Clinical pharmacology of slow channel blocking agents

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ATIONAL and effective pharmacotherapy requires an understanding of the patient’s disease process as well as an appreciation of both the pharmacodynamics and the pharmacokinetics of the drug(s) selected for use. Although the slow channel antagonist drugs have been widely used outside the United States for the past decade, the body of data contributing to our understanding of the clinical pharmacology of these agents is only now beginning to expand. Clinical studies that have shown the dramatic effectiveness of the slow channel blockers in control of supraventricular tachyarrhythmiasif2 and in relief of symptoms associated with vasospastic coronary artery disease3-’ have been largely empiric, and therefore, have demonstrated the potential usefulness of these new drugs largely in qualitative fashion. Further elaboration of the clinical value of the slow channel antagonist compounds will depend heavily on data from which rational dosing schedules can be derived, on which appropriate dosing intervals may be based, and with which predictable drug toxicity may be avoided. The purpose of this article is to examine the information currently available pertaining to the clinical pharmacology of the three slow channel antagonists undergoing advanced clinical evaluation in this country-verapamil, nifedipine, and diltiazem-and which have received preliminary FDA approval for marketing. Other compounds with similar effects on transmembrane calcium flux, such as perhexilene and lidoflazine, have not been studied in this country to the extent the former group has and are not so far along in the lengthy process leading to clinical availability. VERAPAMIL Actions