ETHYL ALCOHOL USES & TOXICITY

ALDEHYDE DEHYDROGENASE

INHIBITOR

ETHYL ALCOHOLCLINICAL USES

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

• 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

ETHYL ALCOHOL TOXICITY

SIDE EFFECTS OF MODERATE DRINKING

• Nausea• Vomiting• Flushing• Hangover• Traffic accidents

ACUTE ALCOHOLIC INTOXICATION

• Unawareness• Unresponsiveness• Stupor• Hypotension• Gastritis

• Hypoglycemia• Respiratory depression• Collapse• Coma• Death

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.

• 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

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)

COMPLICATIONS

• Impaired mental and physical performance• Neurological afflictions

• Polyneuritis• Pellagra• Tremors• Seizures• Loss of brain mass• Wernicke’s encephalopathy• Korsakoff’s psychosis• Megaloblastic anemia

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

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

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

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

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

• 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

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.

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

ALDEHYDE DEHYDROGENASE

INHIBITOR

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 )

• They are :

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

• 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.

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

• 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

SIDE EFFECTS

• Infrequent• Include :

• Rashes• Metallic taste• Nervousness• Malaise• Abdominal upset

• 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

• Available as

ESPERAL, ANTADICT, DEADICT 250 mg tablets

Internationally marketed as ANTABUSE

thank you…