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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Classic triad: reduced consciousness + respiratory depression (RR <12) + pinpoint (miotic) pupils
- Antidote: naloxone 400 mcg IV/IM, repeat every 2–3 minutes until adequate respiration (max initial dose ~2 mg)
- Naloxone has a SHORTER half-life than most opioids — patient may re-sedate after naloxone wears off (1–2 hours)
- Take-home naloxone programmes: IM Pronapen or intranasal Nyxoid provided to opioid users and their families
- Always check for co-ingestion (benzodiazepines, alcohol, paracetamol) and complications (aspiration pneumonia, rhabdomyolysis)
Overview
Opioid overdose occurs from intentional self-harm, recreational misuse, or iatrogenic causes (prescribing errors, particularly in opioid-naive patients or those with renal impairment). Opioids cause dose-dependent respiratory depression by acting on mu-opioid receptors in the brainstem respiratory centres. Death from opioid overdose is almost always from respiratory arrest. Common offending agents include heroin, morphine, methadone (very long half-life), codeine, fentanyl (extremely potent), oxycodone, and tramadol (also has serotonergic and noradrenergic effects). Naloxone is a competitive mu-opioid receptor antagonist that rapidly reverses opioid effects.
Epidemiology
Drug-related deaths in England and Wales have been rising, with opioids being the single biggest contributor. Approximately 2,000–2,500 opioid-related deaths occur annually in the UK. Deaths from illicit fentanyl and synthetic opioids are increasing. Risk factors include IV drug use, polydrug use (opioid + benzodiazepine is particularly dangerous), recent release from prison (loss of tolerance), opioid-naive patients started on strong opioids, and renal impairment (accumulation of active metabolites).
Clinical Features
Symptoms
Reduced level of consciousness (GCS ≤8)
Slow, shallow, or absent breathing (RR <12/min)
Drowsiness progressing to coma
Signs
Pinpoint (miotic) pupils — bilateral, do not respond to light
Respiratory depression (RR <8) or apnoea
Hypotension and bradycardia
Cyanosis
Needle track marks (IV drug users)
Hypothermia
Pulmonary oedema (non-cardiogenic — particularly with heroin)
Investigations
First-line
ABG/VBGType 2 respiratory failure (hypoxia + hypercapnia + respiratory acidosis)
Blood glucoseExclude hypoglycaemia as a cause of reduced consciousness
ECGMethadone causes QT prolongation — risk of torsades de pointes
Second-line
Urine drug screenIdentifies opioids and co-ingestants (benzodiazepines, cocaine, amphetamines)
Paracetamol and salicylate levelsExclude co-ingestion — especially in deliberate self-harm
CKIf prolonged immobility — rhabdomyolysis risk
CXRIf aspiration or non-cardiogenic pulmonary oedema suspected
Management
BNF + TOXBASE + NICE CKS1
ABCDE approach
- Airway: head tilt/chin lift, suction, consider airway adjunct
- Breathing: if not breathing → bag-valve-mask ventilation + call for help
- Give high-flow oxygen
2
Naloxone
- IV: 400 mcg (0.4 mg), repeat every 2–3 minutes until adequate respirations (up to 2 mg initial total)
- IM: 400 mcg if no IV access (onset ~5 minutes) or intranasal (Nyxoid 1.8 mg)
- CRITICAL: naloxone half-life (1–2 hours) is SHORTER than most opioids — patient may re-sedate
- If long-acting opioid (methadone, modified-release): start naloxone infusion after bolus (two-thirds of the initial effective dose per hour)
- Titrate to adequate respiration, NOT full consciousness — avoid precipitating acute withdrawal (pain, agitation, vomiting)
3
Monitoring and observation
- Minimum 6 hours observation after IV naloxone for short-acting opioid overdose
- Longer observation (24+ hours) for methadone or modified-release opioid overdose
- Monitor respiratory rate, SpO2, GCS, pupil size regularly
4
Take-home naloxone
- Provide take-home naloxone kits (IM Pronapen or intranasal Nyxoid) to: opioid users, patients on high-dose opioid prescriptions, prison leavers, household contacts of opioid users
- Train patients and families on when and how to administer
Complications
- Respiratory arrest and death: If not treated promptly
- Aspiration pneumonia: From vomiting with reduced consciousness
- Rhabdomyolysis: From prolonged immobility in coma
- Non-cardiogenic pulmonary oedema: Particularly with heroin
- Acute opioid withdrawal: If naloxone dose is too high — vomiting, diarrhoea, agitation, sweating
UKMLA Exam Tips
- 1Triad: reduced consciousness + pinpoint pupils + respiratory depression = opioid overdose
- 2Naloxone 400 mcg IV every 2–3 min — titrate to adequate breathing, NOT full consciousness
- 3Naloxone wears off BEFORE the opioid — MUST observe for re-sedation (minimum 6 hours, longer for methadone)
- 4Methadone: very long half-life (24–36 hours) — requires prolonged observation and naloxone infusion
- 5Always check for co-ingestion: paracetamol, benzodiazepines, alcohol
- 6Pinpoint pupils DDx: opioids, pontine haemorrhage, organophosphate poisoning, pilocarpine drops
- 7Take-home naloxone is part of UK harm reduction policy
practicetest your knowledge on opioid overdoseApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — clinical pharmacology and beyond.
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