Pharmacogenomics PPT PDF

PHARMACOGENOMICS - PPT NO. 4 (DR. GUPTA) 1. What is pharmacogenomics? A: The study of how genetic variations affect an individual's response to drugs. 2. How do genetic variations impact drug response? A: They can alter drug efficacy, toxicity, and the degree of metabolism in the body. 3. What i...

PHARMACOGENOMICS - PPT NO. 4 (DR. GUPTA) 1. What is pharmacogenomics? A: The study of how genetic variations affect an individual's response to drugs. 2. How do genetic variations impact drug response? A: They can alter drug efficacy, toxicity, and the degree of metabolism in the body. 3. What is the significance of enzyme variability in drug metabolism? A: Variability in enzyme activity can lead to no activity, decreased activity, or overexpression, impacting drug response. 4. What are the major CYP enzymes involved in drug metabolism? A: CYP2C9, CYP2C19, CYP3A4, and CYP2D6. 5. What is a poor metabolizer (PM) phenotype? A: An individual with deficient enzyme activity, leading to slow drug metabolism and potential toxicity. 6. What effect does the PM phenotype have on plasma drug levels? A: Progressive increase in plasma drug levels with repeated dosing, increasing risk of toxicity. 7. What is an ultra-rapid metabolizer (UM) phenotype? A: An individual with high enzyme activity, leading to rapid drug metabolism and potentially reduced drug efficacy. 8. Which drug does the FDA recommend CYP2C9 genotyping for? A: Warfarin and celecoxib. 9. Why is CYP2C19 genotyping important in drug therapy? A: To personalize drug doses for medications metabolized by CYP2C19, avoiding adverse effects or inefficacy. 10. What is the role of CYP3A4 in drug interactions? A: CYP3A4 affects the metabolism of many drugs and is involved in drug-drug and drug-food interactions. 11. What was the outcome of the case presentation involving a mother prescribed codeine postpartum? A: The infant died of respiratory depression due to the mother's ultra-rapid metabolism of codeine to morphine. 12. How does CYP2D6 genotype influence codeine metabolism? A: Poor metabolizers (PMs) experience reduced analgesic effects, while ultra-rapid metabolizers (UMs) are at risk of toxicity. 13. What genotype was found in the mother in the case study involving codeine? A: The mother was a CYP2D6 ultra-rapid metabolizer with a CYP2D6*2A & CYP2D6*2x2 gene duplication. 14. How does a CYP2D6 extensive metabolizer genotype affect drug response? A: They typically have a balanced response but may still be at risk with drugs that have narrow therapeutic ranges. 15. Why is it important to genotype for CYP2D6-dependent drugs? A: Different genotypes (PM, UM) require dose adjustments to avoid toxicity or lack of efficacy. 16. What role do drug transporters play in pharmacokinetics (PK) and pharmacodynamics (PD)? A: They affect drug absorption, distribution, and elimination, influencing therapeutic outcomes. 17. Which transporter reduces CNS drug exposure significantly? A: P-glycoprotein (P-gp) at the blood-brain barrier. 18. What is the clinical significance of P-gp variability? A: Differences in P-gp expression can affect CNS drug distribution and therapeutic efficacy. 19. What is SLCO1B1? A: A hepatic drug transporter responsible for drug uptake into hepatocytes. 20. What effect does decreased SLCO1B1 activity have on drug therapy? A: Increased drug toxicity and altered effectiveness due to reduced drug clearance. 21. What is the significance of SLCO1B1 polymorphisms like *2 and *3? A: They lead to decreased transporter activity, affecting drug pharmacokinetics. 22. How does genetic variability affect the therapeutic use of warfarin? A: Variants in CYP2C9 and VKORC1 affect dose requirements and bleeding risk. 23. What is a major clinical consequence of genetic variation in drug-metabolizing enzymes? A: Variation can lead to inter-individual differences in drug response and adverse effects. 24. Why is genetic testing recommended before starting certain medications? A: To tailor drug choice and dosage based on metabolic genotype, minimizing adverse effects. 25. How do CYP450 polymorphisms affect xenobiotic metabolism? A: They lead to different rates of drug metabolism, impacting efficacy and safety. 26. What are single nucleotide polymorphisms (SNPs)? A: Genetic variations in a single DNA building block that can affect enzyme function. 27. What are nonsynonymous mutations? A: SNPs that result in amino acid changes, potentially altering protein function. 28. How many SNPs have been identified for P-gp? A: 29 SNPs, with 11 coding for nonsynonymous mutations. 29. What is the function of P-gp in the blood-brain barrier? A: To limit drug entry into the CNS, reducing exposure and central effects. 30. What is the role of OATP1B1 in drug metabolism? A: It facilitates hepatic uptake of drugs from the bloodstream. 31. What effect does an overexpressed enzyme due to genetic variation have on drug response? A: Increased metabolism, potentially reducing drug efficacy at standard doses. 32. How does genetic variability in OATP1B1 influence statin therapy? A: Variants can lead to increased statin levels and risk of myopathy. 33. What is the impact of CYP2C19 polymorphisms on clopidogrel therapy? A: Poor metabolizers may have reduced drug activation, leading to decreased efficacy. 34. Why is pharmacogenomics important in personalized medicine? A: It allows for optimized drug therapy tailored to individual genetic profiles. 35. What does CYP stand for? A: Cytochrome P450, a family of enzymes involved in drug metabolism. 36. Why is CYP3A4 significant in pharmacogenomics? A: It metabolizes a large proportion of drugs and is subject to genetic variability. 37. What effect does the CYP2D6 UM phenotype have on morphine production from codeine? A: Increased conversion to morphine, raising the risk of toxicity. 38. What does PM stand for in pharmacogenomics? A: Poor Metabolizer, indicating limited enzyme activity. 39. What is the clinical impact of decreased CYP2C9 activity on NSAID use? A: Increased risk of adverse effects due to slower drug metabolism. 40. What is the main therapeutic risk associated with CYP2C19 PMs taking clopidogrel? A: Reduced antiplatelet effect and increased risk of thrombotic events. 41. How can genetic testing improve patient outcomes in pharmacotherapy? A: By identifying optimal drug and dose based on metabolism profiles. 42. What enzyme metabolizes diazepam? A: CYP3A4, which is affected by drug-drug and drug-food interactions. 43. Why are UMs at risk when taking prodrugs like codeine? A: They convert the prodrug to active metabolites rapidly, increasing toxicity risk. 44. What can cause a decreased response to antidepressants in certain patients? A: Genetic polymorphisms in CYP2D6, leading to altered drug metabolism. 45. How can P-gp variability affect antidepressant therapy? A: Differences in P-gp function can alter drug access to the CNS. 46. What happens if a patient has multiple copies of a CYP enzyme gene? A: They may metabolize drugs more quickly, requiring higher doses for efficacy. 47. What impact does the CYP2C9*2 polymorphism have on warfarin? A: It reduces enzyme activity, increasing bleeding risk at standard doses. 48. What type of mutation is found in CYP2C19 that affects drug metabolism? A: Loss-of-function mutations that impact drug activation. 49. Why might patients with a P-gp polymorphism experience CNS side effects? A: Reduced P-gp function allows more drug to enter the CNS. 50. How does pharmacogenomics benefit cancer therapy? A: By adjusting doses based on metabolizer status to optimize efficacy and safety. 51. What is an extensive metabolizer (EM)? A: An individual with normal metabolic function for a specific enzyme. 52. How can CYP2D6 polymorphisms affect opioid therapy? A: They influence conversion rates of prodrugs like codeine to active metabolites. 53. What role does P-gp play in multidrug resistance? A: It pumps drugs out of cells, reducing drug accumulation and effectiveness. 54. Why is CYP2D6 important in antidepressant metabolism? A: It metabolizes many antidepressants, affecting dosing and side effect profiles. 55. How does genetic variation in drug transporters impact statin use? A: Variants can lead to increased statin levels, raising the risk of muscle toxicity. 56. What is the role of SLCO1B1*5 in simvastatin therapy? A: It decreases transporter function, potentially leading to increased drug levels. 57. How does an individual's genotype for CYP2D6 affect tramadol metabolism? A: UMs convert tramadol to its active form quickly, increasing the risk of side effects. 58. What is a functional effect of CYP2C9*3? A: Reduced enzyme activity, requiring lower doses of drugs like warfarin. 59. What type of drugs are impacted by CYP3A4 polymorphisms? A: Many drugs, as CYP3A4 is involved in the metabolism of a significant portion of medications. 60. Why is pharmacogenomics essential in dosing adjustments? A: It helps tailor doses to the patient's metabolic profile, improving safety. 61. What is the result of increased SLCO1B1 activity? A: Faster drug clearance from the blood, potentially reducing drug efficacy. 62. What is the therapeutic implication of a CYP2D6 poor metabolizer for codeine? A: Reduced conversion to morphine, leading to decreased analgesic effect. 63. How does pharmacogenomics reduce adverse drug reactions? A: By identifying individuals at risk based on their metabolic profiles. 64. What does a P-gp inhibitor do? A: It blocks P-gp, increasing drug accumulation in cells and enhancing effects. 65. What is the primary clinical effect of a CYP3A4 inducer? A: Increased metabolism of CYP3A4 substrates, potentially reducing drug levels. 66. What is the impact of CYP2C19*17 on drug metabolism? A: Increased enzyme activity, leading to faster drug metabolism. 67. How can CYP polymorphisms affect oral contraceptive efficacy? A: Variants can alter hormone metabolism, impacting effectiveness and side effects. 68. What is the purpose of SLCO1B1 genotyping in statin therapy? A: To adjust dose to avoid myopathy in patients with decreased transporter function. 69. How can genetic testing for CYP2D6 benefit tamoxifen therapy? A: By identifying patients who may not effectively metabolize the drug to its active form. 70. What role does CYP1A2 play in drug metabolism? A: It metabolizes certain drugs like caffeine and theophylline, with variability affecting dose needs. 71. How does genetic variability in CYP2B6 affect bupropion therapy? A: Poor metabolizers may experience higher drug levels and risk of side effects. 72. Why might CYP2D6 UMs experience adverse effects with SSRIs? A: Rapid metabolism may reduce efficacy, requiring dose adjustments. 73. What is the effect of the CYP3A5*3 variant on drug metabolism? A: Reduced enzyme activity, affecting drugs like tacrolimus in transplant patients. 74. What genetic factor impacts methotrexate toxicity? A: Variants in the MTHFR gene, affecting folate metabolism and increasing side effects. 75. Why is genetic testing for thiopurine methyltransferase (TPMT) important? A: TPMT deficiency can lead to severe toxicity with drugs like azathioprine. 76. What does the term "pharmacogenomic effect" refer to? A: The influence of genetic variation on drug response, affecting efficacy and safety. 77. How does a CYP1A2 polymorphism impact caffeine metabolism? A: Certain variants slow caffeine metabolism, leading to prolonged effects. 78. What effect does a P-gp inducer have on drug bioavailability? A: It may reduce bioavailability by increasing drug efflux. 79. Why is CYP2C9 genotype important in phenytoin therapy? A: Variants can lead to drug accumulation and toxicity due to slow metabolism. 80. How does CYP2C19*2 affect drug metabolism? A: It is a loss-of-function variant that slows the metabolism of CYP2C19 substrates. 81. What impact does a CYP2D6 PM genotype have on antipsychotic therapy? A: It may require lower doses to avoid side effects from slower drug metabolism. 82. Why is P-gp variability significant in cancer therapy? A: It affects drug penetration into tumors and resistance to chemotherapy. 83. What is a potential risk of CYP3A4 inducers with oral contraceptives? A: Reduced contraceptive effectiveness due to faster metabolism. 84. How does CYP2C9*1 differ from CYP2C9*3? A: *1 is the wild-type (normal function) allele, while *3 reduces enzyme activity. 85. What does a "wild-type" allele mean in pharmacogenomics? A: It refers to the standard version of a gene without mutations affecting function. 86. How does genetic testing aid in chemotherapy? A: It helps adjust doses based on enzyme activity, minimizing toxicity. 87. What is the clinical impact of CYP2D6 gene duplications? A: Increased enzyme activity, often leading to the need for higher drug doses. 88. Why are UGT1A1 polymorphisms significant for irinotecan therapy? A: Variants can lead to increased drug toxicity due to reduced metabolism. 89. How does P-gp influence drug resistance? A: By expelling drugs from cells, it can reduce efficacy in cancer and HIV therapy. 90. What impact do CYP2D6 polymorphisms have on tramadol efficacy? A: Poor metabolizers may have reduced analgesic effects, while UMs face toxicity. 91. How does an individual’s CYP2C9 and VKORC1 genotype affect warfarin dosing? A: Variants in these genes require lower or higher doses to prevent bleeding or clotting. 92. What is a polymorphism? A: A genetic variation that may alter protein function or expression. 93. What is the clinical significance of CYP3A4 in HIV treatment? A: It metabolizes antiretrovirals, and variability affects drug effectiveness and side effects. 94. How does P-gp expression affect blood-brain barrier drug transport? A: High expression reduces CNS drug penetration, impacting therapy for CNS diseases. 95. What is the role of genetic testing in avoiding statin-induced myopathy? A: Identifying SLCO1B1 variants can prevent high-risk patients from severe muscle toxicity. 96. Why is CYP2D6 genotyping relevant for codeine use in pain management? A: To avoid inadequate pain control or toxicity based on metabolizer status. 97. What does the CYP2C19*1/*17 genotype indicate? A: Increased enzyme activity, which may require higher drug doses. 98. Why is personalized medicine crucial for drugs with narrow therapeutic windows? A: Genetic variability can significantly impact safety and efficacy. 99. What are pharmacokinetics and pharmacodynamics? A: PK: How the body processes drugs; PD: How drugs affect the body. 100. Why is understanding pharmacogenomics important for pharmacists? A: To help optimize drug therapy based on genetic profiles, improving patient outcomes.