TDM LAB

• Toxicology


  Study of substances or poisons toxic to the body
• Substances/poisons


  Chemical or physical agents that produce adverse effects of xenobiotics in humans or responses to biological organisms
• Toxic

  Can be toxic if administered in a dose that could disturb the normal physiological homeostasis of the body
• Indications of toxicology


  • Mechanistic
  • Descriptive
  • Regulatory
  • Forensic
  • Clinical
  • Environmental
• Sources of toxins


  • Chemical source
  • Plant source
  • Animal source
• Sites of toxic actions

  • Local (Non specific)
  • Remote (Systemic)
  • Local and Remote
• Duration and frequency of exposure

  • Acute
  • Sub-acute
  • Chronic
• Types of toxic mechanism

  • Direct
  • Indirect
• Classifications of toxic agents

  • According to the target organ
  • According to their use
  • According to source
  • According to their effect
  • According to physical state
  • According to their chemistry
  • According to their poisoning potentiality
  • According to their biochemical mechanisms of action
• Factors affecting action of poison

  • Factors related to the poison
  • Factors related to the individual
  • Factors related to mode of exposure
  • Factors related to environment
• Forensic toxicology


  Concerns with the detection and estimation of poisons for legal purposes
• Xenobiotics


  Defined as an exogenous substance that may have adverse effects on living organisms
• Toxins


  Biologically synthesized either living or in microorganism
• Poisons


  Term used in describing animals, plant, mineral, or gas poisons
• Qualitative methods of analysis

  • Color test
  • Chemical test
• Quantitative methods of analysis

  • Thin layer chromatography
  • GCMS
  • HPLC
  • Immunoassays
• Heavy metal toxicity can be acute or chronic and may be caused by lead, mercury, iron, arsenic, cadmium, thallium, bismuth
• Lead poisoning


  Initially distributed to the soft tissues and slowly redistributed to bone, teeth and hair. Detected by x-ray. Half-life: 1-2 months in blood; 20-30 yr. bone. Treated with chelation therapy.
• Mercury poisoning


  Tremors, depression, memory loss, decreased verbal skills and inflammation of the kidneys. Exposure to inorganic salts of mercury leads to renal damage. Consumption of food contaminated with methyl-mercury causes organic mercury toxicity.
• Arsenic poisoning


  Inhibits sulfhydryl enzymes throughout the body. Crosses the placenta. High affinity to thiol groups in proteins. Symptoms: Headache, confusion, severe diarrhea & drowsiness. Antidote: British anti-Lewisite (BAL).
• Iron poisoning


  Toxicity causes hemosiderosis and hemochromatosis. Toxic effect due to hemorrhagic necrosis in GIT.
• Chelation therapy


  Chelation agent plus metal = chelate. A chelating agent is a chemical compound or drug molecule capable of forming a heterocyclic ring with a metal ion as its closing member.
• Antidotes for metals


  • Lead: Dimercapto succinic acid, Calcium disodium edetate
  • Mercury, Arsenic, Gold: Dimercaprol
• Symptoms of poisoning


  • Headache
  • Confusion
  • Severe diarrhea
  • Drowsiness
• As poisoning develops


  • Convulsions
  • Changes in fingernail pigmentation called leukonychia
• Use for long term exposure

  1. Hair

  2. Nails as specimen for "mees line"
• Chronic exposure


  • Vitamin A deficiency
  • Heart disease
  • Night blindness
• Indication of poisoning


  "Odor of garlic" breath and metallic taste
• Antidote


  British anti-Lewisite (BAL)
• Method


  • Reinsch Test
  • AAS
• Iron is a vital mineral in the human body
• Iron toxicity


  • Causes hemosiderosis and hemochromatosis
• Iron toxic serum levels

  • Mild toxicity: 450-500 ug/dL
  • Severe toxicity: 800-1000 ug/dL
• Toxic effect of iron

  Hemorrhagic necrosis in GIT
• Chelation therapy


  Chelation agent plus metal = chelate
• Chelating agent


  Chemical compound or drug molecule capable of forming a heterocyclic ring with a metal ion as its closing member
• Antidotes for metals


  • Lead: Dimercapto succinic acid, Calcium disodium edetate
  • Mercury, Arsenic, Gold: Dimercaprol
  • Iron: Deferoxamine
  • Copper/Mercury: Penicillamine
  • Cyanide: Sodium nitrite, Sodium thiosulfate, Amyl Nitrite pearls
• Carbon monoxide


  Produced by incomplete combustion of carbon-containing substances
• Sources of carbon monoxide

  • Improperly ventilated furnaces
  • Wood or plastic fire
  • Rubber
  • Cigarette smoking
• Effect of CO


  • CO binds with heme proteins (cytochromes, Hgb and myoglobin)
  • CO + Cytochrome A3 results in inhibition of cellular respiration and electron transport
  • CO + Hgb (myoglobin) reduces oxygen supply to cardiac and skeletal muscles or direct muscle damage