BASIC PHARMACOLOGY OF THE BETA RECEPTOR ANTAGONIST DRUGS
Beta-receptor antagonists share the common feature of antagoniz-ing the effects of catecholamines at β adrenoceptors. Beta-blocking drugs occupy β receptors and competitively reduce receptor occu-pancy by catecholamines and other β agonists. (A few members of this group, used only for experimental purposes, bind irreversibly to β receptors.) Most β-blocking drugs in clinical use are pure antagonists; that is, the occupancy of a β receptor by such a drug causes no activation of the receptor. However, some are partial agonists; that is, they cause partial activation of the receptor, albeit less than that caused by the full agonists epinephrine and isoprot-erenol. As described, partial agonists inhibit the activation of β receptors in the presence of high catecholamine concentrations but moderately activate the receptors in the absence of endogenous agonists. Finally, evidence suggests that some β blockers (eg, betaxolol, metoprolol) are inverse agonists— drugs that reduce constitutive activity of β receptors—in some tissues. The clinical significance of this property is not known.
The β-receptor–blocking drugs differ in their relative affinities for β1 and β2 receptors (Table 10–1). Some have a higher affinity for β1 than for β2 receptors, and this selectivity may have impor-tant clinical implications. Since none of the clinically available β-receptor antagonists are absolutely specific for β1receptors, theselectivity is dose-related; it tends to diminish at higher drug con-centrations. Other major differences among β antagonists relate to their pharmacokinetic characteristics and local anesthetic mem-brane-stabilizing effects.
Chemically, most β-receptor antagonist drugs (Figure 10–5) resemble isoproterenol to some degree (see Figure 9–4).