Intro & PK Basics - Toxin Tango
- Defs: Toxicology (poisons), Poison (harm), Toxin (biogenic), Overdose (>dose).
- Routes: Ingestion, Inhalation, Dermal, Parenteral.
- Toxicokinetics (ADME):
- Absorption: GI factors (pH, motility, area, food).
- Distribution: Vd (↑Vd = tissue bound, poor hemodialysis).
- Metabolism: Liver. Phase I (CYP450: redox, hydrolysis), II (conjugation). Toxic metabolites (paracetamol→NAPQI).
- Excretion: Renal (ion trapping: $pH = pKa + log([A-]/[HA])$), Hepatic.
⭐ Zero-order kinetics (constant amount/time elimination) with 📌 Phenytoin, Ethanol, Aspirin (PEA).
Clinical Approach - Spotting Syndromes
- Initial Approach:
- ABCDEs (see flowchart).
- Monitor vital signs, check glucose, administer O2.
- Focused History:
- AMPLE (Allergies, Medications, Past Hx, Last meal, Events).
- Collateral history, pill bottles/substances.
- Clinical Examination:
- Pupils (size, reactivity).
- Skin (temp, moisture, color).
- Odor (breath).
- Neuro status (mental status, seizures).
- Key Investigations:
- ECG (QRS, QT intervals).
- ABG (acid-base status).
- Osmol gap.
- Anion gap: $AG = Na^+ - (Cl^- + HCO_3^-)$ (Normal 8-12 mEq/L).
- Toxicology screen (note limitations).
Toxidromes Table
| Toxidrome | Agents (e.g.) | CNS | Pupils | Vitals (HR,BP,RR,T) | Skin | Bowel Sounds | Key Sign(s) / Mnemonic |
|---|---|---|---|---|---|---|---|
| Opioid | Heroin, Fentanyl | Depression | Miosis | ↓ All | Cool, dry | ↓ | Respiratory depression |
| Sympathomimetic | Cocaine, Amphetamine | Agitation | Mydriasis | ↑ All | Diaphoretic | ↑ | Seizures, tremors |
| Cholinergic | Organophosphates | Confusion | Miosis | Variable | Diaphoretic | ↑ | 📌 SLUDGEM |
| Anticholinergic | Atropine, TCAs | Delirium | Mydriasis | ↑HR,↑BP,↑T; N RR | Hot, dry, red | ↓ | 📌 "Mad as a hatter, Blind as a bat, Red as a beet, Hot as a hare, Dry as a bone" |
| Sedative-Hypnotic | Benzodiazepines | Depression | Variable | ↓ All | Cool, dry | ↓ | Ataxia, slurred speech |
Decontamination & Elimination - Kick Toxins Out
1. GI Decontamination: Reduce absorption.
- Activated Charcoal (AC): Dose 1 g/kg (ideally <1 hr).
- Ineffective: Metals (Fe, Li), alcohols, corrosives, hydrocarbons, cyanide.
⭐ Activated charcoal is ineffective for metals (iron, lithium), alcohols, corrosives, hydrocarbons, and cyanide.
- Gastric Lavage: Limited: Life-threatening ingestion <1 hr, toxin not AC-bound. Risks: Aspiration.
- Whole Bowel Irrigation (WBI): PEG. For body packers, Fe, Li, SR preps.
2. Enhanced Elimination: Remove absorbed toxin.
- Multiple Dose AC (MDAC): "Gut dialysis".
- Indications: 📌 "PD CQT" (Phenobarbital, Dapsone, Carbamazepine, Quinine, Theophylline).
- Forced Diuresis: Alkaline (salicylates, phenobarbital). Limited use, risks.
- Hemodialysis/Hemoperfusion: Severe poisoning, dialyzable toxins.
- Indications: 📌 "I STUMBLE" (Isopropanol, Salicylates, Theophylline, Urea, Methanol, Barbiturates (long), Lithium, Ethylene glycol).
Specific Antidotes - Heroic Helpers
| Toxin | Antidote | Mechanism / Key Dose |
|---|---|---|
| Paracetamol | N-acetylcysteine (NAC) | Glutathione precursor. Load: 150 mg/kg IV. |
| Opioids | Naloxone | Competitive opioid antagonist. 0.4-2 mg IV, repeat. |
| Benzodiazepines | Flumazenil | GABA-A receptor antagonist. 0.2 mg IV, titrate. |
| Organophosphates | Atropine & Pralidoxime (2-PAM) | Atropine (muscarinic antag.); 2-PAM (AChE reactivator). |
| Methanol/Ethylene Glycol | Fomepizole / Ethanol | Inhibits alcohol dehydrogenase. Fomepizole: 15 mg/kg load. |
| Cyanide | Hydroxocobalamin / Na Thiosulfate + Na Nitrite | Binds CN / MetHb formation & sulfur donor. |
| Iron | Deferoxamine | Chelates iron. Max 15 mg/kg/hr IV. |
| Digoxin | Digoxin Fab antibodies | Binds free digoxin. Dose based on ingestion/serum level. |
| Beta-blockers | Glucagon | $↑\text{cAMP}$, bypasses $\beta$-receptors. 5-10 mg IV. |
| Ca Channel Blockers | Calcium / High-dose insulin | CaCl$_{2}$/gluconate; Insulin euglycemia therapy (HIE). |
| Heavy Metals (Pb,As,Hg) | DMSA, Dimercaprol, Penicillamine | Chelating agents bind metals. |
High‑Yield Points - ⚡ Biggest Takeaways
- Prioritize Airway, Breathing, Circulation, Disability, Exposure (ABCDE) in all poisoned patients.
- Decontamination (e.g., activated charcoal within 1 hour) is crucial but has contraindications.
- Enhanced elimination techniques (e.g., hemodialysis) are reserved for severe, specific poisonings.
- Accurate history, including collateral, and toxidrome identification guide management.
- Timely administration of specific antidotes (e.g., naloxone, N-acetylcysteine) is vital.
- Utilize anion gap and osmolar gap calculations for diagnostic clues in unknown ingestions.
- Supportive care remains the cornerstone of management for most poisonings.
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