Alcohols and Glycols Flashcards
What are the sources of methanol?
Windshield washer fluid
Gasoline antifreeze
What is the lethal methanol dosage?
15 mL of 40% methanol ➔ death
4 mL of 100% methanol ➔ blindness
How is methanol metabolized?
Methanol ➔ (ADH) ➔ formaldehyde (rate-limiting)
Formaldehyde ➔ (ALDH) ➔ formic acid (rapid)
Formic acid ➔ (Folate) ➔ CO2 + H2O
Why does methanol cause metabolic acidosis?
- Methanol is metabolized to formic acid which accounts for much of the anion gap metabolic acidosis
- Formic acid binds to iron & inhibits mitochondrial cytochrome c oxidase causing lactic acidosis
What is the clinical presentation of methanol poisoning?
1st few hrs
- Mild inebriation, gastritis
12-24 h
- Mild CNS depression
- Hyperventilation secondary to acidosis
- Visual disturbance: looking into snow storm, permanent visual loss can occur
- Severe cases: severe acidosis, coma, and CV collapse
- Survivors may develop Parkinson’s
What is the treatment of methanol?
- Inhibition of metabolism
- Ethanol and fomezipole inhibit ADH preventing further production of formic - Removal of parent compound (dialysis) - MAIN treatment
- Adjunctive therapy - folinic or folic acid
- Treatment of acidosis - sodium bicarbonate
- bicarbonate shifts equilibrium in favor of folate
How safe is ethanol vs fomezipole?
Ethanol any ADE - 57%
Ethanol severe ADE - 11%
Fomezipole any ADE - 12%
Fomezipole severe ADE - 2%
Bradychardia and hypotension (uncommon)
What is the definitive diagnostic test of methanol? What are the cons of this test?
Gas chromatography
1. Time consuming
2. Expensive
3. Not readily available
What are the screening tests of methanol?
- POC test
- Immunochromatographic test
- Cut off for +ve test - 4 mmol/L
- Methanol test may cross react with ethanol - Osmole gap
- Normal < 10 mOsm/L
- Serum osmolality must be measured with an osmometer using FREEZING POINT DEPRESSION
- only parent cmpd will increase the osmole gap - Anion gap
- Normal 7+/-4
What is the sensitivity and specificity of osmole gap?
Sens - moderate-high
Spec - low
What are some lab testing issues that can result in an increased osmole gap?
- Anticoagulants in collection tube
- Lab tests not taken simultaneously
- Delay in analysis
- Use of VAPOUR PRESSURE osmometry
What is the mnemonic used for an increased osmole gap?
MEDIE
M - Methanol
E - Ethanol
D - Diuretics
I - Isopropyl Alcohol
E - Ethylene glycol
What is the sensitivity and specificity of anion gap measurement?
Sens - low
Spec - high
What is the mnemonic for elevated anion gap?
CATMUDPILES
C - Carbon monoxide, cyanide
A - Acetaminophen, Alcohol ketoacidosis
T - Toluene
M - Metformin, methanol
U - Uremia
D - Diabetic ketoacidosis
P - Propylene glycol
I - Iron, isoniazid
L - Lactic acidosis
E - Ethylene glycol
S - Salicylates
What are the toxins that can increase both osmole and anion gap? (4)
- Methanol
- Ethylene glycol
- Diethylene glycol
- Propylene glycol
What are the medical conditions that can increase both OG and AG? (4)
- Alcoholic and diabetic ketoacidosis
- Renal failure
- Multiple organ failure
- Critical illness
What are the sources of ethylene glycol?
Antifreeze
Industrial solvent
What is the lethal EG dose?
1-2 mL/kg
1 swallow = 30 mL
What is the metabolism of ethylene glycol?
Ethylene glycol ➔(ADH)➔ glycoaldehyde
Glycoaldehyde➔(ALDH)➔ glycolic acid
Glycolic acid ➔ glycoxylic acid ➔ oxalic acid
What is the pathophysiology of ethylene glycol?
Parent cmpd is non-toxic
Toxicity of EG due to combination of severe metabolic acidosis caused by glycolic acid and the ppt. of calcium oxalate crystals resulting in impaired organ fcn esp. the kidneys.
What is the clinical presentation of EG?
- Initial CNS depression
- After 4-12 h ➔ metabolic acidosis
- Renal failure
- Hypocalcemia w tetanic contractions
- Multiorgan failure
- Survivors ➔ permanent renal failure requiring dialysis
What is the treatment for EG?
- Inhibition of metabolism ➔ ethanol & fomezipole (antidote)
- Removal of parent cmpd ➔ dialysis (main treatment)
- Adjunctive therapy ➔ pyridoxine, thiamine
- Treatment of acidosis ➔ sodium bicarbonate
What is the definitive diagnostic test for EG?
Gas chromatography
What are the screening tests for EG?
- Lactate gap
- In EG poisoning, the glycolate metabolite may be interpreted as lactate on some blood analyzers. This will cause a false +ve lactate elevation on the blood gas analysis. There will be a gap between the lactat on the blood gas and the lactate determine by standard lab analysis of blood chemistry. Only works if analyser is a Radiometer ABL 700 POC analyser. - Urine crystals
- Calcium oxalate monohydrate and dihyrdrate crystals in urine. Spindle and envelope shaped respectively. - Osmole gap and Anion gap (main)
