Verapamil Hydrochloride: Pharmacological Properties and Role in Cardiovascular Therapeutics

Abstract

Verapamil hydrochloride, a prototype calcium antagonist, is now marketed in the United States for the acute treatment of supraventricular tachyarrhythmias and for chronic management of vasospastic and chronic stable angina. It inhibits the slow inward channel in in the heart and blocks calcium influx in smooth muscle. Its intrinsic negative inotropic action, which is apparent in isolated tissues, is offset in vivo by peripheral vasodilation. It has a mild, noncompetitive sympathetic antagonist effect; its most important electrophysiologic action is a depression of AV nodal conduction, accounting for its effect in supraventricular tachyarrhythmias. Its hemodynamic actions are characterized by a complex interplay of changes in preload, afterload, contractility, heart rate, and coronary blood flow. It does not depress cardiac function, except in severe heart failure. The drug has a mild dilator action on coronary arteries and reverses ergonovine-induced vasoconstriction. Controlled trials have established its role in Prinzmetal's variant angina, unstable angina, and chronic stable angina. It has also been found to be effective in obstructive cardiomyopathies. The potential role of verapamil in such conditions as hypertension, cardioprotection, and Raynaud's phenomenon needs further evaluation; at present these indications have not been approved by the Food and Drug Administration. The most common side effects include constipation, skin rash, and dizziness; AV block, heart failure, and sinus arrest may occasionally be encountered, especially when ventricular function is compromised or conduction system disease is present.

Hyaluronan Export through Plasma Membranes Depends on Concurrent K+ Efflux by Kir Channels

“…It reduces the cellular influx of Ca 2+ [20] and thus has an indirect effect on the Ca 2+ activated potassium channel. Fig.…”

Time Course of Verapamil Interaction with Morphine Effects on Physiological Parameters in Rats

“…Antagonism by verapamil of respiratory depression and tachycardia produced by morphine was unrelated to morphine levels in plasma. Thus, the explanation of verapamil-morphine interactions on respiration and cardiovascular function is not pharmacokinetic.Calcium channel antagonists, such as verapamil and diltiam, are used clinically in cardiovascular therapy (Henry 1980;Baky & Singh 1982; Wagniart et a1 1982). Studies of opioid analgesia, tolerance and dependence in rats have used drugs that inhibit calcium binding and transport.…”

“…Calcium channel antagonists, such as verapamil and diltiam, are used clinically in cardiovascular therapy (Henry 1980;Baky & Singh 1982; Wagniart et a1 1982). Studies of opioid analgesia, tolerance and dependence in rats have used drugs that inhibit calcium binding and transport.…”

Pgp efflux pump decreases the cytostatic effect of CENP-E inhibitor GSK923295

“…The combination of Pgp inhibitor verapamil with GSK923295 induced the G2/M arrest in MESSA Dx5 cells followed by apoptosis, which restored the cytostatic effect of GSK923295. Initially, verapamil was developed as a calcium channel blocker [30,31]. Subsequently, it has been reported that verapamil is a chemosensitizing compound which diminishes multidrug resistance and increases the intracellular drug accumulation by competitive inhibition of drug transport through P-glycoprotein [32].…”