ESA 4 - CPT

Question 1

1) A 46 year old is currently taken atorvastatin to reduce his cardiovascular disease risk. He has been experiencing low mood and purchased St John’s Wort which he has been taking for 7 days. It is known that St John’s Wort is an inducer of CYP3A4.

t1/2 = 0.7x Vd/CL.

In this patient, what best describes the effect of the St John’s Wort on the individual terms in the equation for half-life for the statin.

A. Nothing changes all the terms remain the same
B. t1/2 decreases, all other terms remain the same
C. t1/2 decreases, Vd increases CL remains the same
D. t1/2 remains the same, CL increases Vd increases
E. t1/2 decreases, CL increases Vd remains the same

Answer 1

Answer is E. Half-life will decrease as metabolism is increased and therefore excretion. Clearance will go up (inversely proportional to (t1/2) Vd unchanged.

Question 2

2) A diabetic patient is started on treatment with a sulfonylurea. Which of the following statements is correct about the pharmacological action in pancreatic ß-cell by sulfonylureas?

A. ATP sensitive K+ channel activity is agonised increasing insulin release into circulation
B. ATP sensitive K+ channel activity is antagonised, decreasing K+ efflux and increasing insulin release
C. ATP sensitive K+ channel activity is agonised to decrease K+ efflux which increases insulin release
D. Depolarisation decreases both Ca2+ entry and insulin vesicle fusion rate with the cell membrane
E. Depolarisation increases both Ca2+ entry and K+ efflux, which increase insulin release into the circulation

Answer 2

Answer is B.

Question 3

3) A 58 year old male with type 2 diabetes has a total cholesterol of 6.8 mmol/L. He does not have established cardiovascular disease but his CVD risk score is 14%. What cholesterol lowering therapeutic would you try first?

A. Atorvastatin
B. Fenofibrate
C. Ezetimibe
D. Cholestyramine
E. Simvastatin

Answer 3

Answer is A. Statin is most effective option for lowering LDL cholesterol. Fenofibrate would be more appropriate for triglyceride reduction. Cholestyramine (bile acid binding resin) will reduce LDL cholesterol but only by ~ 20% and is not recommended as a first line primary prevention. Simvastatin would reduce LDL cholesterol by the same HMGCoA reductase inhibition as atorvastatin but is less potent (~30 vs 40% reduction in LDL-C at 20 mg dose) which is recommended for type 2 diabetics with no established CVD but a CVD risk score of >10%.

Question 4

4) A 69 year female with atrial fibrillation reports no episodes of palpitations and does not have any other cardiovascular disease. Which antiarrhythmic agent would you prescribe to control rate for this patient?

A. Flecainide
B. Bisoprolol
C. Amiodarone
D. Digoxin
E. Ivabradine

Answer 4

Answer is B. Bisoprolol beta blocker for rate control. Flecainide would be appropriate for rhythm control as would amiodarone. Digoxin is not a first line primary rate control agent. Ivabradine (if current inhibition) used for sinus tachycardia and rate reduction in HF or ACS.

Question 5

5) A 60 year old male has stage b heart failure (structural disease with no symptoms). In addition to an ACE inhibitor, his cardiologist suggests that he take a bet blocker as well. Which of the following is not true of the therapeutic benefit of beta blockers in the management of heart failure?

A. Decrease heart rate
B. Inhibit the effects of noradrenaline on cardiac muscle remodelling
C. Increase renin release
D. Improve systolic function
E. Decrease afterload

Answer 5

Answer is C. beta blockers will decrease renin release which decrease sympathetic output, decrease sodium and water retention, increase bradykinin and vasodilation. All others are true

Question 6

6) Which diuretic is used as an add-on therapy in resistant hypertension (blood pressure not adequately reduced with three first line drugs)?

A. Indapamide
B. Furosemide
C. Bendroflumethiazide
D. Spironolactone
E. Amiloride

Answer 6

Answer is D. spironolactone. Evidence suggests that this potassium sparing diuretic can be effective as an add-on once an A C and thiazide like D have been exhausted.

Question 7

7) Naloxone has been prescribed for a patient admitted to A&E who is suspected of taking an overdose of morphine. It is hoped that the naloxone will reverse the respiratory depression that the patient is presenting with. Dose escalation may be needed if there is little response. Which of the below best describes naloxone in this situation?

Naloxone is a non-competitive antagonist
Naloxone is a more potent agonist
Naloxone shows greater efficacy than morphine
Naloxone has less affinity than morphine
Naloxone is a competitive antagonist

Answer 7

Answer is E. Naloxone is a competitive antagonist, non-selective for all opioid receptors.

Question 8

8) A 44 year old male has been for a health MOT and has been diagnosed with essential hypertension. His blood pressure has been confirmed following ABPM as 158/95. The GP prescribes losartan. Which of the below best describes how it is hoped losartan will reduce his blood pressure?

A. Losartan will inhibit angiotensin converting enzyme
B. Losartan will inhibit calcium channels in vascular smooth muscle cells
C. Losartan will potentiate the action of aldosterone
D. Losartan will inhibit the AT1 receptor
E. Losartan will inhibit the adrenergic stimulation of vascular smooth muscle

Answer 8

The answer is D. Losartan is an angiotensin II receptor antagonist (AT1 receptor), preventing action of ATII. All others are mechanisms of action of other antihypertensive class apart form C which would exacerbate the hypertensive state

Question 9

9) A 54 year old female is visiting her GP practise to have her blood pressure medication reviewed. She currently takes the lowest recommended dose of amlodipine hydrochloride and confirms that she is adherent. Her blood pressure is confirmed to be 145/92. A small reduction on the measurement recorded at her last appointment 3 months ago. What should be recommended?

A. Increase the dose of amlodipine hydrochloride
B. Continue taking the same dose of amlodipine hydrochloride and review in 3 months.
C. Add an ACE inhibitor or ARB
D. Add a thiazide like diuretic
E. Swap the amlodipine hydrochloride for an ACE inhibitor or ARB

Answer 9

The answer is A. The next step should be to increase the dose of the CCB, ensure adherence before adding a second agent.

Question 10

10) A 36 year female has been admitted to a general ward with a severe infection. She has been prescribed i.v. antibiotics. A steady state plasma concentration is reached in 5 hours. What would be the predicted half-life of the antibiotic?

A. 10 hours
B. 25 hours
C. 1 hour
D. 15 hours
E. 7.5 hours

Answer 10

The answer is C. 1 hour. CpSS should be reached in approximately 5 half-lives. 5/5=1.

Question 11

11) A junior doctor is reviewing the medications of an elderly patient. The patient reports that they have stopped taken one of their medications because it was causing side effects described as shaking or tremor. The doctor ascertains that it is a type B adverse drug reaction and goes about reporting it to the Medical and health Products Licensing Agency through the online yellow card system. Which of the below does NOT describe a type B ADR?

A. Dose-related
B. Uncommon
C. Unpredictable
D. Serious/irreversible
E. Associated with high mortality

Answer 11

Answer is A. Type B ADRs are not dose related, they are unpredictable and idiosyncratic.

Question 12

12) A clinical pharmacologist has been in discussion with a 59 year male about the management of his cholesterol levels as part of secondary prevention following an AMI 9 months ago. He already takes statin, but has struggled to tolerate a dose that is needed to reduce cholesterol sufficiently. The pharmacologist suggests adding ezetimibe to a lower dose of atorvastatin. There is evidence that this combination produces synergistic effects. How does the ezetimibe work in this patient?

A. Inhibits the rate limiting step in the mevalonate pathway
B. Activate the gene transcription factor PPARα
C. Inhibits hepatic diacylglycerol acetyltransferase-2
D. Inhibiting the PCSK9 protein
E. Inhibiting NPC1L1 transporter

Answer 12

The answer is E. Acts at the brush border of the small intestinal mucosa inhibiting NPC1L1 transporter which is proposed to be the limiting protein in GI cholesterol absorption. All others are mechanisms of other hyperlipidaemia therapeutics.

Question 13

13) Which of the following is not an ADR of hormone replacement therapies prescribed during menopause.

A. Increased risk of ischaemic heart disease
B. Increased risk of breast cancer
C. Increased risk of venous embolism
D. Increased HDL-C
E. Increased risk of ovarian cancer

Answer 13

The answer is D. in some preparations the effects are less marked but overall there is an increase in HDL-C which is may improve cardiovascular disease risk. Is not an adverse drug reaction.

Question 14

14) Which clotting factor does low molecular weight heparin (LMWH) target specifically and the reason why it requires much less monitoring than UFH?

A. Xa
B. IIa
C. XIa
D. XIIa
E. IXa

Answer 14

The answer is A. LMWH selectively accelerates interaction between antithrombin and factor Xa.

Question 15

15) A study was carried out to compare the vital capacity of coal miners to the vital capacity of farm workers aged 30-39. The study measured the vital capacity of 100 workers from each occupation. Other factors that might affect vital capacity are smoking, exercise and age. The smoking habits of the two worker types are similar, but the coal miners generally exercise less than the farm workers.

Which of the following is a confounding variable in this study?

A. Exercise
B. Vital capacity
C. Smoking habit.
D. Occupation
E. Age

Answer 15

The answer is A. Exercise status may contribute to differences in vital capacity. The exercise status of the two groups is likely to be different. Vital capacity is the variable being measures. Age and smoking have been accounted for (loosely for smoking) and occupation is the comparator.

Question 16

1. If 2.5 mg ramapril produces the same blood pressure lowering affect as 10mg lisinopril, which is correct?

A. Ramapril is more potent than lisinopril
B. Ramapril is more efficasios than lisinopril
C. Ramapril is a full agonist and lisinopril is a partial agonist

Answer 16

A. A drug that causes the same affect at lower doses is more potent. Maximal drug effects would be needed to conclude if b or c were correct.

Question 17

2. A new antibiotic produces toxic affects at a dose of 120 mg TDS in 50% of patients and a clinically desired response at 100 mg TDS in half of the populaton. What is the therapeutic index of this new antibiotic?

A. 1.2
B. 0.83
C. 1.0

Answer 17

A. Therapeutic index is equal to dose that produces toxicity in 50% population/dose that produces clinically desired effect.

Question 18

3. Buprenorphine is a partial agonist for opioid receptors. Can it have an affinity for these receptors that is greater than a full agonist such as codeine?

A. True
B. False

Answer 18

A. Partial agonists can have greater, the same or lower affinity for the same receptor as a full agonist but will have lower efficacy than the full agonist.

Question 19

4. Plasma steady state is reached quicker if the rate of infusion of an i.v. drug is doubled.

A. True
B. False

Answer 19

B. The plasma steady state will increase (will be doubled), but will take just as long to be reached as if the rate was halved.

Question 20

5. The P450 enzyme CYP3A4 is inhibited by grapefruit juice. How would this affect the plasma concentration of simvastatin if a patient were to drink grapefruit juice alongside taking this daily statin?

A. CYP3A4 is not involved in statin metabolism so will not have an affect
B. It could increase plasma concentrations of simavastatin
C. It could decrease plasma concentrations of simvastatin

Answer 20

B. Simvastatin metabolism is in part due to CYP3A4. Inhibition with grapefruit juice could result in elevated plasma concentrations of this statin.

Question 21

6. Steady state plasma concentration will be reached in how many half lifes?

A. 1
B. 3
C. 5

Answer 21

C. Ultimate steady state 100%:
1 t1/2 (100/2) = 50%
2 t1/2 (50 + 50/2) = 75%
3 t1/2 (75 + 25/2) = 87.5%
4 t1/2 (87.5 + 12.5/2) = 93.8%
5 t1/2 (93.75 +6.25/2) = 96.9%

Question 22

7. Liphophilic drugs will readily cross through cell membranes.

A. True
B. False

Answer 22

A. Lipophilic drugs dissolve in the lipid membrane and penetrate the cell surface.

Question 23

8. A patient is taking 80mg atorvastatin for secondary cardiovascular disease prevention. Only 11.2 mg is absorbed unchanged due to incomplete gut absorption and gut wall excretion. What is the oral bioavailability of atorvastain?

A. 100%
B. 7%
C. 14%

Answer 23

C. Bioavailability is the rate and extent at which drug reaches the systemic circulation. Total drug given orally/drug given i.v.(100% bioavailability)X100 = 11.2/80X100=14%

Question 24

9. A 46 year old female patient (70 kg) is prescribed ramapril to manage essential hypertension. Her dose has been increased to 5mg OD. The peak plasma concentration of ramapril was 0.06 mg/L. The apparent volume of distribution is:

A. 1.2 L/kg
B. 84 L/kg
C. 17 L/kg

Answer 24

A. Vd= dose/plasma concentration = 5/0.06 = 83.3 L. Patient is 70 kg, so 84/70 is ~ 1.2 L/kg

Question 25

10. Which of the following reactions is likely to occur during Phase II drug metabolism A. Oxidation B. Reduction C. Glucuronidation

Answer 25

C. Phase II metabolism involves conjugation reactions. Sulfation and gulcuronidation are the most common. Oxidation or reduction occur during Phase I metabolism.

Question 26

1. Which of the following is not a known reaction between beta blockers and thiazide diuretics? A. Hyperglycaemia B. Hyperlipideamia C. Hyperkalaemia

Answer 26

C. Thiazides are likely to cause hypokalaemia and beta blockers don't directly affect this action.

Question 27

2. Which of the below is a common ADR of furosemide? A. Increased LDL cholesterol B. Hypercalaemia C. Impotence

Answer 27

A. B and C are common ADRs associated with Spironolactone

Question 28

3. Labetalol can be used to treat hypertension during pregnancy A. True B. False

Answer 28

A. Oral lebetalol can be used to treat gestational hypertension when other agents (ACEi and ARBs, CCBs) are contraindicated.

Question 29

4. NICE guidelines define hypertensiton as A. >130/90 B. >140/90 C. >120/80

Answer 29

B. 120/80 deemed "normal" ideal for reducing risk of CVD. 130/90 is designated prehypertension, which should be targeted with lifestyle interventions.

Question 30

5. Resistance to blood flow is affected most by A. Length of the vessel B. Class of vessel (named artery, arteiole, capilary etc.) C. Radius of the vessel

Answer 30

C. Part of Poiseuille's law demonstrates that resistance to flow is inversely proportional to the radius of the vessel to the fourth power. Small changes in radius result in big differences in resistance to flow.

Question 31

6. Beta blockers are used in treating left ventricular heart failure by increasing heart rate? A. True B. False

Answer 31

B. Slightly counterintuitively, beta blockers slow the heart, allowing more time for filling and increasing cardiac output.

Question 32

7. Spironolactone affords its initial blood pressure lowering action by: A. causing hyperkalaemia B. blocking clacium entry into vascular smooth muscle cells C. Inhibition of aldosterone activity

Answer 32

C. Although not first line therapy, spironolactone inhibits aldosterone activity at its receptor leading to diuresis. Long term it is suggested that it may have direct effects on the vasculature.

Question 33

8. ACE inhibitors can lower blood pressure by inhibiting the brakdown of bradykinin? A. True B. False

Answer 33

A. ACE inhibitors can lower blood pressure by inhibiting the breakdown of bradykinin as well as their action through ACE inhibition.

Question 34

9. Which class of drugs does losartan belong too? A. ACE inhibitors B. angiotensin receptor blockers C. aldosterone receptor antagonists

Answer 34

B.

Question 35

10. Which of the following calcium channel blockers (CCBs) shows greatest selectivity for vascular smooth muscle? A. amlodopine B. verapamil C. diltiazem

Answer 35

A. Amlodopine is a dihydropyridine like calcium channel blocker that shows little to no acttivity in the cardiac tissues. Verapamil shows selectivity for cardiac tissue with some VSM action and diltiazem sits between them.

Question 36

1. Oestrodiol's major effects do not include: A. Stimulation of growth of the endometrium B. Stimulates production of progesterone receptor C. Inhbition of esrogen receptor production

Answer 36

C. Progesterone acts to inhibit production of the estrogen receptor.

Question 37

2. Testosterone A. Increases HDL:LDL ratio B. Decreases HDL:LDL ratio C. Has no affect on cholesterol profile

Answer 37

A. Increased ratio ( less HDL to other cholesterol) increasing risk of atherosclerotic disease i males.

Question 38

3. Combined oral and progesterone only contraceptive efficacy is _________ by antiepileptic drugs including phenytoin A. Increased B. Decreased C. No change

Answer 38

B. Phenytoin among other drugs increase CYP450 activity which increases metabolism of COCP and POP resulting in reduced efficacy

Question 39

4. Hormone replacment therapy can decrease the risk of venous thromboembolism? A. True B. False

Answer 39

B. Increased risk though effects on a number of proteins in the clotting cascade including increased thrombin activity.

Question 40

5. A type A adverse drug reaction is not A. Rare B. Predictable C. Dose dependent

Answer 40

A. Type A ADRs are predictable and dose dependent. With our clinical knowledge we should be able to foresee them happening, Especially with a clinical history and knowledge of other agents being taken.

Question 41

6. The yellow card system is the responsibility of healthcare professionals only. A. True B. False

Answer 41

B. Although the majority of reports are likely to come through health care professionals, patients and carers can and should report ADRs through this scheme too.

Question 42

7. Tamoxifen is A. Is a pure agonist of the oestrogen receptors B. Is a pure oestrogen receptor antagonist C. Is a selective oestrogen receptor modulator

Answer 42

C. Depending on the tissue, tamoxifen acts as an antagonist (breast tissue) or an agonist (endometrium)

Question 43

8. Oestrogens and their synthetic analogues are not well absorbed in the GI tract. A. True B. False

Answer 43

B. They are well absorbed in the GI tract and undergo significant first pass metabolism in the liver.

Question 44

9. Like >10% of Africans, a man from Ethiopa has the common deffieiceny in CYP2D6. What effect if any would you expect to see if he was using codeine as an analgesic? A. Increased therapeutic benefit, a lower dose may be considered B. Decreased therapeutic effect, an increased dose may be considered C. the analgeisc properties of codeine are not affected by CYPD6 deficiency

Answer 44

B. The active metabolite of codeine requires CYP2D6 oxidation activity. A deficiency would result in less active metabolite being produced and less analgesia.

Question 45

10. In a patient with hepatic disease, what effect will this have on the therapeutic action of tamoxifen? A. Increased B. Deacreased

Answer 45

B. tamoxifen is a pro drug that relies on hepatic metabolism to produce active metabolites.

Question 46

1. GLP-1 agonists like exenatide have shown promising weight reduction effects during long term use. Their actions include A. Decreased insulin secretion B. Decreased gastric emptying C. Increased glucagon production

Answer 46

B. GLP-1 agonists increase insulin secretion and decrease glucagon secretion. Decreased gastric emptying decreases postprandial glycaemia.

Question 47

2. Glucagon raises blood glucose levels in patients who have severe insulin induced hypoglycaemia. A. True B. False

Answer 47

A. Glucagon can be administered i.m., s.c. or i.v. Glycogon synthesis is reduced blocking the effects of insulin in the liver.

Question 48

3. Glicazide is a sulfonylurea. Which of the following is not a primary concern when prescribing it for diabetic managment? A. Cause hypoglycaemia B. Contraindicated in renal impariment C. Cause weight gain

Answer 48

B. Gliclazide is metabolised hepatically so can be used in renally compromised patients with care. Sulfonylureas cause weight gain and relativley more likely to cause hypoglycaemia than metformin.

Question 49

4. Why are insulins made as soluble preparations A. To delay absorption from injection site B. To shorten their half life C. To prevent hexamers being formed

Answer 49

A. Insulin is manufactured as a soluble preparation which delays absorption and overcome the short plasma half life. Soluble insulins form hexamers at site of injection contributing to delay in absorption

Question 50

5. Metformin is likely to be your first choice oral agent in conjunction with insulin in diabetic patients. Which best describes antidiabetic action of this biguanide? A. Increase insulin secretion B. Reduce of hepatic glucose production C. Inhibit fatty acid oxidation

Answer 50

B. Metformin does not affect insulin secretion. It inhibits gluconeogenesis in the liver resulting in less glucose production. metformin also increases fatty acid oxidation and reduce plasma triglycerides.

Question 51

6. Those that can only tolerate a low dose statin should be offered _______ in addtion as secondary prevention A. Fenofibrate B. Evolocumab C. Ezetimibe

Answer 51

C. Fenofibrate is offered in combination with a statin in specialist circumstances, typically in familial hypercholestrolamias but has an increased risk of rhabdomyalysis. Evolocumab is not rourinely prescribed with a statin- cost disctates it should be used in select patients. Guidelines suggest that ezetimibe is a good first choice addition to lower dose statin in secondary prevention.

Question 52

7. Ezetimibe has a large ADR profile beacuse of its systemic actions A. True B. False

Answer 52

B. Ezetimibe is a prodrug that undergoes hepatic metabolism to produce an active metabolite that undergoes significant enterohepatic circulation so the majority of the drug stays within the GI, relatively few ADRs

Question 53

8. Fibrates primary mechanism of action is A. Binding of bile acids B. Inhibition of the NPC1L1 transporter in the small intestines C. Activation of the nuclear transporter PPARα

Answer 53

C. Ezetimibe acts at the NPC1L1 receptor. Bile acid sequestrants such as cholestyarmine act by binding bile acids

Question 54

9. A high dose statin should be offered to all with a CVD risk of >10% as a primary prevention. A. True B. False

Answer 54

B. Low dose statin (typically 20 mg atorvastatin) is recommended for primary prevention.

Question 55

10. Which of the below is not a known action of statins that contributes to reduction in cardiovascular disease risk? A. Improved haemoastatis B. Stabilisation of athersclerotic plaque C. Increase endothelin

Answer 55

C. A and B both reduce the progression of atherosclerosis or reduce the likelihood of plaque rupture leading to thrombus formation and possible AMI or stroke. Statins reduce endothelin which is an autacoid that causes vasoconstriction.

Question 56

1. Clopidogrel is liscensed and prescribed for up to 12 months following an acute myocardial infarction A. in addtion to aspirin B. only if aspirin is contraindicated C. in addtion to prasugrel

Answer 56

A. Aspirin, if not contraindicated is prescribed indefinitely following an AMI. Clopidogrel is recommended in addition to aspirin for up to 12 months in most patients. You would not prescribe prasugrel in addition to clopidogrel as they act at the same site on the P2Y12 receptor.

Question 57

2. Known most commonly as a direct acting oral anticoagulant (DOAC), apixaban affords its action by A. inactivating factor Xa B. inactivating thrombin (IIa) C. inhibiting vitamin K epoxide reductase

Answer 57

A. The DOACs/NOACs afford their anticoagulation properties by selectively inactivating factor Xa.

Question 58

3. Ivabradine reduces heart rate (negative chronotropy) but does not reduce blood pressure. A. True B. False

Answer 58

A. The action of ivabradine on the iF channel in the SA node slows the heart but does not affect blood pressure. It is particularly useful in heart failure and managing angina.

Question 59

4. Which of the following calcium channel blockers is not a class IV antiarrhythmic agent? A. diltiazem B. verapamil C. amlodopine

Answer 59

C. Amlodopine is selective for vascular smooth muscle calcium channels and has little affect in the heart. Verapamil and to a lesser extent diltiazem show greater selectivity for calcium channels in the heart.

Question 60

5. Which of the following statements about low molecular weight heparins (LMWHs) is not true A. they require less monitoring than unfractionated heparin (UFH) B. they are less like to cause heparin induced thrombocytopenia C. the risk of osteoporosis is greater with LMWHs compared to UFHs

Answer 60

C. The risk of osteoporosis is smaller when receiving LMWH compared to UFH over a period of several weeks.

Question 61

6. The predominant ion that governs deploarisation (phase 0) in the sinoatrial node is sodium A. True B. False

Answer 61

B. Sodium ions enter the cell through fast sodium channels in the ventricles in phase 0. In the SA node, phase ) is slower and depends predominantly on calcium influx.

Question 62

7. Which of the following is not true about unfractionated heparin (UFH). A. It inactivates thrombin IIa B. Its activity can be monitored with the activated partial thromboplastin time C. It is primarly given by subcutaneous injection

Answer 62

C. Unfractionated heparin is typically administered by continuous i.v. infusion for full anticoagulation. Low doses can be given s.c. but bioavailability is only ~30%. LMWHs are given s.c. are need only be given 1-2 times a day for full anticoagulation.

Question 63

8. Warfarin..... A. potentiates the action of vatamin K B. inhibits the action of clotting factor IIa C. inhibits the synthesis factor X

Answer 63

C. Warfarin inhibits vitamin K epoxide reductase, which prevents the recycling of vitamin K. Vitamin K is an essential component of the SYNTHESIS of the clotting factors II, VII, IX and X. Does not affect active clotting factors including IIa (the "a" indicates active factor)

Question 64

9. Amiodarone is a class III antiarrhythmic that A. only inhibits potassium channels B. only inhibits soidum and potassium channles C. can act as a beta receptor antagonist

Answer 64

C. Amiodarone is a class III antiarrhythmic but can act on sodium channels, potassium channels, calcium channels and as a non competitive beta blocker.

Question 65

10. The class Ic antiarrhythmic agent flecainide A. decreases the action potential duration B. speeds up tissue condtion during pase 0 C. increases the P-R interval

Answer 65

C. Flecainide decreases the action potential duration, slows tissue conduction during phase 0 and as a result increases the P-R interval.

Question 66

1. Loperamide affords its action through targeting µ receptors in the mesenteric plexus. Which of the following statments is not true? A. Decreases tone of longitudinal and circular smooth muscle B. Increases peristalsis but decreases segmental contractions C. Decreases colonic mass movement by supressing gastrocolic reflex.

Answer 66

B. Loperamide decreases peristalsis but increases segmental contractions. increasing transit time allowing more fluid to be removed from the faeces.

Question 67

2. Evidence suggests that H. pylori erradication is best achieved with combination therapies. Which regimen is reccomended by the Leicestershire commisioning group? A. PPI plus clarithomycin B. PPI plus clarithromycin AND amoxycillin C. clarithromycin AND amxoycillin

Answer 67

B. There are many eradication protocols but local guidelines suggest a triple therapy of a PPI, clarithromycin and amoxycillin (metronidazole if amoxycillin contraindicated, although resistance in south Asian poulations )

Question 68

3. Which of the below best describes the action of histmaine antagonists in their antisecretory action. A. Competatively inhibit histmaine action at H2 receptors in gastric parietal cells. B. Competatively inhibit histmaine action at H1 receptors in gastric parietal cells. C. Non competatively inhibit histmaine action at H1 receptors in gastric parietal cells. D. Non competatively inhibit histmaine action at H2 receptors in gastric parietal cells.

Answer 68

A. Ranitidine and the other anti-secretory histamine antagonists competitively inhibit H2 receptors in the gastric parietal cells.

Question 69

4. Describe the difference between lactulose and macrogols in their laxactive effect in the large bowel

Answer 69

Lactulose acts to draw fluid into the bowel where as macrogols are better at limiting loss of fluid from the stool. They are both osmotic laxatives.

Question 70

5. Metoclopramide decreases intestinal motility A. True B. False

Answer 70

B. Increases intestinal motility (prokinetic) which contributes to its anti-emetic effects.

Question 71

6. Describe how hyoscine hydrobromide may be effective in managing motion sickness. Consdider the mechanism of action and side effect that may contribute to its use.

Answer 71

Muscarinic receptor antagonist, competitively blocks muscarnic ACh receptors. Also some action through the central trigger zone (via 8th cranial nerve). The sedation caused by these agents often contributes to their use for motion sickness.

Question 72

7. Which of the following is not true of neurokinin 1 receptor antagonsists? A. Augment the effects of 5HT3 receptor antagonsits B. Prevent the action of substance P C. Should not be used as an anti-emetic in patients undergoing chemotherapy

Answer 72

C. Neurokinin 1 receptor antagonists are particular useful in chemotherapy patients (specifically cisplatin) because the augment the action of 5HT3 antagonists and corticosteriods.

Question 73

8. Which receptor subtype does the commonly used antiemetic ondansetron inhibit? A. Histamne H1 B. 5HT1 C. 5HT3

Answer 73

C. Ondansetron belongs to the 5HT3 receptor antagonist class of anti-emetics. Particularly useful in vomiting induced by highly emetogenic chemotherapy.

Question 74

9. Proton pump inhbitors increase the metabolism of warfarin and phenytoin A. True B. False

Answer 74

B. PPIs inhibit CYP2C decreasing the metabolism of drugs including warfarin and phenytoin. This is an important DDI considering the large number of people taking warfarin long term.

Question 75

10. Proton pump inhibitors (PPIs) are typically taken p.o. Which is not true of this class of drugs? A. They reversibly inhibit the hydrogen/potassium ATPase proton pump B. They inhibit ~ 90% acid secretion within ~ 24-36 hours C. Given as enteric-coated tablets as they are unstable in acid

Answer 75

A. PPIs irreversibly and covalently bind to the proton pump. Acid secretion requires synthesis of new proton pumps.

Question 76

1. A 64 year male suffers from chronic osteoarthristis in his left knee. He has managed the pain with paracetamol until recently. In discussion with his GP it is decided that he should take naproxen. He currently takes no other medication. What should be co prescribed alongside the naproxen? A. Omeprazole B. Asprin C. NSAID topical gel

Answer 76

A. For patients being prescribed an NSAID for the management of osteoarthritis (likely for a long period of time, possibly before surgery) a PPI should be co prescribed regardless of whether it is a COX-2 or non-selective NSAID. Topical gel is likely to be ineffective if paracetamol is no longer managing the pain. It may help but the PPI should be offered with the NSAID.

Question 77

2. Explain why docusate sodium may be prescribed alongside morphine.

Answer 77

Side effect of opioid analgesics is constipation. Docusate sodium has faecal softening properties and is a stimulant of intestinal smooth muscle which aids peristalsis.

Question 78

3. Naloxone is used to treat opioid addiction. A. True B. False

Answer 78

B. Naloxone is a rapid acting opioid antagonist which can be used in opioid overdose but triggers severe withdrawal effects in opioid addicted people.

Question 79

4. Which of these opioids is a partial agonist at the µ-opioid receptor? A. Morphine B. Buprenorphine C. Fentany

Answer 79

B. Buprenorphine is a potent partial agonist at the -opioid receptor which is associated with its lower abuse potential than morphine

Question 80

5. Opioids inhibit pain in the dorsal horn of the spinal cord? A. True B. False

Answer 80

A. In part they act at opioid receptors to block transmitter release and postsynaptic transmission in the dorsal horn.

Question 81

6. Which of the following drugs has least anti-inflammatory effect? A. Aspirin B. Paracetamol C. Naproxen

Answer 81

B. Paracetamol has little to no anti inflammatory effect, thought in part due to peroxidase production at the site of inflammation

Question 82

7. Suggest two mechanisms by which NSAIDs can cause GI adverse drug reactions

Answer 82

Decreased mucus secretion Decreased bicarbonate secretion Reduced mucosal blood flow pH partitioning and accumulation of NSAID at gastric mucosa Inhibition of PGE2 and PGI2 major factor in these ADRs.

Question 83

8. Which of the prostanoids below show apposing platlet aggregatory action? A. PGE2 and TXA2 B. PGI2 and PGE2 C. PGI2 and TXA2

Answer 83

C. PGI2 inhibits platelet aggregation whereas TXA2 contributes to platelet aggregation. Inhibition of COX-1 in platelets by aspirin inhibits the synthesis of TXA2.

Question 84

9. Which of the following is NSAIDs is least selective for COX-2? A. Aspirin B. Ibuprofen C. Celecoxib

Answer 84

A. Celecoxib is prescribed as a cox-2 selective NSAID. Aspirin at therapeutic doses shows more selectivity for COX-1 and ibuprofen sits in the middle showing little selectivity.

Question 85

1. Before initiating anti-TNF therapy what should be screened for and why?

Answer 85

TB. TNF is essential in granuloma formation so that TB bacilli are walled off. Treatment for TB should be initiated prior therapy if latent or active TB is diagnosed.

Question 86

2. Which of the following is not true of the 6-mercaptopurine (6-MP) metabolite thiopurine methyltransferase (TMPT) A. The TMPT gene is highly polymorphic B. Low TMPT increases risk of myelosupression C. TMPT activity does not influence azathioprine treatment

Answer 86

C. TMPT activity varies across populations and low activity increases risk of toxicity due to prolonged activity of the active metabolites of azathioprine.

Question 87

3. Following surgery to remove a cancerous breast lump, a patient is to commence chemotherapy with the hope of removing any maligant cells that may have been left behind. Suggest two patient specific pieces of information you would need to calculate an appropriate regimen. Why are they important?

Answer 87

``` BMI liver function renal function performance status Narrow therapeutic indices and significant side effect profile means that very specific and tailored doses are required. Renal and hepatic function will dictate ADME. ```

Question 88

4. Disease modifying antirhematic drugs should..... A. Never be used in combination B. Only be given in combination with steroids C. Be considered in combination in severe rheumatoid disease

Answer 88

C. Evidence suggests that combination methotrexate with ciclosporin, sulfasalazine or hydroxycholoquine affords significant benefit in disease management.

Question 89

5. Methotrexate is used both as a chemotherapeutic agent and as a disease modifying antirheumatic drug (DMARD). We know that the mechanism of action for its use as a DMARD differs from how it works as a chemotherapy. What is its chemotherapeutic action? A. Guanine nucleotide cross linker B. Dihydrofolate reductase inhibition C. Inhibition of receptor tyrosine kinases

Answer 89

B. Platinum compounds act like a. | Methotrexate is not a tyrosine kinase inhibitor. Inhibition of dihydrofolate indirectly inhibits DNA synthesis.

Question 90

6. Methotrexate has a half life of circa 30 hours. With what frequency should it be taken? A. Once daily B. Once weekly C. Twice weekly

Answer 90

B. Methotrexate is metabolised to polyglutamates which have long half lives. Should only be given weekly.

Question 91

7. Vinca alkaloids prevent spindle formation. A. True B. False

Answer 91

A. Naturally derived from the periwinkle plant, vinca alkaloids prevent spindle formation by binding to tubulin (and preventing polymerisation) resulting in M-phase arrest.

Question 92

8. NSAIDs reduce symptoms of rheumatoid arthritis and slow its progresion. A. True B. False

Answer 92

B. Symptomatic relief of symptoms but to not slow progression. Some evidence suggests they may hasten disease advancement.

Question 93

9. Tacrolimus is used in patients undergoing transplantation. How does it act? A. TNFα inhibition B. Production of 6-thiosine monophosphate (TIMP) C. Prevents IL-2 production by inhibition of calcineurin

Answer 93

C. TIMP production is part of MOA of antiproliferative agents such as azathioprine. TNF inhibitors are monoclonal antibodies such as infliximab

Question 94

1. How do oseltamivir and zanamavir differ in pharmacokinetics and how does this dictate their routes of administration?

Answer 94

Zanamavir has poor bioavailability (2%) so is administered as a dry powder aerosol. Oseltamivir is a pro-drug which has high bioavailability and is given as an oral tablet.

Question 95

2. Which antiviral agent would be appropriate to treat the first presentation of genital herpes simplex virus? A. Zanamivir B. Valganciclovir C. Acilcovir

Answer 95

C. Oral aciclovir, typically for 7-10 days unless new lesions appear is an appropriate treatment.

Question 96

3. Oseltamivir can be prescribed as post-exposure prophylaxis against influenza. How does it work? A. Inhibition of haemagglutinin B. Inhibition of viral DNA polymerase C. Inhibition of neuraminidase

Answer 96

C. The neuraminidase active site is conserved across influenza sub-types and is an effective target to inhibit viral replication.

Question 97

4. Which of the below is a common ADR of furosemide? A. Increased LDL cholesterol B. Hypercalaemia C. Impotence

Answer 97

A. B and C are common ADRs associated with Spironolactone

Question 98

5. Are antibiotics used routinely in surgery? A. True B. False

Answer 98

A. A single prophylactic dose of antibiotic is typically given peri-operatively to prevent surgical site infection.

Question 99

6. Clarithromycin is prescribed in combination with amoxicillin to treat H Pylori within the Lecicestershire trust. How does it act? A. bacterial ribsome inhbition B. DNA structure disruption C. inhibition of topoisomerases

Answer 99

A. Clarithromycin is a macrolide antibiotic that interferes with bacterial protein synthesis by reversibly binding to the 50S subunit of bacterial ribosome.

Question 100

7. Amoxicillin affords its primary antibacterial action through A. prevention of complete cell wall synthesis B. inhibition of folate synthesis C. disruption of DNA synthesis

Answer 100

A. Amoxicillin is a penicillin member of the beta-lactam family which prevents bacterium from synthesising an intact cell wall when the bacterium divides.

Question 101

8. Why are insulins made as soluble preparations A. To delay absorption from injection site B. To shorten their half life C. To prevent hexamers being formed

Answer 101

A. Insulin is manufactured as a soluble preparation which delays absorption and overcome the short plasma half life. Soluble insulins form hexamers at site of injection contributing to delay in absorption

Question 102

9. Describe what minium inhibitory concentration of an antibacterial agent means?

Answer 102

The lowest concentration of an antibacterial agent that prevents growth of a specific organism (bacteria) in vitro. MIC is both bacteria and antibacterial dependant.

Question 103

1. The class Ic antiarrhythmic agent flecainide A. decreases the action potential duration B. speeds up tissue condtion during pase 0 C. increases the P-R interval

Answer 103

C. Flecainide increases the action potential duration, slows tissue conduction during phase 0 and as a result increases the P-R interval.

Question 104

2. Glicazide is a sulfonylurea. Which of the following is not a primary concern when prescribing it for diabetic managment? A. Cause hypoglycaemia B. Contraindicated in renal impariment C. Cause weight gain

Answer 104

B. Gliclazide is metabolised hepatically so can be used in renally compromised patients with care. Sulfonylureas cause weight gain and relativley more likely to cause hypoglycaemia than metformin.

Question 105

3. Local anesthetics A. Block sodium channels B. Potentiate sodium entry through sodium channels C. Close sodium chanels

Answer 105

A. Local anaesthetics cross the plasma membrane as lipid soluble non ionised molecules. The ionised form then blocks the intracellular end of the open sodium channel.

Question 106

4. Why may a vasocontricting agent be used in cnjunction with a local anaesthetic?

Answer 106

Any of the following: Decrease peak plasma conc. of local anaesthetic. Decrease the minimum effective dose. Increase duration of anaesthesia.

Question 107

5. Describe why inhaled particles that are too small AND too big are ineffective in asthma magment.

Answer 107

Too big and will deposit in the mouth and oropharynx. Too small and will be inhaled into aveoli and exhaled without being deposited in the lungs.

Question 108

6. Describe two features of an adult patient presenting with acute severe asthma.

Answer 108

Including: Unable to complete sentences. Pulse greater than 110 bpm. Resp rate greater than 25/min. Peak flow 33-50% of best or predicted.

Question 109

7. Once addtional agents have been added to an asthmatics care plan they should not be removed. A. True B. False

Answer 109

B. Once control is achieved, stepping down is recommended. The lowest effective dose of inhaled steroid should always be used.

Question 110

8. Tiotropium is licenced for use in severe asthma and COPD. Its primary site of action is... A. M1 receptors B. M3 receptors C. B2 receptors

Answer 110

B. Tiotropium is a long acting muscarinic antagonist with selectivity for m3 receptors.

Question 111

9. Leukotrienes including LTC4 are released by mast cells and eosiophils inducing bronchoconstriction. Which therapeutic agent inhibits their action? A. Montelukast B. Salbutomol C. Tiotropium

Answer 111

A. Montelukast is a leukotriene receptor antagonist, inhibiting the action of leukotienes at their receptors.

Question 112

1. Which is not true of sodium valproate A. It inhibits CYP450 enzymes including 2C9 B. Causes weight loss C. Teratogenic

Answer 112

B. Inhibits CYP2C9. Causes weight GAIN which may be associated with polycystic ovary syndrome prevalence in woman. Causes neural tube defects.

Question 113

2. Anticholinergics have little effect on treating bradykinesia A. True B. False

Answer 113

A. They help restore balance between CNS cholinergic and dopamine activity. They produce the usual common anticholinergic side effects inc. confusion and drowsiness

Question 114

3. Describe how selegiline and rasagaline can be beneficial in the managment of Parkinson's disease?

Answer 114

Inhibit MAO B metabolism of dopamine. Prolong action of L-DOPA reducing dose required and have modest effects when used alone.

Question 115

4. Which of the following is recomended as first line treatment in idopathic Pakinsons' Disease A. levodopa B. rotigotine C. co-careldopa

Answer 115

C. Levodopa with the DOPA decarboxylase inhibitor carbidopa is used. Levodopa alone produces little increase in dopamine crossing the BBB. Rotigotine is formulated as a patch and is not typically used as first line treatment.

Question 116

5. List the 5 types of generalised seizure

Answer 116

Absence, Myoclonic, Tonic-clonic, Tonic and Atonic

Question 117

6. For woman of child bearing age taking anti epileptic medication and COCP, which should be considered? A. oestrogren component of COCPshould be increased B. progesterone component of COCP should be increased C. both should be increased

Answer 117

A. Increased oestrogen by ~50 micrograms and advise to use additional contraceptive methods is suggested.

Question 118

7. Which of the following is true of phenytoin? A. Wide therapeutic window B. Is used in status epilepticus C. Requires very little therapeutic monitoring

Answer 118

B. Is used in status epilepticus, typically following a benzodiazapine if this has been unsuccessful. It has a narrow therapeutic window and exhibits zero order elimination kinetics. Therapeutic monitoring required to guide dosing in patients with large pharmacokinetic variability.

Question 119

8. Metoclopramide decreases intestinal motility A. True B. False

Answer 119

B. Increases intestinal motility (prokinetic) which contributes to its anti-emetic effects.

Question 120

9. Tonic-clonic and absence seizures are types of generalised seizure. A. True B. False

Answer 120

A. Both are generalised seizures that affect the whole brain