Problem+Set+8

Here is the ProblemSet #8 file. The on-line due date is 07-19-2010. Please download it, answer the questions assigned to your LG (LG-WX, LG from Worcester; LG-MX, LG from Manchester), and upload your answer file back accordingly (below). If you have any problems to upload your file back, please send your file directly to me at jonathan.sheng@mcphs.edu and l will do it for you. Each question will be answered by two LGs independently.

Question A. (a) LG-W20:Both glucuronidation and sulfation are phase II reactions. They are both oxidative reactions. In addition, both reactions add ionic hydrophilic moiety to the reactant.

LG-W21:

Question A. (b) LG-W22: Differences 1) Glucuronidation is a phase II detoxification pathway occurring in the liver in which glucuronic acid is conjugated with toxins. Enzymatic sulfation is a phase II enzyme reaction, where it uses the cosubstrate 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to transfer sulfonate to a xenobiotic. 2) Glucuronide formation probably is the major and most common route for xenobiotic Phase II metabolism to water-soluble metabolites. Sulfate conjugation is an important reaction in the biotransformation of steroid hormones, catecholamine neurotransmitters, thyroxine, bile acids, phenolic drugs, and other xenobiotics. 3) Phenolic hydroxyl groups uses conjugation reactions such as sulfation, ether glucuronidation, and methylation. Carboxyl groups use conjugation reactions such as amino acid conjugation and ester glucoronidation. 4) Glucuronidation reaction involes direct condensation of the xenobiotic (or its phase-I product) with the activated form of glucuronic acid, UDP- glucuronic acid (UDPGA). - In Sulfation reactions, xenobiotic is sulfated by transfer of an active sulfate from 3’-phosphoadenosine-5’-phosphosulfate (PAPS) to the acceptor molecule, a cytosolic reaction catalyzed by a multigene sulfotransferases.

LG-W23: Question B. (a) - Identify the therapeutic problem(s) for which the pharmacist's intervention may benefit the patient

Grapefruit juice will inhibit CYP2C9 and increases the anticoagulant effect of coumadin thus increasing his risk for bleeing. Ansaid and rosuvastatin will also increase the anticoagulant effect of coumadin, which will also lead to an increased risk of bleeding. Basically, this guy is going to bleed to death if he continues everything as is!!!

LG-W24:

- Grapefruit juice would increase the plasma level of warfarin in his blood - The potassium in flurbiprofen potassium would increase the plasma level of warfarin in his blood, leading to increased risk of bleeding - Crestor would increase his INR, thus increasing his risk of bleeding

LG-W25:

Question B. (b) LG-W26:

LG-W27:

Question B. (c) LG-W28:

LG-W29:

Question B. (d) LG-W30:

LG-W31:

Question B.(e) LG-W32:

LG-W33: