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Alcohols

Ethanol is a water-soluble aliphatic alcohol produced by fermentation of sugars. It is metabolized primarily in the liver via alcohol dehydrogenase and microsomal ethanol oxidizing systems. Acute effects include intoxication and depression of respiratory and vasomotor centers. Chronic effects include fatty liver, hepatitis, and fetal alcohol syndrome. Treatment of alcoholism includes disulfiram and naltrexone. Methanol, ethylene glycol, and isopropyl alcohol are toxic alcohols metabolized to toxic metabolites and treated with supportive care and inhibitors of metabolism.

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313 views23 pages

Alcohols

Ethanol is a water-soluble aliphatic alcohol produced by fermentation of sugars. It is metabolized primarily in the liver via alcohol dehydrogenase and microsomal ethanol oxidizing systems. Acute effects include intoxication and depression of respiratory and vasomotor centers. Chronic effects include fatty liver, hepatitis, and fetal alcohol syndrome. Treatment of alcoholism includes disulfiram and naltrexone. Methanol, ethylene glycol, and isopropyl alcohol are toxic alcohols metabolized to toxic metabolites and treated with supportive care and inhibitors of metabolism.

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dhainey
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© Attribution Non-Commercial (BY-NC)
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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.

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