ALCOHOL OVERDOSE Kobra Naseri PharmD, PhD of Pharmacology.
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Transcript of ALCOHOL OVERDOSE Kobra Naseri PharmD, PhD of Pharmacology.
ALCOHOL OVERDOSEKobra Naseri
PharmD, PhD of Pharmacology
ETHANOL POISONINGETHANOL POISONING
INTRODUCTION INTRODUCTION
Ethanol (ethyl alcohol,C2H5OH) - is derived from fermentation
of sugars in fruits, cereals, and vegetables.
Ethanol: the most frequently abused intoxicant
PHARMACOLOGY OF ETHANOL 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
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.
PHARMACOKINETICS
90% metabolized in the liver by one of the two
pathways:
1. cytosol: – alcohol dehydrogenase– aldehyde dehydrogenase
2. microsomal alcohol oxidizing system
Metabolism of ethanol
C O 2 + H 2O
A c e ty l C o A
A c e tic a c id
A c e ta ld e hy d e
E tha n o l
Alcohol dehydrogenase
Aldehyde dehydrogenaseAcetaldehyde SyndromeThe mediator of liver toxicity
METABOLIC PATHWAYMETABOLIC PATHWAY
Adult : 6-10 mL/kg
Children : 4 mL/kg
• Slurred speech
• Disinhibited behavior
• CNS depression
• Decreased motor coordination & control
• Hypotension: – decrease in total peripheral
resistance
• Reflex tachycardia
SYMPTOMS OF INTOXICATION
HYPOTHERMIA HYPOTHERMIA
Depresses central thermoregulatory
mechanisms
Decreases shivering
Enhances heat loss through vasodilatation
Sedative effects: lack of behavioral adjustment against exposure to the cold environment
MANAGEMENT OF INTOXICATIONMANAGEMENT OF INTOXICATION
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)
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.).
Hemodialysis efficiently removes ethanol but enhanced removal is rarely needed because supportive care is usually sufficient.
Hemoperfusion and forced diuresis are not effective.
• Legal definition of ethanol intoxication:
BAC > 100 mg/dl
• BAC correlates poorly with degree of intoxication
(because of tolerance)
BLOOD ALCOHOL CONC.BLOOD ALCOHOL CONC.
EFFECTS IN NON-ALCOHOLICS
EFFECTS IN NON-ALCOHOLICS
BAC (mg/dl) Effects 20 - 50 fine motor function
50 - 100 judgment, coordination
100 - 150 Difficulty with walking & balance
150 - 250 Lethargy
300 Coma
400 - 500 Respiratory depression, Hypotension, Hypothermia Convulsion, Death
STAGING OF WITHDRAWALSTAGING OF WITHDRAWAL
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
Rx : ALCOHOL 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
Source
Anti-freeze agents Solvents Cleaning agents Industrial alcohol Dye
Poisoning
Poisoning is common. Adulterated beverages(substituting methanol for ethanol)
Mis-swallowing accidentally
Suicide or homicide Ingestion of just 0.15 mL/kg of 100%
methanol may cause toxicity. Fatal dose : 60-240 mL
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
Gastrointestinal Tract
Skin
Respiratory Tract
Metabolic Pathway
Methanol
Formaldehyde
Formic acid
CO2+ H2O
Alcohol dehydrogenase
Aldehydedehydrogenase
Tetrahydrofolate
Methanol Metabolism
Enzyme Involved: –Alcohol Dehydrogenase(Rate-
Limiting)–AldehydeDehydrogenase
Toxic Products:–Formaldehyde–Formic acid
Formic Acid Toxicity
Inhibition of mitochondrial cytochrome oxidase:
–Histotoxic Hypoxia–Metabolic Acidosis
Elimination
Liver (predominates) Lung Kidney Elimination half life: 3 hours
Clinical feature
Incubation Time
12-72 hours
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.
Neurologic Toxicity
Neurologic Symptoms:–Headache –Dizziness–Amnesia–Restlessness–Acute Mania–Lethargy–Confusion–Coma–Convulsions–Parkinsonism may develop as a sequelae of severe
intoxication.
Ophthalmologic Toxicity
Occur when serum pH drops below 7.2
Low pH → intracellular concentration of formate↑
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
Laboratory Tests
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
Late diagnosis
Visual symptoms Metabolic acidosis with
increased anion gap History of alcohol
consumption and methanol contact
Treatment
Supportive Care
Hemodialysis
Folic acid
Antidotes
Sodium Bicarbonate
Supportive Treatment
Airway management in comatose patient
Intravenous Fluids Cardiac Monitoring Oxygen Supply Ipecac is contraindicated (CNS
depression) Activated charcoal is not effective Sodium bicarbonate
FomepizoleEthanol
Antidotes
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
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
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.
Ethanol
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
Ethanol
Loading DoseGram/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
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
Adjunctive Treatment
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
Formaldehyde
Formic acid
CO2+ H2O
Alcohol dehydrogenase
Aldehydedehydrogenase
Tetrahydrofolate
Ethylene glycol is a sweet, odorless and colorless liquid.
Overdose ETHYLENE GLYCOL
Overdose ETHYLENE GLYCOL
Introducti
on
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
E.G Glycoaldehyde Glyoxalate
Pyridoxine Oxalate Glycine Itself is non-toxic Toxicity being to…
ADH
ADH
Fatal dose in adult : 100 mL
Ethylene glycol
Clinical feature
The first phase: 3 min –12 hours Resemble ethanol intoxication without alcohol
smell Nausea, Vomiting & hematemesis
The major effects are on the CNSComaSeizure Nystagmus
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
The third phase: 24 –72 hours
Flank pain CVA Tenderness
(costovertebral angle) Acute tubular necrosis
Treatment
Focus treatment: Supportive care Treatment with fomepizole Treatment with ethanol Hemodialysis as indicated.
Adjunctive Therapy
Pyridoxine and thiamine to hasten elimination of toxic ethylene glycol metabolites.
Pyridoxine Dose1 to 2 mg/kg administered
intravenously every 6 hours until ethylene glycol level is undetectable.
Thiamine Dose
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
Sodium bicarbonate should not be used routinely but may be used as a temporarily for life-threatening acidosis prior to hemodialysis.