Pceut532_Exam3_2007 Blank

Pceut532_Exam3_2007 Blank - PHARMACEUTICS 405 Winter 2007...

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Unformatted text preview: PHARMACEUTICS 405 Winter 2007 Name ‘ Midterm #3 Student # Feb. 23, 2007 Questions Points 1 3 2. 3 3 3 4. 3 5 3 6. 3 7. 3 8. 3 9. 3 10. 3 11. 3 5 ' 12. 5 13. 25 14. 7 15. 7 16. 7 17. 7 18. 7 TOTAL 100 Student # Part I. Check or fill in the appropriate answer 1. The absorption, distribution and elimination of lipophlic drugs are not affected by membrane transporters because these molecules have high LogP values and can freely cross cell membranes by simple diffusion. (3 pts) True False Valganciclor, the prodrug of ganciclovir, has a much higher oral bioavailability than gancyclovir because it is a substrate of the intestinal peptide transporter PepTl Whereas ganciclovir is not. (3 pts) True False Drugs with oral bioavailabilities < 50% exhibit small increases in oral AUC as a result of CYP3A inhibition. (3 pts) True False Enzyme inducers decrease the AUC of orally administered drugs by decreasing the fraction eScaping gut wall metabolism and the fraction escaping hepatic metabolism. (3 pts) True False Protein binding-based drug interactions involving low extraction ratio drugs are generally not clinically significant. (3 pts) True False Name two drug transporters in the kidney (3 pts) Name three clinically important CYP2C9 substrates and . (3 pts) 10. ll. 12. Name two CYP3A inducers (3 pts) Name a substrate and an inhibitor for CYP2D6 (3 pts) Substrate inhibitor Provide one example of a CYP1A2 inhibition drug interaction (3 pts) Substrate inhibitor Which of the following statements is not true regarding the drug transporter P-gp. (5 pts) a. P-gp is a primary active ABC transporter that utilizes the energy generated from ATP hydrolysis to efflux drugs out of cells. The role of P-gp in oral bioavailability is profound and hard to discern from CYP3A because P—gp and CYP3A enzymes are co-localized in the enteroc‘ytes and share a large overlap of substrates and inhibitors. Rifarnpin is an inducer of intestinal CYP3A, but it does not up regulate P-gp in the gut because P-gp in the gut is not inducible. Inhibition of P-gp increases the absorption of ng substrates like digoxin Ans. Which of the following statements is not true regarding the grapefruit juice—drug interactions? (5 pts) a. The mechanism of grapefruit juice-based drug interactions involves inhibition of hepatic CYP3A mediated metabolism; The effect of grapefruit juice on intestinal CYP3A can last several days after juice intake because CYP3A is irreversibly inhibited. The oral bioavailabilities of the substrates influence the magnitude of the effect of grapefruit juice. The magnitude of the effect of grapefruit juice on the object drug is influenced by the strength of grapefruit juice and its amount and pattern of consumption. Ans. 13. DT has been receiving carbamazepine 500 mg twice daily for 1 year. His average steady state plasma concentration of carbamazepine for this dose is 8 pig/ml. CBZ-epoxide is an active metabolite of carbamazepine. Urine was collected for one dosage interval (12 hrs) and the following amounts in the urine were determined. (25 pts) Carbamazepine (CBZ) 5 mg . CBZ epoxide 30 mg CBZ dihydrodiol 150 mg CBZ diol —glucuronide 75 mg CBZ N—glucuronide 5 mg The elimination half-life of carbamazepine is 20 hours. After direct admmistration of CBZ- epoxide, the elimination half-life of CBZ-epoxide is 10 hours. CYP3A epoxide hydrolase UGT CBZ I CBZ epoxide I CBZ-dihydrodiol I CBZ- diol-glucuronide lurk}. i i CBZ-N—Gluc ——-—————> urine urine urine Using the information provided above, answer the following questions. a. (2 pts) The concentration time curve of CBZ-epoxide is described by pharmacokinetics after carbamazepine is, administered. b. (3 pts) When carbamazepine therapy was first started in DT, the time to maximum pharmacologic effect was reached how long after his first dose? 0. (20 pts) Calculate the CYP3A4 dependent formation clearance of carbamazepine epoxide. Assume that absorption is complete and that the carbamazepine metabolites have been corrected for molar weight. Part 11. Use simple and concise language, preferably 3-5 sentences, to describe the major mechanisms underlying the following observed drug—drug or food-drug interactions. WheneVer applicable, you need to clearly identify the substrate, inhibitor or inducer,‘ and the specific enzymes or transporters on which the interactions have occurred. 14. Digoxin is a drug with a narrow therapeutic widow. When co-administered with quinidine, (digoxin in the blood can reach dangerously high concentrations even when digoxin is given intravenously. (7 pts) 15. Unexpected pregnancy was reported in a number of cases of women using oral contraceptives. It was found that these women also simultaneously use the herbal product, St. John’s wort, for treating depression. (7 pts) 16. The drug mibefradil (Posicor) was Withdrawn from the market as serious adverse reactions were observed between mibefradil and numerous existing drugs such as statins (e.g. lovastatin and simvastatin), dihydropyridines, immunosuppressants and anti—cancer drugs. (7 pts) 17. The oral bioavailability of tetracycline and fluoroquinolone antibiotics is significantly decreased when taken together with dairy products such as milk or yogurt. (7 pts) 18. When felodipine, a calcium channel blocker, was given. orally together with grapefruit juice, a significant increase in felodipine plasma AUC was observed, which results in an abnormal toxic effect of felodipine. Such effect was not observed when felodipine was taken with orange juice. (7 pts) 0.693 T = ———— 1/2 K Ass = 5 K Css = K0 cw=_D.. V'K'T Cl 17 EQUATIONS 0.693'V . T =— 1/2 058 = K“ V'K Css = Css(1— e—KTJ 1% .__ _ DOSng Rate Clearance ...
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This note was uploaded on 01/31/2010 for the course PHCOL 402 taught by Professor Storm,d during the Spring '08 term at University of Washington.

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Pceut532_Exam3_2007 Blank - PHARMACEUTICS 405 Winter 2007...

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