[Pharmacological basis for the therapy of cardiovascular disease with beta-adrenoceptor blocking drugs (author's transl)].

The introduction of beta-adrenoceptor blocking drugs initiated a breakthrough in the treatment of various cardiovascular disorders within the last 20 years. The major cardiac indications for beta-blockers are coronary heart disease, hypertension and arrhythmias. No one beta-adrenoceptor blocking drug has been shown to be more efficacious than another, and efficacy can be related to the stereo-selective blockade of adrenergic beta-receptors. The major side effects and the contraindications are mainly due to beta-adrenoceptor blockade in combination with the organ-specific distribution of beta 1- and beta 2-adrenoceptors. In addition to their specific antagonism beta-receptor blocking drugs can differ in beta 1-adrenoceptor selectivity, intrinsic sympathomimetic activity (ISA) as well as in nonspecific effects. However, these ancillary properties do not seem to be of importance for the therapeutic effect of these drugs. A relative beta 1-selectivity is probably able to reduce the incidence of side effects e.g. in asthmatics, in diabetic patients and in patients with peripheral vascular disease, however, beta-adrenoceptor antagonists should be used with caution in these patients, At the present time, there is no convincing evidence that beta-adrenoceptor antagonists with partial agonist activity are superior in patients with congestive heart failure or in asthmatics. Except at high dosages the nonspecific local anaesthetic or cardiodepressant effects of lipophilic beta-adrenoceptor antagonists (propranolol-oxprenolol-group) also do not seem to be of importance in the therapy of cardiovascular diseases. On the other hand, lipophilicity of a lipophilic beta-adrenoceptor antagonists of the propranolol-oxprenolol-group exhibit serum half-lives in the range of two to six hours, whereas half-lives of six to 24 hours are found with the hydrophilic compounds sotalol, practolol, nadolol and atenolol, respectively, while with regard to lipophilicity and serum half-lives timolol, metoprolol, pindolol and acebutolol fall midway between these extremes. It was well established that the duration of action of the beta-adrenoceptor antagonists is about two or three times longer than would be expected from the pharmacokinetic data. This can be explained by the fact that the pharmacodynamic effect obeys zero order kinetics whereas the decline in serum concentration follows first order kinetics. The pharmacokinetic and pharmacodynamic data of the beta-adrenoceptor blocking drugs are of great value in the therapy inasmuch as the dosage interval must be modified accordingly: whereas the lipophilic compounds have to be taken two to four times per day, one dosage per day seems sufficient with the hydrophilic compounds.