Pharmocogenetics Flashcards
Pharmocogenetics
It is the study of how genetic variations affect the disposition of drugs, including their metabolism and transport and their safety and efficacy
Pharmacokinetic
The process by which a drug is absorbed, distributed, metabolised and eliminated by the body
Pharmacodynamic
The biochemical and physiological effects of drugs and the mechanisms of their actions
Main objectives of Pharm
-Maximise drug efficiency
-Minimise drug toxicity
-Predict patients who will respond well to the intervention
-Assist in new drug discovery and development
-Individual’s genetic makeup will allow selective use of medications such that the drug processing is effectively maximised while side effects are minimised
Thiopurine drugs deficiency
Thiopurine S-methyltransferase (TPMT) deficiency is a condition characterised by significantly reduced activity of an enzyme that helps the body process drugs called thiopurines
-These drugs include 6-thioguanine, 6-mercaptopurine and azathioprine inhibit the immune system
Uses of thiopurines
Treat autoimmune disoreders including Crohn’s disease and rheumatoid arthritis, which occur when the immune system malfunctions
-They also treat several forms of cancer especially in blood-forming tisssues (leukaemia) and immune system (lymphomas)
-Also used in organ transplant recipients to prevent immune system from attacking transplanted organs
Tamoxifen
It is a selective eostrogen receptor modulator (SERM) therapeutic agent used to treat breast cancer in both men and women, and it is also used as a prophylactic agent against breast cancer in women
-It has to be converted to endoxifen which is bioactive by polymorphic enzyme cytochrome P450 2DG (CYP2D6)
CYP P450
Enzymes encoded by the P450 genes that are expressed as membrane-bound proteins predominately found in the endoplasmic reticulum of the liver
-Known as polymorphic enzyme cytochrome
CYP P450 functions
-Involved in oxidation, peroxidation and reductive metabolism
-Responsible for >90% of drug transformation
-Mainly found in liver for drug metabolism of antidepressennts to antihypertensive to chemotherapy
Mutation of CYPD
6-10% European population are deficient in this CYP2D6 enzyme
-efficacy of tamoxifen is likely low in this pop
CYP2D6 alleles
over 70
either cause no change, somewhat decrease or significant decrease
types include extensive metabolisers (EM), intermediate (IM) and poor metabolisers (PM)
-EM is the standard metabolism allele against which others are compared
Genetic test questions
Is there a specific variant of gene
Does patient have variant or variants of panel of genes tested
-Does patient have any variant that can explain their condition
genetic testing of specific variant function
Methods to test for specific variants
-PCR product length
-Restriction sites
Allele-specific PCR
PCR product length
Presence/absence of Restriction sites
Allele-specific PCR
