Clinical pharmacology and prescribing: Poisoning and overdose

• General approach: Assessing the Poisoned Patient | Toxidromes | Investigations in Poisoning | Decontamination and Enhanced Elimination | Antidotes
• Common poisonings: Paracetamol | Salicylate (Aspirin) | Opioids | Benzodiazepines and Other Sedatives | Tricyclic Antidepressants | SSRIs, Antipsychotics and Antiepileptics | Beta-blockers, Calcium Channel Blockers and Digoxin | Lithium, Iron and Hypoglycaemic Agents
• Chemicals and recreational drugs: Toxic Alcohols | Carbon Monoxide and Cyanide | Organophosphates and Household Chemicals | Recreational Drugs | After the Overdose -Psychosocial Care
• Revision: Poisoning at a Glance | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🩺 Poisoning and overdose -page 6 (the last) of the Clinical Pharmacology and Prescribing chapter. Self-poisoning is one of the commonest reasons for acute medical admission in the UK, and paracetamol is the commonest drug involved. Most poisoned patients need only supportive care, but some need urgent antidotes, decontamination or dialysis. Use TOXBASE (the UK National Poisons Information Service database) for every case, and remember that every intentional overdose needs a psychosocial assessment. Self-harm and suicide risk are covered in the Psychiatry chapters.
Your four questions for every poisoned patient: What, how much, when and how -and is the history reliable? Is the patient stable (ABCDE, glucose, ECG)? Is there an antidote, or a way to remove the poison? What is the psychosocial risk, and is the patient safe to leave?

Assessing the Poisoned Patient

• ABCDE first -airway (reduced GCS -recovery position, intubation if GCS 8 or less without improvement), breathing, circulation (hypotension, arrhythmias), disability (GCS, pupils, capillary glucose, seizures), exposure (temperature, injection marks, patches, injuries, pressure areas after a long lie).
• History (from patient, ambulance, family, empty packets):
  • What -substance(s), formulation (modified-release?), alcohol and co-ingestants.
  • How much -calculate mg/kg.
  • When -time of ingestion (single or staggered over more than 1 hour).
  • Why -intentional, accidental (children, older people, dosing errors), recreational.
  • Symptoms; past history; regular medicines; previous overdoses; mental health.
• Assume the history may be unreliable -check paracetamol and salicylate levels in all intentional overdoses (paracetamol is a common hidden co-ingestant).
• TOXBASE (online, free to NHS) and the National Poisons Information Service (telephone 0344 892 0111 for complex cases) -management advice for each poison.
• Observation -many drugs cause delayed toxicity (modified-release, paracetamol, iron, salicylate); monitor for the recommended period.
• Safeguarding -children (accidental vs deliberate), vulnerable adults, domestic abuse.

Toxidromes

• Pupils -small (opioids, organophosphates, clonidine, some antipsychotics); large (anticholinergics, sympathomimetics, serotonergic drugs, withdrawal).
• Hyperthermia -sympathomimetics, serotonin syndrome, NMS, anticholinergics, salicylate, MDMA, malignant hyperthermia.
• Seizures -tricyclics, tramadol, theophylline, bupropion, isoniazid, cocaine, amphetamines, lithium, hypoglycaemia, withdrawal.

Investigations in Poisoning

• For all -capillary glucose, ECG (QRS width, QT, arrhythmias), U&E, LFTs, FBC, clotting (INR), paracetamol and salicylate levels (in intentional or unclear overdoses), venous or arterial blood gas and lactate, CK (long lie).
• ECG clues:
  • Broad QRS (over 100 ms) and a large terminal R wave in aVR -tricyclics (sodium channel blockade); also flecainide, cocaine.
  • Long QT -antipsychotics, citalopram, methadone, antihistamines, hypokalaemia, hypocalcaemia.
  • Bradycardia and heart block -beta-blockers, calcium channel blockers, digoxin, clonidine, organophosphates.
• Blood gas:
  • Raised anion gap metabolic acidosis (anion gap = Na − [Cl + HCO₃], normal about 8–16 mmol/L) -"MUDPILES" causes include Methanol, Uraemia, DKA, Paracetamol (massive), Iron and isoniazid, Lactate (metformin, cyanide, CO), Ethylene glycol, Salicylate.
  • Respiratory alkalosis then metabolic acidosis -salicylate.
  • Respiratory acidosis -opioids, sedatives.
• Osmolar gap -measured minus calculated osmolality (2Na + urea + glucose); raised (over about 10) in toxic alcohol poisoning (methanol, ethylene glycol) and ethanol.
• Specific levels -lithium, digoxin, iron, theophylline, carbamazepine, valproate, phenytoin, ethanol, methanol and ethylene glycol (specialist labs), carboxyhaemoglobin (co-oximetry), methaemoglobin.
• Imaging -abdominal X-ray (iron tablets, packets in body packers, button batteries), chest X-ray (aspiration).
• Urine drug screens -limited value in acute management; positives may reflect past use.

Decontamination and Enhanced Elimination

• Activated charcoal:
  • 50 g orally (adults) -binds many drugs in the gut; most useful within 1 hour of ingesting a potentially toxic amount (longer for modified-release drugs and drugs slowing gastric emptying).
  • Doesn't bind -iron, lithium, alcohols (ethanol, methanol, ethylene glycol), acids, alkalis, metals, petroleum products ("PHAILS" -Pesticides, Hydrocarbons, Acids/Alkalis/Alcohols, Iron, Lithium, Solvents).
  • Contraindicated with an unprotected airway (reduced consciousness -aspiration), bowel obstruction, corrosive ingestion.
  • Multiple-dose activated charcoal -for some drugs with enterohepatic circulation (carbamazepine, theophylline, quinine, dapsone, phenobarbital) -per TOXBASE.
• Gastric lavage and induced vomiting -no longer recommended routinely.
• Whole bowel irrigation (polyethylene glycol) -rarely: large iron or lithium overdoses, modified-release preparations, body packers (specialist advice).
• Urinary alkalinisation (IV sodium bicarbonate -urine pH 7.5–8.5) -salicylate (moderate to severe poisoning), phenobarbital; monitor potassium (hypokalaemia prevents alkalinisation).
• Haemodialysis -for drugs with small volume of distribution, low protein binding and low molecular weight -"BLAST" -Barbiturates, Lithium, Alcohols (methanol, ethylene glycol), Salicylate, Theophylline; also metformin-associated lactic acidosis, valproate (severe). Not effective for tricyclics, digoxin or benzodiazepines.
• Skin and eye decontamination -remove clothing, wash with water (organophosphates, chemicals); prolonged eye irrigation for chemical splashes.

Antidotes

Paracetamol

• The commonest overdose in the UK; causes liver failure (and sometimes kidney failure) via the toxic metabolite NAPQI when glutathione is used up.
• Early symptoms are mild or absent (nausea, vomiting) -don't be reassured; liver damage peaks at 3–4 days (RUQ pain, jaundice, encephalopathy, bleeding, hypoglycaemia).
• Potentially toxic dose -75 mg/kg or more (TOXBASE) -or any amount in a staggered overdose of concern.
• Management by timing (MHRA, TOXBASE):
  • Within 1 hour -consider activated charcoal if 150 mg/kg or more (and airway safe).
  • Single acute ingestion, 4–8 hours -take a paracetamol level at 4 hours (or as soon as possible after); plot on the treatment nomogram -treat if on or above the treatment line (100 mg/L at 4 hours); start acetylcysteine before 8 hours for best protection.
  • Over 8 hours after a potentially toxic dose -start acetylcysteine immediately without waiting for the level; then review with level, LFTs and INR.
  • Staggered overdose (over more than 1 hour) or uncertain timing -the nomogram can't be used -treat with acetylcysteine regardless of the level.
• Acetylcysteine -replenishes glutathione; nearly 100% effective if given within 8 hours; weight-based IV regimen (follow current UK protocol -many hospitals now use a shorter two-bag regimen instead of the traditional three-bag 21-hour regimen; maximum weight for dosing 110 kg).
• Adverse reactions to acetylcysteine -anaphylactoid (non-IgE) reactions -flushing, rash, nausea, bronchospasm, hypotension -stop the infusion, give antihistamine (± bronchodilator), then restart at a slower rate (it is not a true allergy and shouldn't stop future use).
• After treatment -check INR, ALT, creatinine and venous blood gas at the end of the infusion; continue acetylcysteine if abnormal (ALT rising or INR over 1.3) -per TOXBASE.
• Referral to a liver unit -King's College criteria for transplant: arterial pH under 7.3 after fluid resuscitation (or lactate over 3 after fluids), or all three of: INR over 6.5, creatinine over 300 µmol/L, and grade 3–4 encephalopathy. Discuss early if INR, creatinine, lactate or pH are worsening.
• Chronic therapeutic excess -e.g. low body weight, malnutrition, alcohol excess -may cause liver injury at "therapeutic" doses; dose by weight in people under 50 kg.

Salicylate (Aspirin)

• Mechanism -stimulates the respiratory centre (respiratory alkalosis), then uncouples oxidative phosphorylation (metabolic acidosis, hyperthermia, increased metabolic rate).
• Features -tinnitus and deafness, nausea and vomiting, hyperventilation, sweating, fever, dehydration, hypokalaemia, hypoglycaemia (or hyperglycaemia), confusion, seizures, non-cardiogenic pulmonary oedema, AKI, coma (severe -and in children and older people).
• Blood gas -mixed respiratory alkalosis and metabolic acidosis (adults); metabolic acidosis predominates in severe poisoning and children (poor sign).
• Investigations -salicylate level at least 2 hours after ingestion (4 hours for enteric-coated) and repeat (levels can keep rising -delayed absorption, bezoars); U&E, glucose, blood gas, INR.
• Management:
  • Activated charcoal within 1 hour (more than 125 mg/kg); multiple doses may help in some cases.
  • IV fluids, correct potassium (needed for urinary alkalinisation), glucose.
  • Urinary alkalinisation with IV sodium bicarbonate -level over 500 mg/L in adults (350 mg/L in children) or significant metabolic acidosis.
  • Haemodialysis -very high levels (over 700 mg/L), severe metabolic acidosis, seizures, coma, AKI, pulmonary oedema, or failing to respond to treatment.
  • Avoid intubation if possible -losing the respiratory compensation worsens acidosis (if needed, hyperventilate on the ventilator).

Opioids

• Features -reduced consciousness, respiratory rate under 12 (or apnoea), pinpoint pupils, hypotension, hypothermia; non-cardiogenic pulmonary oedema; seizures (tramadol); serotonin syndrome (tramadol, fentanyl, methadone with SSRIs); rhabdomyolysis and compartment syndrome after long lies.
• Naloxone:
  • IV 400 micrograms (or 100–200 micrograms in people dependent on opioids or in palliative care, to avoid acute withdrawal), repeated every 2–3 minutes up to about 2 mg (higher for some synthetic opioids); IM or intranasal if no IV access.
  • Aim for adequate breathing, not full wakefulness -full reversal causes acute withdrawal (agitation, vomiting, aspiration).
  • Short half-life (about 30–90 minutes) -re-sedation after long-acting opioids (methadone, MR morphine, buprenorphine) -observe for at least 6 hours (longer for methadone) and consider a naloxone infusion (e.g. two-thirds of the effective bolus dose per hour).
• Methadone -long half-life; QT prolongation; delayed respiratory depression -observe for 24 hours after significant overdose.
• Buprenorphine -partial agonist; ceiling effect on respiratory depression (less with other sedatives); may need high naloxone doses.
• Codeine and co-codamol overdose -check paracetamol level!
• Harm reduction -take-home naloxone kits for people who use opioids and their families; drug services.

Benzodiazepines and Other Sedatives

• Benzodiazepines and Z-drugs -drowsiness, ataxia, slurred speech, nystagmus; usually low toxicity alone, but dangerous with alcohol, opioids, gabapentinoids (respiratory depression) and in older people and those with lung disease.
• Management -supportive (airway, breathing, observation).
• Flumazenil (benzodiazepine antagonist) -rarely indicated (e.g. iatrogenic over-sedation in a benzodiazepine-naïve patient); contraindicated in benzodiazepine dependence and mixed overdoses (especially tricyclics) -it can cause seizures and arrhythmias.
• Gabapentin and pregabalin -sedation, ataxia, respiratory depression (with opioids); increasingly involved in drug deaths; Schedule 3 CDs.
• GHB / GBL -sudden deep coma with rapid recovery (hours); bradycardia, vomiting; severe withdrawal syndrome in regular users (agitation, delirium, seizures -benzodiazepines, baclofen).
• Alcohol (ethanol) -reduced consciousness, hypoglycaemia (especially children and malnourished), hypothermia, aspiration; consider head injury and other drugs; thiamine (Pabrinex) for at-risk patients; withdrawal management later.
• Barbiturates (rare now) -coma, hypothermia, blisters; haemodialysis for phenobarbital.

Tricyclic Antidepressants

• Very dangerous in overdose (amitriptyline, dosulepin, nortriptyline, imipramine) -small amounts can kill; rapid deterioration is common in the first hours.
• Mechanisms -sodium channel blockade (broad QRS, arrhythmias), anticholinergic effects, alpha-blockade (hypotension), potassium channel blockade (long QT), GABA antagonism (seizures).
• Features:
  • Anticholinergic -dry mouth, dilated pupils, tachycardia, urinary retention, hot dry skin, confusion, agitation.
  • Reduced consciousness, seizures, coma.
  • Hypotension, arrhythmias (broad complex tachycardia, VT, VF).
  • Metabolic acidosis (worsens cardiotoxicity).
• ECG -sinus tachycardia, QRS over 100 ms (risk of seizures), over 160 ms (risk of ventricular arrhythmias), large terminal R wave in aVR, long QT.
• Management:
  • ABCDE; secure the airway early if GCS falling; activated charcoal within 1 hour if airway protected.
  • IV sodium bicarbonate 8.4% (e.g. 50 mL, repeated as needed) for broad QRS, arrhythmias, hypotension or acidosis -even if pH is normal; aim for pH about 7.45–7.55.
  • Benzodiazepines for seizures (avoid phenytoin -sodium channel blocker).
  • Fluids for hypotension, then vasopressors; correct hypoxia and acidosis; lipid emulsion in cardiac arrest (specialist).
  • Avoid flumazenil, class Ia and Ic antiarrhythmics; physostigmine is not recommended.
  • Continuous cardiac monitoring for at least 6 hours (longer if symptomatic or modified-release).

SSRIs, Antipsychotics and Antiepileptics

• SSRIs -relatively safe alone: nausea, vomiting, tremor, drowsiness, tachycardia; serotonin syndrome (especially with combinations); seizures; QT prolongation with citalopram and escitalopram (ECG monitoring); venlafaxine is more toxic (seizures, arrhythmias).
• Serotonin syndrome -supportive, benzodiazepines, cooling; cyproheptadine (oral) if moderate; ICU for severe hyperthermia (see page 3).
• Antipsychotics -sedation, hypotension, tachycardia, QT prolongation, anticholinergic effects (quetiapine, olanzapine, clozapine), dystonic reactions (treat with procyclidine), seizures; NMS (rare in overdose); clozapine -sedation, hypersalivation, seizures.
• Carbamazepine -ataxia, nystagmus, drowsiness, coma, seizures, broad QRS, anticholinergic effects; delayed peaks; multiple-dose activated charcoal; haemodialysis in severe cases.
• Sodium valproate -drowsiness, coma, hyperammonaemia, metabolic acidosis, liver injury, cerebral oedema; L-carnitine in severe cases (specialist); haemodialysis for very high levels.
• Lamotrigine, levetiracetam -usually less toxic; lamotrigine -seizures, broad QRS in large overdoses.
• Dystonic reactions (metoclopramide, haloperidol, prochlorperazine) -oculogyric crisis, torticollis, trismus -IV or IM procyclidine (5–10 mg).

Beta-blockers, Calcium Channel Blockers and Digoxin

• Beta-blockers -bradycardia, hypotension, heart block, cardiogenic shock, hypoglycaemia, bronchospasm; propranolol (membrane-stabilising -seizures, broad QRS) and sotalol (QT, torsades) are especially dangerous.
  • Atropine (for bradycardia), IV fluids, glucagon (bypasses beta-receptors), high-dose insulin euglycaemia therapy (HIET), vasopressors and inotropes, pacing; lipid emulsion or ECMO in refractory cases.
• Calcium channel blockers -verapamil and diltiazem (bradycardia, heart block, hypotension); dihydropyridines (amlodipine -vasodilation, hypotension with reflex tachycardia); hyperglycaemia (insulin release blocked); delayed toxicity with modified-release forms (observe 12–24 hours).
  • Activated charcoal (± whole bowel irrigation for MR), IV calcium (chloride or gluconate), HIET, vasopressors, pacing; lipid emulsion, ECMO.
• Digoxin toxicity (acute overdose or chronic accumulation):
  • Nausea, vomiting, confusion, yellow-green vision, bradycardia, heart block, ventricular ectopics, VT; hyperkalaemia in acute overdose (poor prognostic sign); hypokalaemia worsens chronic toxicity.
  • Digoxin level at least 6 hours after the last dose (any time if toxic); U&E, magnesium, ECG.
  • DigiFab indications -life-threatening arrhythmias, severe bradycardia or heart block not responding to atropine, potassium over about 6 mmol/L (acute overdose), haemodynamic instability, very high levels (per TOXBASE).
  • Avoid IV calcium for hyperkalaemia in digoxin toxicity (traditional caution -use other measures); correct hypokalaemia and hypomagnesaemia; atropine for bradycardia.

Lithium, Iron and Hypoglycaemic Agents

• Lithium:
  • Acute overdose (in a person not taking lithium) -mainly GI symptoms (vomiting, diarrhoea); neurotoxicity is delayed; high levels may be tolerated briefly.
  • Chronic toxicity (on long-term lithium -dehydration, AKI, interacting drugs) -neurological: coarse tremor, ataxia, confusion, myoclonus, seizures, coma -dangerous even at moderately raised levels.
  • Not bound by charcoal; whole bowel irrigation for large acute modified-release overdoses; IV fluids (0.9% saline); stop interacting drugs; serial levels; haemodialysis for severe neurotoxicity, kidney failure or very high levels (per TOXBASE / EXTRIP).
• Iron (often children -ferrous sulfate tablets look like sweets):
  • Toxicity by elemental iron dose -under 20 mg/kg usually mild; 20–60 mg/kg GI toxicity; over 60 mg/kg serious systemic toxicity.
  • Stages -vomiting, diarrhoea, GI bleeding (hours) → apparent recovery → shock, metabolic acidosis, liver failure (12–48 hours) → later gastric strictures.
  • Serum iron at 4 hours; abdominal X-ray (tablets radio-opaque); charcoal doesn't bind iron; whole bowel irrigation for large ingestions.
  • IV desferrioxamine for serious features or high serum iron (per TOXBASE) -urine turns "vin rosé".
• Insulin overdose -prolonged hypoglycaemia (especially long-acting) -IV glucose infusion (10–20%), frequent glucose checks, potassium (hypokalaemia), observe for at least 24 hours or longer; local excision of the injection site rarely.
• Sulphonylureas (gliclazide) -prolonged, recurrent hypoglycaemia (up to days) -IV glucose and octreotide; admit and monitor; even small doses can be dangerous in children.
• Metformin -lactic acidosis in large overdose or with AKI -supportive care; haemodialysis for severe acidosis.

Toxic Alcohols

• Methanol (screenwash, some spirits, illicit alcohol) and ethylene glycol (antifreeze) -not very toxic themselves but metabolised by alcohol dehydrogenase to toxic acids.
• Early -intoxication like alcohol (drunk without the smell), with a raised osmolar gap.
• Later (as metabolites form) -high anion gap metabolic acidosis (osmolar gap falls):
  • Methanol → formic acid -visual disturbance ("snowstorm" vision, blindness -optic nerve damage), headache, abdominal pain, coma.
  • Ethylene glycol → glycolic and oxalic acids -AKI (calcium oxalate crystals in urine), hypocalcaemia, seizures, cardiorespiratory failure.
• Treatment:
  • Fomepizole (or ethanol if fomepizole unavailable) -blocks alcohol dehydrogenase, preventing formation of toxic metabolites.
  • Haemodialysis -removes the alcohol and acids -severe acidosis, visual disturbance, AKI, very high levels.
  • Sodium bicarbonate for acidosis; folic or folinic acid (methanol); thiamine and pyridoxine (ethylene glycol).
• Isopropanol (rubbing alcohol) -ketosis without acidosis; supportive care.

Carbon Monoxide and Cyanide

• Carbon monoxide -faulty boilers, fires, car exhausts, barbecues indoors; binds haemoglobin 200–250 times more strongly than oxygen:
  • Features -headache, nausea, dizziness, fatigue (often several household members or pets affected; better away from home), confusion, chest pain, seizures, coma; "cherry red" skin is rare.
  • Pulse oximetry is falsely normal -measure carboxyhaemoglobin (COHb) on a co-oximetry blood gas (levels may have fallen with oxygen in the ambulance; smokers have up to 10%).
  • Treatment -100% oxygen via a tight-fitting reservoir mask (reduces COHb half-life from about 4–5 hours to about 1 hour) until COHb under about 3% and symptoms resolve; ECG and troponin; hyperbaric oxygen in selected cases (discuss with NPIS); pregnancy needs longer treatment.
  • Delayed neurological sequelae -memory problems, personality change, parkinsonism (days to weeks later).
  • Public health -report; make sure the source is fixed (gas engineer) before return home; CO alarms.
• Cyanide -house fires (burning plastics), industry, some plants:
  • Blocks cellular oxygen use -very high lactate, metabolic acidosis, collapse, seizures, coma, cardiac arrest; normal oxygen saturation.
  • Hydroxocobalamin IV (5 g) -binds cyanide (turns skin and urine red); oxygen; supportive care.

Organophosphates and Household Chemicals

• Organophosphates (insecticides, sheep dips, nerve agents) -irreversibly inhibit acetylcholinesterase → acetylcholine excess:
  • Muscarinic -SLUDGE, bradycardia, bronchorrhoea and bronchospasm ("killer Bs"), small pupils, sweating.
  • Nicotinic -fasciculations, weakness, paralysis, tachycardia, hypertension.
  • CNS -confusion, seizures, coma.
• Management -protect staff (PPE), remove clothing and wash skin; airway and oxygen; atropine in large, doubling doses until secretions dry and chest clear (heart rate over 80); pralidoxime (oxime -reactivates the enzyme if given early); benzodiazepines for seizures; ICU; watch for the "intermediate syndrome" (weakness 1–4 days later -respiratory failure).
• Corrosives (acids, alkalis -drain cleaner, bleach in large amounts) -mouth and throat burns, drooling, stridor, chest pain, perforation; don't induce vomiting, no charcoal; airway assessment, urgent endoscopy (specialist); alkalis cause deeper injury.
• Laundry detergent capsules -vomiting, airway irritation, eye injury, aspiration in children.
• Button batteries (children) -oesophageal impaction causes burns within 2 hours -urgent X-ray and removal; honey en route in some guidance (over 1 year) per specialist advice.
• Paraquat (herbicide, banned in the UK) -lung fibrosis; avoid excess oxygen.
• Lead -abdominal pain, anaemia (basophilic stippling), neuropathy (wrist drop), encephalopathy; chelation.

Recreational Drugs