1. Ethanol enhances GABA and inhibits NMDA receptors in the brain, producing sedative and hypnotic effects. Acute effects include impairment starting at 60-80 mg/dL blood levels. 2. Both physical and psychological dependence can develop with chronic use. Liver damage, gastrointestinal inflammation, and neurological effects like peripheral neuropathy and Wernicke-Korsakoff syndrome are chronic effects. 3. Treatment of acute intoxication involves supportive care, thiamine to prevent Wernicke-Korsakoff syndrome, and glucose for hypoglycemia. Withdrawal is treated with long-acting benzodiazepines. Disulfiram prevents drinking by producing unpleasant reactions when

1. Alcohol
Alcohol
Ethanol Methanol Ethylene glycol

2. Ethanol
Mechanism of action: Ethanol
Ethanol enhances the action of GABA
through GABA-A receptor
It also inhibits NMDA receptor
Ethanol potentiates the action of BZD and
barbiturates and can result in fatal CNS
depression.

4. Pharmacodynamics
#.Two effects:
A. Acute effects
B. Chronic effects

5. Acute effects
1. CNS effects: Sedative & hypnotic
 Sedation, ataxia, impaired judgment,
& slurred speech
 Impairment of driving: 60-
80mg/dLplasma level.
 Gross drunkenness: 120-160 mg/dL

6. Continued
 Unconsciousness, anesthesia and
cardiac depression: ~ or > 300 mg/dL
 Lethal dose- ~ or > 500 mg/dL
#. Molecular MOA: induces GABA
action at GABA-A and inhibit
glutamate to NMDA-r.

7. Continued
2. Other organs:
 Depression of heart [low dose] &
vaso-dilation
 Uterine relaxant
 Increases the effect of sulfonylureas
 Boosts up the antiplatelet action of
aspirin.

8. Chronic effects
#. Both psychologic & physical dependence: An
abstinence syndrome
#. Liver: decreased gluconeogenesis, fat
accumulation ( NAD )- Hepatic dysfunction
 Acetaminophen- to toxic metabolite
#. GIT: Causes inflammation & hemorrhage of
gut

9. Continued
#. Central nervous system:
 Peripheral neuropathy: common
 Wernicke- Korsakoff’s syndrome:
extra ocular muscle paralysis, ataxia,
confusion, ( delirium tremens)-
( Thiamin )

10. Continued
#. Cardiovascular system: hypotension,
anemia and MI
#. Endocrine effects: Gynecomastia,
salt retention, testicular atrophy
#. Fetal alcohol syndrome.
#. Neoplasia: Breast cancer etc.

11. Uses of Ethanol
1.External uses:
 Solvent for many drugs
 Vehicle for medicinal mixtures
 To wash skin burn due to phenol
 As a cool sponge
 Disinfectant for skin & rubefacient in
liniments

12. Continued
2. Internal uses:
 As a analgesic for trigeminal neuralgia
 In methyl alcohol & ethylene glycol
poisoning

13. Drug interaction with alcohol
#. Pharmacokinetic
 Enzyme induction on chronic
administration
• Enzyme inhibition on acute intake.

14. Continued
#. Pharmacodynamic
 Increases the effect of drugs-
sedative hypnotic, TCA, Aspirin, oral
hypo-glycemic drugs.

15. Treatment of Acute Alcohol
Intoxication
#. Supportive measure:
 Prevent respiratory depression &
aspiration pneumonia
 Maintain respiration and circulation
 Fatal blood concentration: 400mg% &
legal limit of intoxication: 100% 7-10
g/h is metabolized

16. Continued
 Give fluids and electrolytes
#. Pharmacological measure:
 Give glucose to treat hypoglycemia
and ketosis
 Thiamine [10 mg] is added to protect
against the Wernike-Korsakoff
syndrome

17. Treatment Alcohol Withdrawal
Syndrome
 Prevent seizures, delirium, &
arrhythmia
 Restore K, Mg, & Phosphate ions
#. Specific therapy:
 A long acting sedative- hypnotic drugs:
e.g. Chlordiazepoxide, diazepam, etc.
 Thiamine 10 mg is suggestive

18. Continued
 Oxazepam is drug of choice in liver
disease
 Phenytoin is administered for seizure
 Propranolol: to treat tremor

19. Disulfiram
 Inhibits acetaldeyde dehydrogease and
accumulates acetaldehyde
 Induces flushing, throbbing headache, nausea,
vomiting, perspiration, hypotention and confusion
( few minutes to several hours )
 Disulfiram ( 250mg ): at bed time.

20. Drugs induce “disulfiram- like
reaction”
 Metronidazole
 Cefoperazone,
 Gresiofulvin,
 Chlopropamide,
 Nitrofurantion,
 Diazine
 Chloral hydrate

21. The drugs reduce craving of
alcohol
 Fluxetine
 Bromocriptine
 Naltrexone
 Acamprosate

22. Methanol
#. MOA: methanol is
 Metabolized to formadehyde and
formic acid by alcohol dehydrogenase
 Severe acidosis and retinal damage.
#. Intoxication: Visual dysfunction,gut
distress, SOB, loss of conscious,
coma & death

23. Treatment of Methanol
 Ethanol: 10% in D/W; loading dose 0.7
ml/kg; then 0.15 ml/kg/h )
 Iv sodium bicarbonate for acidosis
 Potassium for hypokalimea
 Fluids and electrolytes
 Keeps patient in dark room
 Hemodialysis

24. Continued
 Antidote: Fomepizole (100mg) iv is to
be given an inhibitor of Alcohol de-
hydrogenese
 Calcium leucovorin reduces formate in
blood.

25. Ethylene glycol
 Ethylene glycol poisoning: by
inhalation and skin absorption or by
intake
 It is metabolized by ADH and
formation of oxalic acid- severe
acidosis and nephro-toxicity

26. Treatment
#. Supportive measure: same
#. Pharmacological measure:
 Prompt ethyl alcohol intravenous
slowly to prevent toxic metabolite of
ethylene glycol
 Fomepizole if necessary