General Principles of Toxicology

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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

ToxidromeAgents (e.g.)CNSPupilsVitals (HR,BP,RR,T)SkinBowel SoundsKey Sign(s) / Mnemonic
OpioidHeroin, FentanylDepressionMiosis↓ AllCool, dryRespiratory depression
SympathomimeticCocaine, AmphetamineAgitationMydriasis↑ AllDiaphoreticSeizures, tremors
CholinergicOrganophosphatesConfusionMiosisVariableDiaphoretic📌 SLUDGEM
AnticholinergicAtropine, TCAsDeliriumMydriasis↑HR,↑BP,↑T; N RRHot, dry, red📌 "Mad as a hatter, Blind as a bat, Red as a beet, Hot as a hare, Dry as a bone"
Sedative-HypnoticBenzodiazepinesDepressionVariable↓ AllCool, dryAtaxia, 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

ToxinAntidoteMechanism / Key Dose
ParacetamolN-acetylcysteine (NAC)Glutathione precursor. Load: 150 mg/kg IV.
OpioidsNaloxoneCompetitive opioid antagonist. 0.4-2 mg IV, repeat.
BenzodiazepinesFlumazenilGABA-A receptor antagonist. 0.2 mg IV, titrate.
OrganophosphatesAtropine & Pralidoxime (2-PAM)Atropine (muscarinic antag.); 2-PAM (AChE reactivator).
Methanol/Ethylene GlycolFomepizole / EthanolInhibits alcohol dehydrogenase. Fomepizole: 15 mg/kg load.
CyanideHydroxocobalamin / Na Thiosulfate + Na NitriteBinds CN / MetHb formation & sulfur donor.
IronDeferoxamineChelates iron. Max 15 mg/kg/hr IV.
DigoxinDigoxin Fab antibodiesBinds free digoxin. Dose based on ingestion/serum level.
Beta-blockersGlucagon$↑\text{cAMP}$, bypasses $\beta$-receptors. 5-10 mg IV.
Ca Channel BlockersCalcium / High-dose insulinCaCl$_{2}$/gluconate; Insulin euglycemia therapy (HIE).
Heavy Metals (Pb,As,Hg)DMSA, Dimercaprol, PenicillamineChelating 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.

Practice Questions: General Principles of Toxicology

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A farmer with pinpoint pupils, increased secretions and urination. What is the most likely diagnosis?

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Flashcards: General Principles of Toxicology

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Lactic acidosis type _____ is seen without anaerobic state, due to drug use, drug toxicity or DM, renal failure etc.

TAP TO REVEAL ANSWER

Lactic acidosis type _____ is seen without anaerobic state, due to drug use, drug toxicity or DM, renal failure etc.

B

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