{"id":190,"date":"2019-04-24T15:03:38","date_gmt":"2019-04-24T15:03:38","guid":{"rendered":"https:\/\/sepia2.unil.ch\/pharmacology\/?page_id=190"},"modified":"2020-09-04T03:55:55","modified_gmt":"2020-09-04T03:55:55","slug":"pharmacogenetics","status":"publish","type":"page","link":"https:\/\/sepia2.unil.ch\/pharmacology\/applications\/pharmacogenetics\/","title":{"rendered":"Pharmacogenetics"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\"> &#8220;Study of hereditary sources of variation in drug response, their prevalence and mechanism&#8221;<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Description<\/h3>\n\n\n\n<p>Patients vary widely in their responses to drugs.\n Important factors in variability are drug metabolism and drug \ntransport. Interindividual variation of drug metabolism is due to \nseveral factors. Genetic polymorphism is one of them and is defined by \nthe presence, in a normal population, of monogenic traits that exist in \nat least two phenotypes, neither of which is rare (less than 1%). \n<\/p>\n\n\n\n<figure class=\"wp-block-video aligncenter\"><video height=\"346\" style=\"aspect-ratio: 346 \/ 346;\" width=\"346\" controls src=\"https:\/\/sepia2.unil.ch\/pharmacology\/wp-content\/uploads\/2019\/06\/pharmacogenetics_Trim.mp4\"><\/video><\/figure>\n\n\n\n<p>Genetic polymorphism of metabolic enzymes may be due to:<\/p>\n\n\n\n<ol class=\"wp-block-list\"><li>Allelic variants that lead to enzymes with different catalytic activities from that of the wild type form.<\/li><li>Gene suppression.<\/li><li>Gene duplication.<\/li><li>Modification in gene inducibility.<\/li><\/ol>\n\n\n\n<p>Genetic\n variability has been historically illustrated by the metabolism of \nisoniazid. Isoniazid is primarily acetylated in the liver to \nN-acetylisoniazid, a precursor of a hepatotoxic compound. Large \ngenetically controlled ethnic differences exist in the distribution of \nacetylator status (slow and rapid acetylators). Adverse effects may \noccur prevalently in slow acetylators. On the other hand, rapid \nacetylators may be more susceptible to adverse reactions such as \nisoniazid-induced hepatic damage. Later on, it has been found that the \nmajority of metabolic polymorphisms involve the isoenzymes of the \ncytochrome P450 system.<\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"511\" src=\"https:\/\/sepia2.unil.ch\/pharmacology\/wp-content\/uploads\/2019\/07\/graphPharmacogenetics-1024x511.png\" alt=\"\" class=\"wp-image-683\" srcset=\"https:\/\/sepia2.unil.ch\/pharmacology\/wp-content\/uploads\/2019\/07\/graphPharmacogenetics-1024x511.png 1024w, https:\/\/sepia2.unil.ch\/pharmacology\/wp-content\/uploads\/2019\/07\/graphPharmacogenetics-300x150.png 300w, https:\/\/sepia2.unil.ch\/pharmacology\/wp-content\/uploads\/2019\/07\/graphPharmacogenetics-768x383.png 768w, https:\/\/sepia2.unil.ch\/pharmacology\/wp-content\/uploads\/2019\/07\/graphPharmacogenetics.png 1398w\" sizes=\"auto, (max-width: 767px) 89vw, (max-width: 1000px) 54vw, (max-width: 1071px) 543px, 580px\" \/><\/figure><\/div>\n\n\n\n<h3 class=\"wp-block-heading\">Clinical implications<\/h3>\n\n\n\n<p>The clinical implications of genetic polymorphism\n in drug metabolism depend on whether activity or toxicity lies with the\n affected substrate or the metabolite, as well as the importance of the \npathway to overall elimination. If the parent drug is active, there is a\n greater likelihood of adverse reactions in poor metabolizers and \nineffective therapy in extensive metabolizer. Likewise, if the \nmetabolite is active or toxic, there is a greater likelihood of adverse \nreactions in the extensive metabolizers and ineffective therapy in the \npoor metabolizers.\n<\/p>\n\n\n\n<p>Genetic variability may effect drug clearance but also drug bioavailability (for drugs with a high hepatic <a href=\"\/pharmacology\/extractionratio\">extraction ratio<\/a>).<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Related terms<\/h3>\n\n\n\n<p>Genotype: Fundamental assortment of genes of an individual.\n<\/p>\n\n\n\n<p>Genotyping: DNA analysis of a small sample of blood,\n and characterization of the genes involved in the metabolic pathway of \nconcern.\n<\/p>\n\n\n\n<p>Phenotype: Outward characteristic expression of an individual.\n<\/p>\n\n\n\n<p>Phenotyping: Measurements of drug and metabolite \nconcentrations after administration of a drug to an individual. This \nallows the assessment of the activity of a metabolic pathway in the \nindividual. \n<\/p>\n\n\n\n<p>Phenocopying: Transformation of an extensive metabolizer into a poor metabolizer by enzymatic inhibitors.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>&#8220;Study of hereditary sources of variation in drug response, their prevalence and mechanism&#8221; Description Patients vary widely in their responses to drugs. Important factors in variability are drug metabolism and drug transport. Interindividual variation of drug metabolism is due to several factors. Genetic polymorphism is one of them and is defined by the presence, in &hellip; <\/p>\n<p class=\"link-more\"><a href=\"https:\/\/sepia2.unil.ch\/pharmacology\/applications\/pharmacogenetics\/\" class=\"more-link\">Continue reading<span class=\"screen-reader-text\"> &#8220;Pharmacogenetics&#8221;<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"parent":9,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-190","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/190","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/comments?post=190"}],"version-history":[{"count":5,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/190\/revisions"}],"predecessor-version":[{"id":1333,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/190\/revisions\/1333"}],"up":[{"embeddable":true,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/9"}],"wp:attachment":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/media?parent=190"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}