Passmedicine - Pharmacology Questions 1 to 50

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Passmedicine online course 2012Pharmacology (Q1-50)

Question 1 of 250

A 62-year-old is started on allopurinol prophylaxisfollowing his second episode of gout in the past 12

months. What is the mechanism of action of allopurinol?ia

A. A Promotes excretion of uric acidia

B. A Causes the depolymerisation of

intracellular microtubulesia

C. A Uric acid chelator ia

D. A Inhibits xanthine oxidaseia

E. A Xanthine oxidase activator ia

Allopurinol inhibits xanthine oxidase

Xanthine oxidase is responsible for the oxidation of 6 -

mercaptopurine to 6-thiouric acid

Allopurinol

sqweqwesf erwrewfsdfs adasd dhe Allopurinol is used in the prevention of gout. It works by

inhibiting xanthine oxidase

Initiating allopurinol prophylaxis - see indications below

allopurinol should not be started until 2 weeks

after an acute attack has settled

initial dose of 100 mg od, with the dose titratedevery few weeks to aim for a serum uric acid of < 300 µmol/l

NSAID or colchicine cover should be usedwhen starting allopurinol

Indications for allopurinol*

recurrent attacks - the British Society for Rheumatology recommend 'In uncomplicatedgout uric acid lowering drug therapy should bestarted if a second attack, or further attacks

occur within 1 year'

tophi

renal disease

uric acid renal stones

prophylaxis if on cytotoxics or diuretics

*patients with Lesch-Nyhan syndrome often takeallopurinol for life

Interactions

Azathioprine

metabolised to acti ve compound 6-

mercaptopurine

xanthine oxidase is responsible for theoxidation of 6-mercaptopurine to 6-thiouric acid

allopurinol can therefore lead to high levels of

6-mercaptopurine a much reduced dose (e.g. 25%) must

therefore be used if the combination cannot beavoided

Cyclophosphamide

allopurinol reduces renal clearance, thereforemay cause marrow toxicity

Question 2 of 250

Which one of the following immunosuppressant drugsinhibits calcineurin in T cells?ia

A. A Mycophenolate m ofetilia

B. A Basiliximabia

C. A Azathioprineia

D. A Ciclosporinia

E. A Methotrexateia

Ciclosporin + tacrolimus - MOA: inhibit calcineurin thus

decreasing IL-2

Mycophenolate mofetil inhibits inosine monophosphate

dehydrogenase. Azathioprine is metabolised to the

active compound mercaptopurine, a purine analoguethat inhibits DNA synthesis. Methotrexate is anantimetabolite which inhibits dihydrofolate reductase

Ciclosporin

sqweqwesf erwrewfsdfs adasd dhe Ciclosporin is an immunosuppressant which decreasesclonal proliferation of T cells by reducing IL-2 release. It

acts by binding to cyclophilin forming a complex whichinhibits calcineurin, a phosphotase that activatesvarious transcription factors in T cells

Adverse e ffects of ciclosporin (note how everything isincreased - fluid, BP, K

+, hair, gums, glucose)

nephrotoxicity

hepatotoxicity

fluid retention

hypertension

hyperkalaemia

hypertrichosis

hyperplasia of gum



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tremor impaired glucose tolerance

Indications

following organ transplantation

rheumatoid arthritis

psoriasis (has a direct effect on keratinocytesas well as modulating T cell function)

ulcerative colitis

pure red cell aplasia

Question 3 of 250

A 45-year-old man with a history of epilepsy andpsychiatric problems is admitted to the EmergencyDepartment with confusion following a seizure earlier in

the day. On examination he is noted to have a coarsetremor, blood pressure is 134/86 mmHg, pulse is84/min and the temperature is 36.7ºC. What is the most

likely diagnosis?ia A. A Carbamazepine overdoseia

B. A Lithium toxicityia

C. A Benzodiazepine toxicityia

D. A Tricyclic overdoseia

E. A Neuroleptic malignant syndromeia

Lithium: fine tremor in chronic treatment, coarse tremor

in acute toxicity

A tricyclic overdose may present with seizures but it

does not typical cause a tremor

Lithium toxicity

sqweqwesf erwrewfsdfs adasd dhe Lithium is mood stabilising drug used most commonlyprophylatically in bipolar disorder but also as an adjunct

in refractory depression. It has a very narrow

therapeutic range (0.4-1.0 mmol/L) and a long plasmahalf-life being excreted primarily by the kidneys. Lithium

toxicity generally occurs following concentrations > 1.5mmol/L.

Toxicity may be precipitated by dehydration, renalfailure, diuretics (especially bendroflumethiazide) or

ACE inhibitors

Features of toxicity

coarse tremor (a fine tremor is seen in

therapeutic levels)

acute confusion seizure coma

Management

mild-moderate toxicity may respond to volume

resuscitation with normal saline

haemodialysis may be needed in severetoxicity

sodium bicarbonate is sometimes used but

there is limited evidence to support this. By

increasing the alkalinity of the urine it promoteslithium excretion

Question 4 of 250

Which one of the following statements regarding

metformin is true?ia

A. A Should be stopped in a patient admitted with a

myocardial infarctionia

B. A Hypoglycaemia is a recognised adverse e ffect ia

C. A May cause a metabolic alkalosisia

D. A May aggravate necrobiosis lipoidica

diabeticorumia

E. A Increases vitamin B12 absorptionia

Metformin should be stopped following a myocardial

infarction due to the risk of lactic acidosis. It may beintroduced at a later date. Diabetic control may beachieved through the use of a insulin/dextrose infusion

(e.g. the DIGAMI regime)

Metformin

sqweqwesf erwrewfsdfs adasd dhe

Metformin is a biguanide used mainly in the treatmentof type 2 diabetes mellitus. It has a number of actionswhich improves glucose tolerance (see below). Unlike

sulphonylureas it does not cause hypoglycaemia andweight gain and is therefore first-line, particularly if thepatient is overweight. Metformin is also used in

polycystic ovarian syndrome and non-alcoholic fattyliver disease

Mechanism of action

increases insulin sensitivity

decreases hepatic gluconeogenesis

may also reduce gastrointestinal absorption of carbohydrates

Adverse e ffects

gastrointestinal upsets are common (nausea,

anorexia, diarrhoea), intolerable in 20%

reduced vitamin B12 absorption - rarely aclinical problem

lactic acidosis* with severe liver disease or renal failure



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Contraindications**

chronic kidney disease: NICE recommend

reviewing metformin if the creatinine is > 130µmol/l and stopping metformin if > 150 µmol/l

do not use during suspected episodes o f tissuehypoxia (e.g. Recent MI, sepsis)

alcohol abuse is a relative contraindication

stop 2 days before general anaesthetic, restartwhen renal function normal

stop prior to IV contrast e.g. Angiography,restart when renal function normal

*it is now increasingly recognised that lactic acidosis

secondary to metformin is rare, although it remains

important in the context of exams

**metformin is now sometimes used in pregnancy, for

example in women with polycystic ovarian syndrome.

Question 5 of 250

What is the main mechanism of action of simvastatin?ia

A. A Bile acid sequestrantia

B. A Decreases hepatic HDL synthesisia

C. A Inhibits lipoprotein lipaseia

D. A Decreases intrinsic cholesterol synthesisia

E. A Agonists of PPAR-alphaia

Statins inhibit HMG-CoA reductase, the rate-limitingenzyme in hepatic cholesterol synthesis

Statins


Statins inhibit the action of HMG-CoA reductase, therate-limiting enzyme in hepatic cholesterol synthesis

Adverse effects

myopathy: includes myalgia, myositis,

rhabdomyolysis and asymptomatic raisedcreatine kinase. Risks factors for myopathyinclude advanced age, female sex, low body

mass index and presence of multisystemdisease such as diabetes mellitus. Myopathy ismore common in lipophilic statins (simvastatin,

atorvastatin) than relatively hydrophilic statins

(rosuvastatin, pravastatin, fluvastatin) liver impairment: the 2008 NICE guidelines

recommend checking LFTs at baseline, 3months and 12 months. Treatment should bediscontinued if serum transaminase

concentrations rise to and persist at 3 times theupper limit of the reference range

Who should receive a statin?

all people with established cardiovascular

disease (stroke, TIA, ischaemic heart disease,peripheral arterial disease)

NICE recommend anyone with a 10-year cardiovascular risk >= 20%

the management of blood lipids in type 2diabetes mellitus (T2DM) has changed slightly.

Previously all patients with T2DM > 40-years-old were prescribed statins. Now patients > 40-years-old who have no obvious cardiovascular

risk (e.g. Non-smoker, not obese, normotensiveetc) and have a cardiovascular risk < 20%/10years do not need to be given a statin. We

suggest reviewing the NICE T2DM guidelinesfor further information

Statins should be taken at night as this is when the

majority of cholesterol synthesis takes place. This isespecially true for simvastatin which has a shorter half-life than other statins

Current guidelines for lipid lowering*

Total

cholesterol(mmol/l)

LDL

cholesterol

Joint BritishSocieties < 4.0 < 2.0

National ServiceFramework for CHD

< 5.0 < 3.0

SIGN 2007 < 5.0 < 3.0

*current NICE guidelines do not recommend a target

cholesterol in primary prevention

Question 6 of 250

A patient develops a broad complex tachycardia twodays following a myocardial infarction. Intravenousamiodarone is given. Which one of the following best

describes the mechanism of action of amiodarone?ia

A. A Blocks potassium channelsia

B. A Shortens QT intervalia

C. A Blocks sodium channelsia

D. A Opens sodium channelsia

E. A Blocks calcium channelsia

Amiodarone - MOA: blocks potassium channels



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Amiodarone

sqweqwesf erwrewfsdfs adasd dhe Amiodarone is a class III antiarrhythmic agent used inthe treatment of atrial, nodal and ventricular

tachycardias. The main mechanism of action is byblocking potassium channels which inhibits

repolarisation and hence prolongs the action potential. Amiodarone also has other actions such as blockingsodium channels (a class I effect)

The use of amiodarone is limited by a number of factors

long half-life (20-100 days)

should ideally be given into central veins(causes thrombophlebitis)

has proarrhythmic effects due to lengthening of

the QT interval

interacts with drugs commonly used

concurrently e.g. Decreases metabolism of warfarin

numerous long-term adverse effects (seebelow)

Monitoring of patients taking amiodarone

TFT, LFT, U&E, CXR prior to treatment

TFT, LFT every 6 months

Adverse effects of amiodarone use

thyroid dysfunction

corneal deposits

pulmonary fibrosis/pneumonitis

liver fibrosis/hepatitis

peripheral neuropathy, myopathy

photosensitivity

'slate-grey ' appearance

thrombophlebitis and injection site reactions

bradycardia

Question 7 of 250

A 44-year-old Bangladeshi man with a history of mitralstenosis and atrial fibrillation is diagnosed withtuberculosis. He is commenced on anti -tuberculosis

therapy. Three weeks after starting treatment his INRhas increased to 5.6. Which one of the followingmedications is most likely to be responsible for this

increase?ia

A. A Pyrazinamideia

B. A Isoniazidia

C. A Rifampicinia

D. A Ethambutolia

E. A Streptomycinia

Isoniazid inhibits the P450 system

It is important when answering questions relating to

liver enzymes to be sure whether the question is asking

about induction or inhibition. Drugs causing inductionare often well known and Candidates may rush to give

these as the answer. A raised INR is a resultof inhibited liver enzymes

P450 enzyme system


Induction usually requires prolonged exposure to theinducing drug, as opposed to P450 inhibitors, whereeffects are often seen rapidly

Inducers of the P450 system include

antiepileptics: phenytoin, carbamazepine barbiturates: phenobarbitone

rifampicin

St John's Wort

chronic alcohol intake

griseofulvin

smoking (affects CYP1A2, reason why smokersrequire more aminophylline)

Inhibitors of the P450 system include

antibiotics: ciprofloxacin, erythromycin isoniazid

cimetidine, omeprazole

amiodarone

allopurinol

imidazoles: ketoconazole, fluconazole

SSRIs: fluoxetine, sertraline

ritonavir

sodium valproate

acute alcohol intake quinupristin

Question 8 of 250

A 56-year-old man with a history of epilepsy, atrialfibrillation and ischaemic heart disease is noted to have

a rash on his forearms and face in the cardiology clinic.Which one of the following drugs is most likely to beresponsible?ia

A. A Verapamilia

B. A Carbamazepineia

C. A Amiodaroneia

D. A Digoxinia

E. A Clopidogrelia



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A rash on the forearms and face is typical of aphotosensitivity rash

Drugs causing photosensitivity

sqweqwesf erwrewfsdfs adasd dhe Causes of drug-induced photosensitivity

thiazides

tetracyclines, sulphonamides, ciprofloxacin

amiodarone

NSAIDs e.g. piroxicam

psoralens sulphonylureas

Question 9 of 250

A 61-year-old man develops aortic regurgitation after

taking medication for Parkinson's disease. Which oneof the following medications is he most likely to havetaken?ia

A. A Pergolideia

B. A Cabergolineia

C. A Selegilineia

D. A Ropiniroleia

E. A Amantadineia

Pergolide is particularly associated with valvular

dysfunction.

Parkinson's disease: management


Currently accepted practice in the management of patients with Parkinson's disease (PD) is to delaytreatment until the onset of disabling symptoms and

then to introduce a dopamine receptor agonist. If thepatient is elderly, levodopa is sometimes used as aninitial treatment.

Dopamine receptor agonists

e.g. Bromocriptine, ropinirole, cabergoline,apomorphine

ergot-derived dopamine receptor agonists

(bromocriptine, cabergoline, pergolide*) havebeen associated with pulmonary,retroperitoneal and cardiac fibrosis. The

Committee on Safety of Medicines advice thatan echocardiogram, ESR, creatinine and chestx-ray should be obtained prior to treatment and

patients should be closely monitored

patients should be warned about the potentialfor dopamine receptor agonists to cause

impulse control disorders and excessivedaytime somnolence

Levodopa

usually combined with a decarboxylase inhibitor

(e.g. Carbidopa or benserazide) to prevent

peripheral metabolism of levodopa to dopamine

reduced effectiveness with time (usually by 2years)

unwanted effects: dyskinesia, 'on-off' effect

no use in neuroleptic induced parkinsonism

MAO-B (Monoamine Oxidase-B) inhibitors

e.g. Selegiline

inhibits the breakdown of dopamine secretedby the dopaminergic neurons

Amantadine

mechanism is not fully understood, probably

increases dopamine release and inhibits itsuptake at dopaminergic synapses

COMT (Catechol-O-Methyl Transferase) inhibitors

e.g. Entacapone

COMT is an enzyme involved in the breakdownof dopamine, and hence may be used as anadjunct to levodopa therapy

used in established PD

Antimuscarinics

block cholinergic receptors

now used more to treat drug-inducedparkinsonism rather than idiopathic Parkinson's

disease

help tremor and rigidity

e.g. Procyclidine, benzotropine, trihexyphenidyl(benzhexol)

*pergolide was withdrawn from the US market in March

2007 due to concern regarding increased incidence of

valvular dysfunction

Question 10 of 250

Where is the site of action of furosemide?ia

A. A Proximal collecting ductia

B. A Ascending loop of Henleia

C. A Descending loop of Henleia

D. A Distal collecting ductia

E. A Macula densaia

Loop diuretics



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sqweqwesf erwrewfsdfs adasd dhe Furosemide and bumetanide are loop diuretics that act

by inhibiting the Na-K-Cl cotransporter in the thickascending limb of the loop of Henle, reducing theabsorption of NaCl.

Indications

heart failure: both acute (usually intravenously)

and chronic (usually orally) resistant hypertension, particularly in patients

with renal impairment

Adverse effects

hypotension

hyponatraemia

hypokalaemia

hypochloraemic alkalosis

ototoxicity

hypocalcaemia renal impairment (from dehydration + direct

toxic effect)

hyperglycaemia (less common than withthiazides)

gout

Question 11 of 250

A 72-year-old female known to have osteoporosis isstarted on alendronate. Which one of the following side-effects is it most important to warn her about?ia

A. A Sore throatia

B. A Heartburnia

C. A Headacheia

D. A Diarrhoeaia

E. A Palpitationsia

Bisphosphonates can cause a variety of oesophagealproblems

Whilst the development of any new problem following

the introduction of a new drug warrants medical reviewit is particularly important to warn patients startingbisphosphonates about symptoms which could suggest

an oesophageal reaction, especially with alendronate

Bisphosphonates

sqweqwesf erwrewfsdfs adasd dhe Bisphosphonates are analogues of pyrophosphate, a

molecule which decreases demineralisation in bone.They inhibit osteoclasts by reducing recruitment andpromoting apoptosis

Clinical uses

prevention and treatment of osteoporosis

hypercalcaemia

Paget's disease

pain from bone metatases

Adverse e ffects

oesophageal reactions: oesophagitis,

oesophageal ulcers (especially alendronate)

osteonecrosis of the jaw

increased risk of atypical stress fractures of theproximal femoral shaft in patients takingalendronate

The BNF suggests the following counselling for patientstaking oral bisphosphonates

'Tablets should be swallowed whole with plenty

of water while sitting or standing; to be given on

an empty stomach at least 30 minutes beforebreakfast (or another oral medication); patientshould stand or sit upright for at least 30minutes after taking tablet'

Question 12 of 250

A 69-year-old man is started on tamsulosin for benignprostatic hyperplasia. Which one of the following bestdescribes the side-effects he may experience?ia

A. A Urgency + insomniaia

B. A Dizziness + postural hypotensionia

C. A Urinary retention + nauseaia

D. A Urgency + erectile dysfunctionia

E. A Erectile dysfunction + reduced libidoia

Benign prostatic hyperplasia

sqweqwesf erwrewfsdfs adasd dhe Benign prostatic hyperplasia (BPH) is a commoncondition seen in older men.

Risk factors

age: around 50% of 50-year-old men will have

evidence of BPH and 30% will have symptoms.

Around 80% of 80-year-old men have evidenceof BPH

ethnicity: black > white > Asian

BPH typically presents with lower urinary tractsymptoms (LUTS), which may be categorised into:



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voiding symptoms (obstructive): weak or

intermittent urinary flow, straining, hesitancy,

terminal dribbling and incomplete emptying

storage symptoms (irritative) urgency,frequency, urgency incontinence and nocturia

post-micturition: dribbling

complications: urinary tract infection, retention,obstructive uropathy

Management options

watchful waiting

medication: alpha-1 antagonists, 5 alpha-

reductase inhibitors. The use of combinationtherapy was supported by the Medical TherapyOf Prostatic Symptoms (MTOPS) trial

surgery: transurethral resection of prostate(TURP)

Alpha-1 antagonists e.g. tamsulosin, alfuzosin

decrease smooth muscle tone (prostate andbladder)

considered first-line, improve symptoms inaround 70% of men

adverse effects: dizziness, posturalhypotension, dry mouth, depression

5 alpha-reductase inhibitors e.g. finasteride

block the conversion of testosterone todihydrotestosterone (DHT), which is known to

induce BPH

unlike alpha-1 antagonists causes a reductionin prostate volume and hence may slowdisease progression. This however takes time

and symptoms may not improve for 6 months.They may also decrease PSA concentrationsby up to 50%

adverse effects: erectile dysfunction, reducedlibido, ejaculation problems, gynaecomastia

Question 13 of 250

A 65-year-old female is admitted to the EmergencyDepartment following an overdose of a long-acting

propranolol preparation. On admission she isbradycardic with a pulse of 36/min and BP 90/50. Thebradycardia fails to respond to atropine. What is the

most appropriate management?ia

A. A Temporary cardiac pacingia

B. A Haemodialysisia

C. A Glucagonia

D. A Noradrenaline infusionia

E. A Salbutamol infusionia

Beta-blocker overdose management: atropine +

glucagon

Glucagon has a positive inotropic action on the heart

and decreases renal vascular resistance. It is therefore

useful in patients with beta-blocker cardiotoxicityCardiac pacing should be reserved for patients

unresponsive to pharmacological therapy

Beta-blocker overdose

sqweqwesf erwrewfsdfs adasd dhe Features

bradycardia

hypotension

heart failure syncope

Management

if bradycardic then atropine

in resistant cases glucagon may be used

Haemodialysis is not effective in beta-blocker overdose

Question 14 of 250

A 45-year-old man with a history of depression andgastro-oesophageal reflux disease presents due to a

milky discharge from his nipples. The following bloodresults are obtained:

Prolactin 700 mu/l

Which one of his medications is most likely to beresponsible?ia

A. A Omeprazoleia

B. A Fluoxetineia

C. A Metoclopramideia

D. A Cimetidineia

E. A Amitriptylineia

Causes of raised prolactin - the p 's

pregnancy

prolactinoma

physiological

polycystic ovarian syndrome

primary hypothyroidism phenothiazines, metoclopramide, domperidone



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Selective serotonin reuptake inhibitors such as

fluoxetine have rarely been associated with

hyperprolactinaemia but the most likely cause in thispatient is metoclopramide. Cimetidine is generallyassociated with gynaecomastia, rather than

galactorrhoea.

Prolactin and galactorrhoea

sqweqwesf erwrewfsdfs adasd dhe Prolactin is secreted by the anterior pituitary gland withrelease being controlled by a wide variety of physiological factors. Dopamine acts as the primary

prolactin releasing inhibitory factor and hencedopamine agonists such as bromocriptine may be usedto control galactorrhoea. It is important to differentiate

the causes of galactorrhoea (due to the actions of prolactin on breast tissue) from those of gynaecomastia

Features of excess prolactin

men: impotence, loss of libido, galactorrhoea

women: amenorrhoea, galactorrhoea

Causes of raised prolactin

prolactinoma

pregnancy

oestrogens

physiological: stress, exercise, sleep

acromegaly: 1/3 of patients

polycystic ovarian syndrome

primary hypothyroidism (due to thyrotrophin

releasing hormone (TRH) stimulating prolactinrelease)

Drug causes of raised prolactin

metoclopramide, domperidone

phenothiazines

haloperidol very rare: SSRIs, opioids

Question 15 of 250 A 54-year-old man with a history of hypertension comesfor review. He currently takes lisinopril 10mg od,

simvastatin 40mg on and aspirin 75mg od. His bloodpressure is well controlled at 124/76 mmHg but he alsomentions that he is due to have a tooth extraction next

week. What advice should be given with regards to hisaspirin use?ia

A. A Take aspirin as normal but take tranexamic

1g tds acid 24 hours before and after procedureia

B. A Stop 72 hours before, restart 24 hours after procedureia

C. A Stop 24 hours before, restart 12 hours after procedureia

D. A Take aspirin as normalia

E. A Stop 48 hours before, restart 24 hours after procedureia

In the BNF section 'Prescribing in dental practice' itadvises that patients in this situation should continue

taking anti-platelets as normal

Aspirin


Aspirin works by blocking the action of bothcyclooxygenase-1 and 2. Cyclooxygenase isresponsible for prostaglandin, prostacyclin and

thromboxane synthesis. The blocking of thromboxane A2 formation in platelets reduces the ability of plateletsto aggregate which has lead to the widespread use of

low-dose aspirin in cardiovascular disease. Until recentguidelines changed all patients with establishedcardiovascular disease took aspirin if there was no

contraindication. Following the 2010 technologyappraisal of clopidogrel this is no longer the case*.

Two recent trials (the Aspirin for Asymptomatic Atherosclerosis and the Antithrombotic TrialistsCollaboration) have cast doubt on the use of aspirin in

primary prevention of cardiovascular disease.Guidelines have not yet changed to reflect this.However the Medicines and Healthcare productsRegulatory Agency (MHRA) issued a drug safety

update in January 2010 reminding prescribers thataspirin is not licensed for primary prevention.

What do the current guidelines recommend?

first-line for patients with ischaemic heartdisease and following a TIA**

Potentiates

oral hypoglycaemics

warfarin steroids

*NICE now recommend clopidogrel first-line following

an ischaemic stroke (but not for TIAs) and for peripheral

arterial disease

**alongside dipyridamole

Question 16 of 250

A 41-year-old woman is admitted following a deliberateoverdose of ethylene glycol. She is confused and

unable to give any further history. On examination the

pulse is 96 / min, blood pressure is 142/84 mmHg andtemperature 37.1ºC. Blood tests show:

Na+ 139 mmol/l



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K+ 4.0 mmol/l

Chloride 104 mmol/l

Bicarbonate 26 mmol/l

Urea 4.0 mmol/l

Creatinine 88 µmol/l

What is the most appropriate management of thispatient?ia

A. A Ethanolia

B. A Fomepizoleia

C. A Haemodialysisia

D. A Haemofiltrationia

E. A Dantroleneia

Ethylene glycol toxicity management - fomepizole. Alsoethanol / haemodialysis

Fomepizole is now used first-line rather than ethanol in

ethylene glycol toxicity. There is no indication for

haemodialysis at this stage, as a metabolic acidosishas not yet developed

Ethylene glycol toxicity


Ethylene glycol is a type of alcohol used as a coolant or antifreeze

Features of toxicity are divided into 3 stages:

Stage 1: symptoms similar to alcohol

intoxication: confusion, slurred speech,dizziness

Stage 2: metabolic acidosis with high anion gapand high osmolar gap. Also tachycardia,hypertension

Stage 3: acute renal failure

Management has changed in recent times

ethanol has been used for many years

works by competing with ethylene glycol for theenzyme alcohol dehydrogenase

this limits the formation of toxic metabolites(e.g. glycoaldehyde and glycolic acid) whichare responsible for the

haemodynamic/metabolic features of poisoning

fomepizole, an inhibitor of alcoholdehydrogenase, is now used first-line in

preference to ethanol haemodialysis also has a role in refractory

cases

Question 17 of 250

Which one of the following statements regarding statin-induced myopathy is incorrect?ia

A. A Rhabdomyolysis may cause renal failureia

B. A Patients with an elevated creatine kinase

often have no symptomsia

C. A Female sex is a risk factor ia

D. A Creatine kinase does not need to beroutinely checked prior to commencing astatinia

E. A Pravastatin is more likely to cause myopathy

than simvastatinia

Myopathy is more common in lipophilic statins(simvastatin, atorvastatin) than relatively hydrophilicstatins (rosuvastatin, pravastatin, fluvastatin)

Statins

sqweqwesf erwrewfsdfs adasd dhe Statins inhibit the action of HMG-CoA reductase, the

rate-limiting enzyme in hepatic cholesterol synthesis

Adverse e ffects

myopathy: includes myalgia, myositis,rhabdomyolysis and asymptomatic raised

creatine kinase. Risks factors for myopathyinclude advanced age, female sex, low bodymass index and presence of multisystem

disease such as diabetes mellitus. Myopathy is

more common in lipophilic statins (simvastatin,atorvastatin) than relatively hydrophilic statins

(rosuvastatin, pravastatin, fluvastatin)

liver impairment: the 2008 NICE guidelinesrecommend checking LFTs at baseline, 3

months and 12 months. Treatment should bediscontinued if serum transaminaseconcentrations rise to and persist at 3 times theupper limit of the reference range



disease (stroke, TIA, ischaemic heart disease,

peripheral arterial disease)


the management of blood lipids in type 2

diabetes mellitus (T2DM) has changed slightly.Previously all patients with T2DM > 40-years-old were prescribed statins. Now patients > 40-

years-old who have no obvious cardiovascular risk (e.g. Non-smoker, not obese, normotensiveetc) and have a cardiovascular risk < 20%/10

years do not need to be given a statin. Wesuggest reviewing the NICE T2DM guidelinesfor further information



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Total

cholesterol(mmol/l)

LDL

cholesterol

Joint British

Societies

< 4.0 < 2.0


< 5.0 < 3.0

SIGN 2007 < 5.0 < 3.0



Question 18 of 250

Which one of the following drugs may be cleared byhaemodialysis?ia

A. A Beta-blockersia

B. A Tricyclicsia

C. A Aspirinia

D. A Benzodiazepinesia

E. A Digoxinia

Haemodialysis in overdose

sqweqwesf erwrewfsdfs adasd dhe Drugs that can be cleared with haemodialysis -

mnemonic: BLAST

Barbiturate

Lithium

Alcohol (inc methanol, ethylene glycol)

Salicylates Theophyllines (charcoal haemoperfusion is

preferable)

Drugs which cannot be cleared with haemodialysis

include

tricyclics

benzodiazepines

dextropropoxyphene (Co-proxamol)

digoxin

beta-blockers

Question 19 of 250

A patient known to have bipolar disorder presents to theEmergency Department with confusion. Which one of

the following drugs is most likely to precipitate lithiumtoxicity?ia

A. A Frusemideia

B. A Sodium valproateia

C. A Digoxinia

D. A Sodium bicarbonateia

E. A Bendroflumethiazideia

The BNF states that 'loop diuretics are safer than

thiazides' in the interactions section.

Lithium toxicity


Lithium is mood stabilising drug used most commonlyprophylatically in bipolar disorder but also as an adjunctin refractory depression. It has a very narrow

therapeutic range (0.4-1.0 mmol/L) and a long plasmahalf-life being excreted primarily by the kidneys. Lithiumtoxicity generally occurs following concentrations > 1.5

mmol/L.

Toxicity may be precipitated by dehydration, renal

failure, diuretics (especially bendroflumethiazide) or ACE inhibitors

Features of toxicity

coarse tremor (a fine tremor is seen in

therapeutic levels)

acute confusion

seizure

coma

Management

mild-moderate toxicity may respond to volume

resuscitation with normal saline

haemodialysis may be needed in severe

toxicity

sodium bicarbonate is sometimes used but

there is limited evidence to support this. Byincreasing the alkalinity of the urine it promoteslithium excretion

Question 20 of 250

A 62-year-old man with a history of hypertension andepilepsy is noted to have gingival hyperplasia on

examination in the cardiology clinic. Which one of thefollowing drugs is most likely to be responsible?ia

A. A Sodium valproateia

B. A Lisinoprilia

C. A Atorvastatinia

D. A Nifedipineia



11

E. A Carbamazepineia

Gingival hyperplasia: phenytoin, ciclosporin, calcium

channel blockers and AML

Gingival hyperplasia

sqweqwesf erwrewfsdfs adasd dhe Drug causes of gingival hyperplasia

phenytoin

ciclosporin calcium channel blockers (especially nifedipine)

Other causes of gingival hyperplasia include

acute myeloid leukaemia (myelomonocytic andmonocytic types)

Question 21 of 250

A 25-year-old female who works in a photographdevelopment laboratory is taken to the Emergency

Department due to confusion. On admission she ishypoxic and hypotensive. Cyanide poisoning issuspected following discussion with the local poisons

unit. What is the definitive treatment?ia

A. A Haemodialysisia

B. A Hydroxocobalaminia

C. A Penicillamineia

D. A Ferrous sulphateia

E. A Desferioxamineia

Cyanide poisoning

sqweqwesf erwrewfsdfs adasd dhe Cyanide may be used in insecticides, photograph

development and the production of certain metals.Toxicity results from reversible inhibition of cellular oxidising enzymes

Presentation

'classical' features: brick-red skin, smell of bitter

almonds

acute: hypoxia, hypotension, headache,

confusion chronic: ataxia, peripheral neuropathy,

dermatitis

Management

supportive measures: 100% oxygen

definitive: hydroxocobalamin

Question 22 of 250

Which one of the following types of reaction takes place

in phase II metabolism of a drug?ia

A. A Conjugationia

B. A Hydrolysisia

C. A Reductionia

D. A Deaminationia

E. A Dealkylationia

Drug metabolism

phase I: oxidation, reduction, hydrolysis phase II: conjugation

Pharmacokinetics: metabolism


Drug metabolism usually involves two types of biochemical reactions - phase I and phase II reactions

phase I reactions: oxidation, reduction,

hydrolysis. Mainly performed by the P450enzymes but some drugs are metabolised byspecific enzymes, for example alcohol

dehydrogenase and xanthine oxidase. Productsof phase I reactions are typically more activeand potentially toxic

phase II reactions: conjugation. Products aretypically inactive and excreted in urine or bile.Glucuronyl, acetyl, methyl, sulphate and other

groups are typically involved

The majority of phase I and phase II reactions takeplace in the liver

First-pass metabolism

This is a phenomenon where the concentration of adrug is greatly reduced before it reaches the systemiccirculation due to hepatic metabolism. As a

consequence much larger doses are need orally than if given by other routes. This effect is seen in manydrugs, including:

aspirin

isosorbide dinitrate

glyceryl trinitrate



12

lignocaine

propranolol verapamil

Questions concerning zero-order kinetics and acetylator status are also common in the exam

Zero-order kinetics

Zero-order kinetics describes metabolism which is

independent of the concentration of the reactant. This isdue to metabolic pathways becoming saturatedresulting in a constant amount of drug being eliminated

per unit time. This explains why people may fail abreathalyser test in the morning if they have beendrinking the night before

Drugs exhibiting zero-order kinetics

phenytoin

salicylates

heparin

ethanol

Acetylator status

50% of the UK population are deficient in hepatic N-acetyltransferase

Drugs affected by acetylator status

isoniazid

procainamide

hydralazine

dapsone

sulfasalazine

Question 23 of 250

A 67-year-old man with lung cancer is currently takingMST 30mg bd for pain relief. What dose of oralmorphine solution should he be prescribed for

breakthrough pain?ia

A. A 5 mgia

B. A 10 mgia

C. A 15 mgia

D. A 20 mgia

E. A 30 mgia

Breakthrough dose = 1/6th of daily morphine dose

The total daily morphine dose is 30 * 2 = 60 mg,therefore the breakthrough dose should be one-sixth of this, 10 mg

Palliative care prescribing: pain


SIGN issued guidance on the control of pain in adultswith cancer in 2008. Selected points

the breakthrough dose of morphine is one-sixth

the daily dose of morphine

all patients who receive opioids should be

prescribed a laxative

opioids should be used with caution in patientswith chronic kidney disease. Alfentanil,

buprenorphine and fentanyl are preferred

metastatic bone pain may respond to NSAIDs,bisphosphonates or radiotherapy

When increasing the dose of opioids the next dose

should be increased by 30-50%.

Conversion between opioids

From To

Oral codeine Oral morphine Divide by 10

Oral tramadol Oral morphine Divide by 5

From To

Oral morphine Oral oxycodone Divide by 2

The BNF states that oral morphine sulphate 80-90mgover 24 hours is approximately equivalent to one '25

mcg/hour' fentanyl patch, therefore product literatureshould be consulted.

From To

Oral morphine Subcutaneousdiamorphine

Divide by 3

Oral

oxycodone

Subcutaneous

diamorphine

Divide by

1.5

Question 24 of 250

A 40-year-old man with a history of psychiatricproblems and epilepsy comes for review. He complainsthat he is drinking excessive amounts of water and

having to urinate frequently. He has not lost any weightand states that he is compliant with his currentmedications. Blood tests show the following:

Na+

145 mmol/l

K+

4.1 mmol/l

Urea 6.3 mmol/l

Creatinine 101 µmol/l



13

Glucose (random) 6.2 mol/l

Which one of the following medications is most likely tobe responsible for this presentation?ia

A. A Carbamazepineia

B. A Fluoxetineia

C. A Olanzapineia

D. A Sodium valproateia

E. A Lithiumia

This patient has probably developed nephrogenic

diabetes insipidus secondary to lithium therapy.Polyuria, polydipsia and a high-normal sodium are

pointers towards this.

Diabetes insipidus

sqweqwesf erwrewfsdfs adasd dhe Causes of cranial DI

idiopathic

post head injury

pituitary surgery

craniopharyngiomas histiocytosis X

DIDMOAD is the association of cranial Diabetes

Insipidus, Diabetes Mellitus, Optic Atrophy andDeafness (also known as Wolfram's syndrome)

Causes of nephrogenic DI

genetic (primary)

electrolytes: hypercalcaemia, hypokalaemia

drugs: demeclocycline, lithium

tubulo-interstitial disease: obstruction, sickle-

cell, pyelonephritis

Investigation

high plasma osmolarity, low urine osmolarity

water deprivation test

Question 25 of 250

A 19-year-old student is admitted after being foundfriends confused and sweating in her room. She isunable to give a history. On examination temperature is

38.1ºC, pulse 108/min, BP 130/70 mmHg and

respiratory rate 30/min. Heart sounds are normal butshe has bibasal fine inspiratory crackles on her chest.

ABGs on air:

pH 7.28

pCO2 2.8 kPa

pO2 14.2 kPa

What is the most likely diagnosis?ia

A. A Paracetamol overdoseia

B. A Acute pancreatitisia

C. A Mycoplasma septicaemiaia

D. A Legionella pneumoniaia

E. A Aspirin overdoseia

The mixed respiratory alkalosis and metabolic acidosis

in a sweaty, confused patient point towards salicylateoverdose. The development of pulmonary oedema

suggests severe poisoning and is an indication for haemodialysis

Salicylate overdose

sqweqwesf erwrewfsdfs adasd dhe A key concept for the exam is to understand thatsalicylate overdose leads to a mixed respiratory

alkalosis and metabolic acidosis. Early stimulation of the respiratory centre leads to a respiratory alkalosiswhilst later the direct acid effects of salicylates

(combined with acute renal failure) may lead to anacidosis. In children metabolic acidosis tends topredominate

Features

hyperventilation (centrally stimulates

respiration)

tinnitus

lethargy

sweating, pyrexia*

nausea/vomiting

hyperglycaemia and hypoglycaemia seizures coma

Treatment

general (ABC, charcoal)

urinary alkalinization is now rarely used - it is

contraindicated in cerebral and pulmonaryoedema with most units now proceedingstraight to haemodialysis in cases of severe

poisoning haemodialysis

Indications for haemodialysis in salicylate overdose



14

serum concentration > 700mg/L

metabolic acidosis resistant to treatment

acute renal failure

pulmonary oedema

seizures coma

*salicylates cause the uncoupling of oxidative

phosphorylation leading to decreased adenosine

triphosphate production, increased oxygen

consumption and increased carbon dioxide and heat

production

Question 26 of 250

A 70-year-old man who takes warfarin for atrial

fibrillation is found to have an INR of 6.2. Which of thefollowing drugs is he most likely to have recentlytaken?ia

A. A Ciprofloxacinia B. A Flucloxacillinia

C. A St John's Wortia

D. A Carbamazepineia

E. A Aspirinia

Ciprofloxacin is a known inhibitor of the P450 system

and hence may cause an increase in INR.

P450 enzyme system

sqweqwesf erwrewfsdfs adasd dhe Induction usually requires prolonged exposure to the

inducing drug, as opposed to P450 inhibitors, whereeffects are often seen rapidly


antiepileptics: phenytoin, carbamazepine

barbiturates: phenobarbitone

rifampicin

St John's Wort chronic alcohol intake

griseofulvin



antibiotics: ciprofloxacin, erythromycin

isoniazid


amiodarone

allopurinol



ritonavir

sodium valproate


Question 27 of 250

Which one of the following side-effects is least

recognised in patients taking ciclosporin?ia

A. A Hypokalaemiaia

B. A Hyperplasia of the gumia

C. A Hypertensionia

D. A Tremor ia

E. A Excessive hair growthia

Ciclosporin side-effects: everything is increased - fluid,BP, K

+, hair, gums, glucose

Hyperkalaemia rather than hypokalaemia is seen with

ciclosporin use

Ciclosporin


Ciclosporin is an immunosuppressant which decreasesclonal proliferation of T cells by reducing IL-2 release. Itacts by binding to cyclophilin forming a complex which

inhibits calcineurin, a phosphotase that activatesvarious transcription factors in T cells

Adverse e ffects of ciclosporin (note how everything isincreased - fluid, BP, K

+, hair, gums, glucose)

nephrotoxicity

hepatotoxicity

fluid retention

hypertension

hyperkalaemia

hypertrichosis

hyperplasia of gum

tremor impaired glucose tolerance

Indications

following organ transplantation

rheumatoid arthritis

psoriasis (has a direct effect on keratinocytesas well as modulating T cell function)

ulcerative colitis pure red cell aplasia

Question 28 of 250

A 40-year-old woman who is known to be HIV positive

is reviewed in the respiratory clinic. She has recentlystarted treatment for tuberculosis and is complaining of a loss of sensation in her hands Which one of the

following drugs is most likely to be responsible?ia



15

A. A Indinavir ia

B. A Pyrazinamideia

C. A Zidovudineia

D. A Streptomycinia

E. A Isoniazidia

Isoniazid causes peripheral neuropathy

Tuberculosis: drug side-effects

sqweqwesf erwrewfsdfs adasd dhe Common side effects:

Rifampicin

potent liver enzyme inducer

hepatitis, orange secretions flu-like symptoms

Isoniazid

peripheral neuropathy: prevent with pyridoxine

(Vitamin B6)

hepatitis, agranulocytosis

liver enzyme inhibitor

Pyrazinamide

hyperuricaemia causing gout

hepatitis

Ethambutol

optic neuritis: check visual acuity before and

during treatment dose needs adjusting in patients with renal

impairment

Question 29 of 250

A 47-year-old man is reviewed in the smoking cessationclinic. Which one of the following conditions would

contraindicate the prescription of bupropion?ia

A. A History of supraventricular tachycardiaia

B. A Previous episodes of acute pancreatitis ia

C. A Epilepsyia

D. A Depressionia

E. A Hypertensionia

Bupropion: contraindicated in epilepsy

Smoking cessation

sqweqwesf erwrewfsdfs adasd dhe NICE released guidance in 2008 on the management of smoking cessation. General points include:

patients should be offered nicotine replacementtherapy (NRT), varenicline or bupropion - NICE

state that clinicians should not favour onemedication over another

NRT, varenicline or bupropion should normally

be prescribed as part of a commitment to stopsmoking on or before a particular date (targetstop date)

prescription of NRT, varenicline or bupropionshould be sufficient to last only until 2 weeksafter the target stop date. Normally, this will be

after 2 weeks of NRT therapy, and 3-4 weeksfor varenicline and bupropion, to allow for thedifferent methods of administration and mode

of action. Further prescriptions should be givenonly to people who have demonstrated thattheir quit attempt is continuing

if unsuccessful using NRT, varenicline or bupropion, do not offer a repeat prescriptionwithin 6 months unless special circumstanceshave intervened

do not offer NRT, varenicline or bupropion inany combination

Nicotine replacement therapy

adverse effects include nausea & vomiting,

headaches and flu-like symptoms

NICE recommend offering a combination of nicotine patches and another form of NRT(such as gum, inhalator, lozenge or nasal

spray) to people who show a high level of

dependence on nicotine or who have foundsingle forms of NRT inadequate in the past

Varenicline

a nicotinic receptor partial agonist

should be started 1 week before the patientstarget date to stop

the recommended course of treatment is 12weeks (but patients should be monitoredregularly and treatment only continued if notsmoking)

has been shown in studies to be more effectivethan bupropion

nausea is the most common adverse effect.

Other common problems include headache,insomnia, abnormal dreams



16

varenicline should be used with caution inpatients with a history of depression or self-

harm. There are ongoing studies looking at therisk of suicidal behaviour in patients takingvarenicline

contraindicated in pregnancy and breastfeeding

Bupropion

a norepinephrine and dopamine reuptake

inhibitor, and nicotinic antagonist

should be started 1 to 2 weeks before thepatients target date to stop

small risk of seizures (1 in 1,000)

contraindicated in epilepsy, pregnancy and

breast feeding. Having an eating disorder is arelative contraindication

Question 30 of 250

A 62-year-old man is commenced on finasteride for

symptoms of bladder outflow obstruction. Which one of the following adverse effects is most associated withthis treatment?ia

A. A Alopeciaia

B. A Gynaecomastiaia

C. A Prostate cancer ia

D. A Increased levels of serum prostate specific

antigenia

E. A Postural hypotensionia

Finasteride

sqweqwesf erwrewfsdfs adasd dhe Finasteride is an inhibitor of 5 alpha-reductase, an

enzyme which metabolises testosterone intodihydrotestosterone

Indications

benign prostatic hyperplasia

male-pattern baldness

Adverse effects

impotence

decrease libido

ejaculation disorders gynaecomastia and breast tenderness

Finasteride causes decreased levels of serum prostate

specific antigen

Question 31 of 250

A 54-year-old patient takes hydrocortisone 20mg in themornings and 5mg at night for Addison's disease. The

endocrinology consultant would like her to takeprednisolone instead. What dose of prednisoloneshould be started?ia

A. A 5 mgia

B. A 6 mgia

C. A 7 mgia

D. A 10 mgia

E. A 25 mgia

1mg prednisolone = 4mg hydrocortisone

As 1mg prednisolone equals 4mg hydrocortisone then

the actual equivalent daily dose is 6.25mg. This was notgiven as an option in the exam. It would therefore bebetter to err on the side of caution and over replacesteroid initially to avoid the potential risk of

hypoadrenalism

Steroid doses


Equivalence

1mg prednisolone = 4mg hydrocortisone

1mg dexamethasone = 7mg prednisolone

Question 32 of 250

A 41-year-old woman is investigated for hot flushes andnight sweats. Bloods show a significantly raised FSH

level and her symptoms are attributed to themenopause. Following discussions with the patient sheelects to have hormone replacement treatment. What is

the most significant risk of failing to prescribe acombined oestrogen-progestogen preparation rather than an oestrogen-only preparation?ia

A. A Increased risk of venous thromboembolismia

B. A Increased risk of ovarian cancer ia

C. A Increased risk of endometrial cancer ia

D. A Increased risk of breast cancer ia

E. A Increased risk of colorectal cancer ia

HRT: unopposed oestrogen increases risk of endometrial cancer



17

Hormone replacement therapy: adverse effects


Hormone replacement therapy (HRT) involves the useof a small dose of oestrogen (combined with aprogestogen in women with a uterus) to help alleviate

menopausal symptoms.

Side-effects

nausea

breast tenderness

fluid retention and weight gain

Potential complications

increased risk of breast cancer: increased by

the addition of a progestogen

increased risk of endometrial cancer: reduced

by the addition of a progestogen but not

eliminated completely. The BNF states that theadditional risk is eliminated if a progestogen is

given continuously

increased risk of venous thromboembolism:increased by the addition of a progestogen

increased risk of stroke

increased risk of ischaemic heart disease if taken more than 10 years after menopause

Breast cancer

in the Women's Health Initiative (WHI) studythere was a relative risk of 1.26 at 5 years of developing breast cancer

the increased risk relates to duration of use

breast cancer incidence is higher in women

using combined preparations compared tooestrogen-only preparations

the risk of breast cancer begins to decline when

HRT is stopped and by 5 years it reaches thesame level as in women who have never takenHRT

Question 33 of 250

A 78-year-old woman is discharged following a

fractured neck of femur. On review she is making goodprogress but consideration is given to secondaryprevention of further fractures. What is the most

suitable management?ia

A. A Arrange DEXA scan + start strontium

ranelate if T-score < -2.5 SDia

B. A Start oral bisphosphonateia

C. A Arrange DEXA scan + start oralbisphosphonate if T-score < -1.0 SDia

D. A Arrange DEXA scan + start hormonereplacement therapy if T-score < -2.5 SDia

E. A Arrange DEXA scan + start oral

bisphosphonate if T-score < -1.5 SDia

NICE guidelines support starting bisphosphonateswithout waiting for a DEXA scan in such scenarios

Osteoporosis: secondary prevention


NICE guidelines were updated in 2008 on thesecondary prevention of osteoporotic fractures in

postmenopausal women.

Key points include

treatment is indicated following osteoporoticfragility fractures in postmenopausal women

who are confirmed to have osteoporosis (a T-score of – 2.5 SD or below). In women aged 75years or older, a DEXA scan may not be

required 'if the responsible clinician considers itto be clinically inappropriate or unfeasible'

vitamin D and calcium supplementation should

be offered to all women unless the clinician isconfident they have adequate calcium intakeand are vitamin D replete

alendronate is first-line

around 25% of patients cannot toleratealendronate, usually due to upper gastrointestinal problems. These patients

should be offered risedronate or etidronate (seetreatment criteria below)

strontium ranelate and raloxifene are

recommended if patients cannot tolerate

bisphosphonates (see treatment criteria below)

Treatment criteria for patients not taking

alendronate

Unfortunately, a number of complicated treatment cut -

off tables have been produced in the latest guidelinesfor patients who do not tolerate alendronate

Risk factors (for use in the tables below)

parental history of hip fracture

alcohol intake of 4 or more units per day rheumatoid arthritis

T-scores (SD) at (or below) which risedronate or

etidronate is recommended when alendronate cannotbe taken

Age

(years)

No risk

factors

1 risk

factor

2 risk

factors

50 –54 Not indicated – 3.0 – 2.5

55 –59 – 3.0 – 3.0 – 2.5

60 –64 – 3.0 – 3.0 – 2.5

65 –69 – 3.0 – 2.5 – 2.5

70 or older – 2.5 – 2.5 – 2.5



18

T-scores (SD) at (or below) which strontium ranelate or

raloxifene is recommended when alendronate andeither risedronate or etidronate cannot be taken

Age

(years)

No risk

factors

1 risk

factor

2 risk

factors

50 –54 Not indicated – 3.5 – 3.5

55 –59 – 4.0 – 3.5 – 3.5

60 –64 – 4.0 – 3.5 – 3.5

65 –69 – 4.0 – 3.5 – 3.0

70 –74 – 3.0 – 3.0 – 2.5

75 or older – 3.0 – 2.5 – 2.5

Supplementary notes on treatment

Bisphosphonates

alendronate, risedronate and etidronate are all

licensed for the prevention and treatment of post-menopausal and glucocorticoid-induced

osteoporosis

all three have been shown to reduce the risk of both vertebral and non-vertebral fractures

although alendronate, risedronate may besuperior to etidronate in preventing hipfractures

ibandronate is a once-monthly oralbisphosphonate

Vitamin D and calcium

poor evidence base to suggest reduced

fracture rates in the general population at risk

of osteoporotic fractures - may reduce rates infrail, housebound patients

Raloxifene - selective oestrogen receptor modulator

(SERM)

has been shown to prevent bone loss and to

reduce the risk of vertebral fractures, but hasnot yet been shown to reduce the risk of non-

vertebral fractures

has been shown to increase bone density in thespine and proximal femur

may worsen menopausal symptoms

increased risk of thromboembolic events may decrease risk of breast cancer

Strontium ranelate

'dual action bone agent' - increases deposition

of new bone by osteoblasts and reduces the

resorption of bone by osteoclasts

strong evidence base, may be second-linetreatment in near future

increased risk of thromboembolic events

Teriparatide

recombinant form of parathyroid hormone

very effective at increasing bone mineraldensity but role in the management of osteoporosis yet to be clearly defined

Hormone replacement therapy

has been shown to reduce the incidence of

vertebral fracture and non-vertebral fractures

due to concerns about increased rates of cardiovascular disease and breast cancer it is

no longer recommended for primary or secondary prevention of osteoporosis unlessthe woman is suffering from vasomotor symptoms

Hip protectors

evidence to suggest significantly reduce hip

fractures in nursing home patients compliance is a problem

Falls risk assessment

no evidence to suggest reduced fracture rates

however, do reduce rate of falls and should beconsidered in management of high risk patients

Question 34 of 250

A patient is started on cyclophosphamide for

vasculitis associated with Wegener'sgranulomatosis. Which of the following is mostcharacteristically associated with

cyclophosphamide?ia

A. A Haemorrhagic cystitisia

B. A Cardiomyopathyia

C. A Ototoxicityia

D. A Alopeciaia

E. A Weight gainia

Cytotoxic agents

sqweqwesf erwrewfsdfs adasd dhe The table below summarises the mechanism of action and major adverse effects of commonly

used cytotoxic agents

Cytotoxic Mechanism of action

Adverse effects



19

Vincristine Inhibitsformation of

microtubules

Peripheralneuropathy

(reversible)

Cisplatin Causes cross-linking in DNA

Ototoxicity,peripheral

neuropathy,hypomagnesaemia

Bleomycin Degradespreformed DNA

Lung fibrosis

Doxorubicin Stabilizes DNA-

topoisomeraseII complexinhibits DNA &

RNA synthesis

Cardiomyopathy

Methotrexate Inhibitsdihydrofolate

reductase andthymidylatesynthesis

Myelosuppression, mucositis, liver

fibrosis

Cyclophosphamide

Alkylating agent- causes cross-

linking in DNA

Haemorrhagiccystitis,

myelosuppression, transitional cellcarcinoma

Docetaxel Preventsmicrotubuledepolymerisatio

n &disassembly,decreasing free

tubulin

Neutropaenia

Fluorouracil (5-FU)

Pyrimidineanalogue

inducing cellcycle arrest andapoptosis

(works during Sphase)

Myelosuppression, mucositis,

dermatitis

Question 35 of 250

A 39-year-old patient is taking phenelzine, amonoamine oxidase inhibitor, for the treatment of

depression. Which one of the following foods can thepatient safely eat?ia

A. A Bovrilia

B. A Cheeseia

C. A Oxoia

D. A Eggsia

E. A Broad beansia

Monoamine oxidase inhibitors


Overview

serotonin and noradrenaline are metabolisedby monoamine oxidase in the presynaptic cell

Non-selective monoamine oxidase inhibitors

e.g. tranylcypromine, phenelzine

used in the treatment of depression and other psychiatric disorder

not used frequently due to side-effects

Adverse e ffects of non-select ive monoamine oxidaseinhibitors

hypertensive reacting with tyramine containing

foods e.g. cheese, pickled herring, Bovril, Oxo,Marmite, broad beans

anticholinergic effects

Question 36 of 250

Which one of the following drugs is not known to inducethe cytochrome p450 enzyme system?ia

A. A Rifampicinia

B. A Isoniazidia

C. A Phenobarbitoneia

D. A Griseofulvinia

E. A Carbamazepineia

Isoniazid is an inhibitor of the P450 system

P450 enzyme system

sqweqwesf erwrewfsdfs adasd dhe Induction usually requires prolonged exposure to theinducing drug, as opposed to P450 inhibitors, where

effects are often seen rapidly




rifampicin

St John's Wort


griseofulvin




isoniazid


amiodarone

allopurinol




20


ritonavir

sodium valproate


Question 37 of 250

You prescribe sumatriptan to a patient who suffers from

migraines. Which one of the following side-effects ismost commonly associated with this drug?ia

A. A Dystonic reactions such as oculogyric crisis ia

B. A Heartburnia

C. A Tightness of the throat and chest ia

D. A Constipationia

E. A Insomniaia

Triptans

sqweqwesf erwrewfsdfs adasd dhe Triptans are specific 5-HT1 agonists used in the acute

treatment of migraine. They are generally used secondline when standard analgesics such as paracetamoland ibuprofen are ineffective.

Prescribing points

should be taken as soon as possible after the

onset of headache, rather than at onset of aura

oral, orodispersible, nasal spray andsubcutaneous injections are available

Adverse effects

'triptan sensations' - tingling, heat, tightness(e.g. throat and chest), heaviness, pressure

Contraindications

patients with a history of, or significant risk

factors for, ischaemic heart disease or cerebrovascular disease

Question 38 of 250

A 35-year-old female diabetic is started on erythromycinfor gastroparesis. What is the mechanism of action? ia

A. A Promotes gastric emptyingia

B. A Inhibits bacterial overgrowthia

C. A Acts on central chemoreceptor trigger zoneia

D. A Relaxation of pyloric sphincter ia

E. A Stimulates cholecystokinin releaseia

Erythromycin is used in gastroparesis as it has

prokinetic properties

Macrolides


Erythromycin was the first macrolide used clinically.

Newer examples include clarithromycin andazithromycin.

Macrolides act by inhibiting bacterial protein synthesis.If pushed to give an answer they are bacteriostatic in

nature, but in reality this depends on the dose and typeof organism being treated.

Adverse e ffects of erythromycin

gastrointestinal side-effects are common

cholestatic jaundice: risk may be reduced if erythromycin stearate is used

P450 inhibitor

Question 39 of 250

Which of the following may reduce the action of

aminophylline in patients?ia

A. A Ciprofloxacinia

B. A Acute ethanol consumptionia

C. A Omeprazoleia

D. A Smokingia

E. A Erythromycinia

Smoking is known to induce CYP1A2 isoenzyme,reducing the effectiveness of aminophylline

P450 enzyme system

sqweqwesf erwrewfsdfs adasd dhe Induction usually requires prolonged exposure to theinducing drug, as opposed to P450 inhibitors, where

effects are often seen rapidly




rifampicin

St John's Wort


griseofulvin




isoniazid



21


amiodarone

allopurinol



ritonavir

sodium valproate


Question 40 of 250

A woman who is 24-weeks pregnant presents with aproductive cough. On examination crackles can be

heard in the left base and a decision is made to give anantibiotic. Which one of the following is least suitable toprescribe?ia

A. A Ciprofloxacinia

B. A Erythromycinia

C. A Co-amoxiclavia

D. A Cefalexinia

E. A Cefaclor ia

The BNF advises avoiding quinolones in pregnancy due

to arthropathy in animal studies

Pregnancy: prescribing

sqweqwesf erwrewfsdfs adasd dhe Very few drugs are known to be completely safe in

pregnancy. The list below largely comprises of thoseknown to be harmful. Some countries have developed agrading system - see the link.

Antibiotics

tetracyclines

aminoglycosides

sulphonamides and trimethoprim

quinolones: the BNF advises to avoid due toarthropathy in some animal studies

Other drugs

ACE inhibitors, angiotensin II receptor

antagonists

statins

warfarin

sulfonylureas

retinoids (including topical) cytotoxic agents

The majority of antiepileptics including valproate,

carbamazepine and phenytoin are known to be

potentially harmful. The decision to stop such

treatments however is difficult as uncontrolled epilepsy

is also a risk

Question 41 of 250

A 54-year-old man with a history of epilepsy andischaemic heart disease is seen in clinic with a 3 month

history of lethargy. Blood tests are as follows:

Hb 9.6 g/dl

MCV 123 fl

Plt 134 * 109/l

WCC 2.6 *109/l

Which one of his medications is most likely to be

responsible?ia

A. A Clopidogrelia

B. A Atorvastatinia

C. A Carbamazepineia

D. A Atenololia

E. A Phenytoinia

Phenytoin may cause a megaloblastic anaemia byaltering folate metabolism

Phenytoin: side-effects


Phenytoin is associated with a large number of adverseeffects. These may be divided into acute, chronic,idiosyncratic and teratogenic

Acute

initially: vertigo, diplopia, nystagmus, slurred

speech, ataxia

later: confusion, seizures

Chronic

common: gingival hyperplasia, hirsutism,

coarsening of facial features

megaloblastic anaemia (secondary to altered

folate metabolism)

peripheral neuropathy

enhanced vitamin D metabolism causingosteomalacia

lymphadenopathy dyskinesia

Idiosyncratic

fever



22

rashes, including severe reactions such astoxic epidermal necrolysis

hepatitis

Dupuytren's contracture*

aplastic anaemia drug-induced lupus

Teratogenic

associated with cleft palate and congenitalheart disease

*although not listed in the BNF

Question 42 of 250

Which one of the following is least likely to precipitate

haemolysis in a patient with G6PD deficiency?ia

A. A Broad beansia

B. A Sepsisia

C. A Ciprofloxacinia

D. A Primaquineia

E. A Penicillinia

G6PD deficiency


Glucose-6-phosphate dehydrogenase (G6PD)deficiency is the commonest red blood cell enzymedefect. It is more common in people from theMediterranean and Africa and is inherited in a X-linked

recessive fashion. Many drugs can precipitate a crisisas well as infections and broad (fava) beans

Features

neonatal jaundice is often seen

intravascular haemolysis Heinz bodies on blood films

Diagnosis is made by using a G6PD enzyme assay

Some drugs causing haemolysis

anti-malarials: primaquine

ciprofloxacin sulphonamides

Some drugs thought to be safe

penicillins

cephalosporins

macrolides

tetracyclines

trimethoprim

Question 43 of 250

A 52-year-old man with a history of hypertension isfound to have a 10-year cardiovascular disease risk of

28%. A decision is made to start simvastatin 40mg on.Liver function tests are performed prior to initialisingtreatment:

Bilirubin 10 µmol/l (3 - 17 µmol/l)

ALP 96 u/l (30 - 150 u/l)

ALT 30 u/l (10 - 45 u/l)

Gamma-GT 28 u/l (10 - 40 u/l)

Three months later the LFTs are repeated:

Bilirubin 12 µmol/l (3 - 17 µmol/l)

ALP 107 u/l (30 - 150 u/l)

ALT 104 u/l (10 - 45 u/l)

Gamma-GT 76 u/l (10 - 40 u/l)

What is the most appropriate course of action?ia

A. A Continue treatment and repeat LFTs in 1

monthia

B. A Check creatine kinaseia

C. A Reduce dose to simvastatin 10mg on and

repeat LFTs in 1 monthia

D. A Stop treatment and consider alternative lipid

lowering drugia

E. A Stop treatment and refer to

gastroenterology ia

Treatment with statins should be discontinued if serum

transaminase concentrations rise to and persist at 3times the upper limit of the reference range.

Statins

sqweqwesf erwrewfsdfs adasd dhe Statins inhibit the action of HMG-CoA reductase, therate-limiting enzyme in hepatic cholesterol synthesis

Adverse e ffects

myopathy: includes myalgia, myositis,

rhabdomyolysis and asymptomatic raisedcreatine kinase. Risks factors for myopathy

include advanced age, female sex, low bodymass index and presence of multisystemdisease such as diabetes mellitus. Myopathy is

more common in lipophilic statins (simvastatin,atorvastatin) than relatively hydrophilic statins

(rosuvastatin, pravastatin, fluvastatin) liver impairment: the 2008 NICE guidelines

recommend checking LFTs at baseline, 3months and 12 months. Treatment should be

discontinued if serum transaminase



23

concentrations rise to and persist at 3 times theupper limit of the reference range



disease (stroke, TIA, ischaemic heart disease,peripheral arterial disease)


the management of blood lipids in type 2diabetes mellitus (T2DM) has changed slightly.

Previously all patients with T2DM > 40-years-old were prescribed statins. Now patients > 40-years-old who have no obvious cardiovascular

risk (e.g. Non-smoker, not obese, normotensiveetc) and have a cardiovascular risk < 20%/10years do not need to be given a statin. We

suggest reviewing the NICE T2DM guidelinesfor further information




Total

cholesterol(mmol/l)

LDL

cholesterol

Joint BritishSocieties < 4.0 < 2.0


< 5.0 < 3.0

SIGN 2007 < 5.0 < 3.0



Question 44 of 250

Which one of the following may enhance the effects of adenosine?ia

A. A Diltiazemia

B. A Aspirinia

C. A Clopidogrelia

D. A Dipyridamoleia

E. A Aminophyllineia

Adenosine

dipyridamole enhances effect

aminophylline reduces effect

Adenosine

sqweqwesf erwrewfsdfs adasd dhe The effects of adenosine are enhanced by dipyridamole(anti-platelet agent) and blocked by theophyllines. It

should be avoided in asthmatics due to possiblebronchospasm.

Mechanism of action

causes transient heart block in the AV node

agonist of the A1 receptor which inhibitsadenylyl cyclase thus reducing cAMP and

causing hyperpolarization by increasing

outward potassium flux adenosine has a very short half-life of about 8-

10 seconds

Adverse e ffects

chest pain

bronchospasm

can enhance conduction down accessorypathways, resulting in increased ventricular rate(e.g. WPW syndrome)

Question 45 of 250

Which of the following relating to St John's Wort isfalse?ia

A. A Adverse effects in trials is similar toplaceboia

B. A May cause serotonin syndromeia

C. A Mechanism of action is similar to selective

serotonin reuptake inhibitorsia

D. A Causes inhibition of the P450 systemia

E. A Has been shown to be effective in treating

mild-moderate depressionia

St John's Wort is a known inducer of the P450 system

St John's Wort

sqweqwesf erwrewfsdfs adasd dhe Overview

shown to be as effective as tricyclicantidepressants in the treatment of mild-

moderate depression



24

mechanism: thought to be similar to SSRIs(although noradrenaline uptake inhibition has

also been demonstrated)

NICE advise 'may be of benefit in mild or moderate depression, but its use should not beprescribed or advised because of uncertainty

about appropriate doses, variation in the natureof preparations, and potential seriousinteractions with other drugs'

Adverse effects

profile in trials similar to placebo

can cause serotonin syndrome

inducer of P450 system, therefore decreasedlevels of drugs such as warfarin, ciclosporin.The effectiveness of the combined oralcontraceptive pill may also be reduced

Question 46 of 250

Which one of the following drugs demonstratessaturation pharmacokinetics?ia

A. A Enalaprilia

B. A Bendrofluazideia

C. A Atenololia

D. A Phenytoinia

E. A Paracetamolia

Zero-order (saturation) kinetics

phenytoin

alcohol

Pharmacokinetics: metabolism


Drug metabolism usually involves two types of biochemical reactions - phase I and phase II reactions

phase I reactions: oxidation, reduction,

hydrolysis. Mainly performed by the P450enzymes but some drugs are metabolised by

specific enzymes, for example alcoholdehydrogenase and xanthine oxidase. Productsof phase I reactions are typically more active

and potentially toxic

phase II reactions: conjugation. Products aretypically inactive and excreted in urine or bile.

Glucuronyl, acetyl, methyl, sulphate and other groups are typically involved

The majority of phase I and phase II reactions take

place in the liver

First-pass metabolism

This is a phenomenon where the concentration of adrug is greatly reduced before it reaches the systemic

circulation due to hepatic metabolism. As aconsequence much larger doses are need orally than if given by other routes. This effect is seen in many

drugs, including:

aspirin

isosorbide dinitrate

glyceryl trinitrate

lignocaine

propranolol verapamil

Questions concerning zero-order kinetics and acetylator status are also common in the exam

Zero-order kinetics

Zero-order kinetics describes metabolism which isindependent of the concentration of the reactant. This isdue to metabolic pathways becoming saturated

resulting in a constant amount of drug being eliminatedper unit time. This explains why people may fail abreathalyser test in the morning if they have been

drinking the night before

Drugs exhibiting zero-order kinetics

phenytoin

salicylates heparin ethanol

Acetylator status

50% of the UK population are deficient in hepatic N-

acetyltransferase

Drugs affected by acetylator status

isoniazid

procainamide

hydralazine

dapsone sulfasalazine

Question 47 of 250

A 62-year-old man presents with nocturia, hesitancy

and terminal dribbling. Prostate examination reveals amoderately enlarged prostate with no irregular featuresand a well defined median sulcus. Blood tests show:

PSA 1.3 ng/ml

What is the most appropriate management?ia



25

A. A Alpha-1 antagonist ia

B. A 5 alpha-reductase inhibitor ia

C. A Non-urgent referral for transurethral

resection of prostateia

D. A Empirical treatment with ciprofloxacin for 2

weeksia

E. A Urgent referral to urologyia

Alpha-1 antagonists are first-line in patients with benign

prostatic hyperplasia

Benign prostatic hyperplasia


Benign prostatic hyperplasia (BPH) is a commoncondition seen in older men.

Risk factors

age: around 50% of 50-year-old men will have

evidence of BPH and 30% will have symptoms. Around 80% of 80-year-old men have evidenceof BPH

ethnicity: black > white > Asian

BPH typically presents with lower urinary tractsymptoms (LUTS), which may be categorised into:

voiding symptoms (obstructive): weak or intermittent urinary flow, straining, hesitancy,terminal dribbling and incomplete emptying

storage symptoms (irritative) urgency,frequency, urgency incontinence and nocturia

post-micturition: dribbling

complications: urinary tract infection, retention,obstructive uropathy

Management options

watchful waiting medication: alpha-1 antagonists, 5 alpha-

reductase inhibitors. The use of combinationtherapy was supported by the Medical Therapy

Of Prostatic Symptoms (MTOPS) trial

surgery: transurethral resection of prostate(TURP)

Alpha-1 antagonists e.g. tamsulosin, alfuzosin

decrease smooth muscle tone (prostate and

bladder)

considered first-line, improve symptoms inaround 70% of men

adverse effects: dizziness, posturalhypotension, dry mouth, depression

5 alpha-reductase inhibitors e.g. finasteride

block the conversion of testosterone to

dihydrotestosterone (DHT), which is known toinduce BPH

unlike alpha-1 antagonists causes a reductionin prostate volume and hence may slow

disease progression. This however takes time

and symptoms may not improve for 6 months.They may also decrease PSA concentrations

by up to 50%

adverse effects: erectile dysfunction, reducedlibido, ejaculation problems, gynaecomastia

Question 48 of 250

A 45-year-old female with a history of epilepsy is

reviewed in the neurology clinic. Which one of thefollowing features is most likely to be attributable tosodium valproate therapy?ia

A. A Clubbingia

B. A Weight lossia

C. A Hirsuitismia

D. A Renal impairmentia

E. A Tremor ia

Alopecia is much more common than hirsuitism in

patients treated with sodium valproate.

In the BNF tremor is listed as a 'less frequent' sideeffect whereas hirsuitism is listed as a 'very rare' sideeffect.

Sodium valproate

sqweqwesf erwrewfsdfs adasd dhe Sodium valproate is used in the management of epilepsy and is first line therapy for generalised

seizures. It works by increasing GABA activity

Adverse e ffects

gastrointestinal: nausea

increased appetite and weight gain

alopecia: regrowth may be curly

ataxia

tremor

hepatitis

pancreatitis teratogenic

Question 49 of 250

A 35-year-old man with a known history of peanut

allergy is admitted to the Emergency Department with aswollen face. On examination blood pressure is 85/60mmHg, pulse 120 bpm and there is a bilateralexpiratory wheeze. What is the most appropriate form

of adrenaline to give?ia



A. A 10ml 1:10,000 IVia

B. A 0.5ml 1:1,000 IMia

C. A 0.5ml 1:10,000 IMia

D. A 5ml 1:1,000 IMia

E. A Nebulised adrenalineia

Recommend Adult Life Support (ALS) adrenaline doses

anaphylaxis: 0.5ml 1:1,000 IM

cardiac arrest: 10ml 1:10,000 IV or 1ml of 1:1000 IV

Adrenaline


Adrenaline is a sympathomimetic amine with both alphaand beta adrenergic stimulating properties

Indications

anaphylaxis

cardiac arrest

Recommend Adult Life Support (ALS) adrenaline doses

anaphylaxis: 0.5ml 1:1,000 IM

cardiac arrest: 10ml 1:10,000 IV or 1ml of 1:1000 IV

Management of accidental injection

local infiltration of phentolamine

Question 50 of 250

A 69-year-old man with terminal lung cancer isreviewed. He currently takes MST 60mg bd for pain. Hehas become unable to take oral medications and a

decision is made to set-up a syringe driver. What doseof diamorphine should be prescribed for the syringedriver?ia

A. A 60 mgia

B. A 40 mgia

C. A 120 mgia

D. A 30 mgia

E. A 20 mgia

To convert from oral morphine to diamorphine the totaldaily morphine dose (60 * 2 = 120mg) should be

divided by 3 (120 / 3 = 40mg)

Palliative care prescribing: pain


SIGN issued guidance on the control of pain in adultswith cancer in 2008. Selected points

the breakthrough dose of morphine is one-sixth

the daily dose of morphine

all patients who receive opioids should be

prescribed a laxative

opioids should be used with caution in patientswith chronic kidney disease. Alfentanil,

buprenorphine and fentanyl are preferred

metastatic bone pain may respond to NSAIDs,bisphosphonates or radiotherapy

When increasing the dose of opioids the next doseshould be increased by 30-50%.

Conversion between opioids

From To

Oral codeine Oral morphine Divide by 10

Oral tramadol Oral morphine Divide by 5

From To

Oral morphine Oral oxycodone Divide by 2

The BNF states that oral morphine sulphate 80-90mgover 24 hours is approximately equivalent to one '25

mcg/hour' fentanyl patch, therefore product literatureshould be consulted.

From To

Oral morphine Subcutaneousdiamorphine

Divide by 3

Oral

oxycodone

Subcutaneous

diamorphine

Divide by

1.5

Documents

Passmedicine - Pharmacology Questions 1 to 50