This document summarizes information about ethyl alcohol (ethanol). It discusses how ethanol is manufactured through fermentation of sugars by yeast, its pharmacological actions including central nervous system depression, and metabolic effects. Potential acute and chronic effects of alcohol consumption are outlined. The mechanisms of action and pharmacokinetics of ethanol are described. Interactions with other drugs and treatment of alcohol dependence and methanol poisoning are also summarized.

2. Ethyl ALCOHOLs
Dr.Ravi K. Sori
SDM College of Medical Sciences & Hospital
Dharwad

3. Why & What to learn about Alcohol??

4. How it is manufactured ?
• Fermentation - Sugar to Alcohol & Carbon dioxide
(Yeasts + sugar + water = CO2 + ethanol)
Starch Maltose
• Yeasts are living micro-organisms which die in concentrations of alcohol greater than
10 to 15%
• Commercially - obtained from Molasses
Convertase

5. Pharmacological Actions
Local -
On topical application - evaporates quickly & it has a cooling effect
Rubefacient & Counter irritant
Injected s.c.- pain, inflammation & necrosis followed by fibrosis
Astringent action - precipitates surface proteins & hardens the skin
Antiseptic activity - Maximum effect at 70% ( 70% - 90% remains same &
above 90% decreases)

6. Central Nervous System
CNS depressant
Small doses- euphoria, relief of anxiety & loss of social inhibition
Moderate doses- impaired muscular coordination & visual acuity
High doses- mental clouding, impaired judgement, drowsiness & loss of
self control, ataxia, altered gait
200-300mg/dl - Stupor, convulsions, medullary centre paralysis coma &
death

7. MOA
Inhibiting central neuronal nicotinic cholinergic receptors
Inhibiting excitatory NMDA & kainite receptor function
Promoting the function of 5-HT3 receptors
Ethanol also influences many ion channels including K+ channels

8. Cardiovascular system
• Small doses - Cutaneous & gastric vasodilatation, flushing
• Medium doses - Tachycardia & mild rise in BP
• Large doses - Vasodilatation due to direct vascular smooth muscle
dilatation & vasomotor centre depression (clinical implication)

9. Blood
• Tend to raise HDL - cholesterol levels & decreases LDL oxidation
• It may be responsible for the 15-35% lower incidence of CAD
• Mild anaemia is common in chronic alcoholics
• Megaloblastic anaemia - chronic alcoholism - interference with the folate
mechanism

10. Respiratory System
• Stimulation of respiration - by irritation of pharyngeal & buccal mucosa
• Central action - depression

11. GI System
• Dilute alcohol at low doses - stimulate GI secretion - flavour, aroma or direct
action on gastrin secretion, increases appetite
• Higher doses inhibit GI secretion
• Acute consumption - pylorospasm, gastritis, vomiting, reflux etc
• Mallory - Weiss lesion

12. Mallory - Weiss lesion

13. Liver
• Exposes to oxidative stress & causes cellular necrosis followed by
fibrosis
• Acetaldehyde - damage the hepatocytes & induce inflammation
• Alcoholic liver cirrhosis:
Increased lipid peroxidation & glutathione depletion occurs -
combined with vitamin & nutritional deficiencies

14. Renal System
• Alcohol promotes & increased excretion of urine -
ADH inhibition
• Alcohol inhibits the renal secretion of uric acid by an unknown
mechanism that allows uric acid to build up in the blood

15. Other actions
• Uterus: relaxation of uterine muscles
Endocrine:
• Low dose - adrenaline release & hyperglycaemia
• High dose - hypoglycaemia - depletion of hepatic glycogen –
gluconeogenesis is inhibited.
• Aphrodisiac

16. Other actions
• Chronic alcoholism - nutritional deficiencies, associated with
osteoporosis(?)

17. Foetal alcohol syndrome (FAS) - condition affecting children born to alcohol
consuming mothers that is characterized by facial deformities, growth deficiencies,
mental retardation

18. Pharmacokinetics
Absorption:
• Rapidly absorbed from small intestine & colon but slowly from
stomach
• Limited first pass metabolism in stomach & liver Maximal blood
concentration within 30 to 90 minutes
• Can be absorbed through the lungs & skin

19. Distribution:
• Uniformly distributed throughout tissues & body fluids
• Readily crosses placenta & crosses BBB
Elimination:
• Urinary Excretion
• Exhalation
• Metabolism

20. Drug Interactions:
 It potentiates other CNS depressants including hypnotics, opioids &
antipsychotics
 Sulfonylureas, metronidazole & griseofulvin have disulfiram like
reactions
 It is an enzyme inducer
 It increases gastric acidity & potentiates the ulcerative effects of
NSAIDs & other gastric irritant drugs

21. A disulfiram-like drug is a drug that causes hypersensitivity to alcohol
leading to nausea, vomiting, flushing, dizziness,
throbbing headache, chest & abdominal discomfort, &
general hangover-like symptoms among others
These effects are caused by accumulation of acetaldehyde, a major but
toxic metabolite of alcohol formed by the enzyme alcohol dehydrogenase
The reaction has been variously termed a
disulfiram-like reaction, alcohol intolerance, & acetaldehyde syndrome

22.  The prototypical drug of this group is disulfiram (brand name
Antabuse), which acts as an acetaldehyde dehydrogenase inhibitor,
preventing the metabolism of acetaldehyde into acetic acid, & is used
in the treatment of alcoholism
 A variety of other drugs cause disulfiram-like reactions upon
consumption of alcohol as unintended drug interactions & side effects

23. Acute Effects:
 Nausea, Vomiting, hangover & traffic accidents
 CNS Depressant
 Depression of inhibitory control
 Vasodilatation, warm, flushed, reddish skin
 Emotional outbursts
 Decreased memory & concentration
 Poor judgment
 Decreased reflexes
 Decreased sexual response

24. Acute Alcohol Intoxication:
• Estimated ED50: 150 mg/100 ml & LD50 = 500 mg/100ml
• Therapeutic index about 3.5
• Hypotension, hypoglycaemia, respiratory depression coma & death
• Death due to respiratory depression or inhaled vomit
Treatment:
• Gastric lavage
• Endotracheal intubations
• Fluid & electrolyte balance & Glucose infusion
• Thiamine injection 100 mg in 500 ml of glucose IV
• Haemodialysis

25. Chronic alcoholism:
 Dependence
 Wernicke’s encephalopathy
 Psychosis
 Tremors
 Cirrhosis of liver
 Hypertension
 Cardiac abnormalities
 Acute pancreatitis
 Infertility

26. Rx of Alcohol dependence
• Internationally marketed as Antabuse
• ALDH enzyme inhibitor
• Alcohol + disulfiram rise in concentration of aldehyde in blood & tissue
distressing aldehyde syndrome
• Symptoms: flushing, burning sensation, throbbing headache, perspiration,
dizziness, vomiting, visual disturbance, mental confusion, fainting &
circulatory collapse

27. Uses: aversion technique in chronic alcoholics: only to motivated persons
Technique: abstain alcohol overnight and start with 1 gm on day 1 followed by 0.75
gm next day and 0.50 gm next day and so on
Effects start within few hrs of 1st dose and lasts for 2 weeks
Mechanism: irreversible inhibition of ALDH & synthesis of new enzyme takes time &
thus person resolves not to drink for distressing symptoms
Available as 250 mg tablets

28. Ethanol
Alcohol
Acetic acidAcetaldehyde
dehydrogenase dehydrogenase
Aldehyde

29. Uses
• Antiseptic, rubefacient & counterirritant in sprains & to prevent bedsores
• Antiperspirant & aftershave
• Alcohol sponges - to reduce body temperature
• Appetite stimulant and carminative: 30 - 60 ml of 7 - 10%
• Neuralgias: severe cancer pain - injection round the nerve
• Protection from cold
• Alcohol may have a protective effect from heart attack & stroke

30. Contraindications
 Peptic ulcer, hyperacidity
 GERD
 Epileptics - seizures may be precipitated
 Severe liver disease patients
 Unstable personalities
 Pregnant women

31. Ethanol as Antidote
• It is mainly used in the Rx of Methanol poisoning
• Industrial rectified spirit & only of toxicological importance
• Methanol is used to denature ethanol
• It is of no therapeutic value
• Ingestion results in methanol poisoning

32. Methanol
Alcohol
Formic acidFormaldehyde
dehydrogenase dehydrogenase
Aldehyde
Vomiting, headache, vertigo, epigastric pain, dyspnoea, bradycardia, acidosis -
permanent retinal damage, coma & death

33.  Patient in dark room, Ventilation & BP supportive measures
 Gastric lavage - sodium bicarbonate within two hours of consumption of methanol
 I.V. sodium bicarbonate to combat acidosis - large quantity may be required
 Ethanol 10% in water - nasogastric tube with loading dose of 0.7 ml/kg followed by
15 ml/kg/hr by infusion - continue treatment for several days
 Potassium chloride if hypokalaemia occurs
 4-methylpyrazole (Fomepizole) specific inhibitor of ALD
 Haemodialysis