Pharmacology

1. ETHYL ALCOHOL
USES & TOXICITY
ALDEHYDE
DEHYDROGENASE
INHIBITOR

2. ETHYL ALCOHOL
CLINICAL USES

3. CLINICAL USES
• As antiseptic
• Rubefacient and counterirritant for sprains, joint pains etc.
Spirit is generally used as vehicle for other ingredients
• Rubbed into skin to prevent bedsores. Not used on already
formed bedsores.
• Astringent action of alcohol – used in antiperspirants and
aftershave lotions.
• Alcoholic sponges to reduce body temperature in fever.
• Intractable neuralgia and severe cancer pain, injection of
alcohol round the nerve causes permanent loss of
transmission

4. • To ward off cold
– Whiskey or brandy may benefit by causing vasodilatation of blanched
mucosae
– Further exposure after taking alcohol may be deleterious because
alcohol increases heat loss due to cutaneous vasodialatation.
• Appetite stimulant and carminative
– 30-50 ml of 7-10% alcohol as beverages or tinctures (of ginger/
cardamom etc.) before meal
• Reflex stimulation in fainting/ hysteria – 1 drop in
nose
• To treat methanol poisoning

5. ETHYL ALCOHOL
TOXICITY

6. SIDE EFFECTS OF MODERATE
DRINKING
• Nausea
• Vomiting
• Flushing
• Hangover
• Traffic accidents

7. ACUTE ALCOHOLIC INTOXICATION
• Unawareness
• Unresponsiveness
• Stupor
• Hypotension
• Gastritis
• Hypoglycemia
• Respiratory depression
• Collapse
• Coma
• Death

8. TREATMENT
• Gastric lavage - only when the patient is brought soon
after ingesting alcohol (rare)
• If patients are disoriented or comatose (mostly),
maintain patent airway and prevent aspiration of
vomitus
• If respiration is markedly depressed, tracheal
respiration and positive pressure respiration.
Analeptics should not be given, as they may
precipitate convulsions.

9. • In most cases, patients recover with supportive
treatment, maintenance of fluid and electrolyte
balance, correction of hypoglycemia (glucose infusion)
till alcohol is metabolized
• Thiamine should be added ( 100 mg in 500 ml glucose
solution i.v. )
• Hemodialysis hastens the recovery
• Insulin + fructose drip – accelerate alcohol metabolism

10. CHRONIC ALCOHOLISM
• On chronic intake, tolerance develops to subjective and
behavioral effects of alcohol, but is of low degree.
• Pharmacokinetic – reduced rate of absorption due to
gastritis and faster metabolism due to enzyme induction
• Cellular tolerance
• Psychic dependence – even with moderate drinking,
depends on individual’s liking and attitudes.
• Physical dependence – only on heavy and round-the-clock
drinking
• Heavy drinking is associated with nutritional
deficiencies (food is neglected and malabsorption)

11. COMPLICATIONS
• Impaired mental and physical performance
• Neurological afflictions
• Polyneuritis
• Pellagra
• Tremors
• Seizures
• Loss of brain mass
• Wernicke’s encephalopathy
• Korsakoff’s psychosis
• Megaloblastic anemia

12. • Alcoholic cirrhosis of liver
• Hypertension
• Cardiomyopathy
• Congestive heart failure
• Arrhythmias
• Stroke
• Acute pancreatitis
• Impotence
• Gynaecomastia
• Infertility
• Skeletal myopathy

13. • Incidence of oropharyngeal, esophageal and hepatic
malignancy and respiratory infections are high as
immune system is depressed

14. WITHDRAWAL SYNDROME
• When a physically dependent subject stops drinking,
withdrawal syndrome appears within a day
• Severity depends on duration and quantity of alcohol
consumed
• Consists of :
• Anxiety
• Sweating
• Tachycardia
• Tremor
• Impairment of sleep
• Confusion
• Hallucinations
• Delirium tremens
• Convulsions
• Collapse

15. TREATMENT
• Psychological and medical support needed
during withdrawal
• To suppress withdrawal syndrome :
• CNS depressants like barbiturates, phenothiazine,
chloral hydrate as substitution therapy – used in the
past
• Benzodiazepines ( chlordiazepoxide, diazepam ) –
preferred now due to longer duration of action and can
be withdrawn gradually

16. NALTREXONE
• Long acting opioid antagonist
• Reinforcement is weakened.
– In pleasurable reinforcing effects of alcohol, opioid system is involved
through dopamine mediated reward function.
• Helps prevent relapse of alcoholism
• Reduce alcohol craving, number of drinking days and chances
of resumed heavy drinking.
• Approved as adjuvant in comprehensive treatment programs
for alcohol dependent subjects
• Used in most of the deaddiction centres in India

17. • Long acting (1-2 days), hence suitable for opioid
blockade therapy of post addicts
• Dosage : 50 mg/day orally
– No subjective effects are produced and carving subsides
• Side effects : nausea (common), headache,
hepatotoxicity (in high doses)
• Available as NALTIMA – 50 mg tablets

18. ACAMPROSATE
• Weak NMDA receptor antagonist with modest GABAA
receptor agonistic activity
• Used in USA, UK and Europe
• Reduce relapse of drinking, efficacy comparable to that of
naltrexone.
• Started soon after withdrawing alcohol, given continuously
• Dose – 666 mg 2-3 times/day
• Side effects : loose motion (common), nausea, abdominal
pain, itching.

19. • The 5-HT3 antagonist ondansetron and the
antiepileptic topiramate have also shown some
promise in treating alcoholism

20. ALDEHYDE
DEHYDROGENASE
INHIBITOR

21. DISULFIRAM
• Inhibits the enzyme aldehyde dehydrogenase
probably after conversion into active
metabolites.
• When alcohol is ingested after taking
disulfiram,
– acetaldehyde concentration in tissues and blood
rises
– a number of highly distressing symptoms are
produced promptly ( aldehyde syndrome )

23. • They are :
• Flushing
• Burning sensation
• Throbbing headache
• Perspiration
• Uneasiness
• Tightness in chest
• Dizziness
• Vomiting
• Visual disturbances
• Mental confusion
• Postural fainting
• Circulatory collapse

24. • Duration of the syndrome (1-4 hrs) depends
on amount of alcohol consumed
• Due to risk of severe reaction, disulfiram is to
be used with great caution only in well
motivated patients.

25. DISULFIRAM AVERSION THERAPY
• Indicated in abstinent subjects who sincerely desire to leave
the habit
• After making sure that the subject hasn’t consumed alcohol in
past 12 hrs,
Disulfiram is given at a dose of 500 mg/day for one week
followed by 250 mg daily
• Sensitization to alcohol :
• Develops after 2-3 hrs of first dose
• Peak at ~12 hrs
• Last for 7-14 days after stopping it
because the inhibition of aldehyde dehydrogenase with
disulfiram is irreversible and synthesis of fresh enzyme is required for
return of activity

26. • Subject’s resolve not to drink is reinforced by the
distressing symptoms that occur if he drinks a little
bit
• Subject should be cautioned to avoid alcohol
altogether
• Should not be used in patients who are physically
dependent on alcohol

27. SIDE EFFECTS
• Infrequent
• Include :
• Rashes
• Metallic taste
• Nervousness
• Malaise
• Abdominal upset

28. • It also inhibits a number of other enzymes
including
• Alcohol dehydrogenase
• Dopamine β hydroxylase
• Several cytochrome p450 isoenzymes
• Thus, it prolongs t1/2 of many drugs

29. • Available as
ESPERAL, ANTADICT, DEADICT 250 mg tablets
Internationally marketed as ANTABUSE