Chem 14.1

• Toxicology


  One of the special areas of clinical chemistry
• Why study clinical toxicology

  • We encounter poison or toxic substances every day
  • Medications, prescription drugs, and even simple antihistamines can become toxic
  • Alcohol can be tested in the clinical laboratory
  • Even water can be intoxicating due to hyponatremia
  • Toxic substances are not limited to liquids, can also be poisonous gases, elements, venoms, and plants
• Toxicology


  A branch of pharmacology that deals with the adverse effects of chemical, physical, or biological agents on living organisms and the ecosystem, including the prevention and amelioration of such effects
• Classification of terms


  • Poison (exogenous substances)
  • Toxins (endogenous substances)
  • Xenobiotics (substances not normally found in or produced by an organism)
• Not all poisons are xenobiotics, and not all xenobiotics are poisons. Toxins are xenobiotics when introduced to a different species.
• Paracelsus - Father of toxicology
• Pharmacokinetics

  How a drug travels inside the body and reaches its target organs
• Pharmacodynamics


  Interaction between the chemical/drug and its molecular receptor
• Major areas of toxicology

  • Mechanistic
  • Descriptive
  • Regulatory
  • Environmental
  • Forensic
  • Clinical
• "Everything is poison; there is nothing which is not. Only the dose differentiates a poison" - Paracelsus
• Quantal dose-response curve


  Blue area - Therapeutic dose (ED50 - 50% of population exhibits therapeutic effects)

  Red area - Lethal dose (LD50 - Lethal dose that kills 50% of animals)
• Therapeutic Index (TI) / Therapeutic Window


  Allowable concentration of the drug to be used for therapeutic purposes
• Toxidromes


  A constellation of findings, either from the physical examination or from ancillary testing, which may result from any poison
• Toxicants of interest


  • Toxic elements (mercury, lead, arsenic)
  • Alcohols
  • Carbon monoxide
  • Drugs of abuse
  • Therapeutic drugs
• Ethanol


  Most widely abused substance worldwide, found in liquors
• Ethanol metabolism


  Ethanol → Acetaldehyde

  Acetaldehyde → Acetic acid
• Clinical significance of ethanol

  • CNS effects can lead to coma and death

  Liver damage

  Macrocytic anemia due to vitamin B9 deficiency

  Wernicke-Korsakoff syndrome

  Fetal alcohol syndrome

  Cardiovascular diseases
• Isopropanol


  Found mostly as a rubbing alcohol, can cause accidental ingestion especially in children
• Isopropanol metabolism


  Isopropanol → Acetone
• Clinical significance of isopropanol

  • CNS effects more prolonged than ethanol
• Methanol


  Found mostly as a solvent/fuel additive, cases are due to accidental ingestion
• Methanol metabolism


  Methanol → Formaldehyde

  Formaldehyde → Formic Acid
• Clinical significance of methanol

  • Blindness (can be irreversible)

  CNS effects
• Ethylene glycol


  Found mostly in antifreeze agents, detergents, paints, and cosmetics, has a sweet taste leading to accidental ingestion by children
• Ethylene glycol metabolism


  Ethylene Glycol → Glycolaldehyde → Glycolic Acid + Glyoxic Acid + Oxalic Acid
• Clinical significance of ethylene glycol

  • Oxalic acids will precipitate into Calcium Oxalate crystals

  CNS effects

  Renal tubular damage

  Tissue damage from Calcium Oxalate crystal precipitation
• Stages of acute alcohol intoxication

  • 0.01-0.05% - Subclinical (sobriety)

  0.03-0.12% - Euphoria

  0.09-0.25% - Excitement

  0.18-0.30% - Confusion

  0.25-0.40% - Stupor

  0.35-0.50% - Coma

  0.45% and above - Death
• Methanol


  Used for fixing blood smears
• Ethylene Glycol


  • Found mostly on antifreeze agents, detergents, paints, and cosmetics
  • Has a sweet taste
  • Most commonly ingested accidentally by children due to its sweet taste
• Oxalic Acid


  • Will precipitate into Calcium Oxalate crystals
  • Causes CNS Effects
  • Causes Renal Tubular Damage
  • Causes Tissue Damage
• Stages of Acute Alcohol Intoxication

  • Subclinical (Sobriety)
  • Euphoria
  • Excitement
  • Confusion
  • Stupor
  • Coma
  • Death
• Blood Alcohol Concentration


  Percentage of alcohol in the blood by volume
• CNS Influence


  The effect of alcohol on the central nervous system
• Clinical Signs/Symptoms

  The observable effects of alcohol intoxication
• There is an overlap in the concentration but it differs in the upper limit
• Preanalytical Considerations for Alcohol Testing

  • Serum is preferred over whole blood
  • Sample must be kept capped
  • Sodium Fluoride may be used as a preservative
• Spectrophotometric Determination of Ethanol

  1. Uses Ethanol-specific Alcohol Dehydrogenase and NAD+

  2. End-product is Acetaldehyde and NADH

  3. NADH (proportional to Ethanol) is measured at 340 nm
• Interferants in Spectrophotometric Ethanol Determination

  • Lactate and LDH
• Breath Test for Alcohol

  • Alcohol in Capillary Alveolar Blood Equilibrates with Alveolar air in a ratio of 2300:1
  • Commonly performed using Infrared Absorption Spectrometry
• Ethanol Biomarkers


  • Ethyl Glucuronide
  • Ethyl Sulfate
  • Phosphatidylethanol