HomeCoursesMEDSCI 204: Pharmacology and ToxicologyLecture 15 Lecture 15 1. What does a phenotype result from? Expression of genes and environmental factorsWhat does a phenotype result from?== Expression of genes and environmental factors 2. What factors influence disposition of a drug? sex, age, comorbidities, polypharmacyWhat factors influence disposition of a drug?== sex, age, comorbidities, polypharmacy 3. What phyiological differences can influence drug pk? body weight, fat distribution, liver blood flowWhat phyiological differences can influence drug pk?== body weight, fat distribution, liver blood flow 4. What pathological changes can alter pk? Renal failure, hepatic failure, cv functionWhat pathological changes can alter pk?== Renal failure, hepatic failure, cv function 5. What extrinsic factors increase or decrease the activity of a drug metabolising enzyme? Diet, smoking, polypharmacy (allopathic or herbal)What extrinsic factors increase or decrease the activity of a drug metabolising enzyme?== Diet, smoking, polypharmacy (allopathic or herbal) 6. Can enzymes only metabolise one drug? No...overlap specificity exists Can enzymes only metabolise one drug?== No...overlap specificity exists 7. What happens when two drugs share same enzyme for metabolism? Drug with higher Km binds stronger to enzyme and inhibits the other drugWhat happens when two drugs share same enzyme for metabolism? ==Drug with higher Km binds stronger to enzyme and inhibits the other drug 8. What can drug induction cause? Decreased plasma conc, increased active metabolite, increased toxic metaboliteWhat can drug induction cause? ==Decreased plasma conc, increased active metabolite, increased toxic metabolite 9. What is autoinduction? Repeat exposure to a drug increases its own metabolise and clearance by increasing ezymeWhat is autoinduction?== Repeat exposure to a drug increases its own metabolise and clearance by increasing ezyme 10. Describe the process of nuclear hormone receptor transcription factor activation? Ligand binds NR, receptor ligand dissociates and translocates to nucleus, dimerises with a response element, increase in expression of target geneDescribe the process of nuclear hormone receptor transcription factor activation?== Ligand binds NR, receptor ligand dissociates and translocates to nucleus, dimerises with a response element, increase in expression of target gene 11. What NRs have limited endogenous ligands? Hormone-NRsWhat NRs have limited endogenous ligands?== Hormone-NRs 12. Describe the xeobiotic-NRs? Flexible ligand binding regionDescribe the xeobiotic-NRs? ==Flexible ligand binding region 13. What is a feature of target genes of ligand activated NRs? Overlap exists between target genes of receptorsWhat is a feature of target genes of ligand activated NRs?== Overlap exists between target genes of receptors 14. What could happen if St John's wort is taken along with oral contraceptive? Ethynyl estradiol is a substrate of CYP3A4 and St Johns wort is an inducer of CYP3A4 resulting in faster clearance of the oral contraceptiveWhat could happen if St John's wort is taken along with oral contraceptive?== Ethynyl estradiol is a substrate of CYP3A4 and St Johns wort is an inducer of CYP3A4 resulting in faster clearance of the oral contraceptive 15. What does smoking do to metabolic activity? polycyclic aromatic hydrocarbons act as ligands to increase gene expression of CYP1A2 (induction). Stopping smoking will decrease clearance and increase plasma concentrationsWhat does smoking do to metabolic activity?== polycyclic aromatic hydrocarbons act as ligands to increase gene expression of CYP1A2 (induction). Stopping smoking will decrease clearance and increase plasma concentrations 16. How does diet affect drug metabolism? High protein/low carb diet increases metabolism for CYP, high fat/calorie has little effectHow does diet affect drug metabolism?== High protein/low carb diet increases metabolism for CYP, high fat/calorie has little effect 17. What do cruciferous vegetables do to metabolism? Induction of enzymesWhat do cruciferous vegetables do to metabolism?== Induction of enzymes 18. What does aromatic hydrocarbons (chargrilled meats) do to drug metabolism? Induces CYP1A2What does aromatic hydrocarbons (chargrilled meats) do to drug metabolism?== Induces CYP1A2 19. How does gender affect drug metabolism? Hormone differences (menstruel/pregnancy), body typeHow does gender affect drug metabolism?== Hormone differences (menstruel/pregnancy), body type 20. How does age affect metabolism? Physiological/pathophysiologies in elderly, immaturity of enzyme systems in neonatesHow does age affect metabolism? ==Physiological/pathophysiologies in elderly, immaturity of enzyme systems in neonates 21. How does inflammation affect drug metabolism? Inflammatory cytokines (IL-6) down regulates enzymes (NR suppression)How does inflammation affect drug metabolism? ==Inflammatory cytokines (IL-6) down regulates enzymes (NR suppression) 22. What is voriconazole metabolised by?= CYP2C19, CYP3A4 What is voriconazole metabolised by?= CYP2C19, CYP3A4 23. What causes the variation of variconazole metabolism?= Inherited variations of CYP2C19, CYP3A4 pathway, inhibition or induction by other drugs, inflammation (IL-6) due to fungal infection (supression) What causes the variation of variconazole metabolism?= Inherited variations of CYP2C19, CYP3A4 pathway, inhibition or induction by other drugs, inflammation (IL-6) due to fungal infection (supression) Loading...
