Clinical pharmacology of adrenergic-adrenoreceptor-blocking drugs

Abstract

The development of beta-adrenoreceptor-blocking drugs provided an important group of agents to treat the cardiovascular disorders hypertension, angina pectoris, and cardiac arrhythmias and to manage patients with thyrotoxicosis. For clinical purposes, these drugs can be divided into two groups, that is, those with intrinsic sympathomimetic activity (ISA) and those without (non-ISA). The non-ISA drugs include propranolol, which is noncardiac selective: labetalol, which is noncardiac selective with alpha blockade: and metoprolol and atenolol, which are cardiac selective. The drugs with ISA include pindolol, oxprenolol, and alprenolol which are noncardiac selective, and practolol which is cardiac selective. These drugs resemble isoprenaline in chemical structure, but their interaction with the beta-adrenoreceptors causes no response or only a slight response if the drug has ISA. By occupying the receptors, they block excitation by noradrenaline released from the sympathetic nerves and by adrenaline from the adrenal medulla. Drugs with ISA appear to depress cardiac activity and to interfere with bronchodilator drive less than do non-ISA drugs. Beta-blocking drugs differ considerably in their bioavailability because of differences in the rate and extent of metabolism in the first past through the liver after absorption from the gut. The therapeutic dose range varies widely for those with low bioavailability but is more predictable for those with high bioavailability. The drugs also differ in plasma protein binding and in their receptor affinities. In addition to their usual adverse effects, which include exacerbation of cardiac failure, bronchospasm, sleep disturbances, and Raynaud's phenomenon, concern has arisen about possible ocular and mucocutaneous side effects with beta-blocking drugs. This is a recognized problem with practolol, and it is not certain whether it occurs with other beta-blocking drugs. A double-blind study reported here of 110 matched patients, 36 of whom were on pindolol for more than 2 years, did not reveal any evidence of oculomucocutaneous problems related to drug treatment.