Drug antagonism competitive

On receptor basis, drug antagonism will be of two types competitive and noncompetitive antagonism. 

Leukotriene modifiers either inhibit 5-lipoxygenase (zileuton) or competitively antagonize the effects of leukotriene D4 (montelukast and zafirlukast). These agents improve FEV, and decrease asthma symptoms, rescue drug use, and exacerbations due to asthma. Although these agents offer the convenience of oral therapy for asthma, they are significantly less effective than low doses of inhaled corticosteroids.2,33... 

Many of the most useful drugs are antagonists substances that reduce the action of another agent, which is often an endogenous agonist (e.g., a hormone or neurotransmitter). Though the most common mechanism is simple competition, antagonism can occur in a variety of ways. 

More recently the drug has been re-examined to elucidate its properties more thoroughly [230-1]. The first of these studies [230] demonstrated that thymoxamine satisfied the usual criteria [232-7] for competitive antagonism at a-receptor sites (against noradrenaline) but showed no (3-receptor blocking... 

Competition for receptors, hence receptor antagonism, is governed by the law of mass action that is, the interaction between drug and receptor depends on the concentration of drug in the vicinity of the receptor and the number of receptors present. Because agonist and antagonist have an affinity for the same receptors, the two substances compete for binding to the receptors. 

Labetalol produces equilibrium-competitive antagonism at p-receptors but does not exhibit selectivity for Pi- or P2-receptors. Like certain other p-blockers (e.g., pindolol and timolol), labetalol possesses some degree of intrinsic activity. This intrinsic activity, or partial ago-nism, especially at P2-receptors in the vasculature, has been suggested to contribute to the vasodilator effect of the drug. The membrane-stabilizing effect, or local anesthetic action, of propranolol and several other p-blockers, is also possessed by labetalol, and in fact the drug is a reasonably potent local anesthetic. 

The a-blockade produced by labetalol is also of the equilibrium-competitive type. In a manner similar to prazosin, labetalol exhibits selectivity for ai-receptors. Presynaptic a-receptors, which are of the a2 subclass, are not antagonized by labetalol. The drug also has some intrinsic activity at a-receptors, although this action is less than its intrinsic p-receptor-stimulating effects. 

Blockers competitively antagonize the responses to catecholamines that are mediated by (3-receptors (see Chapter 11).These drugs have a number of clinical uses, including treatment of cardiac arrhythmias (see Chapter 10) and angina pectoris (see Chapter 17), for... 

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