CATHOLIC UNIVERSITY OF HEALTH AND ALLIED SCIENCES – BUGANDO

SCHOOL OF PHARMACY
UNIVERSITY EXAMINATION FOR THE DEGREE OF BACHELOR OF PHARMACY-February 2014

PC 400 PHARMACODYNAMIC AGENTS

DATE: ................................................... TIME:............................................
MARKING SCHEME FOR SECTIONS A and B

SECTION A – ANSWER ALL QUESTIONS

For Questions 1- 15 Circle The Most Correct Answer

1. Which statements are correct with respect to the following molecule?

(a) It has a half-life of four to seven days, which is considerably longer than most hypoglycemic agent.
(b) Phase III clinical trials on this drug were halted due to incidences of serious hyper-sensitivity
reactions.
(c) Is under investigation for possible use in the treatment of type 2 diabetes
(d) It is a long-acting glucagon-like peptide-1 agonist approved for the treatment of type 2 diabetes.

2. In the development of propranolol

a) the predecessor, pronethalol was abandoned because of carcinogenicty potential
(b) insertion of an arylethanolamine group into the predecessor structure increased potency.
(c) it was concluded that Art is a discipline pursued with passion while Science is passion pursued with
discipline
(d) the carcinogenicity found with dichloroisoprenaline was eliminated by substituting a naphthalene for
the phenyl ring.

3. In Lanatocide C
a) Digitoxigenin is linked to one to four β-glucose sugars to form the glycoside
(b) Digitoxigenin is linked to a βD-glucose, βD-digitoxose and βD-glucose sugars to form the glycoside
(c) Digitoxigenin is linked to one to four glucose sugars at the 3OH position to form the glycoside
(d) Digitoxigenin is linked to a βD-digitoxose, βD-glucose and βD-digitoxose sugars to form the
glycoside

4. Exenatide was licensed as a Glucagon-like peptide-1in 2005. This drug molecule

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(a) is a hormone extracted from the saliva of the Gila monster
(b) enhances inappropriately elevated glucagon secretion.
(c) enhances glucose-dependent insulin secretion by the pancreatic beta-cell
(d) is administered by intramuscular injection in the thigh, or arm,

5. Which of the following statements the α-glucosidase inhibitors is not correct?

(a) A tertiary amino group in their structure appears to be necessary so as to prevent an essential
carboxyl group of the α-glucosidase from protonating the glycosidic oxygen bonds of the
substrate.
(b) They prevent the hydrolysis of carbohydrates, thus reducing their absorption.
(c) SAR investigations showed the presence of a common pharmacophore in all inhibitors.
(d) Voglibose lowers postprandial glucose levels while Miglitol lowers fasting serum glucose.

6. In the Strtucture Activty Relationships of the thiazide diuretics

a) While the C1 sulfamoyl group is of paramount importance, that at C3 can be replaced with similar
groups.
(b) Any alteration at position 2 results in complete loss of activity.
(c) Reduction of the 3,4-double bond increases potency 3 to 10-fold
(d) Substitution of the 6-position results in loss of diuretic activity

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(i) (ii) (iii) (iv)

About the drug molecules above

a) (i) was synthesized in 1962 as a potential nasal decogenstant
(b) the succinate of (ii) is usually formulated as an immediate release antihypertensive agent.
(c) (iii) was accidentally found to have increased antihypertensive activity and decreased diuretic
activity
(d) (iv) is the prototype structure of all calcium channel antagonists

8.
(i) (ii) (iii)

about the drug molecules (i), (ii) and (iii) above:

a) (i) is a hydrophilic compound which would not pass the blood–brain barrier easily
(b) (iii) is likely to have adrenergic antagonist activity.
(c) (ii) is likely to be water soluble and have a short duration of action
(d) None of the above

9. Which statement regarding the compound on the right is NOT TRUE

(a) Can be quantitatively analyzed using non-aqueous titration with 0.1M perchloric acid
(b) This compound has optical isomers but the commercial preparation is the racemic modification.
(c) It was the first successful beta blocker developed
(d) It showed some signs of carcinogenicity in animal studies during pre-clinical studies.

10. Which of the following statements about the Thiazolidinedione hypoglycemic agents is most
correct?
(a) Troglitazone was the 1st analoque,to be introduced in 1987
(b) ciglitazone was discovered serendipitously

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(c) pioglitazone potentiates the target tissues to insulin sensitivity but has high incidences of cardiac
risks.
(d) troglitazone was withdrawn in 2001 due to rare liver failure, deaths

11. Muraglitazar whose structure is shown here N O CO OH

CH 3 N
O O
O OCH3

(i) stimulates peroxisome proliferator-activated receptors Mu ra glita za r

(ii) increases glucose uptake in adipose, muscle and liver
(iii) increases gluconeogenesis and glycogenolysis
Of the above statements, which one(s) is/are correct
(a) (i) only O O
(b) (ii) only. S O
CO OH
(c) (iii) only. O O
H3 C
(d) (i) and (ii).
Te s a glita za r O
(e) (ii) and (iii) O
R1 S N N R2
12. In the SAR of sulfonylureas (general structure on the right) H H
O

(a) Substitution of R1 with small akyl groups increase activity.

1 s t g e n e ra tio n R1 R2
(b) Substitution of R2 with large aryl groups produces the 1Togeneration
st
lb u ta mid eanalogs. CH 3 CH 2 C
(c) Substitution of R1 with large groups increases activity. Cl CH 2
C h lo p rop a m id e
(d) The sulfonyl group may be replaced by a carbonyl group without loss of activity. O
Ac e to h e xxa mid e

13. Control of diabetes using dietary measures: CH3

(a) Emphasizes the use of oligosaccharides such as those found
2 n ding ebeans and
n e ra tio n peas
(b) Discourages use of saccharin and aspartame as they may lead to weight gain. Cl
HN
G lib e n c la mid e
(c) Weight reduction may be effective in the late stages of the problem
O
(d) Encourages small frequent meals preferably containing polymers OCH3

N HN
G lip izid e H3 C
14. Repaglinide (structure shown to the right) N O
N
O
O CH3
NH COOH
S
H3 C CH3
CO2H

(a) Binds on same receptors as the sulfonylureas leading to secretion

Repaof insulin
glinide ( Prandin) Nateglinide ( starlix)
(b) Has a longer duration of action compared to other hypoglycemic agentss.
(c) Is slightly more basic than the sulfonylureas
(d) Is associated with prolonged hyperinsulinemia

15. The thyroid hormones

(a) 3, 5, 3’ triiodothyronine is present in circulation in greater concentrations than L-thyroxine but is less active.
(b) They are stored by being bound to protein
(c) Their release is influenced by TSH secreted by the anterior pituitary gland
(d) The protein thyroglobulin facilitates their transport through an active mechansim.

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For questions 16 to 20 give a brief response to each question (5 points each)

16. Write short notes on the stereochemistry of cardiac glycosides

CH3
HO
H
CH3 C OH O
D
A B O
H
H

A/B cis
B/C trans
C/D cis

Rings A/B and C/D of the cardiac glycosides are in the cis configuration, whereas the B/C ring juncture is in
the trans configuration. This stereochemistry appears to be an important prerequisite for some but possibly
not all active cardiac steroids.

17. Giving two examples explain how the class III antiarrhythmic agents function
These agents cause delay in repolarization and prolonged refractory period. Includes
Amiodarone – prolongs action potential by delaying K+ efflux but many other effects characteristic of other classes,
Ibutilide – slows inward movement of Na+ in addition to delaying K + influx.

18. Submit a concise explanation on the concept of osmotic diuresis

Any compound that is poorly reabsorbed by the renal tubules and is present in a concentration in excess of that of
electrolytes and dissolved substances in the body fluids will cause water and electrolytes to pass into the more
concentrated solution and become excreted. Thus diuresis and a mobilization of oedema fluid take place.

19. What is the mode of action of mercurial diuretics?

Mercurial diuretics act primarily at the proximal renal tubule. Their action is believed to be due to a binding of mercury
ions with sulfhydryl groups attached to the renal enzymes responsible for production of energy necessary for tubular
reabsorption. Administration of dimercaprol (BAL) or other related vicinal dithiols concomitantly with mercurial
diuretics prevents blocking of the enzymes and abolishes diuresis, because the dithiols have greater affinity for ionic
mercury than the enzyme.

20. Why is D-Thyroxine preferred in the treatment of type II hyperlipidemia?

The mechanism of action of D-thyroxine appears to be stimulation of oxidative catabolism of cholesterol in the liver.
The catabolic products are bile acids which are conjugated with glycine or taurine and extracted via the biliary route into
the feces. Cholesterol biosynthesis is not inhibited.