Toxicology Principles in the Management of Acute Poisonings

Intentional and Unintentional Exposures

• In 2004, approximately 84% of reported poisonings (2 million cases) resulted from unintentional exposures to chemicals.

• Approximately 200 deaths resulted from these unintentional exposures.

• Categories of unintentional exposures include:

  • Therapeutic error and misuse.

  • Animal bites and stings.

  • Food poisonings.

  • Occupational and environmental exposures.

  • Adverse reactions.

  • Unspecified exposures.

• Intentional exposures resulted in less than 20% of reported poisonings, but over 900 deaths occurred.

• Intentional exposure to non-clinically important chemicals for the purpose of obtaining a “high” is a significant public health concern.

Common Substances Involved in Human Exposures (2011)

• The top 5 substance classes most frequently involved in all human exposures in 2011 were:

  • Analgesics (medicines used to relieve pain) (11.7%).

  • Cosmetics/personal care products (8.0%).

  • Household cleaning substances (7.0%).

  • Sedatives/hypnotics/antipsychotics (6.1%).

  • Foreign bodies/toys/miscellaneous (4.1%).

Toxicology Principles in Acute Poisoning Management

• Basic principles of toxicology are crucial in the management of individuals who have become ill from chemicals through intentional or unintentional exposures.

• Important toxicological principles applied in evaluating poisoned individuals include:

  • Exposure and aspects related to reducing absorption.

  • Dose–response considerations.

  • Target tissue and systemic effects.

  • Chemical interactions.

  • Chemical antagonism as a management approach.

  • Acute versus chronic effects.

Reducing Toxicant Absorption

• Absorption is necessary for systemic toxicity.

Respiratory Exposures

• The only ways to reduce absorption are by eliminating the chemical from the breathing zone or shortening the exposure time.

Dermal Exposures

• Absorption of chemicals spilled onto the skin can often be reduced.

• The extent of absorption depends on:

  • The nature of the chemical (e.g., lipid vs. water solubility).

  • Concentration of the chemical.

  • Duration of contact time.

Example: Organophosphate Pesticide Spill

• Washing skin with soap and water as quickly as possible after a spill of a residential-use organophosphate pesticide formulation reduces skin absorption.

• This is especially important for undiluted liquids from the product container and for solid preparations.

• Shortened exposure time coupled with dilution reduces the amount absorbed.

• This process is commonly referred to as “decontamination.”

Oral Consumption

• Reduction of absorption may be accomplished (depending on the chemical) through:

  • Gastric lavage: Used when a patient has ingested life-threatening amounts of a toxic agent up to 1–2 hours previously.

    • Not used for corrosive substances because of increased risk of esophageal and gastric perforations.

    • Not used for petroleum compounds because of the risk of chemical pneumonitis.

  • Activated charcoal: Often used to limit further absorption because it adsorbs a wide variety of drugs and toxic agents, if given within an hour or two of ingestion.

    • Effective for many pharmaceuticals (e.g., aspirin, paracetamol, digoxin, phenobarbitone, and theophylline) as well as many non-pharmaceutical chemicals.

  • Charcoal hemoperfusion: May be a clinical option for chemicals already absorbed into the blood in severe cases of intoxication.

Reducing Toxicity by the Use of an Antidote

• Antidote: Clinical treatment using a chemical(s) to counteract the effects of another.

• Can only be developed upon a thorough understanding of the toxicokinetics and toxicodynamics of the offending agent.

• Because a potential antidote may have additional risks associated with its use, the toxicological properties must be determined as well.

• The ultimate therapeutic goal is to reduce toxicity by interacting with the toxicant in ways that:

  • Directly inhibit its effect through modification of its chemical properties.

  • Inhibit its effect by altering its physical properties.

  • Reduce effects at its sites of action.

  • Facilitate its elimination.

  • Provide for replacement of endogenous protective (e.g., glutathione) or required (e.g., oxygen) chemicals.

Examples of Common Poisonings and Their Antidotes

• Acetaminophen: N-acetylcysteine

• Anticholinergics: Physostigmine

• Benzodiazepines: Flumazenil

• Beta blockers: Glucagon

• Calcium channel blockers: Calcium, glucagon

• Carbamates: Atropine

• Carbon monoxide: Oxygen

• Cyanide: Sodium nitrite/sodium thiosulfate

• Ethylene glycol: Ethanol, fomepizole

• Heavy metals: DMSA, BAL, CaEDTA, penicillamine

• Iron: Deferoxamine

• Lead: DMSA, BAL, CaEDTA, penicillamine

• Methanol: Ethanol, fomepizole

• Nitrates/nitrites: Methylene blue

• Opiates: Naloxone

• Organophosphates: Atropine, pralidoxime

• Snakes (pit viper): Crotalidae antivenin, CroFab