Toxicology

• Pharmacology

  The study of the effects of drugs on the body
• Toxicology

  The study of the harmful effects of substances on the body
• Physical exam findings that may occur due to the toxicity of

  • Opioids
  • Aspirin
  • Beta blockers
  • Anticholinergic substances
• Toxicokinetics


  Absorption, distribution, excretion, and metabolism of toxins, toxic doses of therapeutic agents, and their metabolites
• Toxicodynamics

  The injurious effects of these substances on body functions
• Bioavailability is a component of absorption
• Protein binding and lipophilicity are components of distribution
• CYPs and clearance are components of metabolism
• Renal, hepatic, and clearance are components of excretion
• How a patient can die from toxicity

  • CNS depression
  • Cardiovascular toxicity
  • Cellular hypoxia
  • Seizures
  • Other organ failure
• Initial Management

  1. Airway

  2. Breathing

  3. Circulation

  4. Dextrose
• History

  What was ingested? Medication/substance bottles nearby? What environment was the patient found in?
• Physical Exam

  Vital signs, blood pressure, pulse, respiratory rate, eyes, mouth, skin, abdomen, nervous system
• Toxicologic Labs

  • Blood gases
  • Electrolytes
  • Renal function tests
  • Osmolality
  • EKG
  • Drug screen
• Drug screens are not clinically useful due to false positives/negatives
• Toxicologic Treatment

  1. Decontamination/Elimination

  2. Hemodialysis

  3. ECMO
• Activated charcoal

  Decreases absorption of xenobiotic through adsorption
• Whole bowel irrigation


  Minimizes absorption through decreased transit time
• Orogastric lavage

  Removes substance from stomach
• Hemodialysis


  Removes toxins from the blood for patients without kidney function, who ingest more than kidneys can handle, or who ingest a severe substance warranting faster elimination
• ECMO supports hemodynamic (heart/lung) function while the body eliminates/metabolizes the toxin
• Opioids

  Heroin, morphine, oxycodone, hydrocodone
• Opioids

  • Central pain analgesia through mu receptors
  • Pinpoint pupils
  • Decreased bowel sounds
  • Decreased mental status
  • Depressed respiration
• Naloxone

  Opioid antagonist
• Naloxone

  Competes with opioids at the opioid receptor
• Acetaminophen

  Treats pain, fever
• Acetaminophen pharmacology/pharmacokinetics

  • Onset of clinical efficacy/peak: < 1 hour
  • Duration of clinical efficacy: 4-6 hours
• Acetaminophen toxicokinetics

  • Toxic level of acetaminophen ingested may be 24 hours without symptoms
  • 24-36 hours liver injury appears
  • 36 hours – days multisystem organ failure death
• 4 hour acetaminophen serum drug level obtained to decide to give antidote
• Antidote best given within 8 hours of acetaminophen ingestion
• NAPQI

  Toxic metabolite of acetaminophen
• Glutathione

  Endogenous antidote to NAPQI
• 1. Acetylcysteine

  Exogenous antidote to NAPQI
• Aspirin doses

  • 81mg - 325mg (anti-platelet effects)
  • 325mg - 650mg (pain relief)
  • Excessive amounts (toxicity)
• Aspirin toxicity

  • Tinnitus
  • Respiratory alkalosis
  • Uncoupling oxidative phosphorylation
  • Metabolic acidosis
  • Respiratory acidosis
• Aspirin pharmacology

  • Onset: < 1 hour
  • Duration: 4-6 hours (pain) days (antiplatelet)
  • Absorption: rapidly
  • Time to peak: 1 - 2 hours
• Aspirin toxicology

  • Onset: immediate to delayed
  • Duration: days
  • Absorption: rapid - extreme delay
  • Time to peak: variable
• Sodium bicarbonate

  Alkalinizes serum, urine to "trap" ionized aspirin in lumen of nephron to facilitate excretion
• Beta blockers

  • Beta-1, Beta-2, Alpha-1 effects
  • Exacerbation of direct pharmacology
  • Discovery of new receptor pathways not seen at therapeutic doses
  • Bradycardia, hypotension, other arrhythmias, seizures
• Beta blocker antidote

  Give beta agonist