ALCOHOL OVERDOSE
Kobra Naseri
PharmD, PhD of Pharmacology
ETHANOL
POISONING
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Ethanol (ethyl alcohol,C2H5OH)
- is derived from fermentation of sugars
in fruits, cereals, and vegetables.
Ethanol:
 the
most frequently abused intoxicant
INTRODUCTION
PHARMACOLOGY OF ETHANOL
CNS depressant:
 inhibits neuronal activity
 behavioral stimulation at low blood level
Cross tolerance:
 BZD & barbiturates
Absorption:
 proximal small bowel
Excretion:
 2% ~ 10% by lungs, in urine, in sweat
PHARMACOKINETICS
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Ethanol is readily absorbed (peak30-120 min)
(Vd=0.5-0.7L/kg).
It is rapidly absorbed by diffusion across the
lipid membranes of the stomach and small
intestine.
Coingestion of food or decreased GI motility
produces a delay in absorption and
increases the gastric metabolism of ethanol.
Metabolism of ethanol
90% metabolized in the liver by one of the two
pathways:
1. cytosol:
– alcohol dehydrogenase
– aldehyde dehydrogenase
2. microsomal alcohol oxidizing system
Ethanol
Alcohol dehydrogenase
Acetaldehyde
Aldehyde dehydrogenase
Acetaldehyde Syndrome
Acetic
The mediator of liver toxicity
acid
Acetyl CoA
CO2 +
H 2O
METABOLIC PATHWAY
Adult : 6-10 mL/kg
Children : 4 mL/kg
SYMPTOMS OF INTOXICATION
• Slurred speech
• Disinhibited behavior
• CNS depression
• Decreased motor coordination & control
• Hypotension:
– decrease in total peripheral resistance
• Reflex tachycardia
HYPOTHERMIA
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Depresses central thermoregulatory
mechanisms

Decreases shivering

Enhances heat loss through vasodilatation
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Sedative effects:

lack of behavioral adjustment against
exposure to the cold environment
MANAGEMENT OF INTOXICATION
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Airway protection
Adequate ventilation
IVF replacement
O2 supply
EKG monitoring
Thiamine (50 - 100 mg) IV
Glucose supply (if hypoglycemic)
Active charcoal (if co-ingestion is suspected)
Re-warming (if hypothermic)
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Treatment is mainly supportive.
Protect the airway to prevent aspiration.
Glucose & thiamine administered.
Glucagon is not effective for alcohol induced
hypoglycemia.
Correct hypothermia with gradual rewarming.
Do not induced vomiting or activated charcoal and
gastric lavage in pure ethanol intoxication. Consider
gastric lavage only if the alcohol ingestion was massive
and recent( within 30-45 min.).
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Hemodialysis efficiently removes ethanol
but enhanced removal is rarely needed
because supportive care is usually
sufficient.
Hemoperfusion and forced diuresis are
not effective.
BLOOD ALCOHOL CONC.
• Legal definition of ethanol intoxication:
BAC > 100 mg/dl
• BAC correlates poorly with degree of
intoxication
(because of tolerance)
BAC (mg/dl)
Effects
20 - 50
 fine motor function
50 - 100
 judgment, coordination
100 - 150
Difficulty with walking & balance
150 - 250
Lethargy
300
400 - 500
Coma
Respiratory depression,
Hypotension, Hypothermia
Convulsion, Death
EFFECTS IN NON-ALCOHOLICS
STAGE
ONSET
SYMTOMS
I
6 - 8 hours
Tremor, agitation,
nausea, vomiting
II
24 hours
Hallucinations
III
24- 48 hours
Grand mal seizures
IV
3 - 5 days
Delirium tremens
STAGING OF WITHDRAWAL
Rx : ALCOHOL WITHDRAWAL
• Hydration with D5NS (IV)
• Cross-reacting drugs:
– BZD or Phenobarbital
• Thiamine (IV)
• Magnesium sulfate (IV)
• Admission:
– fail to respond to 2 doses of sedative
Methanol
Physical Nature
Wood alcohol
 CH3OH
 Colorless liquid
 Boiling point: 65°C
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Source
Anti-freeze agents
 Solvents
 Cleaning agents
 Industrial alcohol
 Dye
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Poisoning
Poisoning is common.
 Adulterated beverages
(substituting methanol for ethanol)
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Mis-swallowing accidentally
Suicide or homicide
Ingestion of just 0.15 mL/kg of 100% methanol may cause
toxicity.
Fatal dose : 60-240 mL
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Pediatric cases are usually accidental.
Adult cases usually involve suicidal ingestion or
ingestion of methanol as an alcohol substitute.
Toxic effects are typically severe, if untreated.
Death may occur in untreated patients.
Inhalation or dermal absorption can produce toxicity.
Absorption
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Gastrointestinal Tract
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Skin
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Respiratory Tract
Metabolic Pathway
Methanol
Alcohol dehydrogenase
Formaldehyde
Aldehydedehydrogenase
Formic acid
Tetrahydrofolate
CO2+ H2O
Methanol Metabolism
Enzyme Involved:
–Alcohol Dehydrogenase(Rate-Limiting)
–AldehydeDehydrogenase
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Toxic Products:
–Formaldehyde
–Formic acid
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Formic Acid Toxicity
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Inhibition of mitochondrial cytochrome
oxidase:
–Histotoxic Hypoxia
–Metabolic Acidosis
Elimination
Liver (predominates)
 Lung
 Kidney
 Elimination half life: 3 hours
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Clinical feature
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Incubation Time
12-72 hours
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Factors influencing time to symptoms:
–Amount Ingested
–Concomitant Ethanol Intoxication
–The individual’s Folate Status
Premortal Vital Signs
Hyperpnea usually develops to compensate
metabolic acidosis(Kussmaul’s Respirations)
 Sudden Respiratory Arrest
 Tachycardia
 Blood pressure is stable until death
 Hypotension may develop late in severe cases.
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Neurologic Toxicity
Neurologic Symptoms:
–Headache
–Dizziness
–Amnesia
–Restlessness
–Acute Mania
–Lethargy
–Confusion
–Coma
–Convulsions
–Parkinsonism may develop as a sequelae of severe intoxication.
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Ophthalmologic Toxicity
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Occur when serum pH drops below 7.2
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Low pH → intracellular concentration of formate↑
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Improvement of vision with correction of acidosis, because
formate moves out of the cell
Formate is an inhibitor of cytochrome oxidase, which could inhibit
ATP formation in the optic nerve leading to a stasis of axoplasmic
flow, axonal swelling, optic disc edema and finally loss of visual
function
Ophthalmologic Toxicity
Symptoms:
 Blurred Vision
 Photophobia
 Eye Pain
 Partial or complete loss of vision
 Visual hallucinations (bright lights, snowstorm, dancing
spots, flashes)
Ophthalmologic Toxicity
Signs:
 Optic discs hyperemia
 Retinal edema
 Retinal vessels engorgement
 Papilledema
 Papillary dilation
 Loss of papillary reflex
Gastrointestinal Toxicity
Hemorrhagic Gastritis
 Acute Pancreatitis
 Symptoms:
•Abdominal Pain
•Nausea
•Vomiting
•Diarrhea
•Liver Function Impairment
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Laboratory Tests
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Essential Tests:
1.Serum Electrolytes (Hyperkalemia)
2.Leukocytosis
3.Amylase elevations
4.BUN and Creatinine
5.Glucose (Hyperglycemia)
6.Arterial Blood Gases
 Elevated anion gap acidosis supports the diagnosis.
7.Osmolar gap
8.Elevated lactate levels
9.Serum Methanol Level (greater than 20 mg/dL)
Early diagnosis
History-taking
 Increased osmolar gap
 Blood methanol detection
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Late diagnosis
Visual symptoms
 Metabolic acidosis with increased anion
gap
 History of alcohol consumption and
methanol contact
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Treatment
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Supportive Care
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Antidotes
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Hemodialysis
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Sodium Bicarbonate
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Folic acid
Supportive Treatment
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Airway management in comatose patient
Intravenous Fluids
Cardiac Monitoring
Oxygen Supply
Ipecac is contraindicated (CNS depression)
Activated charcoal is not effective
Sodium bicarbonate
Antidotes
Fomepizole
Ethanol
Fomepizole
Fomepizole(Antizol)
 Fomepizoleis the preferred agent
 4-methylpyrazole (4-MP) “Fomepizole”:a more
potent inhibitor of alcohol dehyrogenase
 No side effect of CNS depression as in ethanol
therapy
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Fomepizole
Indications:
 A history of ingestion when a serum level is
not immediately available
 A Serum methanol level greater than 20
mg/dL
 Unexplained metabolic acidosis with
elevated anion and osmolar gaps
Fomepizole
Metabolic acidosis with elevated anion gap
accompanied by visual signs and symptoms
 Unexplained coma with a high osmolar gap
 Clinical evidence of toxicity
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Fomepizole
Contraindication
 Disulfiram
 Allergic reaction to fomepizole
 Relative contraindication
 Metronidazole
 GI Ulceration
 Child < 5 years
 Severe Hepatic Disease
Fomepizole
L.D: 15mg/kg (IV)
 M.D: 10mg/kg/12h for 4 doses then
15mg/kg/12h
 Each dose is diluted in 100 mL normal
saline or D5W and infused over 30 minutes.
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Ethanol
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Ethanol is a preferential substrate for
alcohol dehydrogenase.
Once alcohol dehydrogenase metabolism is
blocked, methanol is eliminated slowly via
pulmonary and renal excretion.
Ethanol
Indications:
 A history of ingestion when a serum level is
not immediately available
 A Serum methanol level greater than 20
mg/dL
 Unexplained metabolic acidosis with
elevated anion and osmolar gaps
Ethanol
Metabolic acidosis with elevated anion gap
accompanied by visual signs and symptoms
 Unexplained coma with a high osmolar gap
 Clinical evidence of toxicity
 It may be used if fomepizole is not available
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Ethanol
Loading Dose
Gram/kg of Ethanol 10% (Oral)
 Non-Drinker/Child
0.88
 Average Drinker
1.4
 Chronic Drinker
2
Maintenance Dose
100 mg/kg/hour of Ethanol 10% (Oral)
Increase M.D. 2-3 times during hemodialysis
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Ethanol Conc. to 100 -150 mg%
Enhanced Elimination
Hemodialysis effectively removes methanol and its
toxic metabolites
 Elimination rates:
-142 ~ 286 ml/min (methanol)
-148 ~ 203 ml/min (formate)
 Peritoneal dialysis also removes methanol but not as
effectively
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Adjunctive Treatment
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Folate or tetrahydrofolate(Leucovorin) to hasten
elimination of formic acid.
Leucovorin1mg/kg Max 50 mg/dose/IV/4-6 hours
until methanol becomes undetectable.
Folate 1mg/kg Max 50 mg/dose/P.O/4-6 hours until
methanol becomes undetectable.
Metabolic Pathway
Methanol
Alcohol dehydrogenase
Formaldehyde
Aldehydedehydrogenase
Formic acid
Tetrahydrofolate
CO2+ H2O
Overdose ETHYLENE GLYCOL
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Ethylene glycol is a sweet,
odorless and colorless liquid.
Overdose ETHYLENE GLYCOL
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Introduction
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It is a common component of antifreeze used in:
Heating and cooling systems
Brake Fluid
Inks
It is used as an industrial solvent in:
Paints
Plastics
It is used in synthesis of:
Resins
Synthetic Fibers
Waxes
Epidemiology
Poisoning is uncommon.
 Death occurs in patients who do not
receive medical care.
 Poisoning most commonly occurs:
 Accidental ingestion
 Suicidal Attempt

Pathophysiology
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E.G
ADH
Glycoaldehyde
ADH
Glyoxalate
Pyridoxine
Oxalate
Glycine
Itself is non-toxic
Toxicity being to…
Ethylene glycol
Fatal dose in adult : 100 mL
Clinical feature
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The first phase: 3 min –12 hours
Resemble ethanol intoxication without alcohol smell
Nausea, Vomiting & hematemesis
The major effects are on the CNS
Coma
Seizure
Nystagmus
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The second Phase: 12 –14 hours
Tachycardia
 Mild Hypertension
 Pulmonary edema
 CHF
 Due to deposition of calcium oxalate
within the vascular tree, myocardium
and lung parenchyma
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The third phase: 24 –72 hours
Flank pain
 CVA Tenderness (costovertebral angle)
 Acute tubular necrosis
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Treatment
Focus treatment:
 Supportive care
 Treatment with fomepizole
 Treatment with ethanol
 Hemodialysis as indicated.
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Adjunctive Therapy
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Pyridoxine and thiamine to hasten elimination
of toxic ethylene glycol metabolites.
Pyridoxine Dose
1 to 2 mg/kg administered intravenously every 6
hours until ethylene glycol level is undetectable.
Thiamine Dose
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Adult dose is 100 mg/I.V. over 5 minutes every 6 hours until
ethylene glycol level is undetectable.
Pediatric dose is 50 mg/I.V. over 5 minutes every 6 hours
until ethylene glycol level is undetectable.
Sodium Bicarbonate
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Sodium bicarbonate should not be used routinely but may
be used as a temporarily for life-threatening acidosis prior
to hemodialysis.