1 / 63

What Is This?

kostya
Download Presentation

What Is This?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. با توجه به موارد گزارش شده از اپيدمي هاي توده اي مسموميت با متانول در برخي شهرهاي كشور آشنايي با اصول تشخيص و درمان آن اهميت اساسي دارد. مسموميت با متانول يا الكل چوب از جمله اورژانسهايي است كه تشخيص ، درمان و بيماريابي به موقع نقش مهمي را در كاهش مرگ ، كوري و ساير ناتواني هاي جسمي و ذهني ايفا مي كند.

  2. H H C C OH H H H What Is This? (CH3-CH2-OH)

  3. Ethanol H H C C OH H H H Ethyl Alcohol

  4. Methanol H C OH H H Methyl Alcohol

  5. Metabolism II H H ALDH = = H O H O C C C C H H H OH Acetaldehyde Acetate (ALDH – Acetaldehyde Dehydrogenase)

  6. Metabolism I H H H ADH = H OH H O C C C C H H H H Ethanol Acetaldehyde (ADH – Alcohol Dehydrogenase)

  7. Genetic Variation in ALDH Acetaldehyde Dehydrogenase (ALDH) varies in Caucasians, Blacks and Asians. 50% of Asians have inactive ALDH Elevated acetaldehyde cause increased flushing, tachycardia (elevated heart rate), nausea, vomiting & hyperventilation. Disulfiram – inhibits ALDH

  8. شايع ترين علت مسموميت با متانول در كشور مصرف مشروبات الكي آلوده به متانول است

  9. MECHANISM OF ACTION ALCOHOL DEHYDROGENASE ALDEHYDE DEHYDROGENASE METHANOL FORMALDEHYDE FORMIC ACID

  10. MECHANISM OF ACTION METHANOL FORMALDEHYDE OCULAR TOXICITY INHIBITION OF MITOCHONDRIAL RESPIRATION INCREASED FORMIC ACID TOXICITY FORMIC ACID CIRCULATORY FAILURE CIRCULUS HYPOXICUS TISSUE HYPOXIA ACIDOSIS ACIDOSIS LACTIC ACID PRODUCTION Early stage of poisoning GENERAL TOXICITY

  11. MECHANISM OF ACTION ALCOHOL DEHYDROGENASE ALDEHYDE DEHYDROGENASE METHANOL FORMALDEHYDE FORMIC ACID

  12. Toxic Alcohols Rama B. Rao Bellevue/NYU Medical Center New York City Poison Control Center

  13. Alcohols: R-OH OH H H H-C-H H-C-OH H-C-OH H-C-H H-C-OH H H H Methanol 1C Ethanol 2C Ethylene Glycol 2C

  14. Alcohols: R-OH H H H H-C-H H-C-OH H-C-OH H-C-OH H-C-OH H-C-H H-C-H H H Benzyl Alcohol Isopropanol 3C Propylene Glycol 3C

  15. Ethanol OH O O H-C-H C-H C-OH ADH ALDH H-C-H H-C-H H-C-H H H H Ethanol Acetaldehyde Acetic Acid ADH = Alcohol Dehydrogenase ALDH = Aldehyde Dehydrogenase

  16. Methanol • Molecular weight 32 • Low freezing point • Highly volatility H H-C-OH H Methanol

  17. Methanol • Gas Line Antifreeze 100% • Windshield washer fluid 30% • Varnish removers • Fuel for food warming 3-70% • Industrial uses

  18. Methanol Metabolism H O O ADH ALDH H-C-OH H-C-H H-C-OH H H H Methanol Formaldehyde Formic Acid ADH: Alcohol Dehydrogenase ALDH: Aldehyde Dehydrogenase

  19. Methanol Toxicity • Delayed onset (8-12hrs) • Anion gap acidosis • Tachypnea • Visual complaints • Retinal metabolism • “Snow storm” Yang CS et al Eye 2005;19:806-809

  20. Methanol Toxicity • CNS depression • Bilateral hemmorhage putamen • Abdominal pain • Multisystem organ failure University of Western Ontario: Neurology Collection

  21. Ethylene Glycol • Molecular Weight 62 • Low Volatility • High boiling point H H-C-OH H-C-OH H Ethylene Glycol

  22. Ethylene Glycol • Coolant/Antifreeze • Solvents • De-Icer

  23. Ethylene Glycol Metabolism H O O H-C-OH C-H C-OH ADH ALDH H-C-OH H-C-OH H-C-OH H H H Ethylene Glycol Glycoaldehyde Glycolic Acid ADH = Alcohol dehydrogenase ALDH = Aldehyde dehydrogenase

  24. Ethylene Glycol Metabolism O O O C-OH C-OH C-OH LDH H-C-OH H-C-H H-C-OH H O O Glyoxylic Acid Glycolic Acid Oxalic Acid B1, Mg2+ B6 -OH- Ketoadipic Acid Glycine + Benzoic Acid Hippuric Acid LDH = Lactate dehydrogenase

  25. Ethylene Glycol Toxicity • Onset 4-6 hours • Anion gap acidosis • Tachypnea pH

  26. Ethylene Glycol Toxicity • Abdominal pain • Hypocalcemia • Calcium oxalate crystals in urine • Renal failure

  27. Identifying Patients for Treatment: Methanol/EG • Serum ethylene glycol or methanol level • Action level for treatment: 25 mg/dL* * Or any level with acidosis

  28. Treatment NG Tube • Limit absorption: • Prevent metabolism or parent compound to toxic metabolite • Enhance elimination • Parent • Metabolites • Correct Derangements ADH Inhibition Substrates/Other Hemodialysis

  29. Limits of Serum Levels • Useful prior to onset of acidosis or in massive overdoses • Parent compound not directly toxic • Levels not universally available EG or Methanol Anion Gap Time

  30. Arterial Blood Gas/Lactate • Acidosis indicates advanced poisoning • Lactate usually low* • Patients with acidosis should receive treatment *Some glycolates are misidentified as lactate

  31. Adjunctive Information:Ethanol • Serum ethanol inhibits metabolism of EG and Methanol • Onset of toxicity EG/Methanol may be delayed

  32. Adjunctive Information: Osmol Gap • Osmol Gap = Measured-Calculated Osmols • Calculated: 2 Na + BUN + Glucose + Alcohol • N = MW Alcohol/10 • Must use freezing point depression 2.8 18 N

  33. Osmol Gap: Limitations • Normal Osmol gap in between – 14 ± 10 • Normal Osmol Gap in setting of poisoning does not rule out a treatable level • Osmol Gap diminishes as parent compound is metabolized Osmol Gap Anion Gap Time

  34. Adjunctive Information • Ethylene glycol: • Limited utility of fluorescence of urine • May note crystals in urine • Methanol • Hyperemia retina or visual complaints

  35. Treatment: Methanol or Ethylene Glycol • Level  25 mg/dL or • Anion gap metabolic acidosis ( non-lactate) with strong suspicion EG or Methanol exposure

  36. Treatment • Ethanol more avid for ADH • 6-8x more avid than ethylene glycol • 4x more avid than methanol Methanol Ethanol Ethylene Glycol ADH ALDH Aldehyde Acid

  37. Ethanol • Concentration = Dose • Vd of ethanol = 0.6 L/kg • Desired concentration 100-200 mg/dL Vd (wt in kg)

  38. Ethanol • Target concentration 100 mg/dL • Proof is 2x concentration • 80 proof is 40% ethanol or 40 grams/100 mL • 0.8 gm/kg loading IV of 10% solution over 1 hour = 8 mL/kg of 10% solution

  39. Ethanol Infusion • 80-130 mg/kg/hour depending on how fast a patient metabolizes • Needs to be increased to 250 mg/kg/hour or higher during dialysis

  40. Ethanol Infusion: Management • Serial ethanol levels • Watch glucose* and sodium* • Observe for respiratory status* * Especially in children

  41. Fomepizole • A blocker of alcohol dehydrogenase • Has replaced ethanol as the agent of choice in known or suspected exposures • Minimal adverse effects

  42. Hemodialysis • Consult nephrology early in acidemic patients • Levels toxic alcohol  25 mg/dL

  43. Adjuncts for Methanol Poisoning • Sodium bicarbonate • pH < 7.30 • Can ion trap formic acid in urine and enhance elimination • Folate administration • Facilitates conversion of one carbon fragments to CO2 • 1mg/kg up to 50 mg every 4 hours

  44. Adjuncts for Ethylene Glycol Poisoning O O O C-OH C-OH C-OH LDH H-C-OH H-C-H H-C-OH H O O Glyoxylic Acid Glycolic Acid Oxalic Acid B1, Mg2+ B6 -OH- Ketoadipic Acid Glycine + Benzoic Acid Hippuric Acid LDH = Lactate dehydrogenase

  45. Adjuncts for Ethylene Glycol Poisoning • To enhance metabolism away from oxalates* • Thiamine 100 mg every 4- 6 hours • Pyridoxine 50 mg every 4-6 hours * Limited data

  46. Diethylene Glycol • Elixir of Sulfanilamide disaster 1937-38 • Renal failure 105 deaths • U.S. Legislation of Drug Safety

  47. Benzyl Alcohol • Preservative in some medications • Gasping Baby Syndrome • Potentially fatal in neonates H H-C-OH Benzyl Alcohol

  48. Isopropanol • Metabolized to acetone • No acidosis • Supportive care H H-C-H H-C-OH H-C-H H Isopropanol 3C

More Related