Poisoning and Drug Overdose¶
Chapter 470 | Part 12: Endocrinology
KEY CLINICAL POINTS¶
- Poisoning is defined by dose-related adverse effects from chemicals, drugs, or xenobiotics; the dose determines toxicity (Paracelsus principle).
- Carbon monoxide is the leading cause of death from poisoning, but underreporting due to rapid mortality complicates statistics.
- Epidemiology: ~5 million poison exposures annually in the US, with pharmaceuticals involved in 47% of cases and 84% of serious/fatal poisonings.
- Clinical features vary by toxidrome (stimulated, depressed, discordant, normal) and include altered mental status, autonomic instability, and organ dysfunction.
- Management prioritizes airway, breathing, circulation, antidotes, and decontamination, with hemodialysis/hemoperfusion for selected toxins.
1. DEFINITION & OVERVIEW¶
Poisoning refers to dose-related adverse effects from chemicals, drugs, or xenobiotics. The dose makes the poison (Paracelsus). Poisoning may be local (skin, eyes, lungs) or systemic, depending on exposure route, chemical properties, and target organ reserve. Severity depends on functional reserve and individual variability (genetics, enzyme induction, drug interactions).
Table 470-1: Differential Diagnosis of Poisoning Based on Physiologic State¶
| STIMULATED | DEPRESSED | DISCORDANT | NORMAL |
|---|---|---|---|
| Sympathomimetics | Sympatholytics | Asphyxiants | Nontoxic exposure |
| a-Adrenergic agonists | a-Adrenergic antagonists | Cytochrome oxidase inhibitors | Psychogenic illness |
| b-Adrenergic agonists | ACE inhibitors | Inert gases | Toxic time-bombs |
| Muscarinic agonists | Calcium channel blockers | Irritant gases | Slow absorption |
| Cyclic antidepressants | Cardiac glycosides | Methemoglobin inducers | Anticholinergics |
| Opioids | Antipsychotics | Oxidative phosphorylation inhibitors | Carbamazepine |
| Sedative-hypnotics | b-Blockers | AGMA inducers | Concretion formers |
| Local anesthetics | Calcium channel blockers | Alcohol (ketoacidosis) | Extended-release phenytoin sodium capsules |
| Antihistamines | Lithium | Ethylene glycol | Drug packets |
| Antiparkinsonian agents | Membrane-active agents | Methanol | Enteric-coated pills |
| Antipsychotics | Antiarrhythmics | Salicylates | Diphenoxylate-atropine (Lomotil) |
| STIMULATED | DEPRESSED | DISCORDANT | NORMAL |
|---|---|---|---|
| Antispasmodics | Anticonvulsants | Toluene | Opioids |
| Belladonna alkaloids | Antihistamines | Iron | Salicylates |
| Cyclic antidepressants | Antipsychotics | Lithium | Sustained-release pills |
| Mushrooms and plants | Anticonvulsants | Metals | Valproate |
| Hallucinogens | Antipsychotics | Salicylate | Toxic metabolite |
| Cannabinoids (marijuana) | Antipsychotics | Carbon tetrachloride | Acetaminophen |
| LSD and analogues | Antipsychotics | Cyanogenic glycosides | Carbon tetrachloride |
| Mescaline and analogues | Antipsychotics | Organophosphate insecticides | Paraquat |
| Mushrooms | Antipsychotics | Metabolism disruptors | Metabolism disruptors |
Table 470-2: Severity of Physiologic Stimulation and Depression in Poisoning and Drug Withdrawal¶
| PHYSIOLOGIC STIMULATION | PHYSIOLOGIC DEPRESSION | DISCORDANT | NORMAL |
|---|---|---|---|
| Grade 1: Anxious, irritable, tremulous; vital signs normal; diaphoresis, flushing, or pallor, mydriasis, and hyperreflexia sometimes present | Grade 1: Awake, lethargic, or sleeping but arousable by voice or tactile stimulation; able to converse and follow commands; may be confused | Discordant physiologic state | Nontoxic exposure |
| Grade 2: Agitated; may have confusion or hallucinations but can converse and follow commands; vital signs mildly to moderately increased | Grade 2: Responds to pain but not voice; can vocalize but not converse; spontaneous motor activity present; brainstem reflexes intact | Mixed vital-sign and neuromuscular abnormalities | Psychogenic illness |
| Grade 3: Delirious; unintelligible speech, uncontrollable motor hyperactivity; moderately to markedly increased vital signs; tachyarrhythmias possible | Grade 3: Unresponsive to pain; spontaneous motor activity absent; brainstem reflexes depressed; motor tone, respirations, and temperature decreased | Simultaneous coma, seizures, hypotension, and tachyarrhythmias | Toxic time-bombs |
| Grade 4: Coma, seizures, cardiovascular collapse | Grade 4: Unresponsive to pain; flaccid paralysis; brainstem reflexes and respirations absent; cardiovascular vital signs decreased | Vital signs normal while mental status altered | Slow absorption |
1.1 Subtopic¶
Poisoning can mimic other illnesses but is often diagnosed via history, physical exam, toxicologic labs, and clinical toxidromes. Confusion, coma, or unawareness of exposure are common in intentional or severe cases.
2. EPIDEMIOLOGY¶
Over 5 million poison exposures annually in the US, with ~20-25% requiring professional evaluation and 5% hospitalization. Pharmaceuticals account for 47% of exposures and 84% of serious/fatal cases. Carbon monoxide is the leading cause of death from poisoning, but underreporting due to rapid mortality complicates statistics. Fatalities from intentional self-harm (suicide) and opioid complications are rising, with ~106,600 drug overdose deaths in 2021 (age-adjusted rate 32.4/100,000). Synthetic opioids like fentanyl and xylazine drive overdose mortality.
2.1 Risk Factors¶
Children <6 years old, occupational exposure, misreading labels, drug interactions, and psychiatric history (depression, bipolar disorder).
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Toxic effects depend on dose, route, and individual factors (genetics, enzyme activity). Mechanisms include direct toxicity, enzyme inhibition, receptor activation, and metabolic disruption. Examples: Acetaminophen causes hepatic necrosis via NAPQI; cyanide inhibits cytochrome oxidase; opioids depress CNS respiratory centers.
3.1 Key Pathways¶
Drug metabolism, receptor activation, and organ-specific toxicity (e.g., lithium-induced nephrogenic diabetes insipidus).
4. CLINICAL FEATURES¶
Symptoms vary by toxidrome: Stimulated (tachycardia, hypertension, hyperthermia), Depressed (bradycardia, hypotension, CNS depression), Discordant (mixed signs), or Normal (nontoxic). Key signs include altered mental status, autonomic instability, and organ dysfunction (e.g., renal failure, metabolic acidosis).
4.1 Toxidromes¶
Stimulated: Sympathomimetics, anticholinergics. Depressed: Opioids, sedatives. Discordant: Asphyxiants, membrane-active agents. Normal: Psychogenic or delayed toxicity.
5. DIFFERENTIAL DIAGNOSIS¶
Distinguish poisoning from other conditions with similar presentations (e.g., stroke, sepsis). Consider toxic time-bombs, psychiatric illness, or drug withdrawal. Key clues: Unexplained sudden illness, recent drug use, or occupational exposure.
5.1 Red Flags¶
Unexplained sudden illness in healthy individuals, recent psychiatric history, or occupational chemical exposure.
6. INVESTIGATIONS & DIAGNOSIS¶
History: Time, route, agents involved, symptoms, and first-aid measures. Physical exam: Vital signs, neurological status, and signs of toxicity (e.g., mydriasis, cyanosis). Labs: Toxicology screens, metabolic panels, and specific tests (e.g., carboxyhemoglobin for CO, methemoglobin for nitrites).
Table 470-3: Fundamentals of Poisoning Management¶
| SUPPORTIVE CARE | PREVENTION OF FURTHER POISON ABSORPTION | ENHANCEMENT OF POISON ELIMINATION | ADMINISTRATION OF ANTIDOTES | PREVENTION OF REEXPOSURE |
|---|---|---|---|---|
| Airway protection | Gastrointestinal decontamination | Multiple-dose activated charcoal | Neutralization by antibodies | Adult education |
| Treatment of seizures | Eye decontamination | Alteration of urinary pH | Metabolic antagonism | Child-proofing |
| Oxygenation/ventilati on | Skin decontamination | Chelation | Physiologic antagonism | Psychiatric referral |
| Treatment of arrhythmias | Body cavity evacuation | Hyperbaric oxygenation | Extracorporeal removal | Naloxone distribution |
| Correction of temperature abnormalities | Whole-bowel irrigation | Hemodialysis | Hemoperfusion | Linkage to harm reduction services |
| Correction of metabolic derangements | Dilution | Hemofiltration | Plasmapheresis | Notification of regulatory agencies |
6.1 Diagnostic Tools¶
Toxicology screens (urine/blood), ECG for arrhythmias, and imaging for aspiration or foreign bodies.
7. MANAGEMENT & TREATMENT¶
Prioritize airway, breathing, circulation, and antidotes. Decontamination (activated charcoal, gastric lavage) is effective early but less so after 1 hour. Hemodialysis/hemoperfusion for selected toxins (e.g., salicylates, ethylene glycol). Antidotes include naloxone (opioids), physostigmine (anticholinergics), and flumazenil (benzodiazepines).
Table 470-4: Pathophysiologic Features and Treatment of Specific Toxic Syndromes and Poisonings¶
| PHYSIOLOGIC CONDITION, CAUSES | EXAMPLES | MECHANISM OF ACTION | CLINICAL FEATURES | SPECIFIC TREATMENTS |
|---|---|---|---|---|
| Stimulated Sympathetics | Sympathomimetics (decongestants) | Stimulation of central and peripheral sympathetic receptors | Physiologic stimulation (Table 470-2) | Phentolamine, propranolol |
| Anticholinergics | Antihistamines (diphenhydramine) | Inhibition of muscarinic cholinergic receptors | Dry skin, mydriasis, urinary retention | Physostigmine |
| Sedative-hypnotics | Barbiturates | Enhance GABA activity | Respiratory depression, CNS depression | Benzodiazepines, barbiturates |
| CNS syndromes | Extrapyramidal reactions | Dopamine receptor blockade | Akathisia, dystonia | Anticholinergics (benztropine) |
| Methemoglobin inducers | Nitrites | Oxidation of hemoglobin to methemoglobin | Gray-brown cyanosis | Methylene blue, exchange transfusion |
| AGMA inducers | Ethylene glycol | Metabolism to glycolic acid | Metabolic acidosis, renal failure | Hemodialysis, fomepizole |
| PHYSIOLOGIC CONDITION, CAUSES | EXAMPLES | MECHANISM OF ACTION | CLINICAL FEATURES | SPECIFIC TREATMENTS |
|---|---|---|---|---|
| Iron toxicity | Iron tablets | Formation of free radicals | Abdominal pain, hemolysis | Whole-bowel irrigation, deferoxamine |
| Salicylate toxicity | Aspirin | Uncoupling of oxidative phosphorylation | Respiratory alkalosis, AGMA | Hemodialysis, sodium bicarbonate |
7.1 Decontamination¶
Activated charcoal (1 g/kg) within 1 hour of ingestion. Gastric lavage contraindicated in corrosives. Whole-bowel irrigation for foreign bodies.
7,2 Antidotes¶
Naloxone for opioids, physostigmine for anticholinergics, and specific agents for AGMA (fomepizole/ethanol).
8. PROGNOSIS & COMPLICATIONS¶
Mortality is low (<1%) for most poisonings but higher in intentional overdoses (1-2%). Complications include aspiration pneumonia, renal failure, arrhythmias, and multiorgan failure. Long-term sequelae may include hepatic or renal damage.
8.1 Risk Factors¶
Intentional overdose, delayed treatment, and multiorgan involvement increase mortality.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: Avoid certain drugs (e.g., lithium, NSAIDs). Pediatrics: Use age-appropriate dosing and avoid corrosives. Elderly: Increased sensitivity to drugs and comorbidities. Special populations: Consider drug interactions in renal failure or hepatic disease.
9.1 Pregnancy¶
Avoid teratogenic agents; monitor for fetal distress.
10. KEY POINTS & CLINICAL PEARLS¶
- Use toxidrome-based diagnosis (stimulated, depressed, discordant, normal). 2. Prioritize airway, breathing, and circulation. 3. Activated charcoal is effective within 1 hour of ingestion. 4. Hemodialysis is indicated for AGMA (salicylates, ethylene glycol). 5. Naloxone reverses opioid toxicity. 6. Monitor for delayed toxicity (e.g., carbon monoxide, methanol).