Practice Problems
Med Chem Exam II (Winter Quarter, 1998)

The following questions are intended to assist the student in preparing for Exam #2
in Med. Chem. II. They highlight important information in both lecture and lecture guide.

1. What is the role of adenylyl cyclase and its relationship to NE neurotransmission. What is the general role of cAMP as a second messenger and what determines its rate of formation and degradation.

2. How do the bipyridone derivatives exert a positive inotropic action on the heart?

3. Is the net pharmacological effect of forskolin similar to or opposite that of the bipyridone derivatives? Explain.

4. Describe the interaction of the xanthine derivatives with autonomic neurotransmission and neuromodulation.

5. List a drug that acts at each of the 5 sites identified in the following diagram (click here) and has an effect on vascular activity. Describe the pharmacological effect of each drug.

6. Describe the mechanism of vasodilation of sildenafil. Studies of this drug indicate that the NO-generating system must also be operative for maximal sildenafil activity. Describe the interaction between the sildenafil mechanism and the NO system.

7. Draw structures of 2 metabolites of ISDN. What factor(s) determine the route of ISDN metabolism? Which metabolite(s) retain vasodilatory activity? Describe this mechanism of action.

8. Describe the primary pathways of adenosine bioinactivation.

9. List a structural clssification for mibefradil. Show the structure of the product of the reaction between mibefradil and H2SO4. Explain how the calcium-channel blocking activity of mibefradil differs from that of other members of its structural class.

10. Based upon structure-activity relationships, comment on the relative calcium-channel blocking potencies of felodipine and amlodipine with that of nifedipine. Show the product of the reaction of felodipine and amlodipine with HCl. Draw the structure of a "lactone" metabolite formed from both felodipine and amlodipine. Show a chemical reaction that illustrates the instability of these two CCBAs in air.

11. Class I Antiarrhythmics:
  • Explain why tocainide has greater oral bioavailability than lidocaine.
  • Draw structures of 2 metabolites of encainide that are longer-acting antiarrhythmics.
  • Show products of the reaction of procaineamide with (1) HCl, (2) amidase and (3) acetylase. Comment on the theraeputic significance of each reaction.

12. Examine the following diagram (click here) and name the interactive forces depicted at sites 1, 2, 3 4, and 5. Reduction of the lactone double bond in the cardiac glycosides results in a significant reduction in pharmacological activity. Explain this observatoin based upon this diagram. Explain how addition to hydroxyl groups (OH) to the structures of cardiac glycosides affects the biodisposition of these drugs.

13. Diuretics:
  • Use the following diagram (click here) to explain why the elimination half-lives of most NSAIDs may be shortened by coadministration with the diuretic acetazolamide.
  • The diuretic activity of furosemide (F) and ethacrynic acid (EA) results from inhibition of the Na+/K+/Cl--cotransport system in the TAL. Based upon structural aspects explain why/how EA is an irreversible inhibitor of this process while the action of F is reversible in nature.
  • Complete the following structure (click here) so that the resulting drug will be a long-acting Site III diuretic.

14. Using the following diagram (click here) shown how the angiotensin receptor antagonists, candesartan, is structurally complimentary with this site.

15. Illustrate how the drug ramipril can occupy the active site of ACE (click here).

16. Both the bile acid sequestering agents and HMGCoA reductase inhibitors lower plasma cholesterol levels. Compare and contrast the hypolipidemic mechanisms of action of these two drug classes.


Return to: PY421 Home Page