Classify each of these drugs based on their ability to induce or inhibit CYP450 enzymes phenobarbital

Classify each of these drugs based on their ability to induce or inhibit CYP450 enzymes phenobarbitalAnswer 1 Question 5voriconazole Answer 2 Question 5ritonavir Answer 3 Question 5Grapefruit juiceAnswer 4 Question 5

The principal metabolic pathway of phenytoin and phenobarbital in human is aromatic hydroxylation, catalyzed by CYP2C9 and CYP2C19. The reactive intermediate, arene oxide is deactivated by either epoxide hydrolase to dihydrodiol or by the action of glutathione (GSH) and glutathione S-transferase. The pathways of phenytoin metabolism are depicted below. Valproate metabolism by P450 CYP2C9 CYP2A6  Hypersensitivity reactions (idiosyncratic toxicity) to the aromatic antiepileptic drugs in susceptible individuals are believed to stem from the reactions of these reactive intermediates (i.e., arene oxide catechol or o-quinone) with hepatic enzymes or other cellular proteins forming covalently bonded haptens. • Both phenytoin and phenobarbital are potent liver enzyme inducers. (i) Explain why co-administering valproate with phenytoin will increase their idiosyncratic toxicities. (ii) Explain why there are cross-sensitivities in terms of idiosyncratic reactions between phenytoin, phenobarbital, and carbamazepine? (iii) Pharmacogenetic factors determine susceptibility to idiosyncratic reactions to anti-epileptic drugs. What genes may be involved in these reactions and what is the mechanism involved?

Phenytoin ethanol Rifampicin Carbamazepine Isoniazid enalapril barbiturate cimetidine Aspirin Atropine Pencillin VProdrug Acidic drugs Basic drug Enzyme inducers Zero order kinetics Enzyme inhibitors Prodrug Acidic drugs Basic drug Enzyme inducers Zero order kinetics Enzyme inhibitors

Researchers interested in studying a certain cyto- chrome P450 enzyme wish to isolate the enzyme of interest from the many other proteins in the cells. One of their initial steps is to lyse the cells and isolate the organelle which carries the enzyme they want to study. Which organelle will they isolate to find CYP enzymes? * (A) Golgi apparatus (B) Lysosomes (C) Mitochondria (D) Peroxisomes (E) Smooth endoplasmic reticulum

Select multiple drugs for each item*10 pointsPhenytoin ethanol Rifampicin Carbamazepine Isoniazid enalapril barbiturate cimetidine Aspirin Atropine Pencillin VProdrug Acidic drugs Basic drug Enzyme inducers Zero order kinetics Enzyme inhibitors Prodrug Acidic drugs Basic drug Enzyme inducers Zero order kinetics Enzyme inhibitors