Ethyl Alcohol

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Chapter: Essential pharmacology : Ethyl and Methyl Alcohols

Alcohols are hydroxy derivatives of aliphatic hydrocarbons. When unqualified, ‘alcohol’ refers to ethyl alcohol or ethanol. Pharmacology of alcohol is important for its presence in beverages (which have been used since recorded history) and for alcohol intoxication, rather than as a drug.




Alcohols are hydroxy derivatives of aliphatic hydrocarbons. When unqualified, ‘alcohol’ refers to ethyl alcohol or ethanol. Pharmacology of alcohol is important for its presence in beverages (which have been used since recorded history) and for alcohol intoxication, rather than as a drug.


Alcohol is manufactured by fermentation of sugars:



Fermentation proceeds till alcohol content reaches ~ 15%. Then the reaction is inhibited by alcohol itself. Starchy cereals, e.g. barley, when soaked produce malt:



which can then be fermented by yeast to produce alcohol. The major source of commercial alcohol is mollases, a byproduct of sugar industry.


Alcoholic Beverages


There are a large variety of alcoholic beverages.


A. Malted Liquors


Obtained by fermentation of germinating cereals; are undistilled—alcohol content is low (3–6%) e.g. Beers, Stout. Now strong beers (upto 10%) are also available.


B. Wines


Produced by fermentation of natural sugars as present in grapes and other fruits. These are also undistilled.


Light wines Claret, Cider; alcohol content 9–12%, cannot exceed 15%.

Fortified wines Port, Sherry (alcohol 16–22%): distilled beverages are added from outside.

Effervescent wines Champagne (12–16% alcohol): bottled before fermentation is complete.

Wines are called ‘dry’ when all sugar present has been fermented and ‘sweet’ when some is left.


C. Spirits


These are distilled after fermentation; e.g. Rum, Gin, Whiskey, Brandy, Vodka etc. Though the alcohol content of these can vary from 40–55%, in India (and almost internationally) for all licenced brands it is standardized to 42.8% v/v or 37% w/w.


The taste, flavour and value of alcoholic beverages depends not only on alcohol content but on the presence of higher ethers, higher alcohols, aldehydes, esters, polymers, and volatile oils; many of these are formed during ‘maturation’ of the beverage.


Other  Forms  Of  Alcohol


1. Absolute alcohol 99% w/w ethanol (dehydrated alcohol).

2. Rectified spirit 90% w/w ethyl alcohol—from mollases, by distillation.

3. Proof spirit It is an old term. If whisky is poured on gun powder and ignited and it explodes, then it was labelled to be of ‘proof strength’. If water is mixed to it, gun powder will not ignite. 100% proof spirit is 49.29% w/w or 57.1% v/v alcohol


Pharmacological Actions


1. Local Actions


Ethanol is a mild rubefacient and counterirritant when rubbed on the skin. By evaporation it produces cooling. Applied to delicate skin (scrotum) or mucous membranes it produces irritation and burning sensation; should not be applied in the mouth, nose, etc. Injected s.c. it causes intense pain, inflammation and necrosis followed by fibrosis. Injected round a nerve it produces permanent damage.


Alcohol is an astringent—precipitates surface proteins and hardens skin. By precipitating bacterial proteins it acts as an antiseptic. The antiseptic action increases with concentration from 20 to 70%, remains constant from 70 to 90% and decreases above that. That 100% ethanol is more dehydrating but poorer antiseptic than 90% ethanol, shows that antibacterial action is not due to dehydration of bacterial protoplasm. Alcohol does not kill bacterial spores.


2. CNS


Alcohol is a neuronal depressant. Since the highest areas are most easily deranged and these are primarily inhibitory—apparent excitation and euphoria are experienced at lower plasma concentrations (30–100 mg/dl). Hesitation, caution, self-criticism and restraint are lost first. Mood and feelings are altered; anxiety may be allayed. With increasing concentration (100–150mg/dl) mental clouding, disorganization of thought, impairment of memory and other faculties, alteration of perception and drowsiness supervene. At 150–200 mg/dl the person is sloppy, ataxic and drunk; 200–300 mg/dl result in stupor and above this unconsciousness prevails, medullary centres are paralysed and death may occur. Though, alcohol can produce anaesthesia, margin of safety is narrow.


Any measurable concentration of alcohol produces a measurable slowing of reflexes: driving is dangerous. Performance is impaired, fine discrimination and precise movements are obliterated; errors increase, except if fear of punishment and anxiety of failure has already impaired it—performance may be improved by allaying of anxiety and fear.


Effects of alcohol are more marked when the concentration is rising than when it is falling. Some consider it to be a reflection of acute tolerance.


Alcohol can induce sleep but is not a dependable hypnotic. Some individuals report poor quality of sleep and early morning awakening. Sleep architecture may be disorganized and sleep apnoea aggravated. Alcohol raises pain threshold and also alters reaction to it, but is not a dependable analgesic—severe pain can precipitate confusion and convulsions. During the time alcohol is acting on brain, it exerts anticonvulsant action, but this is followed by lowering of threshold: seizures may be precipitated in epileptics. Chronic alcohol abuse damages brain neurones.


The cortex and the reticular activating system are most sensitive to alcohol; other areas get depressed as concentration rises.


Mechanism Of Action


Alcohol was believed to produce CNS depression by a generalized membrane action altering the state of membrane lipids. However, recently specific effect on multiple receptor operated ion channels has been demonstrated at concentrations attained during moderate drinking. Alcohol promotes GABAA receptor mediated synaptic inhibition (through chloride channel opening) as well as inhibits NMDA and kainate type of excitatory amino acid receptors (operating through cation channels). Action of 5HT on 5HT3 inhibitory auto-receptor (having an intrinsic ion channel) is augmented. Some studies suggest that cerebral nicotinic cholinergic receptors (operating through Na+ channel) may also be the targets of alcohol action. Ethanol can indirectly reduce neurotransmitter release by inhibiting voltage sensitive neuronal Ca2+ channels. Blockade of adenosine uptake by alcohol could also contribute to synaptic depression. Turnover of NA in brain is enhanced by alcohol through an opioid receptor dependent mechanism. This is probably important in the pleasurable effects of alcohol and in the genesis of alcohol dependence. Activity of membrane bound enzymes like Na+ K+ ATPase and adenylyl cyclase is also altered. The activity and translocation of channel/enzyme proteins in the membrane could be affected by alcohol through protein kinase C (PKC) and protein kinase A (PKA) mediated alteration in the state of their phosphorylation.



3. CVS 


The effects are dependent on dose.


Small doses: produce only cutaneous (especially on the face) and gastric vasodilatation. 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 doses: cause direct myocardial as well as vasomotor centre depression and there is fall in BP.


Epidemiological studies have confirmed that chronic alcoholism contributes to hypertension and can lead to cardiomyopathy. Atrial fibrillation and other cardiac arrhythmias may occur due to conduction defects and QT prolongation.


4. Blood


Regular intake of small to moderate amounts of alcohol has been found to raise HDLcholesterol levels and decrease LDL oxidation. This may be responsible for the 15–35% lower incidence of coronary artery disease in such individuals. Risk reduction is greatest in high risk subjects and protection is lost if > 3 drinks are consumed daily. Megaloblastic anaemia has been seen in chronic alcoholism due to interference with folate metabolism.


5. Body Temperature


Alcohol is reputed to combat cold. It does produce a sense of warmth due to cutaneous and gastric vasodilatation, but heat loss is actually increased in cold surroundings. High doses depress temperature regulating centre.


6. Respiration


Brandy or whiskey are reputed as respiratory stimulants in collapse. They irritate buccal and pharyngeal mucosa—may transiently stimulate respiration reflexly. However, it is better not to depend on this, because the direct action of alcohol on respiratory centre is only a depressant one.


7. GIT


Alcoholic beverages have variable effect on gastric secretion depending on the beverage itself and whether the individual likes it. However, dilute alcohol (optimum 10%) put in the stomach by Ryle’s tube is a strong stimulant of gastric secretion (especially of acid). It acts directly as well as reflexly. Higher concentrations (above 20%) inhibit gastric secretion, cause vomiting, mucosal congestion and gastritis. Alcoholism is an important cause of chronic gastritis. Lower esophageal sphincter (LES) tone is reduced by alcohol—may accentuate reflux. Bowel movements may be altered in either direction. Acute pancreatitis is a complication of heavy drinking.


8. Liver


Neither alcohol intoxication nor chronic use of moderate amounts cause significant liver damage, provided adequate nutrition is maintained. However, it does mobilize peripheral fat and increases fat synthesis in liver in a dose-dependent manner. Proteins may also accumulate in liver because their secretion is decreased. Chronic alcoholism subjects liver to oxidative stress and causes cellular necrosis followed by fibrosis. Acetaldehyde produced during metabolism of alcohol appears to damage the hepatocytes and induce inflammation, especially on chronic ingestion of large amounts. Increased lipid peroxidation and glutathione depletion occurs. These combined with vitamin and other nutritional deficiencies may be responsible for the so called alcoholic cirrhosis.


Regular alcohol intake induces microsomal enzymes.


9. Skeletal muscle


Alcohol produces little direct effect. Fatigue is allayed by small doses, but muscle work is increased or decreased depending on the predominating central effect. Weakness and myopathy occurs in chronic alcoholism.


10. Kidney


Diuresis is often noticed after alcohol intake. This is due to water ingested with drinks and alcohol induced inhibition of ADH secretion. It does not impair renal function.


11. Sex


Alcohol is reputed as an aphrodisiac. Aggressive sexual behaviour is due to loss of restraint and inhibition. However, performance of the sexual act is often impaired. Chronic alcoholism can produce impotence, testicular atrophy, gynaecomastia and infertility.


12. Endocrine Effects


Moderate amounts of alcohol increase Adr release which can cause hyperglycaemia and other sympathetic effects. However, acute intoxication is often associated with hypoglycaemia and depletion of hepatic glycogen, because gluconeogenesis is inhibited. Glucagon, thus fails to reverse it and glucose must be given.


13. Uterine contractions are suppressed at moderate blood levels.




Rate of alcohol absorption from the stomach is dependent on its concentration, presence of food, and other factors, but is generally quite slow. Absorption from intestines is very fast; peak levels are attained after ~30 min. Thus, gastric emptying determines rate of absorption. Limited first pass metabolism occurs in stomach and liver. Absorption of alcohol from skin of adults is minimal but may be significant in infants given alcohol sponges.


Alcohol gets distributed widely in the body (vol of distribution 0.7 L/kg), crosses blood brain barrier efficiently: concentration in brain is very near blood concentration. It also crosses placenta freely. It is oxidized in liver to the extent of 98%. Even with high doses, not more than 10% escapes metabolism.



In addition to alcohol dehydrogenase, small amounts of alcohol are oxidized by hepatic microsomal enzymes as well. Metabolism of alcohol follows zero order kinetics, i.e. a constant amount (8–12 ml of absolute alcohol/ hour) is degraded in unit time, irrespective of blood concentration. Thus, rate of consuming drinks governs whether a person will get drunk.


Excretion of alcohol occurs through kidney and lungs, but neither is quantitatively significant. Concentration in exhaled air is about 0.05% of blood concentration: this is utilized for medicolegal determination of drunken state. The subject blows in a balloon and alcohol is measured by portable breath analyser.




1.   Alcohol synergises with anxiolytics, antidepressants, antihistaminics, hypnotics, opioids marked CNS depression with motor impairment can occur: Chances of accidents increase.


2.   Individuals taking sulfonylureas (especially chlorpropamide), certain cephalosporins (cefoperazone, moxalactam, cefamandole) and metronidazole have experienced bizarre, somewhat disulfiramlike reactions when they consume alcohol.


3.   Acute alcohol ingestion inhibits, while chronic intake induces tolbutamide, phenytoin (and many other drugs) metabolism.


4.   Insulin and sulfonylureas: alcohol enhances hypoglycaemia acutely.


5.   Aspirin and other NSAIDs cause more gastric bleeding when taken with alcohol.


6.   Alcoholics are more prone to paracetamol toxicity due to enhanced generation of its toxic metabolite.


Food Value


Alcohol requires no digestion and is metabolized rapidly. It is an energy yielding substrate: 7 Cal/g, but these cannot be stored. It also does not supply body building and other essential constituents of food. Those who consume substantial part of their caloric intake as alcohol, often suffer from nutritional deficiencies. Thus, alcohol is an imperfect and expensive food.




Alcohol is seldom prescribed medically. However, its consumption should be avoided by—


1.   Peptic ulcer, hyperacidity and gastroesophageal reflux patients (alcohol increases gastric secretion and relaxes LES).


2.   Epileptics: seizures may be precipitated.


3.   Severe liver disease patients.


4.   Unstable personalities: they are likely to abuse it and become excessive drinkers.


5.   Pregnant women: Even moderate drinking during pregnancy can produce foetal alcohol syndrome resulting in intrauterine and postnatal growth retardation, low IQ, microcephaly, facial and other abnormalities, and immunological impairmentincreased susceptibility to infections. Heavy drinking by mother in addition increases the incidence of miscarriage, stillbirths and low birthweight babies.


Guidelines For Safe Drinking


Physicians are often asked to advise on safe ways of drinking. Various official agencies, physician organizations and alcoholism experts have putforth guidelines in this regard, but they are not uniform. The following may be concluded:


·      On an average 1–2 drinks per day is usually safe.

·      Not more than 3 drinks on any one occasion.

·      Consumption of >3 drinks per day is associated with documented adverse health effects.

·      Do not drive or engage in hazardous activities after drinking.

·      Do not drink if an interacting drug has been taken.

·      Subjects with any contraindication should not drink.

·      Safe limits are somewhat lower for women than for men, because metabolism of alcohol is slower and its bioavailability higher (due to less first pass metabolism in stomach) in women than in men.


[Note: 1 drink = 50 ml of spirits = 150 ml of wines = 400 ml of beer; all have roughly 18 g alcohol, which taken in empty stomach produces a peak alcohol blood level of ~ 25 mg/dl in an adult male of average built.]




A. Side Effects Of Moderate Drinking Nausea, vomiting, flushing, hangover, traffic accidents.

B. Acute Alcoholic Intoxication Hypotension, gastritis, hypoglycaemia, collapse, respiratory depression, coma and death.


Treatment: Gastric lavage is helpful only when the patient is brought soon after ingesting alcohol, which is rare. Since most patients are disoriented or comatose, the first priority is to maintain patent airway and prevent aspiration of vomitus. Tracheal intubation and positive pressure respiration may be needed if it is markedly depressed. Analeptics should not be used—may precipitate convulsions. Most patients will recover with supportive treatment, maintenance of fluid and electrolyte balance and correction of hypoglycaemia by glucose infusion till alcohol is metabolized. Thiamine (100 mg in 500 ml glucose solution infused i.v.) should be added. Recovery can be hastened by haemodialysis. Insulin + fructose drip has been found to accelerate alcohol metabolism. However, its clinical impact is not remarkable.


C. Chronic Alcoholism On chronic intake, tolerance develops to subjective and behavioral effects of alcohol, but is generally of a low degree. It is both pharmacokinetic (reduced rate of absorption due to gastritis and faster metabolism due to enzyme induction) and cellular tolerance. Psychic dependence often occurs even with moderate drinking; depends a lot on individual’s likings and attitudes.


Recent studies have confirmed that a genetic basis contributes to progression from social drinking to alcoholism in about 50% individuals. Alcoholism is often a familial trait. Some differences in sensitivity of various neuronal systems to alcohol among ‘predisposed’ and ‘not predisposed’ individuals have been demonstrated.


There is no single explanation for why people drink. Diverse feelings and behaviours are provoked by alcohol in different individuals and in the same individual on different occasions. Alcohol can make people happy as well as sad, curtious as well as mean, talkative as well as silent, friendly as well as hostile. All this cannot be explained on the basis of pharmacological actions of alcohol alone. Attitudes, beliefs, peer groups, social setting and learned experiences all have a bearing. Alcohol is said to produce good mood, sense of wellbeing, self confidence, sociability, etc. But these infact are learned behaviours. In some societies, alcoholic beverages have become an acceptable form of extending courtesy and of entertainment. Drinking is often related to ‘celebration’ and ‘high living’. There is ‘wine snobbery’ in high social groups.


To some, excess drinking provides the excitement of risk taking. People often boast of their capacity to drink. To the young, drinking may be a symbol of rebellion against the oppressive older generation and rejection of the values of the establishment. ‘Binge drinking’ is a specific behavioural pattern of bouts of excessive drinking. Alcohol is often an excuse for bad behaviour. Society’s view that intoxicated person is unaware of his actions— makes intoxication an attractive state, because there is increased freedom of what one can say or do after drinking. Thus, there are a variety of motivations for drinking.


Physical dependence occurs only on heavy and roundtheclock drinking (if alcohol is present in the body continuously). Heavy drinking is often associated with nutritional deficiencies, because food is neglected and malabsorption may occur. In addition to impaired mental and physical performance, neurological afflictions are common—polyneuritis, pellagra, tremors, seizures, loss of brain mass, Wernicke’s encephalopathy, Korsakoff’s psychosis and megaloblastic anaemia. Alcoholic cirrhosis of liver, hypertension, cardiomyopathy, CHF, arrhythmias, stroke, acute pancreatitis, impotence, gynaecomastia, infertility and skeletal myopathy are other complications. Incidence of oropharyngeal, esophageal and hepatic malignancy and respiratory infections is high; immune function is depressed.


Withdrawal Syndrome consists of anxiety, sweating, tremor, impairment of sleep, confusion, hallucinations, delirium tremens, convulsions and collapse.


Treatment Psychological and medical supportive measures are needed during withdrawal. Many CNS depressants like barbiturates, phenothiazines, chloral hydrate have been used as substitution therapy in the past (to suppress withdrawal syndrome) but benzodiazepines (chordiazepoxide, diazepam) are the preferred drugs now. These have a long duration of action and can be gradually withdrawn later.


Naltrexone: Several studies have demonstrated involvement of opioid system in the pleasurable reinforcing effects of alcohol probably by blunting dopamine mediated reward function. Trials among postaddicts have shown that the long acting opioid antagonist naltrexone helps prevent relapse of alcoholism. It reduced alcohol craving, number of drinking days and chances of resumed heavy drinking. Naltrexone is approved by USFDA for use as adjuvant in comprehensive treatment programmes for alcohol dependent subjects and is being used in India at most deaddiction centres, after the individual has undergone withdrawal and is motivated.


Acamprostate It is a weak NMDAreceptor antagonist with modest GABAA receptor agonistic activity that is being used in Europe for maintenance therapy of alcohol abstinence. In conjunction with social and motivational therapy, it has been found to reduce relapse of the drinking behaviour. The efficacy of acomprostate in this regard is rated comparable to naltrexone.


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


Clinical Uses


Medicinal uses of ethanol are primarily restricted to external application and as a vehicle for liquid preparations used internally.


a)   As antiseptic (see Ch. No. 65).

b)  Rubefacient and counterirritant for sprains, joint pains, etc.

c) Rubbed into the skin to prevent bedsores. It should not be applied on already formed sores. Astringent action of alcohol is utilized in antiperspirant and aftershave lotions.

c)   Alcoholic sponges to reduce body temperature in fever. However, cold water/ice may be better.

d)  Intractable neuralgias (trigeminal and others), severe cancer pain—injection of alcohol round the nerve causes permanent loss of transmission.

e)   To ward off cold—may benefit by causing vasodilatation of blanched mucosae; but further exposure after taking alcohol may be deleterious because alcohol increases heat loss due to cutaneous vasodilatation.

f)    As appetite stimulant and carminative: 30– 50 ml of 7–10% alcohol may be taken as beverages or tinctures before meal.

g)  Reflex stimulation in fainting/hysteria: 1 drop in nose.

h)  To treat methanol poisoning.


Aldehyde Dehydrogenase Inhibitors




It inhibits the enzyme aldehyde dehydrogenase probably after conversion into active metabolites. When alcohol is ingested after taking disulfiram, the concentration of acetaldehyde in tissues and blood rises and a number of highly distressing symptoms (aldehyde syndrome) are produced promptly. These are— flushing, burning sensation, throbbing headache, perspiration, uneasiness, tightness in chest, dizziness, vomiting, visual disturbances, mental confusion, postural fainting and circulatory collapse. Duration of the syndrome (1–4 hours) depends on the amount of alcohol consumed. Because of risk of severe reaction, disulfiram is infrequently used.


Disulfiram has been used as an aversion technique in chronic alcoholics who are motivated and sincerely desire to leave the habit. After abstaining from alcohol overnight, disulfiram is given 1 g on 1st day, 0.75 g on 2nd day, 0.5 g on 3rd and 0.25 g subsequently. Sensitization to alcohol develops after 2–3 hours of first dose, reaches its peak at ~12 hours and lasts for 7–14 days after stopping it, because inhibition of aldehyde dehydrogenase with disulfiram is irreversible: synthesis of fresh enzyme is required for return of activity. Thus, the subject’s resolve not to drink is reinforced by the distressing symptoms that occur if he drinks a little bit. It should not be used in patients who are physically dependent on alcohol.


Side effects of disulfiram (as such) are infrequent, include rashes, metallic taste, nervousness, malaise and abdominal upset. It inhibits a number of other enzymes as well including alcohol dehydrogenase, dopamine β hydroxylase and several cytochrome P450 isoenzymes. Thus, it prolongs t½ of many drugs.


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