Methanol is a colorless, volatile, flammable liquid that is rapidly absorbed through the gastrointestinal tract and distributed throughout the body. It is metabolized into formaldehyde by alcohol dehydrogenase and further into toxic formic acid. Formic acid inhibits cytochrome c oxidase in mitochondria, preventing ATP production and ultimately causing cell death if enough accumulates. Symptoms of methanol poisoning include nausea, blindness, respiratory failure, and death. Treatment involves inhibiting methanol metabolism with ethanol or fomepizole, removing formic acid through hemodialysis, correcting acidosis, and administering folinic acid and sodium bicarbonate.
5. Absorption, distribution metabolism &
Elimination
Methanol is rapidly absorbed
through gastro‐intestinal tract.
The absorption half ‐ life is 5 minutes
and reaches maximum serum
concentration within 30 – 60 minutes
and well dissolves in body water.
The volume of distribution is
equivalent to body water.
elimination half-life 12-20 hours
Absorption
Distribution
Metabolism
Elimination
6. Metabolism of Methanol
ADH: alcohol dehydrogenase
FDH: formaldehyde dehydrogenase
F-THF-S: 10-formyl tetrahydrofolate
synthase
Methanol
Foramaldehyde
Formic acid
CO2 + H2O
ADHFDHF-THF-S
SlowRapidSlow
Accumulation of
Formic acid
7. Mechanism of toxicity
First step:
Electron transport chain
In mitochondriaMethanol
Formic acid inhibits
Cytochrome c oxidase which
is part of electron transport
chain in cell’s mitochondria
8. Mechanism of toxicity
Once cytochrome c oxidase
is blocked by formic acid, ATP
production stops, cells begin
to die and muscles cease
up and cannot function.
Second step:
No ATP production
9. Mechanism of toxicity
Third step:
If enough formic acid is distributed
through the body it can reach
diaphragm and heart stopping
breathing and heart beat
causing death.
10. Mechanism of toxicity
Forth step:
If the formic acid reaches
photoreceptors in eyes and
inhibit cytochrome c oxidase
and make blindness.
When formic acid stops
cytochrome c oxidase the
photoreceptor cells die and
don’t regenerate.
11. Pharmacology
Permanent blindness reported at as little
as 0.1 mL/kg (6-10 mL in adults)
Lethal dose = 1-2 mL/kg.
Symptoms begin 12-24hr after ingestion
(may occur even later if ETOH is co-ingested,
competes with alcohol dehydrogenase and
has greater affinity for the enzyme than
methanol)
12. Symptoms of toxicity
Nausea & vomiting
Atrophy of optic nerve –
blindness (snowstorm)
Headache & dizziness
& CNS suppression &
Bilateral hemmorhage
Decreased heart function
Respiratory failure and
metabolic acidosis
Seizures & death
Cirrhosis and hepatic failure
Abdominal pain and gastritis
13. Treatment
Hemodialysis
Hemodialysis has been used routinely to correct
Acidosis and to remove the toxic metabolite.
Correction of Metabolic Disturbances
A pH below 7.3 should be treated with intravenous
sodium bicarbonate solution to correct the acidosis
to the normal range (7.35–7.45).
It can ion trap formic acid in urine and enhance
elimination.
14. Treatment
Inhibition of Methanol Metabolism
-Ethanol
It has approximately 10 times greater affinity
for alcohol dehydrogenase than does methanol
10% ethanol at a dose of 10 ml/kg IV for 30 minutes.
-Fomepizole
It has been shown to be a potent inhibitor of alcohol
Dehydrogenase.
20 mg/kg in divided doses for 5 days.
Folinic Acid
Degrades formic acid into CO2 & H2O
-1mg/kg up to 50 mg every 4 hours