The second Lilly Prize Lecture, University of Newcastle, July 1977. beta‐Adrenergic receptor blockade in hypertension, past, present and future.

Abstract

All beta‐adrenoceptor blocking drugs that have been described share the common property of being competitive inhibitors. They differ in their associated properties, the presence or absence of cardioselectivity, membrane stabilizing activity, and partial agonist activity. Recently some beta‐adrenoceptor blocking drugs have been reported which also possess alpha‐adrenoceptor blocking activity. The associated properties have been used as a basis for classifying beta‐adrenoceptor blocking drugs (Fitzgerald, 1969, 1972). The presence or absence of cardioselectivity is most useful for dividing beta‐adrenoceptor blocking drugs. The non‐selective drugs (Division I) can be further divided according to the presence or absence of intrinsic sympathomimetic activity (ISA) and membrane stabilizing activity (Fitzgerald's groups I‐IV). Group I possess both membrane activity and ISA, e.g. alprenolol, oxprenolol, group II just membrane action, e.g. propanolol, group III ISA but no membrane action, e.g. pindolol. Fitzgerald placed pindolol in group I but should be placed in group III as it possesses a high degree of beta‐adrenoceptor blocking potency in relation to its membrane activity (Prichard, 1974). Finally drugs in group IV have neither ISA nor membrane action, e.g. sotalol, timolol. The cardioselective drugs (Division II) can be similarly sub‐divided into groups I‐IV according to the presence or absence of ISA or membrane action (Fitzgerald grouped all these together as group V). Lastly there are new beta‐adrenergic receptor blocking drugs which in addition have alpha‐ adrenergic receptor blocking properties (Division III).

Evolution of β-blockers: from anti-anginal drugs to ligand-directed signalling

“…It was also shown that propranolol has anti-arrhythmic properties. Subsequent work established that the anti-hypertensive and anti-arrhythmic properties, together with the reduction in heart rate and cardiac output, are important class actions of β-adrenoceptor antagonists ( Table 1 ) [10] .…”

“…In 1978, Prichard observed: ‘Two important untoward effects from β-adrenergic receptor blocking drugs that should be avoided with foresight in patient selection: heart failure and asthma. Patients in heart failure, or patients with incipient left ventricular insufficiency … are critically dependent on sympathetic activity to the heart to maintain their cardiac output.’ [10] . Indeed, heart failure occurs when the cardiac output is not sufficient to meet the demands of the body so reducing output further with a β-blocker would appear illogical.…”

Beta-Blockers in the Management of Hypertension and/or Chronic Kidney Disease

“…Prichard classified beta-blockers into three types according to their beta1-selectivity and vasodilatory potential [ 4 ]. An additional classification is lipophilic or hydrophilic beta-blockers [ 5 , 6 ].…”