Contents

1. Introduction
2. General Management of Poisoning
   • Resuscitation and Risk Assessment
   • Reducing Drug Absorption
   • Enhancing Drug Elimination
3. Antidotes
4. Specific Drug Overdoses
   • Paracetamol
   • Salicylates (Aspirin)
   • Opioids
   • Benzodiazepines
   • Tricyclic Antidepressants
   • Beta-Blockers and Calcium Channel Blockers
   • Digoxin
   • Lithium
   • Iron
   • Organophosphates
   • Methanol and Ethylene Glycol
   • Cyanide and Carbon Monoxide
5. Polypharmacy
6. STOPP-START
7. Summary
8. Quiz

Abstract

• The general management of poisoning has four pillars: resuscitation, reducing further absorption, enhancing elimination, and specific antidotes where one exists. The UK reference is TOXBASE, the National Poisons Information Service database.
• Important antidotes to commit to memory: paracetamol → N-acetylcysteine, opioids → naloxone, benzodiazepines → flumazenil, warfarin → vitamin K + PCC, dabigatran → idarucizumab, beta-blockers → glucagon, digoxin → DigiFab, organophosphates → atropine + pralidoxime, methanol/ethylene glycol → fomepizole or ethanol, iron → desferrioxamine.
• Polypharmacy (typically 5+ regular medicines) is increasingly common in older adults and the leading source of preventable adverse drug reactions.
• The STOPP-START tool (Screening Tool of Older Persons' Prescriptions / Screening Tool to Alert to the Right Treatment) is a UK-validated framework for medication review in patients aged 65 and over, identifying potentially inappropriate medicines (STOPP) and missed indicated medicines (START).

Core

Introduction

Poisoning is a common reason for emergency department attendance: deliberate self-harm, accidental overdose in older patients with polypharmacy, recreational drug use, and occasional industrial or environmental exposures. The pre-clinical curriculum covers the principles of management, the major antidotes, and a small number of high-yield specific poisonings.

The companion to poisoning is the prescribing review framework STOPP-START, used to identify and reduce inappropriate medicines in older adults: the population most at risk of adverse drug reactions in the first place.

General Management of Poisoning

Resuscitation and Risk Assessment

The first priority is always the patient, not the poison:

1. Airway, breathing, circulation: standard ABCDE approach. Intubation if airway compromised.
2. Disability: check blood glucose, pupils, GCS, temperature.
3. Exposure: remove contaminated clothing in chemical exposure; warm.
4. Specific risk assessment: identify the substance, the amount, the time of exposure, and any co-ingestion.
5. Investigations: standard panel of bloods, paracetamol level in any suspected, undisclosed or mixed overdose (early toxicity is clinically silent), salicylate level if suspected, ECG, blood gas, blood glucose. Toxicology screen if relevant.
6. Get advice: TOXBASE (toxbase.org) is the UK National Poisons Information Service (NPIS) database, free at the point of use to NHS staff. The 24-hour NPIS phone line is also available for complex cases.

Reducing Drug Absorption

Several historical approaches have been abandoned because they cause more harm than good. The current evidence-based options:

• Activated charcoal: binds many drugs in the gut, reducing systemic absorption. Most effective within 1 hour of ingestion (extended in modified-release preparations and for some agents). Standard dose: 50 g orally or via NG tube. Contraindications: reduced GCS without airway protection (aspiration risk), corrosive ingestion, hydrocarbons.

  Charcoal does not bind: lithium, iron, ethanol, methanol, ethylene glycol, strong acids and alkalis (the "HEAL" / "I LIE" mnemonic, with variations).

• Whole bowel irrigation with macrogol: very occasional use for sustained-release preparations, body packers, lithium and iron.
• Gastric lavage (stomach pumping): almost never indicated; risks of aspiration outweigh benefit.
• Induced vomiting with ipecacuanha: no longer recommended.

Enhancing Drug Elimination

Several techniques can speed elimination of certain drugs:

• Urinary alkalinisation with sodium bicarbonate: raises urine pH, traps weak acids in the tubule (ion trapping). Used for salicylate overdose and other weak-acid poisons.
• Multiple-dose activated charcoal, for drugs with enterohepatic circulation (carbamazepine, theophylline, dapsone, quinine, phenobarbital).
• Haemodialysis, for severely ill patients with poisoning by drugs of small volume of distribution and modest protein binding. The classic candidates are summarised by the mnemonic "I STUMBLE" or simply listing them: lithium, salicylates, methanol, ethylene glycol, theophylline, phenobarbital, valproate, metformin (severe lactic acidosis).
• Lipid emulsion (Intralipid), for local anaesthetic systemic toxicity (especially bupivacaine), and considered for some highly lipophilic drug overdoses (TCA, beta-blocker, calcium channel blocker).

Antidotes

Most poisons have no specific antidote: supportive care is the rule. The exceptions are the high-yield material for any UK exam:

Antidote summary: high-yield list

Paracetamol → N-acetylcysteine (NAC)
Opioids → Naloxone
Benzodiazepines → Flumazenil (use cautiously)
Warfarin → Vitamin K + PCC / FFP
Dabigatran → Idarucizumab
-Xaban DOACs → Andexanet alfa / PCC
Heparin → Protamine sulfate
Beta-blockers → Glucagon ± high-dose insulin / glucose
Calcium channel blockers → Calcium gluconate + high-dose insulin / glucose (HIET) as primary therapy; glucagon has limited evidence here
Digoxin → Digoxin-specific Fab antibodies (DigiFab)
Iron → Desferrioxamine
Lead, mercury, arsenic → Dimercaprol, DMSA, EDTA
Methanol / ethylene glycol → Fomepizole (or ethanol IV)
Organophosphates / nerve agents → Atropine + pralidoxime
Cyanide → Hydroxocobalamin (or sodium thiosulfate)
Carbon monoxide → 100% oxygen (hyperbaric in severe cases)
Methotrexate → Folinic acid (calcium folinate)
Local anaesthetic toxicity → Intralipid

Specific Drug Overdoses

Paracetamol

The most common drug taken in deliberate overdose in the UK and the leading cause of acute liver failure. Mechanism, clinical course, and treatment with N-acetylcysteine are covered in detail in NSAIDs. Standard summary:

• Often asymptomatic in the first 24 hours.
• Plot 4-hour paracetamol level on the standard treatment nomogram (UK uses a single line at 100 mg/L at 4 hours since 2012).
• NAC restores hepatic glutathione, neutralising NAPQI. Most effective if started within 8 hours but is given even late if liver injury has developed.
• Severe poisoning: refer to the King's College criteria for liver transplantation.

Salicylates (Aspirin)

The classic biochemistry of salicylate poisoning is worth memorising:

• Early respiratory alkalosis: direct stimulation of the respiratory centre.
• Late metabolic acidosis: uncoupling of oxidative phosphorylation and accumulation of lactate.
• Net result: mixed respiratory alkalosis and metabolic acidosis.
• Other features: tinnitus, hyperthermia, sweating, vomiting, hyperventilation, agitation.

Management:

• Activated charcoal if within 1 hour.
• IV fluid resuscitation with normal saline plus correction of electrolyte abnormalities.
• Urinary alkalinisation with sodium bicarbonate (target urinary pH > 7.5): "ion trapping" of salicylate in the tubule.
• Haemodialysis in severe poisoning (level > 700 mg/L, severe acidosis, renal failure, pulmonary oedema, persistent CNS features, plasma level rising despite measures).

Opioids

The triad of pinpoint pupils, respiratory depression and reduced consciousness is the cardinal presentation. Management is covered in Opioids: airway support, naloxone titrated to respiratory rate (not full reversal, which precipitates withdrawal). Naloxone half-life is short (30-90 min), so patients with long-acting opioid overdose may need a continuous naloxone infusion or repeated doses.

Benzodiazepines

Excessive sedation, respiratory depression (less than opioids unless combined), hypotension. The antidote flumazenil is a competitive antagonist at the benzodiazepine site of GABA_A; it reverses sedation rapidly, but is used cautiously:

• Can precipitate seizures, especially in chronic benzodiazepine users or in mixed overdose with proconvulsants (e.g. TCAs).
• Short half-life: re-sedation is common; usually reserved for clearly iatrogenic overdose (e.g. procedural sedation).

Tricyclic Antidepressants

TCA overdose is one of the most lethal common overdoses. Mechanism is multimodal: anticholinergic, sodium channel blockade, alpha-1 blockade. Clinical features:

• Anticholinergic ("dry as a bone, hot as a hare, blind as a bat, mad as a hatter, red as a beet").
• Hypotension.
• Cardiac arrhythmia: the cause of death. Wide QRS and ventricular arrhythmia.
• Seizures.
• Reduced consciousness.

Management: ABC, activated charcoal if within 1 hour, IV sodium bicarbonate for QRS prolongation (alkalinisation reduces TCA cardiotoxicity), benzodiazepines for seizures.

Beta-Blockers and Calcium Channel Blockers

Both produce bradycardia, hypotension and shock in overdose. Calcium channel blocker overdose can additionally cause hyperglycaemia (insulin secretion is calcium-dependent in pancreatic beta-cells).

Management: ABC, IV fluids, atropine. Specific therapies:

• Glucagon: activates G-protein signalling independently of beta-receptors, raising cardiac cAMP. The first-line "antidote" for refractory beta-blocker overdose.
• Calcium gluconate, for calcium channel blocker overdose.
• High-dose insulin and glucose: "hyperinsulinaemic euglycaemia therapy" (HIET) supports cardiac contractility.
• Intralipid as rescue for highly lipophilic agents.
• Pacing or ECMO in extreme cases.

Digoxin

Digoxin toxicity (covered in Cardiac Arrhythmias) presents with bradyarrhythmias, almost any rhythm disturbance, GI upset (nausea, vomiting, anorexia), confusion, and the classic yellow-green colour vision (xanthopsia).

Management: correct hypokalaemia (caution: severe acute toxicity may produce hyperkalaemia). For severe toxicity (life-threatening arrhythmia, K⁺ > 5 with cardiac features), digoxin-specific Fab antibody fragments (DigiFab) bind digoxin and produce rapid clinical improvement.

Lithium

Lithium has a narrow therapeutic index (0.4-1.0 mmol/L therapeutic). Toxicity at > 1.5 mmol/L. Causes: dehydration, NSAIDs, ACE inhibitors, diuretics (especially thiazides), reduced renal function.

Features:

• Mild: tremor, GI upset, fatigue.
• Moderate: confusion, ataxia, hyperreflexia, myoclonus.
• Severe: seizures, coma, arrhythmia, renal failure.

Management: stop lithium, IV fluids (saline). Haemodialysis for severe poisoning (level > 4.0 mmol/L, or > 2.5 mmol/L with severe symptoms or renal failure). Activated charcoal is ineffective (charcoal does not bind lithium).

Iron

Particularly in childhood accidental ingestion of iron tablets, which can resemble sweets. Five clinical phases:

1. 0-6 hours: GI symptoms (vomiting, haematemesis, melaena).
2. 6-24 hours: apparent improvement.
3. 12-48 hours: shock, metabolic acidosis, hepatic failure, coagulopathy.
4. 2-3 days: recovery or progression.
5. 2-6 weeks: late strictures (gastric outlet obstruction).

Management: whole bowel irrigation may be considered (charcoal does not bind iron); desferrioxamine chelates iron and is given for severe poisoning (level > 90 micromol/L 4 hours after ingestion, or with shock, acidosis or coma).

Organophosphates

Organophosphates (insecticides such as malathion; nerve agents like sarin and Novichok) irreversibly inhibit acetylcholinesterase, producing massive cholinergic stimulation:

• Muscarinic features: SLUDGE: Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis. Plus miosis, bronchospasm, bradycardia.
• Nicotinic features: muscle weakness, fasciculations, eventual paralysis.
• CNS: confusion, seizures, coma.

Management:

• ABC, decontamination (remove clothes, wash skin), staff PPE.
• Atropine: titrated to drying of secretions and reasonable heart rate (not pupil size). Doses required can be enormous.
• Pralidoxime: reactivates acetylcholinesterase before it has irreversibly "aged"; effective only if given within hours of exposure.
• Benzodiazepines for seizures.

Methanol and Ethylene Glycol

Both cause severe metabolic acidosis with high anion gap and high osmolar gap. Toxicity comes from their metabolites (formate from methanol; glycolate and oxalate from ethylene glycol), produced by alcohol dehydrogenase.

Management:

• Fomepizole: competitive inhibitor of alcohol dehydrogenase; preferred treatment.
• Ethanol: alternative; competes for alcohol dehydrogenase.
• Haemodialysis: removes both parent compound and toxic metabolites. Essential for severe poisoning.
• Adjuncts: folinic acid (methanol), pyridoxine and thiamine (ethylene glycol).

Cyanide and Carbon Monoxide

Both are inhaled toxins typically encountered in fires.

Cyanide binds the iron of cytochrome oxidase, halting cellular oxygen use. Features: rapid onset of headache, confusion, seizures, "cherry-red" skin, and high venous oxygen content. Antidote: hydroxocobalamin (binds cyanide to form cyanocobalamin/B₁₂); alternatives are sodium thiosulfate and sodium nitrite.

Carbon monoxide binds haemoglobin with much higher affinity than oxygen, causing functional anaemia and tissue hypoxia. Pulse oximetry is misleadingly normal. Antidote: 100% oxygen; hyperbaric oxygen for severe cases (loss of consciousness, neurological deficit, pregnancy).

Polypharmacy

Polypharmacy is broadly defined as a patient on five or more regular medicines. Prevalence rises with age; around half of UK adults over 75 are on five or more medicines. Polypharmacy is not pejorative if every drug has a clear indication, but it brings cumulative risks:

• Drug interactions.
• Adverse drug reactions.
• Pill burden and reduced adherence.
• Hospital admissions.
• Falls (particularly drugs that lower blood pressure, cause sedation or anticholinergic effects).

The principles of medication review:

• Confirm the indication for each drug is still current.
• Check for new contraindications (e.g. declining renal or hepatic function).
• Identify drug interactions and adjust accordingly.
• Identify drugs that are no longer needed.
• Identify missing indicated drugs (e.g. a statin in someone with established CVD).
• Discuss with the patient: understanding and concordance matter at least as much as the prescription itself.
• Consider lifestyle alternatives.

STOPP-START

The STOPP-START tool is a structured medication review framework developed in Ireland and validated for use in patients aged 65 and over. It complements but does not replace clinical judgement.

STOPP: "Screening Tool of Older Persons' Prescriptions": identifies potentially inappropriate medicines. Examples:

• Long-term benzodiazepines (fall risk).
• NSAIDs in heart failure or stage 4-5 CKD.
• Aspirin without history of cardiovascular disease (limited benefit, real bleeding risk).
• Anticholinergics (TCAs, oxybutynin, first-generation antihistamines) in dementia.
• Non-cardioselective beta-blockers in asthma or significant reactive airway disease (a firmer contraindication than in COPD).
• Long-term PPI without clear ongoing indication.
• Loop diuretic for ankle oedema without heart failure.

START: "Screening Tool to Alert to the Right Treatment": identifies missing indicated medicines. Examples:

• ACE inhibitor in chronic heart failure or post-MI.
• Statin in patients with established cardiovascular disease and life expectancy > 5 years.
• Antiplatelet (aspirin or clopidogrel) after stroke or TIA.
• Vitamin D and calcium supplementation in patients on long-term steroids or with osteoporosis.
• Bisphosphonate in patients with documented osteoporosis or on long-term steroids.
• Beta-blocker in stable angina.
• Levothyroxine in primary hypothyroidism.

The detailed STOPP-START criteria run to over 80 individual items in their current versions; the pre-clinical takeaway is to know the framework, recognise the high-yield examples, and use the principle in any older patient with polypharmacy.

Summary

• Poisoning management: resuscitate, reduce absorption, enhance elimination, give specific antidote. Reference: TOXBASE.
• Activated charcoal is most effective within 1 hour and does not bind lithium, iron, alcohols or strong acids/alkalis.
• High-yield antidotes: NAC (paracetamol), naloxone (opioids), flumazenil (benzodiazepines: use with care), vitamin K + PCC (warfarin), idarucizumab (dabigatran), protamine (heparin), glucagon (beta-blockers), calcium gluconate + insulin (CCBs), DigiFab (digoxin), desferrioxamine (iron), fomepizole (methanol/ethylene glycol), atropine + pralidoxime (organophosphates), hydroxocobalamin (cyanide), 100% O₂ (CO).
• Salicylate overdose: mixed respiratory alkalosis and metabolic acidosis; urinary alkalinisation; haemodialysis if severe.
• TCA overdose: wide QRS, arrhythmia, anticholinergic features, seizures; treat with sodium bicarbonate and benzodiazepines.
• Lithium: narrow therapeutic index; charcoal does not bind; haemodialysis if severe.
• Polypharmacy is the leading source of preventable ADRs in older adults.
• STOPP-START: structured medication review for patients ≥ 65, identifying drugs to stop (STOPP) and missing drugs to start (START).

Reviewed by: Dr. Marcus Judge

Quiz

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