The terms pharmacogenomics and pharmacogenetics tend to be used interchangeably, and a precise, consensus definition of either remains elusive. Pharmacogenomics is the branch of Pharmacology which deals with the influence of genetic variation on drug response in patients by correlating Gene expression Pharmacogenetics is generally regarded as the study or clinical testing of genetic variation that gives rise to differing response to drugs, while pharmacogenomics is the broader application of genomic technologies to new drug discovery and further characterization of older drugs. Genetic diversity is a level of Biodiversity that refers to the total number of genetic characteristics in the genetic makeup of a species A drug, broadly speaking is any chemical substance that when absorbed into the body Pharmacogenomics is the branch of Pharmacology which deals with the influence of genetic variation on drug response in patients by correlating Gene expression In Medicine, Biotechnology and Pharmacology, drug discovery is the process by which drugs are discovered and/or designed Pharmacogenetics considers one or at most a few genes of interest, while pharmacogenomics considers the entire genome. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance Pharmacogenomics is the branch of Pharmacology which deals with the influence of genetic variation on drug response in patients by correlating Gene expression In classical genetics the genome of a Diploid Organism including Eukarya refers to a full set of chromosomes or genes in a Gamete, thereby
Much of current clinical interest is at the level of pharmacogenetics, involving variation in genes involved in, drug metabolism with a particular emphasis on improving drug safety. Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The wider use of pharmacogenetic testing is viewed by many as an outstanding opportunity to improve prescribing safety and efficacy. Driving this trend are the 106,000 deaths and 2. 2 Million serious events caused by adverse drug reactions in the US each year (Lazarou 1998). As such ADRs are responsible for 5-7% of hospital admissions in the US and Europe, lead to the withdrawal of 4% of new medicines and cost society an amount equal to the costs of drug treatment (Ingelman-Sundberg 2005). Comparisons of the list of drugs most commonly implicated in adverse drug reactions with the list of metabolizing enzymes with known polymorphisms found that drugs commonly involved in adverse drug reactions were also those that were metabolized by enzymes with known polymorphisms (see Phillips, 2001). Polymorphism in biology occurs when two or more clearly different Phenotypes exist in the same population of a species — in other words the occurrence of more than one
The first observations of genetic variation in drug response date from the 1950s, involving the muscle relaxant suxamethonium chloride, and drugs metabolized by N-acetyltransferase. Suxamethonium chloride (also known as succinylcholine, scoline, or colloquially as sux) is a medication widely used in Emergency medicine and N-acetyltransferase is an Enzyme that catalyzes the transfer of Acetyl groups from Acetyl-CoA to Arylamines They have wide specificity One in 3500 Caucasians has less efficient variant of the enzyme (butyrylcholinesterase) that metabolizes suxamethonium chloride . The Caucasian race, sometimes the Caucasoid race, is a term of Racial classification, coined around 1800 by Johann Friedrich Blumenbach for the " Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Butyrylcholinesterase, also known as BCHE, is a human Gene. Butyrylcholinesterase is also called serum cholinesterase Metabolism is the set of Chemical reactions that occur in living Organisms in order to maintain Life. As a consequence, the drug’s effect is prolonged, with slower recovery from surgical paralysis. Variation in the N-acetyltransferase gene divides people into “slow acetylators” and “fast acetylators”, with very different half-lives and blood concentrations of such important drugs as isoniazid (antituberculosis) and procainamide (antiarrhythmic). N-acetyltransferase is an Enzyme that catalyzes the transfer of Acetyl groups from Acetyl-CoA to Arylamines They have wide specificity Given an assembly of elements the number of which decreases ultimately to zero the lifetime (also called the mean lifetime) is a certain number that characterizes the rate Isoniazid (also called isonicotinyl hydrazine or INH) is a first-line antituberculous medication used in the prevention and treatment of Tuberculosis Procainamide (proe-KANE-a-mide ( INN, trade names Pronestyl, Procan, Procanbid) is a Pharmaceutical Antiarrhythmic agent used for As part of the inborn system for clearing the body of xenobiotics, the cytochrome P450 oxidases (CYP450) are heavily involved in drug metabolism, and genetic variations in CYP450s affect large populations. A xenobiotic is a Chemical which is found in an Organism but which is not normally produced or expected to be present in it Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of Hemoproteins found in all Domains Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems One member of the CYP450 superfamily, CYP2D6, now has over 75 known allelic variations, some of which lead to no activity, and some to enhanced activity. Cytochrome P450 2D6 (CYP2D6 a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism of Xenobiotics An estimated 29% of people in parts of East Africa may have multiple copies of the gene, and will therefore not be adequately treated with standard doses of drugs such as the painkiller codeine (which is activated by the enzyme). East Africa is the Easternmost Region of the African Continent. Codeine ( INN) or methylmorphine is an Opiate used for its Analgesic, antitussive and antidiarrheal properties
One of the earliest tests for a genetic variation resulting in a clinically important consequence was on the enzyme thiopurine methyltransferase (TPMT). Thiopurine methyltransferase or thiopurine S-methyltransferase ( TPMT) is an Enzyme ( that methylates Thiopurine compounds TPMT metabolizes 6-mercaptopurine and azathioprine, two thiopurine drugs used in a range of indications, from childhood leukemia to autoimmune diseases. Mercaptopurine (also called 6-Mercaptopurine 6-MP or its brand name Purinethol) is an Immunosuppressive drug used to treat Leukemia. Azathioprine is an immunosuppressant used in Organ transplantation Autoimmune disease such as Rheumatoid arthritis and Pemphigus or inflammatory The thiopurine drugs are Purine antimetabolites widely used in the treatment of Acute lymphoblastic leukemia, Autoimmune disorders (e Leukemia or leukaemia (Greek leukos λευκός, "white" aima αίμα, "blood" is a Cancer of the Blood Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues In people with a deficiency in TPMT activity, thiopurine metabolism must proceed by other pathways, one of which leads to the active thiopurine metabolite that is toxic to the bone marrow at high concentrations. Metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind" - specifically the study of their small-molecule metabolite Deficiency of TPMT affects a small proportion of people, though seriously. One in 300 people have two variant alleles and lack TPMT activity; these people need only 6-10% of the standard dose of the drug, and, if treated with the full dose, are at risk of severe bone marrow suppression. An allele (ˈæliːl (UK /əˈliːl/ (US (from the Greek αλληλος allelos, meaning each other) is one member of a pair or series of different forms Bone marrow suppression or myelotoxicity (adjective myelotoxic) is a serious side-effect of Chemotherapy and certain drugs affecting the immune system For them, genotype predicts clinical outcome, a prerequisite for an effective pharmacogenetic test. The genotype is the genetic constitution of a cell an organism or an individual (i In 85-90% of affected people, this deficiency results from one of three common variant alleles. Around 10% of people are heterozygous - they carry one variant allele - and produce a reduced quantity of functional enzyme. Zygosity refers to the genetic condition of a Zygote. In genetics zygosity describes the similarity or dissimilarity of DNA between Homologous Overall, they are at greater risk of adverse effects, although as individuals their genotype is not necessarily predictive of their clinical outcome, which makes the interpretation of a clinical test difficult. The genotype is the genetic constitution of a cell an organism or an individual (i Recent research suggests that patients who are heterozygous may have a better response to treatment, which raises whether people who have two wild-type alleles could tolerate a higher therapeutic dose. A mutant is an individual organism or new genetic character arising or resulting from an instance of Mutation, which is a base-pair sequence change within the DNA The US Food and Drug Administration (FDA) have recently deliberated the inclusion of a recommendation for testing for TPMT deficiency to the prescribing information for 6-mercaptopurine and azathioprine. Mercaptopurine (also called 6-Mercaptopurine 6-MP or its brand name Purinethol) is an Immunosuppressive drug used to treat Leukemia. Azathioprine is an immunosuppressant used in Organ transplantation Autoimmune disease such as Rheumatoid arthritis and Pemphigus or inflammatory Hitherto the information has carried the warning that inherited deficiency of the enzyme could increase the risk of severe bone marrow suppression. Now it will carry the recommendation that people who develop bone marrow suppression while receiving 6-mercaptopurine or azathioprine be tested for TPMT deficiency.
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