Sample/practice exam 2016, questions and answers PDF

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Candidate number: ………………...

Desk number: ……………..

King's College London UNIVERSITY OF LONDON This paper is part of an examination of the College counting towards the award of a degree. Examinations are governed by the College Regulations under the authority of the Academic Board.

4BBY1040 FUNDAMENTALS OF PHARMACOLOGY Sample examination paper TIME ALLOWED: 2 HOURS

The paper is in two sections: Section A. 20 Multiple Choice questions (50% of marks for this exam.). We recommend you spend up to 60 minutes on this section. Fill in your answers on the pink answer sheet. Section B. 7 Short Answer Questions (50% of marks for this exam.). We recommend you spend up to 60 minutes on this section. Fill in your answers on the space provided in this question sheet.

THIS PAPER MUST NOT BE REMOVED FROM THE EXAMINATION ROOM, BUT MUST BE LEFT ON YOUR DESK AT THE END OF THE EXAMINATION TURN OVER ONLY WHEN INSTRUCTED

2016  King’s College London

SECTION A. MULTIPLE CHOICE QUESTIONS 

Answer these MCQs on the pink machine-marked (T/F) sheet provided.

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Write only with a pencil on the pink answer sheet.

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Using the boxes provided (left-hand side of the sheet), indicate the test number (…..), college number (10), and your college candidate number.

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Note that you must fill in every column of the “candidate number” box, with extra zeros in front of your candidate number if necessary (see the example at the top left of the answer sheet). Failure to do this will give you a mark of zero.

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Write the date and your name in the appropriate box (bottom left). Do not make additional marks on the form outside the designated areas.

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Note that the MCQs are of variable length: some have five parts (A - E), others four parts (A – D).

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Answer each part of the multiple choice question separately (each part may be true or false).

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Negative marking applies; marks awarded are: +1 for a correct answer, -0.5 for an incorrect answer, zero for no answer

1. In the pharmaceutical industry: A) structure-activity relationships are a guide for chemical synthesis programs. B) combinatorial chemistry is used to synthesise small numbers of identified chemical compounds. C) Phase 3 clinical trials are designed to test the therapeutic effects of a drug on a small number of patients (less than 100). D) natural products are a useful source of chemical compounds for drug discovery programs E) Phase 2 clinical trials are designed to test the effectiveness of a candidate drug in humans TFFTT 2. With regard to drug agonism and antagonism: A) Partial agonists have low affinity but high efficacy. B) Antagonists have affinity for a receptor but zero efficacy. C) The pA2 value of an antagonist is equal to the negative logarithm of the concentration of antagonist that necessitates that you halve the agonist concentration to produce the same response. D) A plot of the proportion of receptors occupied by a drug vs the drug concentration is a symmetrical sigmoid curve. E) An example of physiological antagonism is the effects of adrenaline and acetylcholine on heart rate. FTFFT Page 2 of 13

3. Receptors for neurotransmitters or hormones: A) are always located in the surface membrane of the cell. B) are proteins. C) may be ion channels D) have zero affinity for antagonists E) can be activated only by an endogenous compound. FTTFF 4. With regard to drugs acting on the parasympathetic nervous system: A) muscarinic agonists increase the motility of the gut. B) atropine tends to decrease the heart rate. C) muscarinic antagonists can be used to dilate the pupil of the eye. D) a side effect of muscarinic antagonists is dry mouth. E) anticholinesterase drugs have a parasympathomimetic action. TFTTT 5. The amino acid sequence of a receptor can: A) give information on the receptor’s structure B) indicate the affinity of a competitive antagonist that binds to the receptor C) help identify regions of the receptor that bind the endogenous ligand D) identify if the receptor is an ion channel or a G-protein coupled receptor E) measure the efficacy of clinically useful agonists TFTTF

6. Concerning the log concentration – response curves shown below: 100% A response

B C

50%

0 -6 -7 Log (drug concentration) A) B) C) D)

(log M) 7

The Kd for the drug described by curve ‘A’ is 1 x 10 Molar Drug ‘B’ is more potent than drug ‘A’ The EC50 for drug ’B’ (in Molar terms) is greater than that for drug ‘A’ Curve ‘C’ could be that for drug ‘A’ in the presence of a reversible competitive antagonist

FFTF Page 3 of 13

7. With regard to drug toxicity: A) thalidomide can be used in the treatment of leprosy: B) the LD50 of a drug in mice is a good indication of the LD50 for humans C) the acute toxicity of alcohol incudes liver cirrhosis D) paracetamol overdose leads to kidney failure E) grapefruit juice reduces the metabolism of many drugs by inhibiting some cytochrome P450 enzymes TFFFT 8. Regarding vascular smooth muscle in vivo: A) the second messenger inositol trisphosphate (IP3) causes calcium release from the sarcoplasmic reticulum B) contraction is caused by dephosphorylation of myosin C) adrenaline binding to 2-adrenoceptors causes relaxation D) adrenaline binding to 1-adrenoceptors causes relaxation E) L-type calcium channel blockers (“calcium antagonists”) are vasodilators TFTFT 9. Concerning drugs acting on receptors: A) B) C) D)

agonists possess affinity but not efficacy the Kd value of a drug for its receptor has units of concentration the affinity of an agonist for its receptor can be determined from the pA2 value the maximum tissue response may be produced when only a fraction of the available receptors have agonist molecules bound FTFT

10. Acetylcholine: A) is synthesised by the enzyme choline acetylsynthase B) is released from cholinergic nerve terminals by exocytosis C) is found in the autonomic nervous system but not the central nervous system D) is released by postganglionic parasympathetic nerves E) is released by preganglionic sympathetic nerves FTFTT 11. Concerning drugs of abuse: A) Nicotine from cigarettes causes an increased risk of platelet aggregation B) Acute use of ecstasy causes an elevation in extracellular levels of 5-HT C) They all activate ascending cholinergic pathways in the brain to produce pleasure D) All are associated with high levels of dependence E) Cannabis users are at increased risk of infection TTFFT

Page 4 of 13

12. When used to relieve the pain felt during angina of effort, organic nitrates (such as glyceryl trinitrate): A) B) C) D) TFTT

lead to the formation of nitric oxide in vascular smooth muscle act mainly by dilating the coronary arteries decrease the work done by heart muscle dilate veins

13. Transmission at the skeletal neuromuscular junction can be blocked by: A) propranolol B) tubocurarine C) prazosin D) atropine E) β-bungarotoxin FTFFT 14. Activation of the sympathetic nervous system leads to: A) stimulation of peristalsis in the gut B) vasoconstriction in arterioles containing 1-adrenoceptors C) release of adrenaline from sympathetic nerve terminals D) a positive chronotropic effect in the heart E) constriction of the bronchioles in the lungs FTFTF 15. In the autonomic nervous system: A) receptors on the cell bodies of the post-ganglionic neurones in the parasympathetic nervous systems are of the nicotinic type B) sweating is controlled by the parasympathetic nervous system C) adrenergic neurotransmission is terminated by reuptake of the transmitter into the presynaptic nerve terminal D) the effects of parasympathetic and sympathetic stimulation on heart rate is an example of physiological antagonism TFTT 16. Reversible competitive antagonists at nicotinic acetylcholine receptors: A) act as muscle relaxants B) produce depolarisation of the muscle end plate C) have an effect that can be reversed by neostigmine D) include suxamethonium (succinylcholine) TFTF

Page 5 of 13

17. Bronchial asthma may be treated clinically by drugs from the following classes:A) non-steroidal anti-inflammatory drugs B) steroidal anti-inflammatory drugs C) xanthine oxidase inhibitors D) selective 1-adrenoceptor antagonists E) muscarinic blockers FTFFT

18. Eating foodstuffs such as cheese and yeast products can lead to a dangerous rise in blood pressure if the patient is also being treated with a “MAO inhibitor” drug. In this situation: A) B) C) D)

MAO is the enzyme monoadrenaline oxidase MAO converts tyrosine in these foodstuffs to tyramine the MAO inhibitor drug leads to increased levels of tyramine in the GI tract. tyramine can enter the circulation from the GI tract if the patient is taking a MAO inhibitor. E) tyramine is a directly-acting sympathomimetic drug. FFTTF

19. In relation to diuretics: A) B) C) D) TTTT

diuretics can be used to decrease oedema in heart failure potassium loss from the body can occur as a result of the action of loop diuretics spironolactone is a potassium-sparing diuretic thiazides are antihypertensive drugs

20. Local anaesthetics: A) include lidocaine (lignocaine) B) containing an ester link are generally shorter-acting than those containing an amide link. C) block small diameter sensory nerve fibres but leave motor fibres unaffected D) have a longer duration of action if co-injected with adrenaline E) are most effective when applied to the skin TTFTF

END OF MCQ SECTION

Page 6 of 13

SECTION B. SHORT ANSWER QUESTIONS ANSWER THESE QUESTIONS ON THIS SHEET BY WRITING ONLY IN THE SPACES PROVIDED. THERE IS NO NEGATIVE MARKING FOR THE QUESTIONS IN THIS SECTION. TOTAL OF 61 MARKS (50% OF EXAM.) FOR THIS SECTION

QUESTION 1. Treatment of cardiovascular diseases.

(10 MARKS TOTAL)

1. Fill in the missing words in the spaces provided:

(6 MARKS)

Cardiac glycosides such as ……… digoxin …………. can be used to increase the force of contraction of heart muscle cells. This increase is called a …………… positive inotropic..……..…..… effect. Cardiac glycosides do this by blocking the …… sodium pump …………………..….…., thereby ………decreasing………..………… [increasing/decreasing] the gradient of …… sodium ……….……ions between the inside and outside of the cell. This in turn decreases the rate of Na/Ca exchange and increases the intracellular calcium concentration inside the cell. Cardiac glycosides used to be the main treatment for heart failure, but nowadays their use is severely restricted because of their dangerous side effect of ….………. arrhythmias. 2. Name two drugs, or classes of drug, that can be used in the treatment of coronary thrombosis (“heart attack”), and for each, explain briefly (in a few words) what their beneficial effect is: (4 MARKS) Drug or class of drug: …………………………………………………………..…..

(i)

Effect: ………………………………………………………………………. (ii)

Drug or class of drug:

…………………………………………………………….…

Effect: ……………………………………………………………………… Most likely answers (though others are possible) are: 

alteplase / thrombolytic drug - breaks down the thrombus / clot / fibrin network in the coronary artery



aspirin / antiplatelet drug – inhibits COX, which produces the pro-aggregatory factor, TXA2 (so inhibits further platelet aggregation).

 clopidogrel / antiplatelet drug - inhibits binding of the pro-aggregatory factor, ADP, to its receptor on platelets Page 7 of 13

QUESTION 2:

(10 MARKS TOTAL)

Cardiovascular diseases A. Stable angina B. Myocardial infarction C. Hypertension D. Cardiac arrhythmias E. Chronic heart failure

Using the letters (A-E) in the list above, fill in the following table to indicate which cardiovascular diseases can be treated with the drugs shown in the leftmost column. Each letter may be used once, more than once, or not at all. There are 10 answers in total, so some boxes should remain blank.

Drugs

Cardiovascular diseases

Ca2+ channel blockers

A

C

D

ACE inhibitors

A

C

E

clopidogrel

B

nicorandil

A

diuretics

C

Page 8 of 13

E

QUESTION 3:

(10 MARKS TOTAL)

In the following diagram of a synapse, ‘NT’ is a neurotransmitter and the symbol receptor. The numbers 1 to 7 denote possible sites of drug action.

is a

Give names for the possible sites of drug action: 1. ……synthesis……………………………………………. 2. ……storage……………………………………………. 3. ……release……………………………………………. 4. ……postsynaptic receptors……………………………………………. 5. ……presynaptic receptors / autoinhibition……………………………………………. 6. ……reuptake……………………………………………. 7. ……enzymatic degradation…………………………………………….

Name the type of receptor in each case that the following antagonists target: 8. Prazosin

………alpha-1 adrenoceptor………………

9. Trifluoperazine

….......D2 dopamine …….

10. Atropine

……. muscarinic …………. Page 9 of 13

QUESTION 4.

(6 MARKS TOTAL)

The following Schild plot shows data obtained in an experiment to investigate the actions of an antagonist on the log concentration – response curves for an agonist.

3

y-axis label:

2

log (dose-ratio – 1) 1

0

-1

-9

-8

-7

-6

-5

log [antagonist] (log M)

1. In the box provided, write a label for the y-axis.

(1 MARK)

2. How many agonist log concentration – response curves were needed to draw up this graph? …………4………………… (1 MARK) 3. Estimate the pA2 value of the antagonist from the above graph:

(1 MARK)

…………8.5…(accept 8.3 to 8.7)………………… 4. Does this Schild plot provide evidence for competitive, reversible antagonism in this case? Give a brief (no more than one sentence) reason for your answer. (2 MARKS) Yes, as slope is ~1 (or is in the range 0.8 – 1.2)

5. If the concentration of agonist required to produce a given response in the absence of -8 -6 an antagonist was 1 x 10 M, whilst that in presence of the antagonist was 1 x 10 M, what would the dose ratio be? (1 MARK) …………100…….………………… Page 10 of 13

(5 MARKS)

QUESTION 5.

From our study of genes for receptors, we can put them in different families, very like human ancestral family trees. In the tree diagram below, receptor “A” is an M1 muscarinic acetylcholine receptor. In each blank box insert the letter from the list below that describes a receptor with the appropriate genetic relationship to receptor A.

F

Distant relative

E

A

Close relative

C

D

Very close relatives

Receptors: A:

M1 muscarinic acetylcholine receptor

B:

Nicotinic acetylcholine receptor

C:

M2 muscarinic acetylcholine receptor

D:

M5 muscarinic acetylcholine receptor

E:

Rhodopsin

F:

GABAB receptor

Page 11 of 13

B

No relative

(9 MARKS TOTAL)

QUESTION 6. Asthma and its treatment

1. By filling in the 3 blank boxes, complete the diagram below to show some of the enzymes and metabolites involved in the production of some mediators that are found in inflammatory diseases such as asthma. (3 MARKS)

membrane-bound phospholipid enzyme phospholipase A2 / PLA2

arachidonic acid

enzyme Cyclo-oxygenase / COX

5-LO (5-lipoxygenase) products

products

prostaglandins

leukotrienes

2. List two effects of “products 2” that are detrimental in asthma:

(2 MARKS)

2 of: bronchoconstriction; oedema; mucus production; cellular infiltration

3. Name one class of drugs that inhibit enzyme 2 and give one example:

(2 MARKS)

glucocorticosteroids e.g. beclomethasone (or: fluticasone, budesonide,, etc.) 4. Name one class of drug that relaxes bronchial smooth muscle directly by elevating intracellular cAMP, and give one example: (2 MARKS) Beta-2 adrenoceptor agonists, e.g. salbutamol (or: salmeterol, terbuatline, etc.)

Page 12 of 13

(1 MARK EACH, 7 MARKS TOTAL)

QUESTION 7. Sympathetic nervous system

The diagram below shows a varicosity (nerve terminal) in a sympathetic post-ganglionic neurone and part of a vascular smooth muscle cell in a systemic arteriole in the skin. L-tyrosine

Sympathetic nerve

Sympathetic nerve

Vascular smooth muscle cell in skin arteriole

1. Name the substance ‘A’, which is the immediate precursor of noradrenaline (NA) in the biosynthesis of noradrenaline: ………….. dopamine …………………………… 2. Which type of receptor is receptor ‘B’? Answer by underlining one option only: muscarinic

nicotinic

alpha-1 adrenoceptor

alpha-2 adrenoceptor

beta-1adrenoceptor

3. Noradrenaline activation of this type of receptor in smooth muscle cells leads to the production of an intracellular second messenger that causes the release of Ca2+ ions from the sarcoplasmic reticulum. Name this second messenger: ……………..…IP3 / inositol trisphosphate…................ 4. What type of receptor is receptor ‘C’? Answer by underlining one option only: muscarinic

nicotinic

alpha-1adrenoceptor

alpha-2 adrenoceptor

beta-1 adrenoceptor

5. What is the effect of noradrenaline binding to this receptor? : ……………decrease in NA release / negative feedback on release…………………..

6. Name the noradrenaline transport process “D” : ………Uptake 1 ………………….. 7. Name a drug that blocks process “D”: ………cocaine …………………………………… Page 13 of 13...