{"id":318,"date":"2020-02-16T10:42:33","date_gmt":"2020-02-16T05:12:33","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=318"},"modified":"2020-02-16T10:42:33","modified_gmt":"2020-02-16T05:12:33","slug":"drug-antagonism","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/drug-antagonism\/","title":{"rendered":"Drug antagonism"},"content":{"rendered":"\n<p><strong>Drug antagonism<\/strong><\/p>\n\n\n\n<ul><li><strong><em>Affinity<\/em><\/strong><em>: <\/em>The tendency of a drug to bind to the receptors.<\/li><li><strong><em>Efficacy<\/em><\/strong><em>: O<\/em>nce bound, tendency to activate the receptor.<\/li><li><strong><em>Agonists:<\/em><\/strong><\/li><\/ul>\n\n\n\n<p><strong><em>&nbsp;<\/em><\/strong>Drugs that bind to physiological receptors and mimic the regulatory effects of the endogenous signalling compounds<\/p>\n\n\n\n<ul><li><strong><em>Partial Agonists:<\/em><\/strong><\/li><\/ul>\n\n\n\n<p><strong><em>&nbsp;<\/em><\/strong>Agents that are only partly as effective as agonists regardless of the concentration employed<\/p>\n\n\n\n<ul><li><strong><em>Inverse Agonists:<\/em><\/strong><\/li><\/ul>\n\n\n\n<p>An agent that binds to the same receptor as an agonist but induces pharmacological response opposite to that of agonist.<\/p>\n\n\n\n<p><img loading=\"lazy\" decoding=\"async\" width=\"369\" height=\"298\" src=\"\"><strong>Threshold:<\/strong>&nbsp; Dose that produces a just-noticeable effect.<\/p>\n\n\n\n<p><strong>ED<sub>50<\/sub>:<\/strong>&nbsp; Dose that produces a 50% of maximum response.<\/p>\n\n\n\n<p><strong>Ceiling:<\/strong>&nbsp; Lowest dose that produces a maximal effect.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"369\" height=\"297\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-8.png?w=369\" alt=\"\" class=\"wp-image-319\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-8.png 369w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-8-300x241.png 300w\" sizes=\"(max-width: 369px) 100vw, 369px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"359\" height=\"255\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-9.png?w=359\" alt=\"\" class=\"wp-image-320\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-9.png 359w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-9-300x213.png 300w\" sizes=\"(max-width: 359px) 100vw, 359px\" \/><\/figure>\n\n\n\n<ul><li><strong><em>Antagonists<\/em><\/strong><strong>:<\/strong><\/li><\/ul>\n\n\n\n<p><strong>\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 D<\/strong>rug that binds to receptors but cannot initiate a cellular response, but prevent agonists from producing a response;<\/p>\n\n\n\n<p>Has affinity, but no efficacy.<\/p>\n\n\n\n<ul><li><strong>Drug Antagonism<\/strong><\/li><\/ul>\n\n\n\n<p>The process of inhibition of an agonist-driven cellular response by another molecule.<\/p>\n\n\n\n<p>effect of drugs A + B &lt; effect of drug A + effect of drug B<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"371\" height=\"218\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-10.png?w=371\" alt=\"\" class=\"wp-image-321\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-10.png 371w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-10-300x176.png 300w\" sizes=\"(max-width: 371px) 100vw, 371px\" \/><\/figure>\n\n\n\n<ol type=\"1\"><li><strong>Physical Antagonism<\/strong><\/li><\/ol>\n\n\n\n<p>Charcoal adsorbs alkaloids and can prevent their absorption<\/p>\n\n\n\n<p>Therapeutic management of alkaloidal poisonings<\/p>\n\n\n\n<ul><li><strong>Chemical Antagonism<\/strong><\/li><\/ul>\n\n\n\n<p>Chemical antagonism refers to the uncommon situation where the two substances combine in solution; as a result, the effect of the active drug is lost<\/p>\n\n\n\n<p><strong>The two drugs react chemically and form an inactive product, e.g.<\/strong><\/p>\n\n\n\n<p>\u2022 KMnO4 oxidizes alkaloids\u2014used for gastric lavage in poisoning.<\/p>\n\n\n\n<p>\u2022 Chelating agents (BAL, Cal. disod. edetate) complex toxic metals (As, Pb).<\/p>\n\n\n\n<p>\u2022 Nitrites form methaemoglobin which reacts with cyanide radical.<\/p>\n\n\n\n<ul><li>Positively charged protamine counteracting negatively charged heparin<\/li><li><strong>Drugs may react when mixed in the same syringe or infusion bottle:<\/strong><\/li><li>\u2022 Thiopentone sod. + succinylcholine chloride (T+S former will get hydrolyzed bcoz of strong alkalinity of the latter)<\/li><li>Phenytoin +glucose solution (Glucose has low pH so phenytoin anion is partly ppt as less soluble acid)<\/li><\/ul>\n\n\n\n<ul><li><strong>Physiological\/functional antagonism<\/strong><\/li><\/ul>\n\n\n\n<p>The two drugs act on different receptors or by different mechanisms, but have opposite overt effects on the same physiological function, i.e. have pharmacological effects in opposite direction,<\/p>\n\n\n\n<p>e.g.\u2022 Histamine and adrenaline on bronchial muscles and BP.<\/p>\n\n\n\n<p>\u2022 Glucagon and insulin on blood sugar level.<\/p>\n\n\n\n<ul><li><strong>Pharmacokinetic Antagonism<\/strong><\/li><\/ul>\n\n\n\n<p>Pharmacokinetic antagonism describes the situation in which the \u2018antagonist\u2019 effectively reduces the concentration of the active drug at its site of action.<\/p>\n\n\n\n<p><strong>Absorption<\/strong><\/p>\n\n\n\n<p>Drugs which slows the gastric emptying such as opioids or antimuscarinic agents reduce absorption in general.<\/p>\n\n\n\n<p>Calcium forming an insoluble complex with tetracycline.<\/p>\n\n\n\n<p>Cholestyramine decreases absorption of digoxin, warfarin.<\/p>\n\n\n\n<ul><li><strong>Metabolism<\/strong><\/li><li>e.g. the reduction of the anticoagulant effect of <strong>warfarin <\/strong>when an agent that accelerates its hepatic metabolism, such as <strong>phenytoin<\/strong>, is given.<\/li><li>Drugs like rifampicin, phenytoin, or carbamazepine are potential enzyme inducers which can lead to OCP failure<\/li><li>Phenobarbitone is used in treatment of kernicterus where it enhances the conjugation of bilirubin.<\/li><li><strong>Elimination<\/strong><\/li><\/ul>\n\n\n\n<p>sodium bicarbonate used for forced alkaline diuresis for barbiturate poisoning.<\/p>\n\n\n\n<p><strong>Receptor antagonism<\/strong><\/p>\n\n\n\n<ul><li>Competitive antagonism\/Surmountable antagonism.<\/li><li>Non-surmountable \/noncompetitive antagonism<ul><li>Allosteric<\/li><\/ul><ul><li>Irreversible<\/li><\/ul><\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"389\" height=\"291\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-11.png?w=389\" alt=\"\" class=\"wp-image-322\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-11.png 389w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-11-300x224.png 300w\" sizes=\"(max-width: 389px) 100vw, 389px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"312\" height=\"158\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-12.png?w=312\" alt=\"\" class=\"wp-image-323\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-12.png 312w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-12-300x152.png 300w\" sizes=\"(max-width: 312px) 100vw, 312px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"286\" height=\"175\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-13.png?w=286\" alt=\"\" class=\"wp-image-324\" \/><\/figure>\n\n\n\n<ul><li>USES- to prevent the activity of drugs<\/li><\/ul>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp;&nbsp; -to reverse the effects of drugs that have already been consumed.<\/p>\n\n\n\n<ul><li>&nbsp;Naloxone reverse opioid overdose caused by drugs such as heroin or morphine.<\/li><li><img loading=\"lazy\" decoding=\"async\" width=\"267\" height=\"109\" src=\"\">Flumazenil is an antidote to benzodiazepines.<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"440\" height=\"303\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-14.png?w=440\" alt=\"\" class=\"wp-image-325\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-14.png 440w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-14-300x207.png 300w\" sizes=\"(max-width: 440px) 100vw, 440px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"267\" height=\"108\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-15.png?w=267\" alt=\"\" class=\"wp-image-326\" \/><\/figure>\n\n\n\n<p><strong>Allosteric Antagonism<\/strong><\/p>\n\n\n\n<p>Binds to a site other than the agonist binding site called as allosteric site.<\/p>\n\n\n\n<ul><li>Maraviroc is a negative&nbsp;<a href=\"https:\/\/en.wikipedia.org\/wiki\/Allosteric_regulation\">allosteric modulator<\/a>&nbsp;of the&nbsp;<a href=\"https:\/\/en.wikipedia.org\/wiki\/CCR5\">CCR5<\/a>&nbsp;receptor<\/li><\/ul>\n\n\n\n<p>The drug binds to CCR5, thereby blocking the HIV protein&nbsp;<a href=\"https:\/\/en.wikipedia.org\/wiki\/Gp120\">gp120<\/a>&nbsp;from associating with the receptor.&nbsp;<a href=\"https:\/\/en.wikipedia.org\/wiki\/HIV\">HIV<\/a>&nbsp;is then unable to enter human&nbsp;<a href=\"https:\/\/en.wikipedia.org\/wiki\/Macrophage\">macrophages<\/a>&nbsp;and&nbsp;<a href=\"https:\/\/en.wikipedia.org\/wiki\/T_cell\">T cells<\/a>.<\/p>\n\n\n\n<p>Cinacalcet &nbsp;<a href=\"https:\/\/en.wikipedia.org\/wiki\/Allosteric_activation\">allosteric activation<\/a><\/p>\n\n\n\n<p>Cinacalcet increases the sensitivity of calcium receptors on parathyroid cells to reduce parathyroid hormone (PTH) level<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"425\" height=\"290\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-16.png?w=425\" alt=\"\" class=\"wp-image-327\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-16.png 425w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-16-300x205.png 300w\" sizes=\"(max-width: 425px) 100vw, 425px\" \/><\/figure>\n\n\n\n<p>The resulting shifts to the right of the agonist dose response curves are converted to dose ratios (DR) and utilized in the Schild equation to construct a Schild regression<\/p>\n\n\n\n<p><strong>Clinical Significance of drug antagonism<\/strong><strong><\/strong><\/p>\n\n\n\n<p><strong>\u2022 Correcting adverse effects of drug;<\/strong><\/p>\n\n\n\n<p>e.g., chlorpromazine induced extrapyramidal reactions which are due to cholinergic activation can be countered by benzhexol<\/p>\n\n\n\n<p>\u2022 <strong>Treating drug poisoning;<\/strong><strong><\/strong><\/p>\n\n\n\n<p>&nbsp;e.g., morphine with naloxone, organophosphorus compounds with atropine<\/p>\n\n\n\n<p>\u2022 <strong>Predicting drug combinations which would reduce drug efficacy,<\/strong><\/p>\n\n\n\n<p>&nbsp;e.g., the penicillin and tetracycline combination is inferior to penicillin alone in pneumococcal meningitis.<\/p>\n\n\n\n<p><strong>Detecting Antagonism during Drug Development Process<\/strong><\/p>\n\n\n\n<ul><li>Preclinical studies- Bioassay<\/li><li>ADR Reporting<\/li><li>Phase IV- Pharmacovigilance<\/li><li>Case Reports and Publishing research<\/li><li>Drug interactions between herbal drugs and allopathic drugs<\/li><\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Drug antagonism Affinity: The tendency of a drug to bind to the receptors. Efficacy: Once bound, tendency to activate the receptor. Agonists: &nbsp;Drugs that bind to physiological receptors and mimic the regulatory effects of the endogenous signalling compounds Partial Agonists: &nbsp;Agents that are only partly as effective as agonists regardless of the concentration employed Inverse[&#8230;]\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/318"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=318"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/318\/revisions"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=318"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=318"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=318"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}