Healthcare in India

Ethyl and Methyl Alcohols

Alcohols are hydroxy derivatives of alipheatic 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 drugs.
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.
There are a large veriety of alcoholic beverages

  • 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.
  • 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.
Effervecent wines Champagne (12-16 % alcohol): botled before fermentation is complete.
Wines are called ‘dry’ when all sugar present has been fermented and ‘sweet’  when some is left.

  • Spirits : There are distilled after fermentation; e.g. Rum, Gin, Whiskey, Brandy, Vodka etc. Though  the alcohol content of these can very 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

  • Absolute alcohol : 99 % w/w ethanol (dehydrated alcohol.)
  • Rectified spirit : 90 % w/w ethyl alcohol-from mollases, by distillation.
  • Proof spirit : It is an old term. If whisky is poured on gun powder and ignited and it explodes, then it was labeled 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.
  • Local actions : Ethanol is a mild rubefacient and counterirritant when rubbed on the skin. By evaporation it produced cooling.. Applied to delicate skin (scrotum) or mucous membrances 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.

  •  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-critcism and restraint are lost first. Mood and feelings are altered; anxiety may by allayed. With increasing concentration (100-150 mg/dl) mental clouding, disorganization of throught, 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 centers 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 reflelxes; 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 hyponotic. Some individuals report poor quality of sleep and early morning awakening. Sleep arechitecture may be disorganized and sleep apnoea aggravated. Alcohol raises pain threshould and also alters reaction to it, but is not a dependable analgestic-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 neurons.
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 membrance 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 kainite type of excitatory amino acid receptors (operating through cation channels). Action of 5-HT on 5-HT3 inhibitory autoreceptor (having an intrinsic ion channel) is augmented. Some studies suggest that cerebral nicotinic cholinergic receptors (operting 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 effect of alcohol and in the genesis of alcohol dependance. Activity of membrane bound enzymes like Na+ K+ ATPase and adenylyl cyclase is also altered. The activity and transiocation 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.

  • 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 conjucnctival 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 center 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 Q-T prolongation.

  • Blood : Regular intake of small to moderate amounts of alcohol has been found to raise HDL-cholesterol 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.
  • 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 center.
  • 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 center is only a depressant one.
  • GIT : Alcoholic beverages have a variable effect on gasric 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. ]
  • Liver : Neither alcohol intoxication nor chronic use of moderate amounts cause significant liver damage, provided adequate nutrition is maintained. However, it does mobilized 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 followd by fibrosis. Acetaldehyde produced during metabolism of alcohol appears to damage the hepatocytes and induce inflammation, especially on chronic ingestion of large amonts. 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.

  • 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.
  • 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.
  • Sex : Alcohol is reputed as an aphrodisiac. Aggressive sexual behavior 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.
  • Endocrine Effects : Moderate amounts of alcohol increase Adr release which can cause hyperglycaemia and other sympathetic effects. However, acute intoxication is often associated with ypoglycaemia and depletion of hepaticglycogen, because gluconeogenesis in inhibited. Glucagon, thus fails to reverse it and glucose must be given.
  • 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 generally quite slow. Absorption from intestines is very fst; peak levels are attained after-30 min. Thus, gastric emptying determines rate of absorption. Limited first pass meabolism 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 Lkg), 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 he patic 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, 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 analyzer.

  • Alcohol synergises with anxiolytics, antidepressants, antihistaminics, hypnotics, opioids ® marked CNS depression with motor impairment can occur: Chances of accidents increase.
  • Individuals taking sulfonylureas (especially chlorpropamide), certain cephalosporins (cefoperazone, moxalactam, cefamandole) and metronidazole have experienced bizarre, somewhat disulfiram-like reactions when they consume alcohol.
  • Acute alcohol ingestion inhibits, while chronic intake induces tolbutamide, phenytoin (and many other durgs) metabolism.
  • Insuling and sulfonylureas: alcohol enhances hypoglycaemia acutely.
  • Aspirin and other NSAIDs cause more gastric bleeding when taken with alcohol.
  • Alcoholics are more prone to paracetamol toxicity due to to enhanced generation of its toxic metabolite.


Food value

Alcohol requires no digestion and is metabolized rapidaly. 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---

  • Peptic ulcer, hyperacidity and gastroesophageal reflux patients (alcohol increases gastric secretion and relaxes LES).
  • Epileptics: seizures may be precipitated.
  • Severe liver disease patients.
  • Unstable personalities: they are likely to abuse it and become excessive drinkers.
  • 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 impairment®increased susceptibility to infections. Heavy drinking by mother in addition increase the incidence of miscarriage, stillbirths and low birth-weight babies.

Guidelines for safe drinking : Physicians are often asked to advise on safe ways of drinking. Various official agencies, physician organization and alcoholism experts have putforth guidelines in this regards, 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.
    • Subject 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 need 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 accelellrate 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 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 and 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 symbole 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 and 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 round-the-clock 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 afflications are  common-polyneuritis, pellagra, tremors, seizures, losss of brain mass, Wernicke’s encephalopathy, Korsakoff’s psychosis and mealoblastic anaemia. Alcoholic cirrhosis of liver, hypertension, cardiomyopathy, CHF, arrhthmias, stroke, acute pancreatitis, importence, 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 withdrawan 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 post-addicts 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 US-FDA for use as adjuvant in comprehensive treatment programmes for alcohol dependent subjects and is being used in India at most deaddiction centers, after the individual has undergone withdrawal and is motivated.
Acamprostate : It is a weak NMDA-receptor 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 5-HT3 antagonist ondansetron and the antiepileptic topiramate have also shown some promise in treating alcoholism.


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

  • As antiseptic
  • Rubefacient and counterirritant for sprains, joint pains etc.
  • Rubbed into the skin to prevent bedsores. It should not be applied on already formed sores. Asringent action of alcohol is utilized in antiperspirant and aftershave lotions.
  • Alcoholic sponges to reduce body temperature in fever. However, cold water/ice may be better.
  • Intractable neuralgias (trigeminal and others), severe cancer pain-injection of alcohol round the nerve causes permanent loss of transmission.
  • To ward off cold-may benefit by causing vasodilation of blanched mucosase; but further exposure after talking alcohol may be deleterious because alcohol increases heat loss due to cutaneous vasodilatation.
  • As appetite stimulant and carminative: 30-50 ml of 7-10 % alcohol may be taken as beverages or tinctures before meal.
  • Reflex stimulation in fainting/hysteria: 1 drop in nose.
  • To treat methanol poisoning.

Aldehyde dehydrogenase inhibitors
Disulfiram : It inhibits the enzyme aldehyde dehydrogenase probably after conversion into active metabolites. When alcohol is ingested after talking disulfiram, the concentration of acetaldehyde in tissues and blood rises and a number of highly distressing symptoms (aldehydesyndrome) 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, disfulfiram 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 disfulfiram 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 incluing alcohol dehydrogenase, dopamine b hydroxylase and several cytochrome P450 isoenzymes. Thus, it prolongs t ? of many durgs.
ESPERAL, ANTADICT 250 mg tab. (internationally marked as ANTABUSE)

METHYL ALCOHOL (Methanol, Wood Alcohol)
Methyl alcohol is added to rectified spirit to render it unfit for drinking It is only of toxicological importance. Unscrupulous mixing of methylated spirit with alcoholic beverages or its inadvertent ingestion results in methanol poisoning.
Methanol is metabolized to formaldehyde and formic acid by alcohol and aldehyde dehydrogenases respectively, but the rate is 1/7 th that of ethanol. Like ethanol, it follows zero order kinetics and t ? of 20-60 hours has been   measured.
Methanol also is a CNS depressant, but less potent than ethanol. Toxic effects of methanol are largely due to formic acid, since its further metabolism is slow and folate dependent. A blood level of >50 mg/dl methanol is associated with severe poisoning. Even 15 ml has caused death; fatal dose is regarded to b 75-100 ml.
Manifestations of methanol poisoning are vomiting, headache, epigastric pain, uneasiness, dyspnoea, bradycardia and hypotension. Delirium may occur and the patient may suddenly pass into coma. Acidosis is prominent and entirely due to production of formic acid. The specific toxicity of formic acid is retinal damage. Blurring of vision, congestion of optic disfollowed by blindness always precede death which is due to respiratory failure.

Treatment :

  • Keep the patient in a quiet, dark room; protect the eyes from light.
  • Gastric lavage with sod, bicarbonate if the patient is brought within 2 hours of ingesting methanol. Supportive measures to maintain ventilation and BP should be instituted.
  • Combat acidosis by i.v. sod, bicarbonate infusion-the most important measure; prevents retinal damage and other symptoms; large quantities may be needed.
  • Pot. Chloride infusion is needed only when hypokalemia occurs due to alkali therapy.
  • Ethanol 100 mg/dl in blood saturates alcohol dehydrogenase and retards methanol metabolism. This helps by reducing the rate of generation of toxic meabolites. Ethanol (10 % in water) is administered through a nasogastric tube; loading dose of 0.7 ml/kg is followed by 0.15 ml/kg/hour drip. Because pharmacokinetics of alcohol is unstable and no. i.v. formulation is available, maintenance of effective concentration is difficult and needs to be repeatedly measured. Moreover, the enzyme saturating concentration of ethanol itself produces intoxication and can cause hypoglycaemia. Treatment has to be continued for severl days because the sojourn of methanol in body is long.
  • Haemodialysis: clears methanol as well as formate and hastens recovery.
  • Fomepizole (4 methylpyrazole) is a specific inhibitor of alcohol dehydrogense-retards methanol metabolism. A loading dose of 15 mg/kg i.v. followed by 10 mg/kg every 12 hours till serum methanol falls below 20 mg/dl, has been found effective and safe. It has several advantages over ethanol, like longer 5 ? and lack of inebriating action, but is not available commercially in India.
  • Folate therapy : Calcium leucovorin 50 mg injected 6 hourly has been shown to reduce blood formate levels by enhancing its oxidation. This is a promising adjuvant approach.

 Ethylene glycol poisoning : Ethylene glycol poisoning has occurred sporadically, especially among children. It is an industrial solvent, coolant and antifreeze. It is oxidized in the body by alcohol dehydrogenase to glycoaldehyde and then to glycolic acid-glyoxylic acid-oxylic acid in steps. Ethylene glycol itself can cause intoxication similar to ethanol, but generation of metabolites results in acidosis, cardiopulmonary complications and renal tubular necrosis.
Fomepizole used in the same manner as for methanol poisoning is the drug of choice. It is approved by US-FDA for this indication and has ‘orphan drug status’. Ethanol is employed as an alternative.