Prescribing Safety on PLAB 1: How to Handle Drug Interactions, Contraindications, and the "Next Drug" Question

Prescribing safety questions are among the most predictable on PLAB 1 — and among the most frequently dropped. The pharmacology itself is rarely exotic; what catches candidates out is not knowing how UK clinical guidelines frame the decision, or misreading what the question is actually asking.

Why Prescribing Safety Gets Its Own Blueprint Area

The UKMLA content map dedicates specific coverage to safe prescribing because the GMC expects every doctor joining the UK register to make sound medication decisions from day one. That means PLAB 1 will test more than recall of drug names. It tests whether you recognise a dangerous interaction before you write the prescription, whether you adjust a dose appropriately for a patient whose kidneys are struggling, and whether you know which drug to reach for second when the first is contraindicated.

This is a high-stakes area in clinical practice, and the exam reflects that. Expect four to eight questions per sitting that fall squarely into prescribing safety, with several more scattered across other clinical topics where a prescribing decision is embedded in the stem.

The Drug Interactions You Must Know Cold

Not every interaction in the BNF will appear on PLAB 1. The exam favours interactions that are clinically serious, relatively common in UK practice, and testable in a short vignette. Prioritise these categories:

• Warfarin and enzyme inducers/inhibitors. Rifampicin dramatically reduces warfarin effect; fluconazole and metronidazole increase bleeding risk. The exam often presents an INR that is suddenly out of range and asks what caused it.
• ACE inhibitors and potassium-sparing diuretics. Combining an ACE inhibitor with spironolactone or amiloride risks dangerous hyperkalaemia. Know the mechanism, not just the pair.
• NSAIDs and multiple co-prescriptions. NSAIDs interact harmfully with anticoagulants, antihypertensives, lithium, and methotrexate. A vignette where an elderly patient is started on ibuprofen for knee pain is a classic setup.
• SSRIs and other serotonergic agents. Tramadol, linezolid, and triptans all carry serotonin syndrome risk when combined with an SSRI. The exam will give you a clinical picture of agitation, tremor, and hyperthermia.
• Metformin and contrast media or acute illness. NICE guidance recommends withholding metformin in certain situations to avoid lactic acidosis. Recognise the scenario.
• Lithium toxicity triggers. NSAIDs, thiazide diuretics, and ACE inhibitors all raise lithium levels. Questions often describe a tremor or confusion in a psychiatric patient who has been started on a new drug.

When you revise interactions, work from the mechanism outwards. If you understand why rifampicin induces CYP450 enzymes, you can reason your way through any drug it is paired with, not just warfarin.

Prescribing in Pregnancy and Renal Impairment

These two clinical contexts generate a reliable cluster of PLAB pharmacology questions every sitting. The exam is testing whether you can apply a general prescribing principle to a specific patient, which is exactly what the UKMLA blueprint demands.

In pregnancy, the core question is always: does the benefit justify the risk, and is there a safer alternative? Drugs to flag immediately include:

• ACE inhibitors and angiotensin receptor blockers — contraindicated, particularly in the second and third trimesters
• Tetracyclines — affect fetal bone and teeth development
• Sodium valproate — carries serious teratogenic risk; NICE and the MHRA have issued strong guidance on this; know that this is not just a relative caution
• Warfarin — associated with embryopathy in the first trimester; low-molecular-weight heparin is the alternative
• Methotrexate — absolutely contraindicated; requires reliable contraception

In renal impairment, your job is to spot drugs that accumulate when clearance falls. The BNF gives specific guidance for each drug, but the exam tests the concept more than the precise eGFR thresholds. High-yield examples include metformin (withhold if eGFR falls below the relevant threshold per NICE guidance), NSAIDs (worsen renal function and cause fluid retention), digoxin (narrow therapeutic index, renally cleared), and gentamicin (requires careful dosing and monitoring). When a stem mentions a creatinine or eGFR alongside a drug question, that is your signal — the renal function is there for a reason.

Reading the "Most Appropriate Next Drug" Stem

This question pattern is one of the most commonly mishandled on PLAB 1. The stem gives you a patient already on a drug, often describes a side effect or contraindication, and asks what you should prescribe instead or add next. Candidates lose marks here in one of three ways: they pick the drug that would normally come first (ignoring that it is already in use or contraindicated), they ignore a contraindication buried in the patient's history, or they apply guidelines from their home country rather than UK practice.

A reliable approach:

1. Identify what is already prescribed and why it cannot continue. The contraindication or side effect is always explicit if you read carefully.
2. Check the patient demographics. Pregnancy, age, eGFR, allergies — these are clues, not decoration.
3. Apply the relevant UK pathway. For hypertension, NICE stepped-care guidance determines what comes next based on age and ethnicity. For pain, the WHO analgesic ladder structures your thinking. For antibiotic choice, Public Health England guidance and local formulary principles apply.
4. Eliminate, do not just select. Cross off options that are contraindicated before you pick between the remaining plausible answers.

Drilling this stem type with immediate feedback is one of the fastest ways to improve. The Ant PLAB question bank includes a dedicated prescribing safety category with worked explanations for every option — not just the correct answer — which helps you understand why the distractors are wrong, which is often where the learning sits.

Keeping the BNF in Its Proper Place

The BNF is your reference, not your revision method. For PLAB 1, you need to have internalised the most clinically important interactions and contraindications so that you can reason under time pressure. Use the BNF during revision to check your reasoning — for example, after you have decided that a drug is contraindicated in renal impairment, verify in the BNF that you are right and note the mechanism.

Candidates who try to memorise the BNF rarely do well in prescribing safety questions because the exam tests judgement, not lookup speed. Candidates who understand the principles — enzyme induction, renal clearance, teratogenicity mechanisms, receptor pharmacology — and have practised applying them in single-best-answer format tend to answer these questions confidently.

If you want to see where your prescribing knowledge actually stands, review your performance analytics in the Ant PLAB question bank after completing a full pharmacology block — the breakdown by sub-topic will show you whether your gap is in interactions, renal dosing, or pregnancy, so you can target your revision precisely.

FAQ

Does PLAB 1 expect me to know exact BNF dose adjustments for renal impairment? No — the exam tests whether you recognise that a dose adjustment or drug change is needed, and why. You are not expected to recall a specific milligram figure; you are expected to know which drugs are hazardous when renal function is compromised and to choose the safer alternative.

How much of the PLAB 1 pharmacology section focuses on drug interactions versus contraindications? Both appear regularly, and many questions combine them — for example, a patient with a contraindication who is also on an interacting drug. Rather than tracking proportions, ensure you are comfortable with the mechanism behind each high-yield interaction and contraindication, because the exam tests understanding more than memorisation.

Is sodium valproate in pregnancy likely to appear on PLAB 1? Yes, and it deserves careful attention. The regulatory guidance around valproate has strengthened significantly in recent years, and awareness of its teratogenic risk and the requirement for a Pregnancy Prevention Programme is now considered baseline knowledge for any doctor working in the UK. The exam may present it as a prescribing decision or as a question about counselling a patient of childbearing potential.