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

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

The antihypertensive effect of an oral slow release (retard) formulation of verapamil was evaluated in a negative (placebo) and positive (nifedipine) controlled study. After a run-in period of one week without antihypertensive therapy, 54 patients were classified as having mild to moderate hypertension (diastolic blood pressure 95-115 mm Hg) and assigned randomly to one of three groups (n = 18 each). These received one of the following treatments over 2 weeks: either placebo b.i.d., or a nifedipine retard preparation 20 mg b.i.d., or a verapamil retard preparation 240 mg b.i.d. Assessments of blood pressure were made at rest and during a standardized bicycle stress test. Data were recorded at baseline and at the end of each week. After one week of treatment, 1 patient receiving nifedipine and 14 patients receiving placebo dropped out of the study because their diastolic pressures were equal to or above the values before treatment. After two weeks of treatment, 13 of 18 patients on verapamil and 9 of 18 patients on nifedipine had resting diastolic pressures less than or equal to 90 mm Hg. Also systolic pressure and blood pressures during exercise were significantly lowered by both active drugs. Verapamil caused a fall in heart rate during rest and under maximal exercise. Undesired side effects from verapamil were constipation (6 of 18) and headache (1 of 18); those from nifedipine were flush or headache (5 each of 18); ankle edema, dizziness, or tachycardia were each reported by one patient. In comparison with placebo values, verapamil lengthened the atrioventricular conduction time (PQ-interval) significantly, however, PQ-interval did not exceed 0.24 s.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Controlled study on the treatment of hypertension with verapamil in retard form]. 390 62

The acutely hypertensive patient may present with a broad spectrum of dysfunction. Given the wide variety of signs and symptoms, clinical settings, pathophysiological mechanisms, and type of end organ dysfunction, there is no ideal antihypertensive agent. In selecting an agent for treating such patients, the physician must consider efficacy in a variety of settings, rapidity of onset of action, duration of action, and ease of administration. In addition, one should keep in mind the risk of producing hypotension, the contraindication profile, the side-effect profile, and the cost and long-term usefulness of the agent. In this review, the calcium channel blockers verapamil and nifedipine are compared with drugs such as nitroprusside, diazoxide, hydralazine, labetalol, and clonidine. Verapamil, by intravenous administration, has a rapid onset of action, a reasonable duration of effect, a good side-effect profile, and appears to be useful on a long-term basis. Nifedipine, by oral or buccal administration, is useful in a variety of settings and had a rapid onset of action and reasonable duration of effect. In addition, nifedipine rarely causes hypotension, has minimal contraindications, an excellent side-effect profile, reasonable cost, and long-term utility. There is now extensive worldwide experience with verapamil and nifedipine in acute hypertension. They compare favorably with currently used agents.
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PMID:Calcium-channel blockers in acute hypertension. 393 8

High doses of verapamil, diltiazem or nifedipin were administered to three groups of eight patients each, with severely abnormal left-ventricular (LV) function (mean ejection fraction 0.29). Various haemodynamic measurements were made immediately before and 30 minutes after drug administration: LV ejection fraction, ratio of peak systolic pressure to endsystolic volume index, stroke index, pulmonary capillary closing pressure, and maximal diastolic filling rate. None of these were reduced. In fact, ejection fraction rose by a mean of 0.05, stroke index by a mean of 5 ml/m2, while p.c. closing pressure and contractility did not alter significantly. Verapamil and diltiazem reduced the pressure X rate product (an important determinant of oxygen consumption); nifedipine reduced total systemic resistance. It is concluded that verapamil and diltiazem can be used with advantage in cases of unstable angina, if there are severe abnormalities of LV function; they are to be preferred to beta-blockers in this situation. Nifedipin is the calcium antagonist of choice in hypertension and abnormal LV function.
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PMID:[Verapamil, diltiazem or nifedipine in severe left ventricular functional disorder? A comparative study of the immediate hemodynamic effects]. 394 Aug 29

Forty-three patients with mild to moderate hypertension (supine diastolic blood pressure 95 to 115 mm Hg) were entered into a short-term (3 months) study. All received verapamil, 120 mg 3 times a day. After 1 month of treatment on verapamil alone, supine diastolic blood pressure was normalized (less than 95 mm Hg) in 29 patients (67%). These patients continued with verapamil at the same dosage. In 14 nonresponders (supine diastolic blood pressure greater than 95 mm Hg) a combination of althiazide (15 mg/day) and spironolactone (25 mg/day) was added. This resulted in diastolic blood pressure normalization in 9 additional patients. Verapamil induced a slight but moderate decrease in heart rate after 1 month, but no further decrease was observed thereafter. During the trial, 21% of patients reported adverse effects, mostly transient and mild. No patient had to discontinue treatment because of them. Twenty-six patients on verapamil alone were followed for 1 year. Systolic and diastolic blood pressure was adequately controlled in all patients except 1. In 13 the dosage was decreased to 120 mg 2 times a day. There were no significant differences in blood pressure between this group and patients given 120 mg 3 times a day. It is concluded that verapamil is an effective and safe antihypertensive agent in mildly to moderately hypertensive patients. Because a dosage of 120 mg 2 times a day was as effective as 120 mg 3 times a day, the former should be recommended, as it may improve patient compliance.
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PMID:Short- and long-term treatment of mild to moderate hypertension with verapamil. 395 30

The antihypertensive effect of finoptin (verapamil) and corinfar (nifedipin) and their impact on the hemodynamics and the repolarization complex of the ECG were studied in 52 patients with essential hypertension and 48 patients with secondary arterial hypertension. The calcium antagonists were found to effectively decrease the blood pressure by reducing the peripheral resistance. Verapamil may be recommended for the monotherapy of mild and moderate forms of arterial hypertension, whereas corinfar should be used in cases of marked hypertension and at the third stage of therapy. Patients with electrocardiographic signs of myocardial ischemia show the normalization of the ST segment and a decreased depression of T wave under the impact of corinfar.
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PMID:[Treatment of arterial hypertension with calcium antagonists]. 398 59


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