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Ethyl alcohol3

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Pharmacology

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Ethyl alcohol3

  1. 1. ETHYL ALCOHOL USES & TOXICITY ALDEHYDE DEHYDROGENASE INHIBITOR
  2. 2. ETHYL ALCOHOL CLINICAL USES
  3. 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. 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. 5. ETHYL ALCOHOL TOXICITY
  6. 6. SIDE EFFECTS OF MODERATE DRINKING • Nausea • Vomiting • Flushing • Hangover • Traffic accidents
  7. 7. ACUTE ALCOHOLIC INTOXICATION • Unawareness • Unresponsiveness • Stupor • Hypotension • Gastritis • Hypoglycemia • Respiratory depression • Collapse • Coma • Death
  8. 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. 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. 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. 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. 12. • Alcoholic cirrhosis of liver • Hypertension • Cardiomyopathy • Congestive heart failure • Arrhythmias • Stroke • Acute pancreatitis • Impotence • Gynaecomastia • Infertility • Skeletal myopathy
  13. 13. • Incidence of oropharyngeal, esophageal and hepatic malignancy and respiratory infections are high as immune system is depressed
  14. 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. 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. 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. 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. 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. 19. • The 5-HT3 antagonist ondansetron and the antiepileptic topiramate have also shown some promise in treating alcoholism
  20. 20. ALDEHYDE DEHYDROGENASE INHIBITOR
  21. 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 )
  22. 22. • They are : • Flushing • Burning sensation • Throbbing headache • Perspiration • Uneasiness • Tightness in chest • Dizziness • Vomiting • Visual disturbances • Mental confusion • Postural fainting • Circulatory collapse
  23. 23. • 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.
  24. 24. 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
  25. 25. • 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
  26. 26. SIDE EFFECTS • Infrequent • Include : • Rashes • Metallic taste • Nervousness • Malaise • Abdominal upset
  27. 27. • 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
  28. 28. • Available as ESPERAL, ANTADICT, DEADICT 250 mg tablets Internationally marketed as ANTABUSE

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