Intrinsic sympathomimetic activity: clinical fact or fiction?
The therapeutic importance of the ancillary pharmacologic property of partial agonist activity, or intrinsic sympathomimetic activity (ISA), of a beta-adrenoceptor antagonist is controversial. Its pharmacologic definition and accepted physiologic potential are now joined by convincing evidence that ISA may have important therapeutic implications. The ability to support basal cardiac functions while preventing the potential hazards of random sympathetic stimulation is an important attribute of this property, particularly in the damaged heart. The beneficial effects of ISA on peripheral blood flow, systemic vascular resistance and left ventricular afterload are established. Although all beta-blocking drugs are contraindicated in patients with asthma, ISA appears to be at least as important as cardioselectivity in offsetting some of the increase in airway resistance that results from beta blockade alone both at rest and during exertion. These pharmacodynamic consequences of ISA may explain the lesser reduction in exercise tolerance afforded by beta-blocking drugs with ISA than by those without. ISA may also enhance the primary oxygen-sparing effects of beta blockade in the ischemic myocardium by reducing coronary resistance, enhancing coronary blood flow, and reducing anaerobic metabolism. The adverse effects of beta-blocking drugs on blood lipids and carbohydrate metabolism also appear to be largely negated in drugs with ISA. The risks of rebound effects from abrupt withdrawal are significantly less in drugs with ISA than in those without.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001980:Bronchi / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013329:Structure-Activity Relationship; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D013566:Sympathomimetics / Q000494:pharmacology* / Q000627:therapeutic use; D014655:Vascular Resistance / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D013566:Sympathomimetics