What are type A and type B adverse drug reactions?
Type A reactions are augmented pharmacological effects of the drug, and they are the common ones. Type B reactions are bizarre, not predicted from the pharmacology, and rarer but more often serious.
- Type A: dose-related, predictable, common, low mortality (hypoglycaemia with insulin, bleeding with warfarin, sedation with opioids).
- Type B: dose-independent, idiosyncratic or immune-mediated, unpredictable, higher mortality (anaphylaxis, Stevens-Johnson syndrome, DRESS).
- Type C: long-term use. Type D: delayed effects. Type E: end of use, such as withdrawal. Type F: failure of therapy, often from an interaction.
Timing helps classify the reaction. Anaphylaxis occurs within minutes to hours, DRESS typically 2 to 8 weeks after starting, and cutaneous reactions such as Stevens-Johnson syndrome in the first weeks. Effects of amiodarone can appear months after starting.
Classic drug and adverse reaction pairs
| Drug | Reaction | Key point |
|---|---|---|
| ACE inhibitor | Dry cough; angioedema; hyperkalaemia | Cough is bradykinin-mediated; switch to an ARB. Angioedema can occur at any time; stop |
| Statin | Myopathy; rhabdomyolysis | Muscle pain; check CK; risk with interacting drugs |
| Amiodarone | Thyroid, lung, liver, corneal, skin effects | Long half-life; effects persist after stopping |
| Lithium | Tremor, vomiting, confusion, ataxia, seizures | Toxicity with dehydration, NSAIDs, ACE inhibitors, thiazides |
| Metoclopramide | Acute dystonia, oculogyric crisis | Young adults and children; short-term use only |
| Sulfonylureas | Hypoglycaemia | Risk in renal impairment and older people |
| SGLT2 inhibitors | Ketoacidosis, genital infection, volume depletion | DKA can occur with near-normal glucose; Fournier gangrene is rare |
| Flucloxacillin, co-amoxiclav | Cholestatic jaundice | Can start after the course has finished |
| Fluoroquinolones | Tendon rupture, neuropsychiatric effects | Stop at first tendon pain; extra risk with corticosteroids |
| Allopurinol, carbamazepine, lamotrigine | Severe skin reactions | Early rash needs urgent review; lamotrigine needs slow titration |
| Abacavir | Hypersensitivity | HLA-B*5701 testing before starting |
| Beta-blockers | Bradycardia, bronchospasm, masked hypoglycaemia | Caution in asthma and diabetes |
How do you decide which drug caused a reaction?
Work back from the onset of the problem to the most recent change in treatment. A new drug or dose increase in the right time window is the leading suspect.
- List all drugs with start dates, dose changes and recent interacting additions.
- Check whether the reaction fits the known profile of each drug in the BNF.
- Check the timing: immediate, within weeks or after months.
- Consider other causes, such as infection, disease progression or dehydration.
- Dechallenge: stop the suspected drug and see whether the reaction settles.
- Rechallenge only when safe, and never after a severe reaction such as angioedema or a severe cutaneous reaction.
In a drug-induced liver injury, stop the suspected drug and look at the pattern of ALT versus ALP. In drug reaction questions, an old stable drug is usually less likely than a recent start, unless an interaction or worsening renal function has raised its level.
What is anticholinergic burden?
Anticholinergic burden is the cumulative effect of several drugs with antimuscarinic activity, and it is a classic cause of confusion and falls in older people. Effects include dry mouth, constipation, urinary retention, blurred vision, tachycardia and delirium.
Common contributors are oxybutynin, tricyclic antidepressants such as amitriptyline, chlorphenamine, procyclidine and some antipsychotics. Review and stop where possible, and avoid starting anticholinergics in older people with dementia.
What is the Yellow Card scheme, and how does the BNF list frequency?
The Yellow Card scheme is the MHRA system for reporting suspected adverse reactions, and healthcare professionals, patients and carers can all report. Report all suspected reactions for black-triangle medicines and vaccines, and serious suspected reactions for established medicines. Proof of causation is not needed.
The BNF lists side-effects by frequency, with very common being 1 in 10 or more, common 1 in 100 to 1 in 10, uncommon 1 in 1000 to 1 in 100, rare 1 in 10 000 to 1 in 1000, very rare fewer than 1 in 10 000, and frequency not known.
Check yourself
- What distinguishes a type A from a type B reaction?
- Which ACE inhibitor reaction is a reason to avoid the class altogether?
- What are the early features of lithium toxicity?
- Which drug causes acute dystonia in young people?
- Why can SGLT2 inhibitors cause ketoacidosis with a normal glucose?
- How does flucloxacillin liver injury differ in timing?
- How do you decide which drug caused a new rash?
- What can be reported on a Yellow Card?
Questions people ask
What is the difference between type A and type B reactions?
Type A reactions are predictable, dose-related and common. Type B reactions are unpredictable, not dose-related, and rarer but more severe.
Why do ACE inhibitors cause a cough?
They reduce bradykinin breakdown, causing a dry cough. An ARB is the usual alternative for cough. After ACE inhibitor angioedema, avoid the class and use an ARB only with caution and specialist advice.
Who can submit a Yellow Card?
Healthcare professionals, patients and carers can all report suspected adverse reactions to the MHRA. Certainty about causation is not required.
What is anticholinergic burden?
The combined antimuscarinic effects of multiple drugs, causing confusion, constipation, retention and falls, particularly in older people.
How does the BNF describe side-effect frequency?
As very common, common, uncommon, rare, very rare or frequency not known, with defined ranges from 1 in 10 or more down to fewer than 1 in 10 000.
Related revision notes
Sources: BNF; MHRA Yellow Card scheme; MHRA Drug Safety Update; NICE guidance. 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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