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  • Title: [Pharmacological control of heart rate].
    Author: Sirtori CR, Franceschini G.
    Journal: Ann Ital Med Int; 1994 Oct; 9 Suppl():29S-35S. PubMed ID: 7857754.
    Abstract:
    Heart rate, an important risk factor of coronary mortality, is highly correlated with numerous anthropometric and biochemical variables: height, body weight and hyperlipidemia; it varies, furthermore, with smoking and age and can be modified during pharmacotherapy for hypertension. From meta-analyses on different cardiovascular treatments, given after coronary events, only the efficacy of drugs significantly reducing heart rate is borne out (beta-blockers with sympathomimetic activity, or calcium-antagonists with a prevalent vasodilatory action do not provide a protective effect). Among calcium-antagonists, while the mechanism of action is similar at the cell level (delay of opening of voltage-operated slow channels), the distribution of activity within the vascular system varies markedly. Dihydropyridines (e.g., nifedipine) exert a dominant peripheral effect, with consequent vasodilation, whereas phenylalkylamines (verapamil) have both peripheral vasorelaxant and cardiac negative chronotropic activity, because of a reduced sinus node action potential. A relative tachycardia may occur with dihydropyridines, secondary to the activation of baroreceptors; the compensatory heart mechanism operated by verapamil antagonizes this reflex tachycardia. The activity of verapamil on the atrioventricular conduction allows both a slowing of functional recovery of the channel in hyperexcitable conditions (supraventricular tachycardia), and, moreover, increased diastolic intervals, with consequent improvement of coronary flow. New molecules can selectively reduce the sinus node activity without exerting other effects (hypotensive, anti-arrhythmic). From a comparative evaluation of these molecules with verapamil, it clearly emerges how this latter can provide a more acceptable pharmacodynamic profile, both for the hypotensive activity, and also for the control of reflex tachycardia, with a consequently improvement of coronary flow.
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