Ethyl alcohol (Ethanol)

Pharmacological action

1.       Local actions

  • Mild rubifacient and counterirritant when rubbed on the skin
  • By evaporation it produces cooling
  • Applied on delicate skin (scrotum) and mucous membrane, it produces irritation and burning sensation
  • Injected sc, it causes intense pain, inflammation and necrosis followed by fibrosis
  • Injected around a nerve, it produces permanent damage
  • Applied to surface, alcohol is astringent- precipitates surface proteins and hardens the skin
  • By precipitating bacterial proteins, it acts as antiseptic. The antiseptic action increases with concentration from 20 to 70%, remains constant from 70-90% and decreases above that
  • Alcohol does not kill bacterial spores

2.       CNS

  • Alcohol is a neuronal depressant
  • Excitation and euphoria are experienced at low concentration (30-60 mg/dl). Hesitation, caution, self-criticism and restraint are lost first
  • Mood and feeling are altered; anxiety may be allayed
  • With increasing concentration (80-150 mg/dl) mental clouding, disorganization of thought, impairment of attention, memory and other facilities, alteration of gait and perception and drowsiness supervene
  • At 150-200 mg/dl the person is sloppy, ataxic and drunk, black outs occurs
  • 200-300 mg/dl results in stupor and above this unconsciousness prevails, medullary centres are paralysed and death may occur
  • Alcohol can induce sleep but is not a dependable hypnotic 
  • Hangover (headache, dry mouth, laziness, disturbed mood, impaired performance) may occur next morning
  • Alcohol raises pain threshold and also alters reaction to it- severe pain can precipitate confusion and convulsions
  • GABAA receptors play a central role in mediating the effects of ethanol in the CNS. GABA is the primary inhibitory neurotransmitter and activation of GABAA receptors by GABA tends to decrease neuronal excitability. (1)
  • At neurochemical level, the moderate consumption of alcohol selectively affects the function of GABA, glutamatergic, serotonergic, dopaminergic, cholinerigc and opioid neuronal systems. Genetic factors and gender also play role in metabolism and behavioral effects. There is a positive effect of moderate ethanol consumption on cognitive performance in the aging human. (2)
  • 24 hour ethanol drinking has little efefct on CNS functional neuronal activity in alcohol preferring rats. (3)
  • Ethanol has many direct and indirect effects on the central nervous system, in moderation it can have some beneficial effects. There is no safe limit to alcohol consumption in pregnancy. In adults, acute intoxication can lead to cardiopulmonary depression and death. (4)
  • Tingling sensations in the mucous membrane of the mouth and throat appear with blod level of 10mg%, passes into stuporous condition at 300 mg% and at high levels (400mg%) falls into a state of deep anesthesia which may lead to death. (5)

3.       CVS

  • Small doses roduce only cutaneous and gastric vasodilation. Skin is warm and flushed and there may be conjunctival injection; BP is not affected
  • Moderate doses cause tachycardia and a mild rise in BP due to increased muscular activity and sympathetic stimulation
  • Large dose cause direct myocardial as well as vasomotor centre depression and there is fall in BP
  • Chronic alcoholism contributes to hypertension and can lead to cardiomyopathy. Atrial fibrillation and other arrhythmias may occur due to conduction defects and Q-T prolongation. 
  • The effects of alcohol on the heart include modification of the risk of coronary artery disease, the development of alcoholic cardiomyopathy, exacerbation of conduction disorders, atrial and ventricular dysrhythmias and an increased risk of hypertension, hemorrhagic stroke, infectious endocarditis and fetal heart abnormalities. (6)
  • The regukar heavy ethanol consumption is associated with alcoholic cardiomyopathy which is expressed as impairment of left ventricular function to overt heart failure. Soon after the onset if chronic ethanol consumption, the negative ionotropic effect of acute ethanol is temporarily counteracted by adaptive mechanism leading to expression of a temporary positive ionotropic effect. (7)
  • The patients who consume >90 g of alcohol a day for > 5years are at risk of developing asymtomatic alcoholic cardiomyopathy (ACM). Those who continue to drink become symptomatic and develops signs and symptoms of heart failure. (8)
  • Ethanol exerts a direct reversible effect on cardiac purkinje fibres. These effects probably results from a physical altertion from sarcolemma. The metabolic byproducts of ethanol do not exert a direct electrophysiological effect on canine purkinje fibers or huinea pig atria. (9)  
  • Moderate consumption of up to 2 drinks per day for men and 1 drink per day for women is associated with the greatest potential benefit at the lowest overall risk. (10)
  • Favourable changes in several cardiovascular biomarkers (higher levels of high density lipoprotein cholestrol and adiponectin and lower levels of fibrinogen) provide indirect pathophysiological support for a protective efefct of moderate alcohol use on coronary artery disease. (11)

4.       Blood

  • Regular intake of small to moderate amount of alcohol raise HDL cholesterol and decrease LDL oxidation
  • Mild anemia is common in chronic alcoholics
  • Megaloblastic anemia occurs in chronic alcoholics due to interference with folate metabolism
  • Ethanol impairs platelet function and that impaired function is due ti both extracorpuscular factors and platelet injury. (12)
  • Consumption of commonly ingested quantities of alcohol causes development of a hypocoagulable state in men but has no efefct on the coagulable status in women. (13)
  • Acute ethanol intake affect blood fibrinolysis activity in a way which might precipitate a state of increased risk of thrombotic diseases. (14)
  • The effect of alcohol on blood pressure is predominantly due to alcohol consumed in the few days immediately preceding blood pressure measurement, with alcohol consumption before few days exerting little effect on blood pressure. (15)
  • There is a direct and reversible pressor efefct of regular moderate alcohol consumption in normotensive men and alcohol plays a major role in the genesis of early stages of blood pressure elevation. (16)

5.       Body temperature

  • It produce a sense warmth due to cutaneous and gastric vasodilatation
  • High doses depress temperature regulating centre
  • Alcohol acts acutely to abolish all thermoregulatory control functions. The physiological mechanisms for the dissipation of body heat as well as those for heat production are ancapacitataed by the drug. Alcohol is a poikilithermic agent, thus the decline in body temperature observed in animals typically at the laboratory room temp of 20 deg C – 24 deg C represents the result of a cold challange and is not due to a postulated hypothermic effect of alcohol. (17)
  • The high ambient pressure may counteract rather than potentiate the hypothermic effect of ethanol. (18)
  • There is a dose dependent biphasic alteration in behaviour and body temperature, where a low dose produces excitation and hyperthermia while a high dose causes increase state of depression and dose dependent hypothermia. (19)
  • There is serotoninergic involvement in the effect of ethanol on body temperature. (20)

6.       Respiration

  • Act as respiratory stimulants in collapse as they irritate buccal and pharyngeal mucosa which may transiently stimulate respiration reflexly
  • Direct action of alcohol on respiratory centre is a depressant one
  • Clinically relevant ethanol concentration in blood increase the sodium permeability of the plasma membrane and depress active sodium transport by suppressing Na, K-ATPase activity, thus intracellular sodium concentration increases. Chronic ethanol induced cell necrosis is related to increased intracellular calcium that accompanies the increase in sodium permeability. Critically elevated concentrations of calcium in the cytoplasm activate autlytic enzymes and is responsible for structural damage to the cell. (21)
  • Alcohol intake does not have a significant effect on respiratory ciliary beat frequency. (22)
  • Acute alcohol abuse causes damage to and functional impairment of several organs affecting carbohydrate and fat metabolism. Mitochondria participate with the convrion of acetaldehyde into acetate and the generation of increased amount of NADH. (23)

7.       GIT

  • Dilute alcohol (optimum 10%) put in the stomach by ryle’s tube is a strong stimulant of gastric secretion. It acts directly as well as reflexly
  • Higher concentration (above 20%) inhibit gastric secretion, cause vomiting, mucosal congestion and gastritis
  • Lower esophageal sphincter (LES) tone is reduced by alcohol
  • Drinking accentuate gastric reflux
  • Bowel movement may be altered in either direction

8.       Liver

  • It mobilize peripheral fat and increases fat synthesis in liver in a dose dependent manner
  • Proteins also accumulate in the liver because their secretion is decreased
  • Chronic alcoholism exposes liver to oxidative stress and causes cellular necrosis followed by fibrosis
  • Acetaldehyde produced during the metabolism of alcohol appears to damage the hepatocytes and induce inflammation, especially on chronic ingestion of large amount
  • Increased lipid peroxidation and glutathione depletion occurs
  • Regular alcohol intake induces microsomal enzymes
  • Liver injury is caused by direct effect of the metabolic byproducts of ethanol as well as by inflammation caused by these byproducts. Corticosteroids, antioxidants, antibiotics and certain polyunsaturated fats can be used in the treatment of alcoholic liver disease. (24)
  • Ethanol interferes with liver regeneration which is necessary to recover from alcoholic liver injury. (25)
  • The adhesion molecules may be associated with the initiation of hepatic injury during alcohol intoxication. (26) 
  • Ethanol increases the activity of δ- aminolaevulinate synthetase in rat liver. Alcohol may affect the oxidation/reduction state of the mitochondria thus leading to a sequence of reactions culminating in derepression of ALA synthetase activity by substrate induction. (27)

9.       Skeletal muscle

  • Fatigue is allayed in small doses, but muscle work is increased or decreased depending on the predominanting central effect
  • Weakness and myopathy occurs in chronic alcoholism
  • The muscle compositional changes are seen over acute periods of ethanol toxicity associated with impaired synthesis of protein. The contribution of cellular proteolytic system is minimal. The effect is predominantly seen in muscles containing type II fibers. (28)
  • Ethanol causes smaller reduction in responses of the heart and skeletal muscles at clinical concentration but marked reduction at higher concentrations. At high concentrations, ethanol causes greater reductionin excitability of the skeletal muscle than that of the heart. (29)
  • Acute impairment of alcohol metabolism is seen with alcohol consumption. Chronic alcohol use is associated with abnormalities in muscle protein synthesis. (30)
  • Alcohol inhibits skeletal muscle cell proliferation at the beginning of proliferation phase. It delays skeletal muscle differentiation, it has no significant effect on skeletal muscle DNA or protein content during the proliferation phase. (31)

10.   Kidney

  • Diuresis occurs after alcohol intake
  • Does not impair renal function
  • Alcohol related changes are seen in the structure and function of the kidneys. There is impairment in the ability to regulate volume and composition of the fluid and electrolytes in the body, inpaired sodium and fluid handling. It may even cause acute renal failure. Chronic alcoholic patients experience low blood concentrations of key electrolytes as well as potentially severe alterations in the body’s acid base balance. (32)
  • Chronic ethanol administration decreases the renal tubular reabsorption and reduces the renal function. This is associated with changes in membrane composition and lipid peroxidation. (33)
  • Ethaniol mediated diuresis cannot be explained by intrinsic effects of ethanol on kidney, atleast in an isolated and denervated perfused rat kidney model. (34)
  • With chronic alcohol intake for 12 weeks, urea and creatinine in the serum and TBARS level in kidney is raised while glutathione content and activities of glutathione peroxidase, glutathione reductase and superoxide dismutase is reduced. Catalase activity is also reduced. Chrionic alcohol exposure for longer duration is associated with deleterious effects in the kidney. (35)

11.   Sex

  • Alcohol is an aphrodisiac
  • Aggressive sexual behavior is due to loss of restraint and inhibition
  • Chronic alcoholism can produce impotence, testicular atrophy, gynaecomastia and infertility both in men and women

12.   Endocrine effects

  • Moderate intake of alcohol increase Adr release which can cause hyperglycemia and other sympathetic effects
  • Acute intoxication is associated with hypoglycemia and depletion of hepatic glycogen, because gluconeogenesis is inhibited

13.   Uterine contractions are suppressed at moderate blood levels

Mechanism of action

  • Several neurohumoral systems are concurrently affected producing a complex pattern of action
  • Alcohol enhance GABA release at GABAsites in the brain
  • It also inhibits NMDA and kainite type of excitatory amino acid receptors
  • Action of 5-HT on 5-HT3 inhibitory autoreceptor is augmented
  • Ethanol indirectly reduce neurotransmitter release by inhibiting voltage sensitive neuronal Ca2+ channels
  • It also activates specific type of K+ channels in certain brain areas
  • Release and turnover of DA in brain is enhanced through β endorphin release in nucleus accumbens and an opioid receptor dependent mechanism
  • Activity of membrane bound enzymes like Na+K+ATPase and adenylyl cyclase is also altered


  • Rate of absorption from the stomach is dependent on its concentration, presence of food and other factors
  • Absorption from the intestine is very fast, peak level is attained after 30 min
  • Limited first pass metabolism occurs in stomach and liver
  • Alcohol gets distributed widely in the body , crosses blood brain barrier efficiently, concentration in brain is very near blood concentration
  • It also crosses placenta freely
  • Alcohol is oxidized in liver to extent of 98%.
  • Even in high doses, not more than 10% escape metabolism
  • In addition to alcohol dehydrogenase, small amount of alcohol are oxidized by hepatic microsomal enzyme (mainly CYP2E1)
  • Metabolism of alcohol follows zero order kinetics, i.e. constant amount (8-12 ml of absolute alcohol/ hour) is degraded in unit time, irrespective of blood concentration
  • Ethanol is rapidly detectable in the expired air. The usual blood:expired ratio is 2300:1 and breath clearance at rest is 0.16L/h. The renal clearance of ethanol is 0.06L/h and swaet clearance is 0.02 L/h. (36)
  • Excretion of alcohol occurs through kidney and lungs. Concentration in exhaled air is about 0.05% of blood concentration


  1. Alcohol synergises with anxiolytics, antidepressants, antihistamines, hypnotics, opioids – marked CNS depression with motor impairment can occur. Chances of accident increases
  2. Individuals taking sulfonylureas, cefoperazone or metronidazole have experienced bizarre disulfiram like reaction
  3. Acute alcohol ingestion inhibits, while chronic intake induces CYP enzymes (especially CYP2E1).
  4. Formation of toxic metabolite of paracetamol is increased in chronic alcoholics
  5. Metabolism of tolbutamide, phenytoin and is also affected by acute and chronic alcohol intake
  6. Hypoglycemic action of insulin and sulfonylureas is enhanced by alcohol ingestion
  7. Aspirin and other NSAIDs cause more gastric bleeding when taken with alcohol


Intake of alcohol should be avoided by:

  • Peptic ulcer, acidity and gastroesophageal reflux patients (alcohol increases gastric secretion and relaxes LES)
  • Epileptics: seizures may be precipitated
  • Severe liver disease patient
  • Unstable personalities: they are likely to abuse it and become excessive drinkers
  • Pregnant women: causes fetal alcohol syndrome resulting in intrauterine and post natal growth retardation, low IQ, microcephaly, cranio-facial and other abnormalities, immunological impairment.

Clinical uses

  1. As antiseptic
  2. Rubefacient and counterirritant for sprains, joint pains etc.
  3. Rubbed into the skin to prevent bedsores. It should not be applied to already formed sores
  4. Alcohol sponges to reduce body temperature in fever.
  5. Intractable neuralgias (trigeminal and others), severe cancer pain. Injection of alcohol around the nerve causes permanent loss of transmission
  6. To ward off cold.
  7. As an appetite stimulant and carminative: 30-50 ml of 7-10% alcohol may be taken as beverages or tinctures before meal
  8. Reflex stimulation of fainting/ hysteria: 1 drop in nose
  9. To treat methanol poisoning


A.      Side effects of moderate drinking:

  • Nausea, vomiting, flushing
  • Hangover, traffic accidents

B.      Acute alcoholic intoxication

  • Unawareness, unresponsiveness
  • Stupor, hypotension
  • Gastritis, hypoglycemia
  • Respiratory depression
  • Collapse, coma and death


  • Gastric lavage
  • Maintain patent airway and prevent aspiration of vomitus
  • Maintain fluid and electrolyte balance
  • Correction of hypoglycemia by glucose infusion
  • Thiamine should be added
  • Insulin + fructose drip has found to accelerate alcohol metabolism

C.      Chronic alcoholism

  • Tolerance (pharmacokinetic and cellular tolerance)
  • Psychic dependence
  • Physical dependence occurs only on heavy and round the clock drinking
  • Impaired mental and physical performance

Complications include:

  • Polyneuritis, pellagra, tremors
  • Loss of brain mass
  • Wernicke’s encephalopathy
  • Korsakoff’s psychosis
  • Megaloblastic anemia
  • Cirrhosis of liver
  • Hypertension, cardiomyopathy, CHF, arrhythmias, stroke
  • Acute pancreatitis
  • Infertility
  • Skeletal myopathy

Treatment include:

  • Psychological and medical support
  • CNS depressants like barbiturates, phenothiazines, chloral hydrate. BZDs (chlordiazepoxide, diazepam) are preferred
  • Naltrexone 


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