What makes a medicine high-risk?
A medicine is high-risk when a small, common error produces serious or fatal harm. The same few features recur, and recognising the feature tells you the safeguard the exam wants.
- Narrow therapeutic index: the effective and toxic doses are close (digoxin, lithium, aminoglycosides, warfarin).
- Dose depends on a patient factor: weight, renal function or age (LMWH, DOACs, gentamicin, IV paracetamol).
- Unit or frequency confusion: units, micrograms versus milligrams, weekly versus daily (insulin, methotrexate).
- Wrong-route or wrong-dilution risk: concentrated potassium, vinca alkaloids.
- Needs monitoring after the first prescription: INR, levels, U&E.
In the PSA the question is usually not which drug, but what makes this prescription safe. Look for the patient factor the case supplies, such as a low eGFR, a low body weight or an interacting new drug.
High-risk medicines: hazard and safe-prescribing rule
| Drug | Main hazard | The rule |
|---|---|---|
| Warfarin | Bleeding; INR changes with interactions | Indication-specific INR target; check INR after any new interacting drug |
| DOACs | Bleeding if the drug accumulates | Dose by indication and creatinine clearance; check renal function |
| LMWH | Bleeding; accumulation in renal impairment | Dose by weight and renal function; check platelets if prolonged |
| Insulin | Hypoglycaemia; tenfold errors | Write units in full; use an insulin syringe or pen; never stop basal insulin in type 1 diabetes |
| Opioids | Respiratory depression; constipation | Start low in opioid-naive patients; co-prescribe a laxative; reduce in renal impairment |
| Methotrexate (oral, inflammatory disease) | Marrow suppression from daily dosing | Once WEEKLY; write the day; one strength of tablet |
| Potassium (IV) | Cardiac arrest if given too fast or undiluted | Premixed bags; never a bolus; rate limits and U&E monitoring |
| Digoxin | Toxicity: arrhythmia, nausea, visual change | Lower dose in renal impairment; correct potassium; level at least 6 hours post dose |
| Lithium | Toxicity with dehydration or interacting drugs | Prescribe by brand; level 12 hours post dose; avoid NSAIDs; ACE inhibitors, ARBs and thiazides raise levels, so avoid or monitor levels closely |
| Aminoglycosides | Nephrotoxicity and ototoxicity | Dose by weight; levels and renal function; shortest course |
| Vinca alkaloids | Fatal if given intrathecally | Intravenous only; never by any other route |
| IV paracetamol | Hepatotoxicity from overdose; mg versus mL error | Prescribe in mg and state the volume; weight-based under 50 kg; lower maximum daily dose if risk factors |
How do you prescribe anticoagulants safely?
Anticoagulant safety starts with a bleeding-risk and renal-function check before the first dose. Each class then has its own trap.
- Warfarin: the INR target depends on the indication, and many antibiotics, azoles and amiodarone raise the INR. Vitamin K and prothrombin complex concentrate are used for serious bleeding.
- DOACs: choice and dose depend on the indication and on creatinine clearance (Cockcroft-Gault), not eGFR. Dabigatran is the most dependent on renal excretion. Idarucizumab reverses dabigatran; other DOACs have their own reversal routes in local guidance.
- LMWH: dose by weight for treatment and adjust in renal impairment. Unfractionated heparin is monitored by APTT and is reversed by protamine.
- Combined antiplatelet and anticoagulant use raises bleeding risk and needs a clear indication.
Insulin, opioids and controlled drugs: what are the rules?
Insulin must always be prescribed with the word units written in full. U or IU can be misread as a number, and an ordinary syringe must never be used to draw up insulin.
- Name the product and the device. Never draw up insulin from a pen or cartridge with a syringe.
- Only soluble (short-acting) insulin is given intravenously.
- Type 1 diabetes needs basal insulin continued even when not eating, to avoid ketoacidosis.
Opioids need a start-low approach in opioid-naive and elderly patients, a regular laxative, and a lower dose or a different opioid in renal impairment because morphine metabolites accumulate. Immediate-release and modified-release morphine are different products: name the formulation. Naloxone reverses respiratory depression, but its action is shorter than that of many opioids, so observation continues.
Controlled drugs have extra prescribing rules. A Schedule 2 or 3 prescription for the community must state the dose, the form and (where appropriate) the strength, and the total quantity or number of dose units in both words and figures. Check the BNF for the schedule of a drug and local policy for ward practice.
Which drugs have a weekly dose or a never-route?
Oral methotrexate for inflammatory disease is taken once a week, and a daily prescription is a recognised cause of fatal marrow suppression. Write the day of the week in the prescription, prescribe one tablet strength, and arrange blood monitoring. Folic acid is usually given on a different day from the methotrexate.
Concentrated potassium chloride must be diluted before use and never given as an intravenous bolus. Prefer ready-made infusion bags, set a maximum infusion rate according to local policy and check U&E. Do not give it to a patient with hyperkalaemia or severe renal impairment without senior advice.
Vinca alkaloids such as vincristine are given by intravenous infusion only. Intrathecal administration is fatal, so these drugs are supplied and labelled to prevent a spinal route. Intrathecal chemotherapy is restricted to trained staff under strict local procedures.
IV paracetamol is prescribed in milligrams, with the volume stated, never as a volume alone. The maximum for adults over 50 kg is 4 g in 24 hours. Under 50 kg, dose by weight. In adults of 50 kg or more with risk factors such as malnutrition, chronic alcohol use, dehydration or liver disease, a lower maximum daily dose applies; check the BNF.
Which narrow-therapeutic-index drugs need levels?
Digoxin, lithium and aminoglycosides are prescribed with a plan for levels and renal function. Digoxin toxicity is more likely with hypokalaemia, renal impairment and interacting drugs such as amiodarone, verapamil and clarithromycin, so the dose is reduced or the interaction avoided.
Lithium is prescribed by brand because formulations differ in bioavailability. Dehydration, new NSAIDs, ACE inhibitors, ARBs and thiazides raise lithium levels. Gentamicin is dosed by weight, usually once daily, with a level and renal function checked according to the local protocol.
Check yourself
- Which two patient factors most often change a DOAC dose?
- How should insulin be written on a chart, and which syringe is used?
- What is the frequency rule for oral methotrexate, and what is the classic error?
- Why is a concentrated potassium ampoule never given as a bolus?
- Which drugs raise lithium levels?
- When is a digoxin level taken relative to the dose?
- Which route is fatal for vincristine?
- How does IV paracetamol dosing change under 50 kg?
Questions people ask
What are the highest-risk medicines in the PSA?
Anticoagulants, insulin, opioids, methotrexate, potassium, digoxin, lithium and aminoglycosides recur most often. Each has a standard safeguard that the exam expects you to apply.
How should insulin doses be written?
Write the word units in full beside the number, never U or IU, and name the insulin product. Use an insulin syringe or pen, not an ordinary syringe.
Why is methotrexate a high-risk drug?
Oral methotrexate for inflammatory disease is a weekly drug, and accidental daily dosing can cause fatal marrow suppression. Always state the day of the week.
Can potassium chloride be given as a bolus?
No. Concentrated potassium chloride must be diluted and infused at a controlled rate, because rapid administration can cause cardiac arrest.
What is the maximum daily dose of paracetamol for adults?
For adults over 50 kg it is 4 g in 24 hours. Use weight-based dosing under 50 kg, and a lower maximum daily dose where there are risk factors for liver injury (check the BNF).
Related revision notes
Sources: BNF; NICE guidance on anticoagulants and diabetes; National Patient Safety Agency alerts on high-risk medicines; MHRA Drug Safety Update. These notes are for exam revision and are not patient-specific advice; in the exam and in practice, the BNF is the authority.
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