Mock Pharmacology Module 1

A 68-year-old man with chronic kidney disease (eGFR 25 mL/min/1.73m²) is commenced on a renally cleared antimicrobial.

Which single pharmacokinetic parameter most directly determines his steady-state drug concentration during maintenance dosing?

Clearance

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Volume of distribution

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Bioavailability

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Half-life

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Absorption rate constant

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A 70 kg patient requires digoxin loading to achieve a target concentration of 1.0 microgram/L (target range 0.5–0.9 microgram/L for heart failure per Australian guidelines).

Assuming a volume of distribution of 7 L/kg and bioavailability of 0.7 for oral tablets, what oral loading dose most closely achieves this target?

700 micrograms

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350 micrograms

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490 micrograms

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1000 micrograms

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1400 micrograms

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A patient is started on a drug with a half-life of 20 hours given at a fixed regular interval without a loading dose.

Approximately how long until steady-state concentrations are reached?

90 hours

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20 hours

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40 hours

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60 hours

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200 hours

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A 55-year-old man with hypertension is taking enalapril 10 mg daily with an inadequate blood pressure response.

Based on dose–response data, what is the most appropriate next step regarding antihypertensive control?

Add a second antihypertensive agent from a different class

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Increase enalapril to 40 mg daily as this will substantially improve BP

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Increase enalapril to 20 mg daily, expecting a large incremental BP fall

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Cease enalapril as it has failed

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Measure serum ACE inhibitor concentration

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Half-life is a derived parameter.

Which combination of physiological parameters determines a drug’s half-life?

Volume of distribution and clearance

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Clearance and bioavailability

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Absorption rate and clearance

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Volume of distribution and bioavailability

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Protein binding and absorption rate

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Which statement regarding oral bioavailability (F) is most accurate?

A drug with low F tends to have high inter-individual variability in exposure

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A drug with low F has low inter-individual variability in exposure

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A drug with high F has high inter-individual variability in exposure

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Bioavailability of furosemide is markedly increased in decompensated heart failure

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The intravenous route always guarantees a faster onset of therapeutic effect than oral

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A 74-year-old woman with decompensated heart failure has an inadequate response to oral furosemide 40 mg daily.

Based on loop diuretic pharmacodynamics, which statement best explains the appropriate approach?

In heart failure the natriuretic threshold concentration is raised, so a higher dose is needed to reach the efficient range

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Loop diuretics have a linear dose–response with no ceiling

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Continuous low concentrations are more natriuretic than intermittent peaks

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Intravenous and oral furosemide have identical bioavailability

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Doubling the dose interval frequency is always more effective than increasing dose amount

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A patient on phenytoin presents with suspected phenytoin toxicity. A trough level returns as low (subtherapeutic).

What is the most appropriate interpretation?

The low concentration refutes phenytoin toxicity, so an alternative cause should be sought

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Confirms phenytoin toxicity

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The dose should be increased immediately

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The result is unreliable and should be ignored

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Free phenytoin cannot be estimated from total levels in any circumstance

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A 40-year-old man on phenytoin 300 mg daily has a level of 40 micromol/L (reference 40–80 micromol/L). The dose is increased to 400 mg daily and he develops nystagmus, ataxia and a level of 120 micromol/L.

Which pharmacokinetic property best explains this disproportionate rise?

Saturable (zero-order/Michaelis-Menten) metabolism

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First-order (linear) elimination

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Increased volume of distribution

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Enhanced renal clearance

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Reduced protein binding

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Regarding trough plasma dabigatran concentration and clinical outcomes, which statement is most accurate based on RE-LY analyses?

Higher trough concentrations are associated with increased major bleeding risk

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Bleeding risk is unrelated to trough concentration

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Lower trough concentrations reduce ischaemic stroke risk

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Concentration has no relationship with either stroke or bleeding

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The 150 mg twice daily dose always achieves lower trough concentrations than 110 mg twice daily

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A morbidly obese patient requires a loading dose of a highly lipophilic drug.

Compared with a lean patient, how is the volume of distribution and half-life likely to differ?

Volume of distribution increased, half-life prolonged

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Volume of distribution decreased, half-life shortened

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Volume of distribution unchanged, half-life unchanged

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Volume of distribution increased, half-life shortened

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Volume of distribution decreased, half-life prolonged

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A 60-year-old man is treated with once-daily gentamicin for Gram-negative sepsis.

Which pharmacodynamic property best justifies extended-interval (once-daily) dosing?

Concentration-dependent killing with a prolonged post-antibiotic effect

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Time-dependent killing with minimal post-antibiotic effect

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Bacteriostatic activity requiring continuous exposure

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Efficacy correlating with time above MIC

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Absence of any post-antibiotic effect

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Which dosing strategy best exploits the pharmacodynamic profile of a beta-lactam antibiotic against a serious Gram-negative infection?

Extended or continuous infusion to maximise time above MIC

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A single high peak concentration once daily

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Rapid bolus dosing to maximise peak/MIC

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Reliance on the post-antibiotic effect to permit long dose intervals

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Dosing based solely on area under the curve/MIC without regard to time

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Current guidelines recommend AUC-guided vancomycin dosing for serious MRSA infection.

What is the recommended target AUC24/MIC ratio (assuming MIC 1 mg/L)?

400–600

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100–200

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200–300

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700–900

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1000–1200

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Which of the following substances is eliminated predominantly by zero-order kinetics at therapeutic/typical concentrations?

Ethanol

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Digoxin

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Gentamicin

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Metformin

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Warfarin

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A patient is a poor metaboliser via CYP2D6.

Which statement best reflects the clinical implication regarding hepatic drug clearance?

Low clearance of one CYP2D6 substrate predicts low clearance of another CYP2D6 substrate

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All hepatically metabolised drugs will have reduced clearance

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Clearance of CYP3A4 substrates will also be reduced

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Renal clearance will be correspondingly reduced

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"Liver metabolism" is a single unified process

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A patient on aspirin requires urgent surgery. Despite aspirin’s short plasma half-life (~20 minutes), why does its antiplatelet effect persist for several days after cessation?

Aspirin irreversibly inhibits platelet COX-1, so effect lasts the platelet lifespan

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Aspirin has a very long terminal half-life

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Aspirin is stored in adipose tissue and slowly released

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Aspirin's active metabolite has a half-life of 7 days

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Renal excretion of aspirin is markedly delayed

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A 75-year-old man weighs 70 kg with a serum creatinine of 100 micromol/L.

Using the Cockcroft-Gault equation, what is his estimated creatinine clearance?

51 mL/min

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34 mL/min

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61 mL/min

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72 mL/min

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88 mL/min

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A stable patient on warfarin (INR 2.5) is commenced on rifampicin for tuberculosis.

What is the most likely effect on warfarin requirements over the following two weeks?

Warfarin requirement increases due to CYP enzyme induction

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Warfarin requirement decreases due to enzyme inhibition

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No change, as warfarin is not hepatically metabolised

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Immediate supratherapeutic INR within 24 hours

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Warfarin should be ceased permanently

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A patient with rheumatoid arthritis is treated with a therapeutic monoclonal antibody (IgG).

Which mechanism predominantly determines its clearance?

Target-mediated drug disposition and reticuloendothelial catabolism

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Renal glomerular filtration

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Hepatic CYP450 metabolism

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Biliary excretion of intact antibody

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Pulmonary elimination

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An 88-year-old woman (weight 48 kg) is admitted with lethargy 4 days after commencing trimethoprim 300 mg daily for a urinary tract infection.

Her serum potassium is 6.8 mmol/L (3.5–5.2), serum creatinine 140 µmol/L (45–90), bicarbonate 18 mmol/L (22–32) and she is not on any renin-angiotensin system inhibitor or NSAID.

Which single mechanism best explains this adverse drug reaction?

Trimethoprim blocks the epithelial sodium channel in the distal nephron

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Trimethoprim inhibits aldosterone synthesis in the adrenal cortex

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Trimethoprim causes rhabdomyolysis with potassium release

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Trimethoprim inhibits the Na⁺/K⁺-ATPase pump in myocytes

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Trimethoprim precipitates acute tubular necrosis

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A 62-year-old man with decompensated cirrhosis (Child-Pugh C) requires analgesia and blood pressure management. F

or which drug is clearance MOST dependent on hepatic blood flow and therefore likely to fall substantially with portosystemic shunting and reduced perfusion?

Propranolol

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Warfarin

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Phenytoin

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Diazepam

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Naproxen

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A 76-year-old woman weighs 55 kg with a serum creatinine of 95 µmol/L (45–90).

Using the Cockcroft-Gault equation, what is her estimated creatinine clearance, and how should this influence dosing of a renally cleared, narrow-therapeutic-index drug?

~45 mL/min – reduce dose or extend interval

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~28 mL/min – reduce dose or extend interval

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~60 mL/min – standard dosing acceptable

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~80 mL/min – standard dosing acceptable

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~15 mL/min – avoid the drug entirely

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A 58-year-old man develops significant myalgia and a creatine kinase of 1400 U/L (<200) after commencing simvastatin 40 mg daily. Genotyping reveals a reduced-function SLCO1B1 variant.

Which mechanism best explains his increased susceptibility?

Reduced hepatic uptake of simvastatin via OATP1B1, raising plasma concentrations

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Increased CYP3A4-mediated activation of simvastatin

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Enhanced renal tubular secretion of simvastatin metabolites

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Increased HMG-CoA reductase expression in muscle

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Reduced plasma protein binding increasing free drug

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A 34-year-old man of Han Chinese ancestry is to commence carbamazepine for focal epilepsy.

Which pharmacogenetic test result would most strongly contraindicate carbamazepine due to risk of Stevens-Johnson syndrome/toxic epidermal necrolysis?

HLA-B*15:02 positive

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CYP2C9 poor metaboliser status

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Slow acetylator (NAT2) status

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Reduced-function SLCO1B1 allele

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CYP2D6 ultra-rapid metaboliser status

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An 80-year-old man is commenced on amlodipine for hypertension. He develops bilateral ankle oedema, and a diuretic (frusemide) is added, following which he becomes hypokalaemic and postural, and later falls, sustaining a wrist fracture.

What is the single most appropriate initial action?

Recognise a prescribing cascade, cease amlodipine and reassess the oedema

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Add potassium supplementation and continue both agents

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Add midodrine to treat postural hypotension

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Increase frusemide dose to control oedema

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Add fludrocortisone for postural symptoms

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A 55-year-old woman on procainamide for arrhythmia develops arthralgia, serositis and a positive anti-histone antibody after several months. She is characterised as a slow acetylator.

Which statement best explains the relationship between acetylator phenotype and this reaction?

Slow acetylators develop drug-induced lupus earlier and more frequently

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Slow acetylators clear procainamide faster, reducing lupus risk

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Fast acetylators are at highest risk of drug-induced lupus

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Acetylator status has no bearing on procainamide toxicity

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Slow acetylation increases renal clearance of procainamide

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A frail 84-year-old woman is admitted following a fall. She was recently started on temazepam for insomnia.

Which age-related pharmacodynamic change best accounts for her heightened susceptibility to sedation and falls?

Increased sensitivity to GABAergic and opioid-mediated sedation

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Reduced sensitivity of GABA receptors to benzodiazepines

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Increased beta-adrenoceptor sensitivity to agonists

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Reduced muscarinic sensitivity to anticholinergic effects

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Increased renal clearance of temazepam

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A hospital medication safety committee is prioritising interventions using the “A PINCH” high-risk medication framework.

Which combination of agents correctly represents medications that cause the greatest harm when used in error under this framework?

Anti-infectives, potassium/electrolytes, insulin, narcotics/sedatives, chemotherapy, heparin/anticoagulants

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Paracetamol, iron, nystatin, colchicine, hydrochlorothiazide

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Antihistamines, proton-pump inhibitors, iodine, nitrates, calcium

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Antacids, phosphate, inhalers, NSAIDs, corticosteroids, H2 antagonists

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Antiemetics, penicillins, inotropes, nitrous oxide, calcium, heparin

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Mock Pharmacology Module 1

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