Comprehensive Notes on Poison Metabolism and Toxicity

Learning Objectives

  • Students should be able to:
    • Identify different routes of poisoning.
    • Understand how poisons are absorbed, metabolized, and eliminated from the body.
    • Recognize factors that affect poisoning in humans.

Routes of Administration of Poisons

Types of Routes
  • Ental: Absorption through the gastrointestinal tract mucosa.
    • Oral
    • Sublingual
    • Rectal
  • Par-Ental: Includes areas besides the ental route.
    • Subcutaneous
    • Intramuscular
    • Intravenous
    • Intra-arterial
    • Intra-thecal
    • Intra-peritoneal
    • Intra-amniotic
  • Inhalational Route: Absorption via lungs; high blood supply and thin air-blood barrier enhance toxicity.
  • External Application: Absorbed through the skin into systemic circulation.
  • Instillation: Direct absorption through mucous membranes in organs like eyes and ears.
  • Administration in Orifices: Rapid drug transfer via rectum/vagina/nose through thin membranes.

Absorption and Effects of Poisons

Before Absorption
  • Local effects such as irritation or corrosion at the site of introduction.
  • Possible vomiting due to local irritation; remaining poison in the stomach gets absorbed into the blood.
After Absorption
  • Poisons are dealt with in various ways:
    • Biotransformation occurs predominantly in the liver.
    • Drugs/metabolites act on target organs based on affinity.
Excretion
  • Main routes of excretion: urinary tract, intestines, bile, sweat glands, saliva, breast milk, lungs.

Factors Affecting Toxicity

  • Dose:
    • High doses: Quick action leading to severe effects.
    • Moderate doses: Cause acute poisoning.
    • Low doses: May lead to chronic poisoning on repeated exposure.
  • Physical State of Poison:
    • Gaseous/volcanic poisons are quickly absorbed.
    • Liquid poisons act faster than solids.
    • Example: Rati seeds have higher potency when crushed.
  • Chemical Composition:
    • Pure substances like arsenic or mercury are less toxic than their soluble salts.
  • Concentration: Concentrated forms are absorbed faster and are more fatal.
  • Presence of Food: Food can dilute poisons and protect stomach walls; absorption is faster on an empty stomach.
  • Age Factors: Tolerance levels vary across age groups; children may react more severely than adults to certain drugs.

Metabolism of Poisons

  • Most poisons/drugs are metabolized into less toxic compounds in the liver and excreted via kidneys.
  • Some metabolized compounds can be more toxic than the original poison (e.g., methanol forms formic acid).
  • Industrial exposure can increase metabolic capacity in workers, often requiring lower doses to see toxic effects.

Cumulative and Tolerance Effects

  • Cumulative Poisoning: Some poisons accumulate in the body (e.g., lead) and may not show effects until reaching high tissue concentrations.
  • Tolerance: Diminished effect occurs through repeated use, as body adapts to drugs (e.g., barbiturates, alcohol).
  • Hypersensitivity: Some persons may have unpredictable adverse reactions to drugs that are otherwise tolerated by the general population.

Interactions Between Substances

  • Synergism: Combined effect of two substances can be greater than their individual effects (e.g. barbiturates and alcohol).
  • Antagonism: One substance can reduce the effects of another (e.g., opium and naloxone).
  • Allergic Reactions: Immune response to substances, with severe effects often occurring upon re-exposure after an initial harmless encounter.