Download Final exam 2013 File - Fiji National University | E

College of Engineering,
Science and Technology
School of Sciences
Natabua Campus, PO Box 5529
Lautoka.
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CHM 708: Medicinal Chemistry
Final Examination, Trimester 3, 2013
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Time allowed: three (3) hours plus 10 minutes reading time
100 marks (50% of final grade)
INSTRUCTIONS
1. There are six (06) questions in this paper, which is seven (07) pages
long.
2. Question 1 is compulsory (40 marks).
3. Answer an additional three questions from questions 2 - 6 (20
marks each).
4. Write your answers in the answer booklet provided.
5. Start the answer of each question on a new page of your answer
booklet.
6. Write answers of all parts of a question at one place in the answer
booklet.
7. This exam is worth 50% of the overall marks for this unit.
8. You must score at least 40/100 marks (40%) to pass this unit, as well
as 50% overall.
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Question 1 (compulsory)
(a) Define or explain the following terms.
(i) Metabophore.
(ii) Allosteric effect.
(iii) Therapeutic index
[6 marks]
(b) Explain why a molecule that is extremely insoluble in either water or lipid will usually NOT
make an effective drug. In order to overcome this problem, many drugs contain amine
groups, with pKa values ~ 9. Explain how these amine groups can help solve the above
problem.
[6 marks]
(c) In addition to the active compound, several components with various functions are included
in the formulation of oral tablets. Write down one example each of a compound, that is used
for the following functions.
(i) Lubricant.
(ii) Binder.
(iii) Filler.
[3 marks]
(d) Explain the difference between the Occupation Theory and the Two-State Model of drugreceptor interactions. What phenomenon is explained by the latter but not the former?
[6 marks]
(e) There are five major types of receptors (based on mechanism), which can be targeted by
drugs. One type are the voltage-gated ion channels. List any three of the remaining four.
[3 marks]
(f) List four examples of drugs which are natural products, i.e., isolated from plants, fungi, or
other organisms.
[4 marks]
(g) Rational Drug Design is a modern approach to developing new drugs, based on a detailed
knowledge of the biochemistry of the condition being treated and the structure(s) of the
receptor(s) involved. Outline the steps involved in this process, up to the point of preclinical trials.
[7 marks]
(h) Given below is a list of drugs and a list of the diseases or conditions that can be treated using
those drugs. Write down the name of each drug, and next to it write down the disease or
condition the drug is used to treat.
Drugs
(i) Oxymorphone
(ii) Diazepam
(iii) Propranolol
(iv) Dexamethasone
(v) Ampicillin
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Disease / condition
A. Insomnia / sleep disorder.
B. Bacterial infection
C. Inflammation
D. Severe pain
E. Angina pectoris / cardiac arrhythmia
[5 marks]
Answer any three of the remaining questions
Question 2
(a) Briefly describe the role of gamma-aminobutyric acid (GABA) in the transmission of nerve
signals in the central nervous system.
[4 marks]
(b) Shown below is a synthesis of the barbiturate amobarbital, a GABA agonist. Give the
structures of the missing reagents A and B.
[4 marks]
(c) Explain why benzodiazepines have largely replaced barbiturates as GABA agonist drugs.
[2 marks]
(d) Benzodiazepines are used as sedatives / hypnotics (drugs that induce sleep). List two other
uses of these drugs.
[4 marks]
(e) List two other categories of GABA agonists which are used as sedatives or hypnotics.
[2 marks]
(f) Which one or more of the following molecules is a benzodiazepine? Write down the letter(s)
corresponding to the molecule(s) in your answer script.
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[4 marks]
Question 3
Shown below is the structure of the common analgesic morphine.
(a) What is the natural source of morphine?
[2 marks]
(b) Write down 4 side-effects of morphine, including the one that causes death in the event of an
overdose.
[4 marks]
(c) How important is the phenolic OH group for the activity of morphine? Give an example to
illustrate your answer.
[4 marks]
(d) Show by means of a chemical reaction how you would convert morphine into heroin.
[3 marks]
(e) Explain why heroin is more potent than morphine.
[3 marks]
(f) Do the following structural modifications increase or decrease the activity of morphine?
(i) Removal of the ring containing the N atom.
(ii) Oxidising the alcoholic OH group to a ketone.
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(iii) Introduction of a OH group at C-14 (indicated in the figure above).
(iv) Replacement of the NCH3 group with a NCH2CH2Ph group.
[4 marks]
Question 4
(a) The following classes of drugs are used to treat Type 2 diabetes mellitus. Briefly explain the
mechanism of action of any two of these classes of drugs.
 Sulphonylureas
 Thiazolidinediones
 -Glycosidase inhibitors.
[6 marks]
(b) The "statins," e.g., lovastatin and atorvastatin, are a class of drugs that lower cholesterol
levels. Briefly describe their mechanism of action.
[3 marks]
(c) Shown below are three synthetic steroids.
(i) Based on their structural features, classify each of the above as agonists one of the
following: androgen, oestrogen, progestin, glucocorticoid.
(ii) Which of the three above molecules would you use as an anti-inflammatory agent?
[4 marks]
(d) Progesterone is the only natural progestin. Briefly describe its role in pregnancy. Why can
progesterone NOT be used in oral contraceptive pills? What combinations of compounds are
used for that purpose?
[5 marks]
(e) Shown below is the progestin antagonist mifepristone (RU 486). Describe its clinical use.
[2 marks]
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Question 5
(a) Cancer results from induced abnormalities in the genetic material of cells. List three major
agents that cause cancer.
[3 marks]
(b) Shown below are seven important anti-cancer agents.
(i) Classify each of the above drugs into one of the following categories: nitrogen mustard,
anti-mitotic, DNA intercalating agent, pyrimidine antimetabolite, aziridine, folic acid
antagonist, oestrogen antagonist, topoisomerase inhibitor, DNA replication inhibitor.
[7 marks]
(ii) For any five (05) of the above drugs, describe the mechanism of action. Be as specific as
possible.
[10 marks]
Question 6
(a) Shown below are four anti-bacterial drugs, labelled W, X, Y, and Z.
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(i) Classify each of the above drugs into one of the following classes: penicillin, macrolide,
tetracycline, quinolone, sulphonamide, and/or aminoglycoside.
(ii) For each class that you chose, briefly describe the mechanism of anti-bacterial activity.
[12 marks]
(b) Many bacteria have evolved resistance to penicillin antibiotics. Describe how this resistance
occurs, and the action that can be taken to counter this particular form of resistance.
[3 marks]
(c) Until the mid-twentieth century, tuberculosis was one of the deadliest diseases affecting
humans. It is caused by the bacterial species Mycobacterium tuberculosis.
(i) Name another major disease caused by a mycobacterium.
(ii) Describe a characteristic of mycobacteria that differentiates them from other bacteria.
(iii) List three drugs that are used to treat tuberculosis.
[5 marks]
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