poisons 2

• Methanol


  • "wood alcohol"
  • Denaturant, paint remover, solvent
• Methanol


  • Metabolites: formaldehyde, formic acid

  
• Mechanism of Methanol Toxicity

  1. Toxicity attributed to formate

  2. Cytochrome oxidase inhibition, decreasing ATP production

  3. Increased anaerobic glycolysis

  
• Signs and symptoms of Methanol toxicity


  • Visual disturbances
  • Metabolic acidosis

  
• Methanol Metabolism


  Methanol

  
• Methanol Management


  1. Correction of acidosis

  2. Antidote: Ethanol (IV) or Fomepizole (IV)

  
• Ethylene Glycol


  • 1,2-dihydroxyethane
  • Excreted via kidney

  
• Ethylene Glycol Toxicity


  • Severe metabolic acidosis
  • CNS depression (1st stage)
  • Cardiopulmonary effects (2nd stage)
  • Acute renal failure (3rd stage)
  • Seizures (treat with diazepam, phenytoin)

  
• Ethylene Glycol Metabolism


  Ethylene Glycol

  
• Ethylene Glycol Management


  1. Ethanol

  2. Hemodialysis (with NaHCO3)

  3. Thiamine + pyridoxine

  4. Leucovorin (folinic acid) & folic acid

  5. 4-methylpyrazole (alcohol dehydrogenase inhibitor)

  6. Fomepizole (alcohol dehydrogenase inhibitor)

  7. Calcium source (to counteract CaC2O4 formation)

  
• Ethanol


  "Spiritus rectificatus", Alcohol, USP; Spirits
• Ethanol


  • Fermented grain, fruit juice and honey
  • Wine, beer and liquor
• Ethanol Chemical Properties


  • Colorless aliphatic HC molecule
  • Weakly polar (water and lipid soluble)
• Ethanol Oxidation


  • 7.1 kCal/g
  • Malnourishment occurs
• Ethanol Metabolic Pathway


  Ethanol
• General Mechanisms of Ethanol Toxicity

  • Direct effect on cell membrane fluidity and membrane protein modification
  • Free radicals and ROS formation
  • Formation of phosphatidyl ethanol
  • Formation of FAEEs
  • Mitochondrial dysfunction
• Mechanisms of Ethanol-Induced Organ Toxicity

  • CNS: Ethanol is a CNS depressant, alters neurotransmission
• Clinical Manifestations of Acute Ethanol Toxicity

  • Sedation and relief of anxiety
  • Reduced tension and coordination
  • Impaired concentration and reaction time
  • Tachycardia
  • Severe: Slurred speech, ataxia and altered emotions
• Management of Acute Ethanol Intoxication

  1. Prevent severe respiratory depression and pulmonary aspiration

  2. Glucose for hypoglycemia and ketosis

  3. Electrolyte solution for vomiting (Potassium nutrients) and dehydration

  4. Thiamine, folate and magnesium
• Major Systemic Effects of Chronic Ethanol Consumption


  • Liver: Steatosis, alcoholic hepatitis, cirrhosis, liver cancer
• Management of Chronic Ethanol Intoxication

  1. Disulfiram (most common)

  2. Naltrexone (animal research and clinical experience indicate link between alcohol and opioids, but Naltrexone + Disulfiram is a big no-no)

  3. Nalmefene (under study)

  4. Magnesium, K phosphate, multivitamins and folate

  5. Thiamine for Wernicke-Korsakoff Syndrome

  
• Isopropanol


  • Volatile alcohol with fruity odor and slight bitter taste
  • Present in rubbing alcohol, industrial solvents, paints, disinfectants and drugs
  • Ingested accidentally by nonalcoholics and intentionally by alcoholics
  • 2x more toxic than ethanol, less toxic than methanol
• Isopropanol can cause metabolic acidosis
• Lethal Dose of Isopropanol

  120 mL
• Clinical Manifestations of Acute Isopropanol Toxicity

  • CNS depression: drowsiness, poor balance, staggering gait, slurred speech, poor coordination, sweating, stupor, coma or even death due to respiratory depression
• Management of Acute Isopropanol Toxicity

  1. Supportive: respiratory support and cardiac monitoring

  2. Gastric lavage and hemodialysis
• Formaldehyde


  • Colorless gas with a pungent odor
  • Found in formalin and methanol
  • Preservative, hardening and reducing agent, sterilant and corrosion inhibitor
• Formaldehyde Toxicity Signs and Symptoms


  • Local: mucosal irritation
  • Systemic: CNS depression, coma, metabolic acidosis
• Formaldehyde Management


  1. Generally supportive

  2. Ammonia & NaHCO3
• Acetone


  Nail-polish remover, airplane glue, varnish and rubber cement
• Acetone Toxicity Signs and Symptoms

  • CNS depression: coma, respiratory depression
• Acetone Management


  Milk or water
• Hydrocarbons


  • Mostly derived from petroleum distillation
  • Gasoline, kerosene
  • Toxic due to respiratory tract injury because of aspiration
  • Benzene: acute myeloblastic leukemia; aplastic anemia
• Hydrocarbon Management


  1. Respiratory support

  2. (+) mineral oil
• Cyanide


  • Sources: Prunus, Pear, Apple, Bamboo, Cassava, Lima beans, Linseed, Drugs: Nitroprusside, Laetrile, Nitrites, HCN (gas)
  • Toxic, 70 mg
• Mechanism of Cyanide Toxicity

  1. Inhibits oxidative phosphorylation, inhibits cytochrome oxidase, forces cell to revert to anaerobic metabolism generating excess lactic acid

  2. Primary symptoms: CNS & CVS disturbances, seizure, central respiratory depression

  3. Odor of bitter almonds

  
• Cyanide Management


  1. Removal from source, decontamination, activated charcoal or gastric lavage if ingested recently

  2. Administer cyanide antidote package (amyl nitrite, sodium nitrite, sodium thiosulfate)
• Lee Jones Test can detect cyanide in gastric aspirate, but has false positives with other substances
• Carbon Monoxide


  Incomplete combustion or second-hand smoke
• Lactic acidosis


  Generates excess lactic acid