Pharmacogenetics involves variations in drug effect due to genetic predisposition.
The activity of enzymes that metabolize the drug, often varies greatly, making the metabolism highly variable in healthy people. The elimination rate of drugs varies by up to 40 times. Genetic factors and aging seem to be responsible for the majority of these fluctuations.
Pharmacogenetics involves variations in drug effect due to genetic predisposition. The activity of enzymes that metabolize the drug, often varies greatly, making the metabolism highly variable in healthy people. The elimination rate of drugs varies by up to 40 times. Genetic factors and aging seem to be responsible for the majority of these fluctuations. Pharmacogenetic variations (z. B. respect acetylation, hydrolysis, oxidation or enzymes that metabolize drugs) may have clinical consequences (s. Examples of pharmacogenetic fluctuations). For example, if patients metabolize certain drugs quickly, they may require higher and more frequent doses to achieve therapeutic concentrations. When patients metabolize certain drugs slowly, they may need to avoid toxic effects lesser and greater distances lying in cans, in particular for drugs with a narrow therapeutic index. For example, patients with inflammatory bowel disease who require azathioprine therapy, now routinely on the thiopurine methyltransferase (TPMT) genotype tested to determine the most appropriate starting dose for the drug therapy. Most genetic differences can not be predicted prior to drug therapy, but in a growing number of drugs (eg., Carbamazepine, clopidogrel, warfarin) were attributed changes in efficacy and toxicity risk specific to certain genetic variants. In addition, numerous environmental and developmental factors may come together and to genetic factors and drug response influence in interaction (s. Genetic, environmental and development-related factors that may cause variations in response to drugs). Examples of pharmacogenetic variations incidence fluctuation effects acetylation, fast – the need for higher or more frequent doses of drugs that are acetylated to produce the desired therapeutic response acetylation, slowly (inactivation of the drug by the liver-N- (such as isoniazid.) acetyltransferase) Approximately 50% of the US population Increased susceptibility to adverse drug reactions that are acetylated (z. B. in Isoniazid, peripheral neuritis; with hydralazine or procainamide, lupus) aldehyde dehydrogenase-2 deficiency Approximately 50% of Japanese, Chinese and other Asian populations When alcohol consumption significantly increases the acetaldehyde in the blood, facial flushing, increased heart rate, sweating, muscle weakness and sometimes catecholamine-mediated vasodilation with euphoria effect Genetic polymorphisms of the CYP2C9 30% in a study common in East Asians reduced enzymatic activation of clopidogrel, which leads to reduced inhibition of platelet aggregation and an increased risk of thrombosis in high risk patients G6PD deficiency 10% of dark-skinned men Higher prevalence in individuals When using oxidizing agents, such as certain antimalarials (with Mediterranean ancestry z. As chloroquine, primaquine), there is an increased risk of hemolytic anemia Genetic polymorphisms of the CYP2C9 and the vitamin K epoxide reductase complex subunit 1 (VKORC1) – Increased Warfarinwirkung *, increased bleeding HLA-B * 1502 1 to 6 /10.000 in countries with predominantly fair-skinned population in some Asian countries by about 10 times higher increased risk of adverse drug reactions to carbamazepine, including severe dermatologic reactions (eg. as Stevens-Johnson syndrome) pseudocholinesterase Mange l in plasma approximately 1/1500 People Decreased succinylcholine inactivation Conventional succinylcholine doses prolonged paralysis of respiratory muscles and sometimes lasting apnea that requires mechanical ventilation until the drug can be eliminated via an alternative route * In a study CYP2C9 were or VKORC1 -Genvarianten responsible for about 40% of the variance in warfarin dosing. Genetic, environmental and development-dependent factors, the fluctuations can cause in the response to drugs