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Toxic Alcohols

Toxic Alcohols. John Kashani D.O. Attending, St. Joseph’s Emergency Department Staff Toxicologist, New Jersey Poison Center. Case. An 18 year old male is brought into the ED by his mother when he was difficult to awaken in the AM

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Toxic Alcohols

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  1. Toxic Alcohols John Kashani D.O. Attending, St. Joseph’s Emergency Department Staff Toxicologist, New Jersey Poison Center

  2. Case • An 18 year old male is brought into the ED by his mother when he was difficult to awaken in the AM • He was partying the night before, he is not able to provide a history • He becomes progressively more obtunded while in the ED

  3. Case • A 22 year old frustrated medical student drinks a bottle of formaldehyde he stole from gross anatomy lab • He complains of throat and esophageal irritation and has had multiple episodes of emesis

  4. Case • A 65 year old man is found comatosed • His wife states that he has been depressed recently and has been drinking heavily • An empty bottle of antifreeze was found in his kitchen garbage can

  5. Case • A 17 year old female ingests a bottle of rubbing alcohol • She appears drunk, has multiple episodes of emesis and complains of abdominal pain

  6. Case • A 25 year old man presents to the ED with blurry vision • For the past few days he has been feeling “cruddy” • He admits to the ingestion of homemade everclear 3 days prior

  7. Objectives • Outline the “toxic” alcohols and potentially toxic alcohols • Discuss the pharmacology, kinetics and pathophysiology of the toxic alcohols • Discuss the clinical manifestations, diagnosis and management of patients poisoned by these agents

  8. Introduction • Alcohols are hydrocarbons that contain a hydroxyl group • A compound with two hydroxyl groups is called a diol or a glycol • Toxic alcohols commonly refer to methanol, ethylene glycol and isopropyl alcohol

  9. Introduction • Less common but potentially toxic alcohols include diethylene glycol, benzyl alcohol and the glycol ethers

  10. Ethylene Glycol • Coolant mixtures • Antifreeze • Air craft de-icing solutions • Solvent (inks, pesticides and adhesives) • Brake fluid • Heat exchangers and condensers • Glycerin substitute

  11. Propylene glycol • Commonly used as a diluent for parental preparations • Environmentally safe alternative to ethylene glycol antifreeze

  12. Benzyl alcohol +

  13. Methanol • Antifreeze (window washer fluid) • Anti icing agent • Octane booster • Ethanol denaturant • Extraction agent • Solvent • Fuel source

  14. Methanol • Varnish and paint removers • Industrial solvent • Manufacture of acetic acid, formaldehyde and inorganic acids

  15. Isopropanol • Synthesis of acetone, glycerin • Solvent for oils, gums and resins • Deicing agent • Rubbing alcohol • Hair care products, skin lotion and aerosols

  16. Diethylene glycol • Solvent • Sprinkler antifreeze • Paints, cosmetics HEAA +

  17. Glycol ethers • Solvents • Semiconductor industry • Fingernail polishes and removers • Dyes, ink, cleaners, degreasers • Brake fluid, car wax, injector cleaner • Various household cleaning products

  18. Pharmacology and Kinetics • Exposure may occur dermally, pulmonary and GI • Pulmonary absorption depends on vapor pressure • Rapidly absorbed by the gastrointestinal route

  19. Pharmacology and Kinetics • Time to peak concentration • Ethylene glycol = 1 - 4 hrs • Methanol, isopropyl alcohol = 30 - 60 minutes • VD is 0.6L/kg

  20. Pharmacology and Kinetics • Ethylene glycol and methanol are metabolized by alcohol dehyrogenase and aldehyde dehydrogenase • Isopropanol is metabolized by alcohol dehydrogenase • Binding affinities for • ethanol>methanol>ethylene glycol

  21. Pharmacology and Kinetics • Methanol metabolism may be delayed (up to 72 hours) • The volatility of methanol contributes to its pulmonary excretion (10-20%) • Ethylene glycol is metabolized over 3 – 8 hours • Undergoes multiple oxidations

  22. Pharmacology and Kinetics • Ethylene glycol is not appreciably excreted by the lungs • Isopropanol is rapidly metabolized to acetone via alcohol dehyrogenase • 20% is excreted unchanged • Acetone is predominantly renally excreted

  23. (CH2OH)2 Ethylene glycol ADH CH2OHCHO Glycoaldehyde ADH CH2OHCOOH Glycolic Acid ADH Glyoxylic Acid CHOCOOH thiamine B6 Mg++ Oxalic Acid Glycine + Benzoic Acid Alpha-hydroxy-beta-ketoadipic acid Hippuric Acid

  24. CH3OH Methanol ADH Formaldehyde CH2O ADH CHOOH Formic Acid Folate CO2 + H2O

  25. Isopropyl alcohol CH3CHOHCH3 ADH CH3COCH3 Acetone

  26. The Usual Suspects

  27. Formic acid • Metabolic acidosis • Inhibits cytochrome oxidase: • Decreased ATP production • Increased anaerobic glycolysis & lactate

  28. NAD+ NADH + H+ R-OH ADH

  29. NADH H+ NAD+ Lactate Pyruvate NAD+ CO2 NADH H+ NADH Acetyl-CoA NAD+

  30. Clinical Manifestations • Clinical manifestations may be related to the parent compound or metabolites • There may be an initial asymptomatic period • Inebriation (unreliable) • Isopropyl>ethylene glycol>methanol

  31. Clinical Manifestations • Vasodilation – hypotension and reflex tachycardia • Hypoglycemia • Anion gap acidosis • Methanol and ethylene glycol • Visual disturbances (”snow Field”) • Formic acid is a retinal toxin

  32. Clinical Manifestations • ATN may develop secondary to calcium oxalate crystalluria • Cranial nerve deficits have been reported with ethylene glycol

  33. Clinical Manifestations • Ispopropanol ingestion usually does not cause major toxicity unless a large amount is ingested • CNS depression, hemorrhagic gastritis and tracheobronchitis

  34. Diagnosis • Both ethylene glycol and methanol result in an anion gap acidosis • Isopropyl alcohol usually does not result in an anion gap acidosis • Hypocalcemia may be seen in ethylene glycol intoxication • Chelation of calcium by oxalate – calcium oxalate crystals

  35. Diagnosis • The absence of crystals is an unreliable finding • The urine of a patient with ethylene glycol ingestion may fluoresce • Short lived, unreliable

  36. Calcium oxalate Crystals

  37. The “Osmolar Gap” Measured Serum Osmolarity Minus Calculated Serum Osmolarity [ 2(NA) + BUN/2.8 + Glucose/18+Etoh/4.6]

  38. * At 100 mg/dl

  39. AG mOsm mEq/L OG 0 Time since Ingestion

  40. Quantitative testing • If quantitative levels are readily available they can be used to determine proper management • Best method is gas chromatography with flame ionization • Subject to false positives

  41. Management • ABC’s • +/---- NGT aspiration • AC/ipecac/lavage = Bad move • Thiamine and pyridoxine in the setting of ethylene glycol toxicity • Folic acid in the setting of methanol toxicity

  42. Management • Sodium bicarbonate as needed • Inhibition of Alcohol dehydrogenase • Ethanol • Fomepizole

  43. Ethanol: - Oral or IV - CNS depression - Difficult titration - Frequent levels - Hypoglycemia Fomepizole: - IV - No CNS depression - Easy dosing - No levels to monitor - More predictable pharmacokinetcs - No Hypoglycemia - Cost Ethanol vs Fompepizole

  44. Fomepizole…because shit happens

  45. (CH2OH)2 Ethylene glycol X ADH CH2OHCHO Glycoaldehyde ADH Glycolic Acid CH2OHCOOH ADH Glyoxylic Acid CHOCOOH Thiamine 100 mg IV/day B6 100 mg/day Mg++ Oxalic Acid Glycine + Benzoic Acid Alpha-hydroxy-beta-ketoadipic acid Hippuric Acid

  46. CH3OH Methanol X ADH Formaldehyde CH2O ADH Formic Acid CHOOH Folate CO2 + H2O

  47. Case • An 18 year old male is brought into the ED by his mother when he was difficult to wake up in the AM • Apparently he was partying the night before, he is not able to provide a history • He becomes progressively more obtunded while in the ED

  48. Case • A 22 year old frustrated medical student drinks a bottle of formaldehyde he stole from gross anatomy lab • He complains of throat and esophageal irritation and has had multiple episodes of emesis

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