1.	Match each of the drug structures on the structure page with the following.



(7)	Cardiac glycoside

(9)	Antihypertensive � angiotensin receptor antagonist

(1)	Coronary vasodilator � organonitrate

(11)	Histamine H1-receptor antagonist

(3)	Antiarrhythmic, Na+-channel blocker, amide derivative

(8)	Antihypertensive - ACE inhibitor

(4)	Antihypertensive, Ca2+-channel blocker, dihydropyridine derivative

(2)	Smooth muscle relaxant � xanthine derivative

(5)	Antihypertensive, diuretic, thiazide derivative

(6)	Histamine receptor agonist

(10)	Hypocholesterolemic � HMGCoA reductase inhibitor

2. Draw structures for the following:

a. A metabolite of drug # 1 that retains the therapeutic activity of the parent drug:

b. The metabolite of drug # 1 responsible for its pharmacological activity:

3. Draw the structure of the product of the reaction of H₂NCH₂CH₂NH₂ with drug # 2.

4. Draw the structure of a derivative of drug # 3 that would be therapeutically useful by the oral route of administration.

5. Drug # 4 forms a lactone metabolite. Show the metabolic steps required to form this metabolite.

6. Draw the structure of a derivative of drug # 5 that would be approximately 10-fold more potent.

7. Draw the structure of a bioinactive metabolite of drug # 6.

8. Drug # 7 is a potent inhibitor of ATPase enzymes. It has been proposed that the lactone function of drug # 7 interacts irreversibly with sulfhydryl groups (SH) of this enzyme. Show this reaction.

9. Drug # 8 is formulated as the maleate salt for oral administration. Draw the ionic structure of this salt.

10. Illustrate four interactive sites of drug # 9 with the following diagram of its receptor.

11. Drug # 10 is a prodrug. Draw the structure of its pharmacologically-active metabolite.

12. Draw the structure of a metabolite of drug # 11 that both (i) retains the pharmacological activity of the parent drug and (ii) possesses no proarrhythmic potential.

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Correct responses are identified in RED in the following.

13. Drug # 1 is:

	Classified as an organonitrate derivative and used for antianginal therapy

	Bioactivated by organic nitrate reductase forming nitrate (NO3�) ion

	Steric factors are responsible for more rapid denitration of the
 2-nitrate ester function

	Bioactivated to NO which increases vascular smooth muscle concentrations of cAMP



14. The pharmacological mechanism of action of drug # 2 has been proposed to involve:

	Nonselective phosphodiesterase inhibition

	ß-Adrenoceptor antagonism

	Adenosine receptor antagonism

	Calcium channel blocking activity



15. Drug # 3 is biotransformed by the following route(s):

	Oxidative N-dealkylation

	N-acetylation

	Alcohol oxidation

	Amide hydrolysis



16. Select the most accurate statement(s) about drug # 4.

	This drug can form a salt with HCl

	It is structurally classified as an aralkylamine calcium-channel blocker

	The cis isomer of this drug is a more potency calcium-channel blocker than the trans

		isomer

	The bulky oxadiazole ring induces the proper pharmacophoric conformation on this drug



17. The potency of drug # 5 is primarily determined by the:

	SO2 function at position 1

	Electronegative Cl at position 6

	Primary sulfonamide at position 7

	Lipophilic substituent at position 3



18. The agonist drug # 6 can be modified by the following structural modification(s)

    to produce an antagonist:

	Replacement of the NH2 by carbamate (NHCOOR)

	Replacement of the imidazole ring with a bulky, lipophilic, polycyclic moiety

	Lengthening of the alkylamino side chain

	Reduction of the imidazole ring double bonds to produce the more lipophilic 

	imidazoline ring system



19. The half-life of drugs such as drug # 7 is largely influenced by the:

	Lipophilicity of the steroid ring system

	Unsaturated lactone function

	Number of hydroxyl groups in the structure

	Stereochemistry at the 3-position



20. The mechanism of pharmacological action of drug # 8 involves:

	Inhibition of hydroxymethyl glutaryl coenzyme A reductase

	Antagonism of angiotensin II action at AT1 receptors

	Inhibition of renin thus lowering tissue levels of angiotensin I

	Inhibition of angiotensin converting enzyme therapy 

	reducing tissue levels of angiotensin II



21. Select the most accurate statement(s) about drug # 9.

	An AT1 receptor agonist that must be bioactivated by alcohol dehydrogenase

	An acidic drug that may be formulated for oral administration as a sodium salt

	An antagonist at angiotensin AT1 receptors 

	A therapeutically-useful antihypertensive agent.



22. Select the most accurate statement(s) about drug # 10.

	A hypocholesterolemic agent that stimulates the hepatic clearance of cholesterol

	An antihypertensive agent that inhibits angiotensin converting enzyme

	A hypocholesterolemic agent that inhibits cholesterol biosynthesis

	A HMGCoA reductase inhibitor whose potency would be increased by replacement of its

		polycyclic carbocycle structural feature with a polycyclic heterocycle feature



23. Select the most accurate statement(s) about drug # 11.

	Structurally classified as a piperidine derivative; contains a chiral center
		at the secondary alcohol carbon

	Metabolized to a carboxylic acid metabolite that retains much of the

	pharmacological activity of the parent drug

	Therapeutically classified as a second generation agent because of its significant

	distribution to the CNS as a site of action

	Pharmacologically classified as a histamine H2-receptor antagonist.









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