Clinical Toxicology - Graduate Pharmacy Notes

Clinical Toxicology - Short Notes

Author: Introduction to Clinical Toxicology - Yen-Chia Chen, MD

1. Introduction to Poison & Toxicology

Poison Definition: Any substance that can cause adverse effects to a living organism when exposed. Systemic poisoning requires absorption.

Historical Perspective:
• Dioscorides (40-80 AD): Classified poisons into Animal, Vegetable, Mineral, and Gases.
• Paracelsus (1493-1541): Introduced the dose-response concept: "All things are poison... the dose determines that a thing is not a poison."
• Bonaventure Orfila (1787-1853): Father of modern toxicology; forensic/chemical analysis; classified poisons into six groups.

2. Initial Evaluation of Poisoned Patient

Clinical History (Why, Where, What, When)

  • Why: Accidental vs. Intentional
  • Where: Inside vs. Outside (available poisons)
  • What: Inquire EMS, friends, family
  • When: Time since ingestion/exposure
  • Initial presentation: Seizures, emesis, changing vital signs

Suspicion of Intoxication (Harrison’s Internal Medicine)

  • Unexplained illness in a previously healthy person
  • History of psychiatric disease (especially depression)
  • Recent change in health, economic status, or social relationship
  • Onset while working with chemicals or after ingestion of food/drink/medications
  • Onset after arriving from a foreign country or after arrest

3. Toxic Syndromes (Toxidromes)

Assessment based on Vital Signs + End-organ manifestations (CNS, Eyes, GI, Skin, Mucous membranes, GU).

Toxidrome Key Agents Signs & Symptoms Treatment
Anticholinergic Antihistamines, Atropine, TCAs, Jimson weed Mad as a hatter, Blind as a bat (mydriasis), Hot as a hare, Dry as a bone, Red as a beet + Tachycardia, Ileus, Urinary retention. NO sweating. Supportive. Physostigmine controversial (contraindicated in TCA OD).
Cholinergic Organophosphates, Carbamates SLUDGE/DUMBELS: Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis + Miosis, Bradycardia, Bronchorrhea, Bronchospasm. Atropine (2-5mg IV, repeat), Pralidoxime (2-PAM) (1-2g bolus, then infusion), Benzos.
Sympathomimetic Amphetamine, Cocaine, PCP, Ecstasy Amped Up: Agitation, Mydriasis, Tachycardia, Hyperthermia, Diaphoresis. Benzodiazepines. Avoid beta-blockers (risk of unopposed alpha). Watch for rhabdo, MI, ICH.
Opioid Morphine, Heroin, Fentanyl Depressed mental status, Miosis, Hypoventilation. Naloxone (start 0.2mg), supportive airway.
Serotonin Syndrome SSRIs, MAOIs, TCAs (combination) Triad: Autonomic instability, Neuromuscular rigidity/hyperreflexia/clonus, Altered mental status. Benzodiazepines, Cyproheptadine (antihistamine).
Case 1: 20yo male, agitated, picking at invisible bugs, dilated pupils, dry membranes, flushed face, dry armpits. → Anticholinergic toxidrome.
Case 2: 56yo farmer, vomiting, drooling, lacrimation, miosis, urine/diarrhea soliage. → Cholinergic toxidrome.
Case 3: 23yo M, agitated, combative, hallucinating, tachycardic, tachypneic, diaphoretic, fever. → Sympathomimetic toxidrome.

4. Principles of Management

Concepts

  • Toxicodynamics: What poison does to body (mechanism).
  • Toxicokinetics: What body does to poison (ADME).

Management Based on Toxicokinetics

  1. Alter Absorption (Decontamination):
    • Activated Charcoal (dose, binding, aspiration risk).
    • Gastric lavage (risk of aspiration/perforation).
    • Whole Bowel Irrigation (maybe).
    • Ipecac - NO.
  2. Administer Antidote (See table below)
  3. Basics: ABCs, Poison Control Center, ECG, ABG, Blood chem (Anion/Osm gap), drug screens (APAP, ASA).
  4. Change Catabolism: e.g., Fomepizole (ADH inhibitor), Ethanol, NAC, Sodium thiosulfate.
  5. Distribute Differently: e.g., DigiFab (digoxin), Deferoxamine (iron), HBOT (CO), Dimercaprol (heavy metals).
  6. Enhance Elimination:
    • Urinary Alkalinization (NaHCO3 for salicylates, phenobarbital).
    • Hemodialysis/Hemoperfusion (for small Vd, low MW, low protein bound toxins: salicylate, methanol, ethylene glycol, lithium, theophylline).

Also Read Basic Toxicology

Common Antidotes

  • Opiates: Naloxone
  • Benzodiazepines: Flumazenil
  • Acetaminophen: N-acetylcysteine (NAC)
  • Organophosphates: Atropine + Pralidoxime
  • Iron: Deferoxamine
  • Lead: DMSA
  • Methemoglobinemia: Methylene Blue
  • Methanol/Ethylene Glycol: Fomepizole or Ethanol
  • Isoniazid (INH): Pyridoxine (B6)
  • Digoxin: Digibind (Digoxin Immune Fab)
  • Cyanide: Sodium nitrite + Sodium thiosulfate

5. Specific Poison Highlights

Tricyclic Antidepressants (TCAs)

Mechanism: Na+ channel blockade (wide QRS), Anticholinergic, Alpha blockade (hypotension), GABA inhibition (seizures), K+ channel blockade (long QT).

ECG: Wide QRS, long QT, prominent terminal R wave in aVR.

Treatment: NaHCO3 for wide QRS, IVF/vasopressors, Intralipid, Benzos for seizures.

Digoxin/Cardiac Glycosides

Sources: Digoxin, Foxglove, Oleander, Cerbera manghas.

Mechanism: Inhibits Na-K-ATPase → ↑ intracellular Ca2+, ↑ vagal tone.

Symptoms: Bradycardia, heart blocks, ventricular arrhythmias (VPC, VT, VF), hyperkalemia.

Treatment: Digibind (acute: 10 vials, chronic: 1-2 vials). Avoid calcium in hyperkalemia (can worsen arrhythmias).

Important Considerations:
• Multiple drug ingestion is common.
• Some drug combinations are dangerous.
• One drug may mask another's effects.
• Rule out intracranial bleeding or metabolic coma mimicking poisoning.

6. Summary & Key Principles

  1. Start with ABCs and supportive care (mainstay of management).
  2. Identify toxidrome from history and physical exam.
  3. Use toxicokinetic principles to guide decontamination, antidote use, and elimination enhancement.
  4. Antidote use must be individualized to toxin and patient condition.
  5. Avoid procedures (like aggressive decontamination) that may cause complications without clear benefit.
  6. If unable to identify toxin, re-evaluate and continue supportive resuscitation.