Pharmacogenomics Flashcards
Pharmacodynamic vs Pharmacokinetic
Susceptibility of slow and fast acetylators
Thiopurine-S-Methyltransferase (TMPT) Polymorphism causes:
•Defect causes severe hematapoietic toxicity following standard doses of anticancer and antiinflammatory drugs such as mercaptopurine, 6-thioguanine and azathioprine.
Uridine Diphosphate Glucuronosyltransferase (UGT) Polymorphism causes:
Transcriptional regulation of UGT is mediated by series of TA repeats in the proximal promoter. Deficiency in UGT1A1-catalyzed bilirubin glucuronidation is associated with 7 TA repeats in the promoter (UGT1A1*28) resulting in Gilbert’s syndrome.
UGT polymorphism is associated with increased toxicity (myelosuppression and diarrhea) following use of irinotecan, a topoisomerase I inhibitor used in the treatment of several cancers
CYP2D6 Oxidation Polymorphism causes:
PM = poor metabolizer
CYP2C9 Oxidation Polymorphism causes
Warfarin resistance. There are two types of warfarin resistance: incomplete and complete. Those with incomplete warfarin resistance can achieve the benefits of warfarin treatment with a high dose of warfarin. Individuals with complete warfarin resistance do not respond to warfarin treatment, no matter how high the dose. If people with warfarin resistance require anticoagulant therapy and take the average warfarin dose, they will remain at risk of developing a potentially harmful blood clot
CYP2C19 Oxidation Polymorphism causes:
CYP2C19 biotransforms many clinically useful drugs including clopidogrel. Poor CYP2C19 metabolizers are at high risk of treatment failure due to insufficient levels of active metabolite. These patients are at increased risk for heart attack, stroke, stent thrombosis and death due to inadequate therapeutic effects from clopidogrel treatment.
Polymorphisms in beta-2 adrenergic receptor gene (ADRB2) affect response to
bronchodilators such as albuterol and isoproterenol
Changes in the function of SLCO1B1 transporter cause
can increase the severity of statin-related muscle damage
•Simvastatin is among the most commonly used prescription medications for cholesterol reduction. A single coding single-nucleotide polymorphism in SLCO1B1 increases systemic exposure to simvastatin and risk of muscle toxicity.
What is naloxone’s primary pharmacological action
Naloxone hydrochloride is essentially a pure opiate antagonist. The precise mechanism of action of the opiate antagonist effects of naloxone is not fully understood. Naloxone is thought to act as a competitive antagonist at mc, κ, and σ opiate receptors in the CNS
