15 Pharmacogenetics Flashcards
How can genetics change the body’s response to drugs?
Changes to structure or activity of a protein e.g. enzyme, transporter, target.
What does the gene TPMT control?
Clinical relevance?
Thiopurine methyltransferase.
Inactivates azathioprine, 6-mercaptopurine and 6-thioguanine.
Polymorphisms may induce greater toxicity due to DNA damage from active molecules.
What does the gene NAT2 control?
N-acetyltransferase activity.
Liver enzymes that inactivate drugs via acetylation.
Which drugs are affected by different acetylation status’? (3).
Isoniazid.
Sulfasalazine.
Hydralazine.
What does the BCHE gene control?
Clinical significance of homozygote mutation?
Butyrylcholinesterase activity.
Reduced activity - risk of death with succinylcholine use.
What is the genetic basis of aminoglycoside induced hearing loss?
Mitochondrial MT-RNR1 gene encodes 12s rRNA. Mutation changes structure to resemble 16S rRNA of E.coli. Amino glycoside binds to patients rRNA, inducing hearing loss.
Which two genes account for 50% of warfarin dosage variability?
CYP2C9.
VKORC1.
What is the clinical significance of the gene HLA-B*15:02?
Carbamazepine use may lead to Stephen-Johnson syndrome.
What is the clinical significance of the gene ADRB2?
Beta blockers and beta agonists are ineffective.
Which genes are linked to the development of malignant hyperthermia? (2).
RYR1.
CACNA1S.
What is the clinical significance of the gene UGT1A1?
Increased toxicity of irinotecan (chemo).
What is the clinical significance of the gene DPD?
Increased toxicity of 5-fluorouracil (chemo).
What is the clinical significance of the gene G6PD?
Primaquinine, fava beans and sulphonamides induce heamolysis.
What is the clinical significance of the gene CYP2C19?
Decreased activity of clopidogrel.
What is the proper name for herceptin?
Trastuzumab.
