Pharmacology and drug metabolism Midterm
1. Most drugs are at least slightly lipophilic. Why is this important from a clinical perspective and how is it related to Fick’s law?
2. What is ADME and why is it important in the drug discovery process?
3. Umassazole is a drug that is primarily eliminated by oxidation via CYP3A4, which is found in the intestine and the liver. How could you determine if the metabolism occu
ed primarily in the intestine or in the liver?
4. What does a Vd of 20 L indicate? What about 5000 L? If the fu of a drug changed from 0.1 to 0.05, how would this change Vd and what would it indicate?
5. What is the first pass effect? What are the contributing factors to this effect? What percentage of an oral dose of a drug would you expect to reach the central circulation if it is 75% abso
ed, 30% metabolized by the intestine and 60% metabolized by the liver?
6. For a 70 kg patient, if the Vd of a drug is 7 L/kg, the Ab is 50 mg and the fu is 0.1, what is the Ap, At, Cp, Cpu, Ct, Ctu, fut, fraction in plasma and fraction in tissue?
7. A drug binds plasma proteins (fu = 0.5) has a renal clearance of 500 mL/min and 60% of the dose is excreted unchanged. What is the total body clearance and nonrenal clearance. What are the likely relative contributions to its clearance by the various processes in the renal tubule?
8. Alprazolam has the following characteristics: volume of distribution: 0.84 L/kg, total body clearance (plasma): 73.5 mL/min, renal clearance: 18.2 mL/min, BP: 0.818, and fu: 0.268. Calculate half-life, hepatic clearance, hepatic intrinsic clearance, hepatic extraction ratio and hepatic bioavailabity. Use 1500 mL/min for hepatic blood flow.
9. Compare and contrast the catalytic cycles of the CYP450 and UGT enzymes. Be sure to discuss any coenzymes or redox partners that each enzyme family uses.
10. CYP3A4 is one of the most important isoforms for drug metabolism. Explain its role in detail for all aspects of metabolism (intestinal and hepatic). Also discuss its substrate specificity, where it is located, and how its specific localization is ideal for drug metabolism.
11. Warfarin can be hydroxylated at 5 different positions. In a separate file, draw 3 of these possible structures and upload the file.
12. Compare and contrast the following pairs of terms:
a. Pharmacokinetics vs. Pharmacodynamics
. Renal vs. Hepatic clearance
c. N-dealkylation vs. deamination
d. Phase I vs. Phase II metabolism
e. Passive Diffusion vs. Facilitated Diffusion