Toxicology Resource: Antidotes, Doses, and Available Preparations

1. Introduction to Toxicology

• Definition: Toxicology is the study of the harmful effects of substances on living organisms.

• Branches of Toxicology:

  • Clinical Toxicology: The study of the effects of poisons on humans.

  • Environmental Toxicology: The study of environmental contaminants.

  • Forensic Toxicology: The study of poisons for legal purposes.

• Common Routes of Exposure:

  • Ingestion, inhalation, dermal contact, injection, and eye contact.

• Factors Influencing Toxicity: Dosage, age, sex, health condition, route of exposure, and genetic factors.

2. Classification of Toxic Substances

• Drugs and Medications (e.g., opioids, benzodiazepines)

• Pesticides and Herbicides

• Heavy Metals (e.g., lead, mercury, arsenic)

• Industrial Chemicals (e.g., chlorine, ammonia)

• Biological Toxins (e.g., botulinum toxin, ricin)

• Environmental Pollutants (e.g., carbon monoxide, radon)

Common Antidotes in Toxicology

Toxin	Toxic Dose	Antidote	Mechanism of Action	Route & Dosage of Antidote	Available Preparations
Acetaminophen (Paracetamol)	>150 mg/kg (acute) or prolonged use (chronic toxicity)	N-acetylcysteine (NAC)	Restores glutathione, detoxifies toxic metabolite	Oral: 140 mg/kg loading dose, followed by 70 mg/kg every 4 hours for 17 doses. IV: 150 mg/kg loading dose, followed by 50 mg/kg and 100 mg/kg every 4 hours	Oral suspension, IV solution
Organophosphates (Pesticides)	Varies by compound; 1-5 mg/kg can be lethal	Atropine & Pralidoxime	Atropine blocks muscarinic effects, pralidoxime reactivates acetylcholinesterase	Atropine IV: 1–2 mg initially, repeat every 5–15 minutes until symptoms resolve. Pralidoxime IV: 1-2 g initially, repeat after 30 minutes if symptoms persist	IV solutions
Cyanide	>0.5 mg/kg (oral or inhalation)	Sodium nitrite & Sodium thiosulfate	Forms methemoglobin, binds cyanide	Sodium Nitrite IV: 300 mg bolus Sodium Thiosulfate IV: 12.5 g after sodium nitrite	IV solutions
Opioids	>0.1 mg/kg (depending on opioid type, lethal doses vary)	Naloxone (Narcan)	Competitive antagonist at opioid receptors	IV/IM/SubQ: Start with 0.4–2 mg, repeat every 2–3 minutes if needed (higher doses for potent opioids)	Injectable (IV, IM, SubQ), nasal spray
Methanol / Ethylene glycol	Methanol: >30-50 mL (pure), Ethylene glycol: >100 mL (pure)	Fomepizole or Ethanol	Inhibit alcohol dehydrogenase, prevent toxic metabolites	Fomepizole IV: 15 mg/kg loading dose, followed by 10 mg/kg every 12 hours. Ethanol IV: 10 mg/kg loading dose, then 1.5 mg/kg every hour	IV solutions (fomepizole), ethanol solution
Iron	>40 mg/kg (acute)	Deferoxamine (Desferal)	Binds free iron to prevent organ damage	IV/IM: 15 mg/kg every 4–6 hours, up to 24 hours depending on iron level	IV solution, IM formulation
Digoxin	>3 ng/mL (serum concentration)	Digoxin-specific antibody (ovine-derived)	Binds and neutralizes digoxin	IV: Administer bolus doses based on severity, generally 1–3 vials (total dose varies)	IV solution (ovine-derived)

Notes on Toxic Doses:

• Acetaminophen: Toxicity can be seen in children with ingestions greater than 150 mg/kg, and the threshold varies for chronic toxicity.

• Organophosphates: Toxic doses can vary depending on the specific chemical. Low to moderate doses (1–5 mg/kg) can cause significant toxicity or death, especially in the case of highly toxic organophosphates.

• Cyanide: Exposure to cyanide at doses above 0.5 mg/kg is potentially lethal, particularly if inhaled or ingested in concentrated forms.

• Opioids: Lethal doses depend on the opioid involved. For example, fentanyl is extremely potent, with toxic effects from as little as 0.1 mg.

• Methanol and Ethylene Glycol: Toxicity is observed after ingestion of amounts greater than 30-50 mL (methanol) or 100 mL (ethylene glycol) of pure substance.

• Iron: Acute iron poisoning occurs in doses greater than 40 mg/kg of elemental iron, and children are particularly susceptible.

• Digoxin: Serum digoxin concentrations above 3 ng/mL indicate toxicity, but clinical symptoms often appear with lower levels depending on the individual.

Dosing of Antidotes:

• N-acetylcysteine (NAC): For acetaminophen toxicity, NAC should be administered within 8–10 hours of ingestion for maximum benefit.

• Atropine & Pralidoxime: In organophosphate poisoning, atropine should be given promptly to counteract cholinergic symptoms, and pralidoxime should follow for cholinesterase reactivation.

• Naloxone (Narcan): Opioid overdoses are usually treated with naloxone, which may require repeated doses, especially in cases involving potent opioids like fentanyl.

• Sodium nitrite & Sodium thiosulfate: Used together in cyanide poisoning, these antidotes act by neutralizing cyanide toxicity and enhancing detoxification.

• Fomepizole or Ethanol: Used for methanol and ethylene glycol poisoning, either of these antidotes blocks the enzyme alcohol dehydrogenase, preventing the production of toxic metabolites.

• Deferoxamine: Administered for iron toxicity to bind and excrete excess iron through urine.

These antidote doses and toxic doses are general recommendations and may vary based on patient condition, age, and weight. Always follow institutional protocols or consult toxicology experts for specific cases.