PLAB 1 Pharmacology & Prescribing — Questions and Answers
Question 1: A patient with atrial fibrillation is started on warfarin. Which of the following drugs, if added, would most significantly increase the risk of bleeding by inhibiting warfarin metabolism?
- Rifampicin
- Carbamazepine
- Fluconazole (Correct answer)
- St John's Wort
Correct answer: Fluconazole
Fluconazole is a potent inhibitor of CYP2C9, the main enzyme responsible for warfarin metabolism. This significantly increases warfarin levels and bleeding risk. Rifampicin, carbamazepine, and St John's Wort are inducers of CYP enzymes and would reduce warfarin efficacy.
Question 2: A 70-year-old woman with heart failure is started on spironolactone. Which electrolyte abnormality must be monitored closely?
- Hypokalaemia
- Hyperkalaemia (Correct answer)
- Hyponatraemia
- Hypercalcaemia
Correct answer: Hyperkalaemia
Spironolactone is a potassium-sparing diuretic (aldosterone antagonist). It causes potassium retention, risking hyperkalaemia, which can cause life-threatening arrhythmias. Regular U&E monitoring is essential, especially if the patient is also on ACE inhibitors or ARBs which also raise potassium.
Question 3: A patient with type 2 diabetes has an eGFR of 25 ml/min/1.73m². Which diabetes medication must be stopped or dose-reduced due to risk of lactic acidosis?
- Sitagliptin
- Metformin (Correct answer)
- Gliclazide
- Insulin
Correct answer: Metformin
Metformin is contraindicated when eGFR falls below 30 ml/min/1.73m² due to the risk of lactic acidosis (accumulation of metformin due to impaired renal excretion). NICE guidelines recommend stopping metformin if eGFR < 30 and dose reduction if eGFR 30–45.
Question 4: A 25-year-old woman presents 2 hours after taking 20 paracetamol tablets (10g). She is asymptomatic. Serum paracetamol level is above the treatment line on the nomogram. What is the most appropriate treatment?
- Activated charcoal only
- IV N-acetylcysteine (NAC) (Correct answer)
- Oral methionine
- Supportive care and monitoring only
Correct answer: IV N-acetylcysteine (NAC)
IV N-acetylcysteine (NAC) is the antidote for paracetamol overdose. It replenishes glutathione, which is depleted by the toxic metabolite NAPQI, preventing hepatocellular damage. Treatment should be started when the level plots above the treatment line on the Rumack-Matthew nomogram. Activated charcoal may also be given within 1 hour of ingestion.
Question 5: Which antibiotic is contraindicated in pregnant women due to the risk of 'grey baby syndrome' in neonates?
- Amoxicillin
- Chloramphenicol (Correct answer)
- Erythromycin
- Cefalexin
Correct answer: Chloramphenicol
Chloramphenicol inhibits mitochondrial protein synthesis. Neonates lack adequate hepatic glucuronyl transferase to metabolise it, leading to accumulation and 'grey baby syndrome' (circulatory collapse, abdominal distension, cyanosis, death). It is avoided in pregnancy and neonates.
Question 6: A patient on warfarin develops a DVT and is found to have a supratherapeutic INR of 8.5 with minor bleeding from the gums. What is the most appropriate management?
- Stop warfarin, give IV vitamin K 5mg, and transfuse FFP
- Stop warfarin and give oral vitamin K 1–2mg; review in 24 hours (Correct answer)
- Continue warfarin and observe
- Stop warfarin and give idarucizumab
Correct answer: Stop warfarin and give oral vitamin K 1–2mg; review in 24 hours
For INR 5–8 with minor bleeding (BCSH guidelines): stop warfarin, give low-dose oral vitamin K (1–2mg). This will partially reverse anticoagulation within 6–12 hours without fully reversing it (important if anticoagulation is needed ongoing). IV vitamin K and FFP are reserved for serious/life-threatening bleeding.
PLAB 1 Pharmacology & Prescribing
A patient with atrial fibrillation is started on warfarin.
Which of the following drugs, if added, would most significantly increase the risk of bleeding by inhibiting warfarin metabolism?