MEDizzy - Two drugs act on the same tissue or organ via activation of

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General pharmacology

Two drugs act on the same tissue or organ via activation of different receptors, resulting in effects that are qualitatively the opposite of one another. An example would be the direct effects of norepinephrine and acetylcholine on heart rate. This represents which of the following types of antagonism?

ExplanationPhysiologic, or functional, antagonism occurs when two drugs produce opposite effects on the same physiologic function by interacting with different types of receptors. A practical example of this, in addition to what is described in the question, is the use of epinephrine as a bronchodilator to counteract the bronchoconstriction that occurs when the parasympathetic nervous system releases ACh or when we administer bethanechol or an acetylcholinesterase inhibitor to a patient with asthma. ACh constricts airway smooth muscle by acting as an agonist on muscarinic receptors. Epinephrine relaxes airway smooth muscle cells and dilates the bronchi through its agonist activity on β2-adrenergic receptors. Chemical antagonism (a) typically is said to occur when two drugs combine with each other chemically, and the activity of one or both is reduced or abolished. For example, dimercaprol chelates lead and reduces the toxicity of this heavy metal; and calcium in certain foods or beverages (e.g., milk) interacts with tetracycline antibiotics and reduces bioavailability. Competitive antagonism (b) is one of the two main types of pharmacologic antagonism (d). It occurs when two compounds (drugs) compete for the same receptor site—both having an affinity for the receptor, only one having efficacy (or one having much more efficacy than another with partial agonist activity). With competitive antagonism, this is a reversible inter-action (because both the agonist and the antagonist can dissociate from the receptor sites)—and a surmountable (“overcomeable”) one. It is certainly the most common form of drug-drug antagonism when we think of often-used therapeutic agents. Thus, atropine (the prototype muscarinic receptor antagonist) antagonizes the effects of ACh on the S-A node by competing for the same population of receptors. Propranolol does the same with respect to antagonizing the β1-stimulatory effects of epinephrine, norepinephrine, and other β agonists on the heart. Irreversible antagonism, the other main type of pharmacologic antagonism (d), generally results from the binding of an antagonist to the same receptor site as the agonist by covalent interaction or by a very slowly dissociating noncovalent interaction. An example of this antagonism is the blockade produced by phenoxybenzamine on α-adrenergic receptors, resulting in a long-lasting reduction in the ability of norepinephrine, epinephrine, or other sympathomimetics to activate the α-adrenergic receptors. Dispositional antagonism (c) is a term sometimes used to describe the ability of one drug to enhance the elimination (and so reduce the serum levels and intensity of responses to) of another drug. Thus, it is mainly a pharmacokinetic interaction. Its most common basis involves one drug enhancing the metabolic inactivation and elimination of another drug. For example, phenytoin (anticonvulsant/antiepileptic drug) or rifampin induces the hepatic metabolic inactivation of warfarin, reducing (antagonizing) warfarin’s anticoagulant activity by reducing its serum levels.