ETHANOL
n Chemistry
¡ Ethyl alcohol
¡ Water-soluble aliphatic alcohol
¡ Product of fermentation of sugars
n Pharmacokinetics
¡ Absorbed in the stomach and small intestine
¡ Highly lipid soluble widely distributed in the
body
¡ 1st pass hepatic metabolism
¡ Biotransformation primarily (90%) in the liver:
n Alcohol dehydrogenase pathway
n Hepatic microsomal ethanol oxidizing system (MEOS)
n Catalase system
¡ Excretion: Urine, exhaled air, sweat, saliva
ETHANOL METABOLISM: Alcohol
Dehydrogenase Pathway
Stage 1 CH3-CH2OH + NAD+
Alcohol dehydrogenase
CH3-CHO (Acetaldehyde) + NADH + H-
Stage 2 CH3CHO + H2O
Aldehyde dehydrogenase
CH3-COOH (Acetate) + (2H)
Stage 3 CH3-COOH + 4(O)
2CO2 + 2H2O
ETHANOL METABOLISM:
MEOS & Catalase System
Ethanol
MEOS / Catalase
(NADPH / O2)
Acetaldehyde
Aldehyde dehydrogenase
Acetate
ETHANOL
n Mechanism of Action
¡ Increased membrane fluidity
n Ion fluxes across the membrane
n Conformational changes in enzymes
n Neurotransmitter release
¡ Enhancement of chloride ion influx
hyperpolarization of the membranes
ETHANOL: Pharmacologic Effects
¡ CNS effects
n Euphoria tolerance, physical and psychological dependence
n Removal of inhibitions: Increased self-confidence, silly speech
and harmless antics; antisocial
n Impairment of vision: Reduced visual acuity; diplopia at 200-300
mg/100 ml
n Muscular incoordination: Slurred speech and staggering gait;
coma and gen. anesthesia
n Lengthened reaction time: 100-200 mg/100 ml increase of 10–
50%
¡ Posterior pituitary gland depression
n Reduced secretion of ADH diuresis
n Inhibition of oxytocin secretion delayed parturition at term
ETHANOL: Pharmacologic Effects
¡ Hypothalamus
n Hypothermia
¡ Vasomotor and respiratory centers depression
n Vasodilation Decreased BP
n Suppression of respiration
¡ GIT
n Increased gastric acid secretion
n Increased salivary secretion
¡ LIVER
n Alcoholic fatty liver alcoholic hepatitis cirrhosis liver
failure
¡ Lipid metabolism, platelet function, and atherosclerosis
n Increased plasma HDL concentration
n Inhibition of platelet aggregation
ETHANOL: ALCOHOL
EQUIVALENT & SUGGESTED
DAILY ALLOWANCE
ETHANOL
n Shot: 30 ml
n Glass: 200 ml
n Proof: Mixture of ethanol and water containing 50% by
volume of ethanol
n Formula: Gms. ethanol per serving = 5 volume or (proof X
2) X ml/serving X 0.8 (density of ethanol)
n Reasonable limit: oz. = 28 gms ethanol
ETHANOL: Adverse Reactions
Acute
¡ Frank intoxication (>200
mg/100 ml): Slurred speech,
difficulty of locomotion, loss
of inhibitions at blood alcohol
level
¡ Depression of respiratory and
vasomotor centers (>500
mg/100 ml ethanol
concentration)
¡ Acidosis, hypoglycemia,
elevated ICP coma or
stupor (300-400 mg/100 ml)
ETHANOL: Adverse Reactions
Chronic
¡ Morning nausea and vomiting, gastritis, ulceration of the
GIT, pancreatitis, alcoholic hepatitis, cirrhosis of the liver,
increased incidence of CA of the mouth, larynx,
esophagus; immunosuppression increased incidence of
infections.
¡ Impaired testicular synthesis reduced serum
testosterone and sperm motility, impotence, signs of
feminization.
¡ Alcoholic polyneuropathy: Numbness, pain, muscle
wasting in the legs.
¡ Wernicke encephalopathy: Ocular abnormalities
(nystagmus) due to excessive ethanol use and deficiency
of thiamine.
ETHANOL: Adverse Reactions
Chronic
n Korsakoff’s syndrome:
¡ Impairment of memory of recent events
¡ Lessened learning ability
¡ Disorientation in space and time
¡ Polyneuritis: Pain in the extremities and paralysis of the
arms and legs (deficiency of thiamine or B1)
n Fetal alcohol syndrome (FAS):
¡ Retarded body growth
¡ Mental retardation and behavioral abnormalities
¡ Microcephaly
¡ Underdevelopment of midfacial region (appears as flattened
face)
¡ Congenital cardiac abnormalities
Blood Alcohol Concentration and
Clinical Effects in Nontolerant
Individuals
ETHANOL: Manifestations of Alcohol
Withdrawal
n Acute alcoholic hallucinosis: Auditory, visual, tactile, and
olfactory.
n Delirium tremens
¡ Occurs after heavy and excessive drinking for 2-6 weeks.
¡ 1st stage – “Shakes”: Restlessness, insomnia, tremor, fear,
perspiration, headache.
¡ 2nd stage – “Horrors”: Hallucinations, delirium.
n Rx: Benzodiazepines
ETHANOL: Drug Interactions
ETHANOL: Clinical Uses
n As antiseptic in 50-95% solutions
(70% - optimum concentration)
n As an aid in reducing fever
n For the treatment of peripheral vascular disease (as
vasodilator)
n As antidote in methanol and ethylene glycol poisoning
n As solvent and preservative in many drugs
Management of Acute Alcohol
Intoxication and Alcohol Withdrawal
Syndrome
n ACUTE ALCOHOL INTOXICATION (to prevent severe
respiratory depression and aspiration of vomitus)
¡ Glucose
¡ Thiamine
¡ Electrolyte solutions, especially containing potassium if
vomiting is severe
n ALCOHOL WITHDRAWAL SYNDROME (to prevent seizures,
delirium, and arrhythmias)
¡ BZD
ETHANOL: Treatment of
Alcoholism
1. Disulfiram or Tetraethylthiuram (Antabuse)
¡ Aversion therapy as pharmacologic adjunct in the treatment
of alcoholism.
¡ MOA: Irreversibly inhibits aldehyde dehydrogenase by
binding to the sulfhydryl groups of the enzyme (also
metabolite: diethyldithiocarbamic acid) Accumulation of
acetaldehyde
¡ Acetaldehyde syndrome: Cutaneous sensation of heat,
flushing, vasodilation, hypotension, palpitation, increased
HR, vomiting, unconsciousness, and collapse.
¡ Pharmacokinetics:
n Adequately absorbed in the GIT.
n Distributed widely throughout the body.
n Peak plasma concentration within 1-2 hours.
ETHANOL: Treatment of
Alcoholism
¡ Contraindicated in patients with a history of severe
myocardial disease or coronary occlusion, psychosis, or
hypersensitivity.
¡ Drugs which cause a disulfiram-like reaction with ethanol:
Acetohexamide – Cefoperazone – Cephamandole –
Ceftriaxone – Chloramphenicol – Griseofulvin –
Metronidazole – Moxalactam – Phentolamine – Procarbazine
– Tolazamide – Tolbutamide – Chloral hydrate
¡ Inhibits also the metabolism of other therapeutic agents as:
Phenytoin, oral anticoagulants, and Isoniazid.
2. Daidzin
¡ Chinese herbal medicine used traditionally to cure
alcoholics.
¡ Inhibits aldehyde dehydrogenase.
ETHANOL: Treatment of
Alcoholism
3. Naltrexone
¡ Orally active, long-acting, opioid receptor
antagonist that blocks the effects at opioid
receptors.
¡ Administered OD at a dose of 50 mg.
¡ Contraindications: In patients with elevated serum
transaminase and who are taking Disulfiram
hepatotoxic effects; patients who are physically
dependent on opioids acute withdrawal
syndrome.
4. Acamprosate
¡ Weak NMDA receptor antagonist and GABA receptor
activator.
¡ Reduces short-term and long-term relapse rates.
METHANOL
n Methyl alcohol or wood spirit or wood alcohol
n Derived from destructive distillation of wood.
n Found in the home in windshield-washing products
n Absorbed through the skin or respiratory and GI tracts.
n Biotransformed by alcohol dehydrogenase to
formaldehyde and formic acid.
n Used mainly as industrial solvent, gasoline additive,
METHANOL: Poisoning
n Visual disturbance (blurred vision) partial or complete
blindness (formic acid damage to retinal cells and
degeneration of the optic nerve), CNS depression, nausea,
vomiting, slowed respiration, bradycardia, and coma.
n Dx: Formaldehyde odor in breath and urine.
n Treatment
1. Supportive: Correction of acidosis, maintenance of
respiration, monitoring of electrolytes, providing nutrition
2. Dialysis
3. Administration of ethanol (competes with methanol for
alcohol dehydrogenase); 4-methylpyrazole (inhibits alcohol
ETHYLENE GLYCOL
n Biotransformed to axalic, glycolic, and formic acids by
alcohol dehydrogenase; oxalate crystals are deposited in
the kidneys where they are toxic.
n Poisoning:
¡ Stage 1: Transient excitation, CNS depression
¡ Stage 2: Severe metabolic acidosis
¡ Stage 3: Delayed renal insufficiency
n Rx: Dialysis and administration of Ethanol and
Fomepizole (inhibit alcohol dehydrogenase reduced
biotransformation into oxalate)
n Used in anti-freeze formulations and as industrial
solvents.
ISOPROPYL ALCOHOL
n Isopropanol or 2-propanol
n Available as 70% rubbing alcohol.
n Biotransformed to acetone by alcohol dehydrogenase.
n t ½ of 2.5 – 3 hours.
n Lethal dose: 150 – 240 ml.
n 2x more potent than ethanol as CNS depressant.
n Toxicity: Nausea, vomiting, dizziness, CNS depression,
coma, respiratory depression.
n Rx: Supportive – Maintain vital functions and
hemodialysis.
n Used as antiseptic and as topical agent to reduce fever; in
windshield de-icers.
