Lege Artis Medicinae

[Verapamil treatment in hypertension]

FARSANG Csaba1

JUNE 30, 1992

Lege Artis Medicinae - 1992;2(01 KLSZ)

[The author describes the mechanisms of action of verapamil, the first calcium antagonist, and also shortly summarizes its indications and ways of administration in hypertension. Its role in antihypertensive combinations and interactions are also conscisely dealt with.]

AFFILIATIONS

  1. Fővárosi Szent Imre Kórház I. sz. Belgyógyászat Budapest

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Lege Artis Medicinae

[The calcium channel blocker verapamil basic properties, pharmacokinetics, interactions, side effects]

KÉKES Ede, FARSANG Csaba

[The family of calcium channel blockers is very large and includes its prototype, the monophenylalkylamin drug, verapamil. It is a non-selective vasodilator which exerts a powerful effect equally on myocardium, conducting and nodal tissue of the heart, and both central and peripheral vasculature. Verapamil is almost completely absorbed after oral administration. However, because of extensive first-pass hepatic metabolism, only about 20% of the drug is bioavailable. The elimination phase is slow with a half-time varying from 5 to 7 hours. Orally administered verapamil is extremely well tolerated drug with a very low incidence of gastric intolerance, constipation, vertigo, facial flushing headache and pruritus. During intravenous administration the most common side effects are hypotension and and occasional AV conduction disturbances, or bradycardia. Main contraindications are listed. Coadministration of beta receptor blokers, digitalis and disopyramid should be avoided. ]

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[Effects of verapamil on cardiac arrhythmias]

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[Verapamil, a „first generation" calcium anta gonist and synthetic papaverine derivate, was initially introduced as a potent peripheral and coronary vasodilator. It was later found to have significant antiarrhythmic activity, the mechanism of which was related to selective inhibition of transmembrane fluxes of the calcium. The electrical activity of the sinus node and of the atrioventricular (AV) node depends primarily on slow inward Ca2+ currents, therefore it is logical to expect that calcium antagonists will be effective here. The main electrophysiologic effects of verapamil include the slowing of conduction and the prolongation of refractoriness in the atrio ventricular node without significantly affecting intraatrial or intraventricular conduction. Thus, verapamil has been effective in the acute termination of reentry tachycardia in volving the atrioventricular node and in slowing the ventricular response during atrial fibrillation or flattern. Since verapamil has little, if any, effect on the electrical activity of the ventricle or the His Purkinje system, it does not provide effective therapy for controlling ventricular tachycardias. This paper focuses on a detailed discussion of the various arrhythmias that respond to calcium antagonist therapy. ]

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[Antianginal effects of verapamil]

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[Verapamil is the prototype of the calcium antagonists. Administration of the drug produces a beneficial antianginal effect due to de creased preload and afterload through vasodilation without marked reflex tachycardia and also due to a special influence on myocardium (negative inotropy and positive lusitropy) in all forms of ischaemic heart disease. Verapamil is also a strong coronary dilator drug. Verapamil was given in doses of 240–360 mg daily. The investigators concluded that exercise tolerance increased and the number of anginal attacks and nitroglycerin (sublingual) consumption decreased. The rate-pressure product is reduced on verapamil. Its cardio protective effect on myocardial structure is still an object of discussion.]

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[The main aims of therapy in hypertrophic cardiomyopathy, in which ways the symptoms of the patients can be decreased and their survival can be made longer, are as follows: to ameliorate the impaired ventricular relaxation during diastole, to decrease or abolish the obstruction to the left ventricular outflow in systole, as well as to prevent or abolish the atrial and ventricular arrhythmias. Verapamil treatment can be advantageous in each of the above respect. The author describes the characteristics and pathophysiology of the disease in order to understand the favourable effects of Verapamil. On the basis of the literature he gives an outline of the experiences attaining with the application of the drug. He makes the reader acquainted with the results of follow-up studies and with his own observations treating 35 patients with verapamil.]

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[Hypertensive crisis becomes manifest in two clinically well distinguishable forms. Life threatening cases require immediate intervention, while in cases not immediately life threatening, the situation is less critical, but a delay in treatment may lead to serious organ damage. The authors administered 5 mg verapamil intravenously during 3 minutes to 46 patients (mean age 65,7 years, 31 women, and 15 men). The initial blood pressure of 226/125 mmHg decreased to 193/97 mmHg, and the heart rate decreased from 98/min to 81/min three minutes following the injection (p < 0,01 at both parameters). No significant change was observed in either the blood pressure or the heart rate during the subsequent 30 minutes. As a side-effect, flushing was observed in two cases. Based on the literature and their own experiences, the authors recommend intravenous verapamil as the drug of choice for life-threatening hypertensive crises associated with angina pectoris and cerebrovascular circulatory disorder in cases where EKG is available. ]

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