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

The chief site of action of the calcium antagonist drugs is the slow calcium channel in two tissues: the atrioventricular node and vascular smooth muscle. The exact mode whereby these agents work is still unknown, but recently studies with radioligands suggest that the binding site for the dihydropyridines such as nifedipine is different from the site for the verapamil group (including diltiazem). In some way these agents 'close' or 'block' the calcium channels. Verapamil and diltiazem are active against the calcium channel of the atrioventricular node which nifedipine in clinical doses is not; in contrast, nifedipine is more active on peripheral vascular arterial muscle, presumably inhibiting the calcium channel more strongly. An intracellular site of action of these agents on calmodulin in vascular smooth muscle cannot be excluded. Clinically, the chief calcium antagonists (verapamil, nifedipine, diltiazem) constitute a powerful group of cardioactive agents with a spectrum of therapeutic actions rather similar to beta-adrenoceptor blockade, being effective in angina of effort and rest, and hypertension. Critical differences are dependent on the individual properties of the calcium antagonists. Thus only verapamil and diltiazem are effective in inhibiting the AV node while the dihydropyridines such as nifedipine are only vasodilators in clinical doses. As a group, calcium antagonists cause vascular dilation and do not cause bronchial constriction, in contrast to the beta-adrenoceptor blocking agents. In many patients these diverse properties allow safe combination of calcium antagonists and beta-adrenoceptor blockers if due care is observed.
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PMID:Calcium antagonists. Mechanisms, therapeutic indications and reservations: a review. 632 68

Calcium antagonists have recently emerged as a class of drugs for the treatment of angina, hypertension and certain cardiac arrhythmias. Verapamil is the prototype calcium antagonist and has the most clearly defined antiarrhythmic properties. Other agents in the class include D-600 (gallopamil), tiapamil, nifedipine, and diltiazem. The antiarrhythmic effects of these compounds can be correlated with their electrophysiological properties which may differ significantly among different compounds and also between isolated tissues in intact animals and man. As a class they do not increase the effective refractory period of the atria, ventricle, His-Purkinje fibres or the accessory pathways in the heart. The dominant effect is slowing of conduction in the AV node with the prolongation of the AV nodal refractory period. The most marked changes are produced by verapamil, the least with nifedipine which is devoid of antiarrhythmic actions. Verapamil and its congeners as well as diltiazem terminate paroxysmal supraventricular tachycardia and slow the ventricular response in atrial flutter and fibrillation. They are also of prophylactic value in preventing recurrences of paroxysmal supraventricular tachycardia and controlling the ventricular response in atrial flutter and fibrillation during long term oral therapy. Their value in ventricular arrhythmias is uncertain but they are unlikely to be effective except in those complicating coronary artery spasms. The relative merits and potencies of various calcium antagonists in different arrhythmias need further studies.
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PMID:Calcium antagonists. Clinical use in the treatment of arrhythmias. 633 97

Renal function and renin release were studied in anesthetized, uninephrectomized dogs during intrarenal infusions of the calcium influx blockers, verapamil and nifedipine. Verapamil increased renal blood flow by 20% (p less than 0.05) but did not alter glomerular filtration rate. Verapamil produced five-to-seven fold increases in urine flow and the rates of excretion of sodium and chloride (p less than 0.01). Significant increases in the rates of excretion of potassium, calcium and magnesium were also observed. Despite its striking effects on renal function, verapamil, in nonhypotensive doses, failed to alter renin secretion. Intrarenal infusion of nifedipine had no consistent effect on renal blood flow or the rate of glomerular filtration but increased urine flow and the rates of excretion of sodium and chloride by more than three fold (p less than 0.01). Nonhypotensive doses of nifedipine had no significant effect on renin release. In dogs with a denervated nonfiltering kidney, an intrarenal verapamil or nifedipine infusion did not produce a significant change in renin release. This study demonstrates a striking effect of calcium entry blockers on the reabsorption of sodium, chloride, and water by the renal tubules in intact dogs but renin release did not increase unless hypotension occurred.
Hypertension
PMID:Effects of intrarenal infusion of calcium entry blockers in anesthetized dogs. 634 59

Verapamil and nifedipine are calcium-blocking agents that have a selective dilator effect on resistance vessels. Both drugs have been shown to lower arterial pressure when given in long-term therapy under conditions of a double-blind controlled trial. Both agents may be effective as sole therapy or when given in combination with a diuretic; nifedipine has been used successfully in conjunction with beta-adrenoceptor antagonist/diuretic combinations. Calcium-blocking agents do not evoke tolerance in long-term treatment; in contrast to other directly acting dilator drugs, they do not consistently lead to a rise in plasma renin activity and they induce little or no sodium retention. Calcium-blocking agents do not all share the same mechanism of action, and they vary considerably in their effect on the heart. These differences may be important in determining which compound is best suited for use in particular clinical situations.
Hypertension
PMID:Long-term efficacy of calcium antagonists in resistant hypertension. 634 71

The pharmacokinetics, clinical efficacy, and adverse effects of three calcium-channel blocking agents--verapamil, nifedipine, and diltiazem--are reviewed. Verapamil, nifedipine, and diltiazem are absorbed well after oral dosing, but absolute bioavailability of each is reduced substantially by a first-pass effect. Each drug is metabolized extensively (verapamil and diltiazem to moderately active metabolites) by the liver. A substantial percentage of each drug is bound to plasma proteins, but the binding is of clinical importance only for nifedipine (92--98% protein bound). Intravenous verapamil has become the agent of first choice for treatment of acute paroxysmal supraventricular tachycardia (PSVT); use of chronic oral verapamil therapy for prophylaxis remains controversial. Verapamil and diltiazem have been evaluated with mixed results for atrial flutter and fibrillation. For treatment of myocardial ischemia, calcium-channel blockers may be of some value (possibly in combination with nitrates of B blockers). All three agents have been studied in patients with exertional angina with good results. Calcium-channel blockers appear to be equal with nitrates for treatment of variant angina. Patients with hypertropic cardiomyopathy have been treated with verapamil and nifedipine with promising results. Nifedipine has been effective for treatment of essential hypertension. Adverse effects of calcium-channel blockers have been relatively minor or infrequent. Diltiazem overall has the best side-effect profile, with adverse effects causing discontinuation of therapy in about 2--10% of patients; verapamil in intermediate (8--10%) and nifedipine the worst (17%) in this respect. The most common side effects generally are fatigue, headache, dizziness, skin rash, and peripheral edema. While they generally should be reserved for patients in whom more conventional therapy has failed (except those with PSVT), calcium-channel blockers appear to have a valid role as reserve agents for exertional and variant angina, cardiomyopathy, and hypertension.
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PMID:Update on calcium-channel blocking agents. 635 66

Verapamil is widely used in the treatment of supraventricular tachyarrhythmias as well as for hypertension and control of symptoms in angina pectoris. Unlike other calcium antagonists, detailed pharmacokinetic data are available for verapamil. Plasma concentrations of verapamil appear to correlate with both electrophysiological and haemodynamic activity after either intravenous or oral drug administration, although considerable intra- and intersubject variation has been found in the intensity of pharmacological effects resulting at specific plasma drug levels. Verapamil is widely distributed throughout body tissues; animal studies suggest that drug distribution to target organs and tissues is different with parenteral administration from that found after oral administration. The drug is eliminated by hepatic metabolism, with excretion of inactive products in the urine and/or faeces. An N-demethylated metabolite, norverapamil, has been shown to have a fraction of the vasodilator effect of the parent compound in in vitro studies. After intravenous administration, the systemic clearance of verapamil appears to approach liver blood flow. The high hepatic extraction results in low systemic bioavailability (20%) after oral drug administration. Multicompartmental kinetics are observed after single doses; accumulation occurs during multiple-dose oral administration with an associated decrease in apparent oral clearance. Norverapamil plasma concentrations approximate those of verapamil following single or multiple oral doses of the parent drug. Because of the complex pharmacokinetics associated with multiple-dose administration and the variation in individual patient responsiveness to the drug, 'standard' dosing recommendations are difficult to determine; use of verapamil must be titrated to a clinical end-point. Further, the potential for alteration in verapamil's disposition by the presence of hepatic dysfunction or cardiovascular disorders which result in altered hepatic blood flow is only now becoming apparent. A potentially toxic interaction has been reported between verapamil and digoxin, in which renal excretion of the glycoside is impaired, but the true clinical significance of this remains debatable. Combination therapy with verapamil and beta-adrenoceptor blocking compounds has been advocated by some investigators, but may be hazardous because of the additive negative inotropic and chronotropic effects inherent in both agents.
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PMID:Clinical pharmacokinetics of verapamil. 636 51

In hypertensive emergencies, sublingual nifedipine (10 to 30 mg) is the treatment of choice. Nifedipine, however, may lead to reflex activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system as well as fluid retention when used as a monotherapy for a longer period of time. In chronic arterial hypertension, verapamil, and especially diltiazem seem to be superior to nifedipine. Verapamil (360 to 480 mg a day) and diltiazem (180 to 270 mg a day) produce a consistent antihypertensive effect throughout a 24-hour period. During dynamic or isometric exercise, their antihypertensive potency is equivalent to that of beta blockers. Overall response rate in patients with mild to moderate hypertension is 80 percent with monotherapy. In refractory hypertension, combination with thiazide, reserpine, or clonidine may be useful. Calcium blockers are preferred in older patients with chronic arterial hypertension, and in patients with low renin hypertension, coronary heart disease, peripheral vascular disease, or obstructive airways disease.
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PMID:Treatment of hypertension with calcium channel blockers: European data. 638 98

The effect of verapamil on different metabolic parameters has been studied after changing the treatment of hypertension from hydrochlorothiazide to verapamil monotherapy. Verapamil 80 to 160 mg b.i.d. was continued for 6 months. The antihypertensive efficacy of verapamil was comparable to that of hydrochlorothiazide. Plasma total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and free fatty acids did not change significantly after the change in treatment; serum total cholesterol, LDL-cholesterol and HDL-cholesterol were 7.28 +/- 1.80 (m +/- SD), 5.11 +/- 1.59 and 1.65 +/- 0.39 mmol/l at the end of the hydrochlorothiazide period and 7.10 +/- 1.92, 5.09 +/- 1.70 and 1.56 +/- 0.35 mmol/l at the end of the verapamil period, respectively. The only statistically significant differences were the increases in total and LDL-cholesterol after three months on verapamil as compared to the basal values before diuretic therapy. Marked changes were not observed in fasting blood glucose, insulin or C-peptide values. Serum uric acid concentration decreased significantly (p less than 0.001) from 326 +/- 66 to 252 +/- 53 mmol/l, and serum potassium level increased significantly (p less than 0.01) from 3.5 +/- 0.4 to 3.9 +/- 0.3 mmol/l, on verapamil as compared to the diuretic period. Serum calcium decreased from 2.45 +/- 0.10 to 2.37 +/- 0.08 mmol/l (p less than 0.01) and calcium excretion increased significantly (p less than 0.01) to 5.43 +/- 2.55 mmol/24 h during verapamil administration from the level of 3.56 +/- 2.78 mmol/24 h whilst on the diuretic.
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PMID:Metabolic parameters after changing from hydrochlorothiazide to verapamil treatment in hypertension. 638 53

We have compared cardiac performance, hypertrophy and sensitivity to calcium and verapamil of hearts of six to nine-month-old spontaneously hypertensive rats (SHR), two-kidney, one clip renal hypertensive rats (RHR) and age-matched controls. Cardiac output and heart rate were measured using an isolated perfused heart preparation. Mean blood pressure (BP) and heart weight were equally increased in SHR and RHR as was optimal left atrial filling pressure. Cardiac output was increased in both SHR and RHR at any given work load; this improvement was seen especially in SHR and at high aortic pressure (160 cm H2O) was significant in SHR but not RHR. In low [Ca2+], 0.6 mM, cardiac output of RHR and controls fell markedly, but changed little in SHR, whereas in high [Ca2+], 5.1 mM, cardiac performance deteriorated in SHR but was improved in RHR and controls. Verapamil 2 X 10(-7) M reduced Ca2+ responsiveness of RHR and controls threefold but had no effect in SHR. The results suggest there may be an abnormality of cardiac calcium utilization in inherited but not in acquired hypertension.
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PMID:Calcium sensitivity and cardiac performance in genetic and renal models of hypertension. 659 2

The calcium entry blocker, verapamil, enhanced morphine analgesia, but neither methadone nor propoxyphene analgesia was affected by verapamil in the mouse hot-plate test. To explain this, it was hypothesized that methadione and propoxyphene differ from morphine because they, like verapamil, block calcium channels and subsequent studies were done to confirm this. Verapamil, methadone and propoxyphene all depressed barium-induced bovine adrenal catecholamine release and KCl-induced contractions of guinea pig ileum, which are known to be calcium-dependent events. Calcium reversed opioid-induced inhibition in both tissues. Morphine did not affect either catecholamine release or ileal contractions. Procaine also did not influence catecholamine release or ileal contraction. Therefore, local anesthesia was eliminated as a mechanism for the inhibitory action of methadone and propoxyphene in these tissues. Opioids which block calcium channels should, like verapamil, produce bradycardia and hypotension. In the spinal vagotomized rat, methadone, propoxyphene, and verapamil produced bradycardia and hypotension, whereas, morphine produced tachycardia and (at low doses) hypertension. The results of this work suggest that methadone and propoxyphene, in contrast to morphine, block calcium channels in a manner similar to verapamil, and that some pharmacological and especially toxicological differences between these drugs are due to different degrees of verapamil-like calcium channel blockade.
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PMID:Calcium channel blockade by certain opioids. 666 95


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