetic parameters are grossly altered. Clearance decreases, elimination half-life is substantially prolonged, and bioavailability more than doubles. In addition, the volume of distribution increases. Whereas renal disease has no impact on the pharmacokinetics of diltiazem and verapamil, elimination half-life of nifedipine increases in relation to the degree of renal impairment due to an increase in volume of distribution. Systemic clearance, however, remains unchanged. The data so far available indicate that the plasma concentrations of these drugs correlate with both their electrophysiological and haemodynamic effects. However, no effective therapeutic plasma concentration range has been firmly established. As reliable clinical end-points are available for dose titration of calcium antagonists, it is doubtful whether therapeutic drug monitoring will be of great value. Calcium antagonists are often administered in combination with a variety of other drugs. Thus, the potential for both pharmacodynamic and pharmacokinetic drug interaction exists. The interaction between digoxin and these drugs is of clinical importance. Verapamil and diltiazem cause a significant increase in plasma digoxin concentrations. In contrast, nifedipine does not lead to a significant increase in the plasma digoxin concentration. The mechanism responsible for this interaction is inhibition of both renal and non-renal digoxin clearance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacokinetics of verapamil, nifedipine and diltiazem. 354 36

In a single-blind, placebo-controlled crossover study the effects of verapamil (450 +/- 30 mg/day) and propranolol (160 +/- 20 mg/day) on endurance time during submaximal exercise were compared in eight patients with essential hypertension. The drugs were given in randomized order. Each active drug period was preceded by a placebo phase. Endurance tests were performed during both placebo periods and treatment with verapamil and propranolol by bicycle ergometry. Both drugs were equally effective in decreasing resting blood pressure. Verapamil and propranolol reduced exercise heart rate, the effect of propranolol being more pronounced. With placebo, endurance time during exercise was 57 +/- 11 minutes; with propranolol it was 32 +/- 7 minutes (P less than 0.05). Verapamil had no influence on endurance time. The study demonstrates that in contrast to propranolol, verapamil has no influence on exercise tolerance during submaximal work in patients with hypertension.
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PMID:The effects of verapamil and propranolol on exercise tolerance in hypertensive patients. 355 58

Hypersensitivity reactions to heparin preparations with a wide spectrum of clinical manifestations have been reported frequently in the past, but are a rarity now. A 88 year old man was admitted for physical therapy of a collum femoris fracture. Treatment with a diuretic, Reserpine and Verapamil was continued. Chest x-ray revealed a large thoracic aortic aneurysm. From the 12th to the 18th day of low dose heparin prophylaxis with calcium heparin, 7500 U twice daily, at least eight attacks of asthma or cyanosis were observed, starting about two hours after heparin injection. The last attack began suddenly with wheezing, tachypnoea and cough and was associated with apprehension, a sudden blood pressure increase and severe cyanosis. Ventilation improved with oxygen and a beta 2-stimulator, but hypertension and cyanosis lasted for three hours. After discontinuation of heparin no further attacks occurred. Causes other then heparin could not be found. Despite the use of porcine mucosa heparin, avoidance of preservatives and use of low doses a hypersensitivity reaction occurred in our case. The delayed onset after preceding subcutaneous application as well as difficulties in separating the reaction from complications of underlying disease may delay heparin discontinuation.
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PMID:[Asthma attacks in low-dose preventive use of heparin in a male with femoral neck fracture and aortic aneurysm]. 366 60

We studied verapamil pharmacodynamics and disposition in seven young, ten elderly, and seven very elderly hypertensive males. Maximal decrease in mean (+/- SD) blood pressure tended to be greater in the elderly (-13.5 +/- 5.9 mm Hg) and the very elderly patients (-15.9 +/- 9.6 mm Hg) compared with that in young patients (-7.3 +/- 4.2 mm Hg). Disparate effects on heart rate responses were noted with reflex tachycardia in young patients compared with decreases in heart rate among the elderly and very elderly. Sensitivity to verapamil-induced prolongation in electrocardiographic P-R interval was less in the very elderly, and maximal prolongation in P-R interval induced by verapamil was less in the elderly and very elderly. Verapamil disposition was also age related. Total verapamil clearance was decreased in elderly (10.5 +/- 3.5 mL/min X kg; p less than 0.05) and very elderly (8.0 +/- 4.1 mL/min X kg; p less than 0.01) when compared with that in young patients (15.5 +/- 4.5 mL/min X kg). Elimination half-life was prolonged in the elderly (7.4 +/- 3.3 h; p less than 0.01) and very elderly (8.0 +/- 1.2 h; p less than 0.01) compared with that in young patients (3.8 +/- 1.1 h). Our data indicate age- and hypertension-related physiologic changes result in predictable pharmacokinetic changes. However, the complex alterations in verapamil pharmacodynamic responses indicate an interaction between direct drug effects and age- and disease-related changes in hemodynamic and autonomic nervous system function.
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PMID:Verapamil pharmacodynamics and disposition in young and elderly hypertensive patients. Altered electrocardiographic and hypotensive responses. 374 Jun 73

Verapamil is a racemic mixture of two optical isomers, the (-)-form being the more active component. Recent studies indicate a rapid hepatic transformation of (-)-verapamil, which results in different concentration-effect relationships after oral and intravenous administration. In practice the important pharmacokinetic properties of verapamil are low bioavailability (20%), predominant elimination by metabolism (greater than 95%) and a relatively short half-life (t1/2, beta is 3-5 h). After repeated dosing, the rate of hepatic drug clearance seems to decrease. Slow release (SR) formulations of verapamil may offer certain therapeutic advantages during long-term treatment. A comparison of conventional (C) and SR tablets in a 1-week treatment of eight cardiac patients showed a relative bioavailability (AUCSR/AUCC) of 90 +/- 30%. More stable serum drug levels were maintained by 12-hourly administration of SR verapamil. A further study using a new 240 mg SR preparation in patients with arterial hypertension showed that even a single daily dose can be sufficient for adequate blood pressure control over 24 h.
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PMID:Pharmacokinetics of conventional and slow-release verapamil. 375 58

Calcium ion (Ca++) serves an important role as an activation messenger; it initiates or regulates key cellular processes including contraction in the heart and vascular smooth muscle. Ca++ acts as both an electrical and a chemical signal. Upon entering the cell, the positively charged Ca++ carries an inward (depolarizing) current that contributes to pacemaker activity in the sinoatrial node and to atrioventricular conduction. Ca++ also binds to anionic surfaces of cell membranes and to anionic groups of both extracellular and intracellular proteins. The intracellular calcium-binding proteins include troponin and calmodulin, which when bound to Ca++ initiate contraction in cardiac and smooth muscles, respectively. Calcium channel blockers inhibit the entry of calcium into the cell, and thus prevent calcium from gaining access to the high-affinity, intracellular calcium-binding proteins. Verapamil and diltiazem decrease myocardial contractility and inhibit smooth muscle tone, while the dihydropyridines are mainly vasodilators. All of these drugs can play an important role in the treatment of hypertension.
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PMID:Mechanisms of action and differences in calcium channel blockers. 376 7

The effects of intravenous verapamil administration (0.1 mg/kg as a bolus followed by an infusion of 0.007 mg/kg/min) were studied using high-temporal-resolution radionuclide angiography in 27 patients with hypertension. Verapamil administration increased heart rate from 69 +/- 11 to 75 +/- 12 beats/min (p less than 0.001) and decreased systolic, diastolic and mean blood pressures (BPs) from 155 +/- 21/102 +/- 12 mm Hg (mean 119 +/- 14) to 142 +/- 19/95 +/- 12 mm Hg (mean 109 +/- 13) (p less than 0.001 for all). Ejection fraction decreased significantly (from 65 +/- 10% to 60 +/- 11%, p less than 0.005); peak filling rate, however, increased significantly only in patients in whom it was subnormal in the basal study (from 2.2 +/- 0.4 to 3.0 +/- 0.6 end-diastolic counts/s, p less than 0.001). These latter patients had significantly higher values of left ventricular (LV) mass index than patients with normal or increased peak filling rate (129 +/- 22 vs 112 +/- 22 g/m2, respectively, p less than 0.05). The isovolumic relaxation period changes were inversely related to the baseline values (r = 0.83, p less than 0.001). In the subgroup of patients in whom isovolumic relaxation period lengthened, time to end systole decreased (from 360 +/- 31 to 329 +/- 30 ms, p less than 0.025) and time to onset of rapid filling increased (from 420 +/- 31 to 451 +/- 34 ms, p less than 0.025), whereas these 2 intervals had opposite patterns in patients in whom isovolumic relaxation period decreased or did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of intravenous verapamil administration on left ventricular diastolic function in systemic hypertension. 382 3

Male Wistar rats with one-kidney, one clip renal hypertension were maintained on either a regular or a low salt diet for 3 weeks after clipping. At that time mean blood pressure in the unanesthetized rats was equally elevated in sodium-depleted (n = 17) and in sodium-replete rats (n = 19), but plasma renin activity was significantly higher in the former (p less than 0.05). Infusion of the calcium entry blocker verapamil at a rate of 0.05 mg/kg/minute decreased blood pressure within 60 minutes to a similar extent in rats kept on a salt-deficient diet and in rats fed a regular salt diet. In all rats taken as a group, there was a close, direct correlation (r = 0.87, p less than 0.001) between the magnitude of the blood pressure response to verapamil and the pretreatment blood pressure levels. Verapamil markedly accelerated heart rate and stimulated renin release in all rats. In additional groups of sodium-depleted (n = 8) and sodium-replete renal hypertensive rats (n = 7), nifedipine administration (4 micrograms/kg/min i.v.) within a 45-minute observation period caused a blood pressure fall (p less than 0.001) and heart rate acceleration (p less than 0.001) that were comparable in both groups. These findings suggest that in the rat with renal hypertension the short-term blood pressure response to the calcium antagonists verapamil and nifedipine is not influenced by the state of sodium balance and plasma renin activity. In this experimental model of hypertension, the magnitude of the blood pressure lowering effect of calcium entry blockers appears to be proportional to pretreatment blood pressure levels.
Hypertension
PMID:Does renin determine the blood pressure response to calcium entry blockers? 388 3


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