Pharmacodynamic studies on the antihypertensive effectiveness of beta-blocking drugs

Beta-adrenoceptor antagonists are effective antihypertensive agents in the majority of patients with uncomplicated essential hypertension. Their antipressor activity is greater on systolic than diastolic pressure and greatest during dynamic exertion. Their circulatory effects are maximum within 1-2 hours of ingestion and the antipressor effects of a single dose are detectable for over eight hours. Both the immediate and long-term blood pressure lowering effects of these drugs are dose-related. The reduction in exercise systolic pressure is related to the logarithm of the dose of each drug; the reductions in pressure at rest follow no simple mathematical function. There is wide individual variation in the plasma concentrations achieved after a given oral dose, although the averaged values follow a linear regression. There are wide discrepancies between plasma-concentration profile and magnitude and duration of antihypertensive activity; blood pressure lowering activity persists for significantly longer than the drug is detectable in plasma. The antihypertensive effects of the beta-blocking drugs are enhanced during chronic administration without habituation. Their effects are specific but independent of the immediate presence of the drug, i.e. blood pressure lowering activity persists after clearance of the drug from the body. The ancillary pharmacological properties of these drugs neither augment nor detract from their antihypertensive potency, although the possession of intrinsic vasodilator activity enhances reduction in the blood pressure standing at rest. Beta-blocking drugs add a new dimension to antihypertensive treatment in their specific potential to reduce the coronary consequences of the disease.