Toxicology & Overdose
Name the toxidrome, reach for the antidote
Recognizing the toxidromes
Pupils and skin name the toxidrome. Read the pupils, skin, and vital signs before any level returns. Dry versus sweaty skin is the fastest way to split the two agitated, mydriatic toxidromes: anticholinergic (dry) and sympathomimetic (diaphoretic).
| Toxidrome | Pupils | Skin | Other features | Classic agents | Treatment |
|---|---|---|---|---|---|
| Anticholinergic | Dilated | Hot, DRY, flushed | Delirium, urinary retention, ↓ bowel sounds, tachycardia | Diphenhydramine, TCAs, atropine, antipsychotics, jimsonweed | Physostigmine if severe |
| Sympathomimetic | Dilated | DIAPHORETIC | Agitation, hypertension, tachycardia, hyperthermia | Cocaine, amphetamines, MDMA | Benzodiazepines |
| Cholinergic | Constricted | Wet | DUMBBELS secretions, bradycardia, bronchospasm | Organophosphate and carbamate insecticides, nerve agents | Atropine + pralidoxime |
| Opioid | Pinpoint | Normal | Respiratory and CNS depression | Heroin, fentanyl, prescription opioids | Naloxone |
| Sedative-hypnotic | Normal or small | Normal | CNS depression, slurred speech, ataxia | Benzodiazepines | Supportive; flumazenil rarely |
Anticholinergic. Hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter, full as a flask (urinary retention). Physostigmine reverses severe toxicity but is avoided when a TCA with a wide QRS is involved.
Cholinergic. DUMBBELS: Diarrhea, Urination, Miosis, Bradycardia/Bronchorrhea/Bronchospasm, Emesis, Lacrimation, Salivation. Atropine blocks the muscarinic effects and is titrated until secretions dry, because bronchorrhea and bronchospasm are what kill. Pralidoxime (2-PAM) reactivates acetylcholinesterase and must be given before the organophosphate-enzyme bond "ages"; carbamates bind reversibly and do not age.
Sympathomimetic. Cocaine, amphetamines, and MDMA cause agitation, mydriasis, diaphoresis, hypertension, hyperthermia, and tachycardia. Benzodiazepines are first-line. Avoid unopposed β-blockade in cocaine toxicity: it leaves α-mediated vasoconstriction unchecked and can worsen hypertension and coronary ischemia.
Opioid and sedative-hypnotic. Pinpoint pupils with respiratory depression (the killer) and CNS depression mean opioids; reverse with naloxone, and watch for re-sedation because naloxone wears off before long-acting opioids. Benzodiazepine overdose also depresses the CNS; flumazenil reverses it but is rarely used because it can precipitate seizures.
Decontamination and antidotes
Activated charcoal adsorbs many drugs if given within 1–2 hours of ingestion, in a patient who can protect the airway. It does NOT bind alcohols, iron, lithium, potassium, or caustics. Whole-bowel irrigation is used for iron, lithium, sustained-release drugs, and body packers. Gastric lavage and syrup of ipecac are largely abandoned.
| Poison | Antidote or key therapy |
|---|---|
| Acetaminophen | N-acetylcysteine |
| Salicylates | Sodium bicarbonate; hemodialysis if severe |
| Tricyclic antidepressants | Sodium bicarbonate |
| Methanol, ethylene glycol | Fomepizole (or ethanol); hemodialysis |
| Carbon monoxide | 100% oxygen; hyperbaric oxygen if severe |
| Cyanide | Hydroxocobalamin (plus sodium thiosulfate) |
| Iron | Deferoxamine |
| Digoxin | Digoxin-specific antibody fragments |
| β-blockers | Glucagon |
| Methemoglobinemia | Methylene blue |
| Isoniazid | Pyridoxine |
Acetaminophen
NAPQI burns the liver; NAC saves it. In overdose, CYP2E1 converts excess acetaminophen to toxic NAPQI, which depletes glutathione and causes centrilobular (zone 3) hepatic necrosis. Chronic alcohol use, which induces CYP2E1 and lowers glutathione, increases susceptibility.
Rumack-Matthew nomogram. Plot a level drawn 4 or more hours after a single acute ingestion; a level above the treatment line mandates N-acetylcysteine (NAC). If the ingestion time is unknown or the overdose was staggered, the nomogram does not apply and NAC is started on clinical grounds.
N-acetylcysteine replenishes glutathione to detoxify NAPQI. It is most effective within 8 hours but is still given late.
- Stage 1 (0–24 h)Asymptomatic or nausea; deceptively well.
- Stage 2 (24–72 h)RUQ pain; transaminases rise.
- Stage 3 (72–96 h)Peak hepatotoxicity; fulminant liver failure.
- Stage 4 (>96 h)Recovery or death.
Salicylates and tricyclic antidepressants
Salicylates: alkalinize, then dialyze. Overdose produces a mixed primary respiratory alkalosis (direct respiratory center stimulation) plus a high anion gap metabolic acidosis, with tinnitus, tachypnea, fever, and vomiting. Sodium bicarbonate alkalinizes serum and urine; ionized salicylate is trapped in the tubule and excreted. Replete potassium, since hypokalemia blocks urinary alkalinization. Hemodialysis is indicated for severe toxicity: level >100 mg/dL, altered mental status, renal failure, or pulmonary edema.
If a salicylate-poisoned patient must be intubated, match the high minute ventilation; losing the compensatory hyperventilation worsens acidemia and drives salicylate into the brain.
TCAs: wide QRS, push bicarbonate. Tricyclic overdose gives the 3 C's (Coma, Convulsions, Cardiotoxicity) from fast sodium-channel blockade, plus anticholinergic signs and α-blockade hypotension. The ECG shows a QRS >100 ms and a terminal R wave in aVR. IV sodium bicarbonate overcomes the sodium-channel blockade and narrows the QRS; treat seizures with benzodiazepines.
Toxic alcohols and poisonous gases
Methanol is metabolized to formic acid, causing visual disturbance (blurring, "snowfield" vision, blindness) and a high anion gap metabolic acidosis with an elevated osmolar gap. Treat with fomepizole (an alcohol dehydrogenase inhibitor) or ethanol, plus folate and hemodialysis.
Ethylene glycol (antifreeze) becomes oxalic acid, forming envelope-shaped calcium oxalate crystals in the urine with AKI and hypocalcemia, plus high anion and osmolar gaps. Treat with fomepizole (or ethanol), thiamine and pyridoxine, and hemodialysis.
Osmolar gap = measured minus calculated osmolality (2 × Na + glucose/18 + BUN/2.8); a gap >10 suggests an unmeasured alcohol. Isopropanol raises the osmolar gap and causes ketosis WITHOUT acidosis because it is metabolized to acetone.
Carbon monoxide binds hemoglobin about 240 times more tightly than oxygen and left-shifts the dissociation curve, so tissues are hypoxic while standard pulse oximetry reads falsely normal. Suspect it with headache and nausea in several members of one household, space heaters, or fires. Diagnose with a carboxyhemoglobin level. Treat with 100% oxygen; use hyperbaric oxygen for severe cases (loss of consciousness, neurologic deficits, pregnancy).
Cyanide inhibits cytochrome c oxidase (complex IV), halting aerobic ATP production and forcing a severe lactic (high-gap) acidosis; venous O₂ saturation is HIGH because tissues cannot use oxygen. Suspect it after house fires or nitroprusside infusion. The antidote is hydroxocobalamin, which binds cyanide to form cyanocobalamin, plus sodium thiosulfate.
A very high venous O₂ saturation with profound lactic acidosis after smoke inhalation points to cyanide.