 Pharmacology of alcohol

 Management of chronic alcoholism

 Treatment of alcoholic liver diseases
 Alcohols are hydroxy derivatives of aliphatic hydrocarbons

 Alcohol refers to ethyl alcohol or ethanol

 Pharmacology of alcohol is important for its presence in beverages

and for alcohol intoxication rather than as a drug

(C2H5OH)
 Alcohol is manufactured by fermentation of sugars

C6H12O6 (Glucose) 2CO2 + 2C2H5OH

 Starchy cereals e.g. barley, when soaked produce malt, which

can then be fermented by yeast to produce alcohol

STARCH MALTOSE

 The major source of commercial alcohol is mollases, a byproduct

of sugar indusrty
 There are a large variety of alcoholic beverages

 Obtained by fermentation of germinating cereals

 These are undistilled
 Alcohol content is low (3-6%)
 E.g. : Beers, Strong beers (upto 10%)

 Produced by fermentation of natural sugars (present in grapes and

other fruits)
 These are also undistilled
 Light wines (9 to 12 %)
 Effervescent wines (12- 16 %)
 Fortified wines (16-22 %)
  These are distilled after fermentation
 E.g. Rum, Whiskey, Brandy, Vodka, Etc.
 Alcohol content of these can vary from 40-55 %

1. Absolute alcohol: 99% ethanol by volume(dehydrated

alcohol)

Ethyl alcohol containing no more than 1 percent water

2. Rectified spirit: 95.5% ethyl alcohol by volume – From

mollases, by distillation
 (Redness of Skin) (Mild irritant)
 In concentration 40-50 %, Mild rubefacient and counterirritant

 It is an astringent- precipitates surface proteins and hardens

skin

 S.C. injection causes intense pain, inflammation and necrosis

followed by fibrosis

 At 70 % conc., it acts as an antiseptic by precipitating bacterial

proteins

(Antiseptic action increases with concentration from 20-70%

remains constant from 70-90 % and decreases above that)
  It is a neuronal depressant
Blood ethanol concentration Actions
At low plasma concentrations Excitation and euphoria
(30-100 mg/dl)

At 100-150 mg/dl Mental clouding, disorganization of

thoughts, memory impairment,
drowsiness
At 150-200 mg/dl person is sloppy and ataxic

At 200-300 mg/dl Stupor , unconsciousness,

medullary centres are paralyzed &
death

 It produces CNS depression by a generalized membrane action

altering the state of membrane lipids
 Alcohol promotes GABAA receptor mediated neuronal
inhibition – through chloride channel opening
 Inhibits NMDA excitatory amino acid receptors
(operating through cation channels)

 Indirectly reduces neurotransmitter release by

inhibiting voltage sensitive neuronal Ca2+ channels

 Pleasurable effects of alcohol and alcohol dependence

are mediated through an opioid receptor dependent
mechanism
Effects are depending on dose

 Small doses: produce only cutaneous (facial) and gastric

vasodilation, BP is not affected

 Moderate doses: tachycardia & mild rise in BP due to increased

muscular activity & sympathetic stimulation

 Large doses: Cause direct myocardial as well as vasomotor centre

depression, Fall in BP

Chronic alcoholism contributes to hypertension,

results in cardiomyopathy
 intake of small amount of alcohol: raise HDL &
decrease LDL
 Risk reduction in high risk subjects

 Protection is lost if 3 or more than 3 drinks are

consumed daily

 Megaloblastic anaemia in chronic alcoholics due

to interference with folate metabolism
 It is well known for combating cold e.g. RUM

 It produces sense of warmth due to cutaneous & gastric

vasodilation but

 High doses depress temperature regulating centre

 Brandy and whiskey are well known as respiratory stimulant in
collapse

 They irritate buccal & pharyngeal mucosa which stimulate

respiration reflexly

 But the direct action of alcohol on respiratory centre is depressant

 Dilute alcohol (10%) is a strong stimulant of gastric secretion

 Above 20% inhibit gastric secretions, cause vomiting and

gastritis

 Decreases tone of LES which may cause reflux

 Alcoholism is an important cause of chronic

gastritis, acute pancreatitis, etc.
 Chronic alcoholism subjects liver to oxidative stress and
causes cellular necrosis followed by fibrosis

 Acetaldehyde (produced during metabolism) damages the

hepatocytes & induce inflammation (on chronic use)

 Increases lipid peroxidation and depletes glutathione

 With vitamin and other nutritional deficiency it leads to

alcoholic cirrhosis
 Muscle work is increased or decreased depending on the
predominating central effect

 Weakness & myopathy occurs in chronic alcoholism

 Diuresis occurs after alcohol intake

 Due to water ingested with drinks and
 Due to alcohol induced inhibition of ADH secretion
 It is well known aphrodisiac- stimulates sexual desire

 Chronic alcoholism can produce impotence, testicular atrophy,

gynaecomastia and infertility
 Moderate amounts increase Adr release which can cause
hyperglycaemia and other sympathetic effects

 Acute intoxication is associated with hypoglycaemia and depletion

of hepatic glycogen

 Uterine contractions are suppressed at moderate blood levels

 Absorption from stomach & intestines is very fast/rapid
 Rate of alcohol absorption from the stomach is dependent on its conc, presence
of food and other factors
 Absorption of alcohol is slow in presence of food
 Peak levels are attained after ~30 min
 Absorption of alcohol from skin of adults is minimal
 Alcohol gets distributed widely in the body
 It crosses BBB efficiently
 It also crosses placenta freely
 90-98% is oxidized in the liver

Ethyl Alcohol Acetaldehyde Acetate CO2 +H2O

(Acetyl CoA)
Excretion of alcohol occurs through kidney and lungs
 It requires no digestion
1gm = 7.1 Calories
 It is metabolized rapidly

 It is an energy yielding substrate: 7.1 cal/g

 But these calories can not be stored

 It does not supply body building and other essential

constituents of food
 Medicinal uses are primarily restricted to external application
and

 As a vehicle for liquid preparations used internally

1. As antiseptic
2. Rubefacient & conterirritant for sprains & joint pains, etc.
3. As antiperspirant and aftershave lotion (Astringent action)
4. Alcoholic sponges to reduce body temp in fever
5. As appetite stimulant and carminative
6. To treat methanol poisoning
 Peptic ulcer, hyperacidity and gastroesophageal reflux patients

 Epileptics

 Severe liver disease

 Pregnant women: Can produce foetal alcohol syndrome

 Side effects of moderate drinking
 Nausea, vomiting, flushing, hangover

 Acute alcoholic intoxication

 Hypotension, gastritis, hypoglycemia, collapse, respiratory
depression, coma and death

 Treatment:
1. Gastric lavage is helpful only if patient is brought soon after ingesting
alcohol

2. Maintenance of patient airway & prevent aspiration of vomitus

3. Maintenance of fluid & electrolyte balance and correction of

hypoglycemia by glucose infusion till alcohol is metabolized
Thiamine 100 mg in 500 ml glucose can be added.
4. Recovery can be increased by haemodialysis
 Chronic alcoholism
 On chronic intake: Tolerance develops to subjective and behavioral effects of alcohol
 Physical dependence occurs only on heavy drinking (if alcohol is present in the
body continuously)

 Impairment of mental & physical performance

 Neurological problems are common: polyneuritis, pellagra, tremors, seizures,

loss of brain mass, encephalopathy, psychosis and megaloblastic anaemia

 Alcoholic cirrhosis of liver, hypertension, cardiomyopathy, CHF, arrythmias,

stroke, acute pancreatitis, impotence, gynaecomastia, infertility and skeletal
myopathy are other complications

 Incidence of oropharyngeal, esophageal and hepatic malignancy

 Respiratory infection is high and immune function is depressed
 Chronic ethanol Withdrawal syndrome
 Consists of anxiety, sweating, tremor, impairment of sleep, confusion,
hallucinations, convulsions and collapse

 Pharmacotherapy:
1. Psychotherapy

2. Drug Therapy
Naltrexone : Long acting Opioid antagonists

1. Because of involvement of opioid system in reinforcing effects of alcohol

2. It prevents relapse of alcoholism
3. It can reduce alcohol craving, number of drinking days and chances of
resumed heavy drinking
4. It is approved by US-FDA as adjuvant in treatment of alcohol dependent
subjects
5. It is being used in India at most deaddiction centres
Acamprosate
1. It is a weak NMDA receptor antagonist with modest GABA A receptor
agonistic activity
2. It is used for therapy of alcohol abstinence
3. It also reduces relapse of the drinking behavior
 It inhibits the enzyme aldehyde dehydrogenase after conversion
into active metabollites

 It has been used as an aversion technique in chronic alcoholics

who are motivated and sicerely desire to leave the habit

 After abstaining (not consuming) from alcohol overnight ,

disulfiram is given,
 1 gm on 1st day
 0.75 gm on 2nd day
 0.50 gm on 3rd day
 0.25 gm subsequently

 Effect lasts for 7-14 days after stopping it, because inhibition of
aldehyde dehydrogenase is irreversible
 The subjects decide not to drink is reinforced by the
distressing symptoms (aldehyde syndrome) that occur if
he/she drinks a little bit

Aldehyde Syndrome:

 When alcohol is ingested after taking Disulfiram , the

concentration of acetaldehyde increases in tissues & blood and
a number of highly distressing symptoms are produced.

 Flushing, burning sensation, throbbing headache, perspiration,

uneasiness, tightness in chest, dizziness, vomiting, visual disturbances,
mental confusion and circulatory collapse

 Duration of syndromes: 1- 4 hr (depending on amount of alcohol

consumed)
 Side effects are infrequent

 Rashes, metallic taste, nervousness, malaise, and abdominal

upset

 It inhibits other enzymes as well including alcohol

dehydrogenase, dopamine β- hydroxylase and several
cytochrome P450 isoenzymes, thus, it prolongs t1/2 of many
drugs
 It is only of toxicological importance

 Mixing of Methylated spirit with alcoholic beverages results

in methanol poisoning

 It is metabolized to formaldehyde and formic acid by

alcohol dehydrogenase and aldehyde dehydrogenase resp.
 Methanol also is a CNS depressant but less potent than
ethanol

 Toxic effects of methanol are due to formic acid

 Blood levels > 50 mg/dl is associated with severe poisoning

 Even 15 ml of methanol can cause blindness and 30 ml can

cause death

 Fatal dose 75-100 ml

 Manifestations of methanol poisoning are
 Vomiting
 Headache
 Epigastric pain (upper central region of abdomen)
 Uneasiness
 Dysponea
 Bradycardia
 Hypotension
 Coma

 Acidosis is prominent due to production of formic acid

 The specific toxicity of formic acid is retinal damage

 Blurring of vision, congestion of optic disc followed by
blindness

 Toxicity can lead to death due to respiratory failure

 Keep the patient in dark room and protect the eyes from
sunlight

 Gastric lavage, if the patient is brought within 2 hrs of

ingesting methanol

 Supportive measures should be taken for maintaining

Ventilation and BP

 Combat Acidosis by Sod. Bicarbonate i.v. infusion – This

prevents retinal damage and other symptoms
 Pot. Chloride is needed only if 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

metabolites

 Ethanol (10% in water) is administered through nasogastric

tube
 Loading dose: 0.7 ml/kg followed by 0.15 ml/kg/hr

 Haemodialysis: clears methanol as well as formate and

accelerate recovery
 Fomepizole

 Specific inhibitor of alcohol dehydrogenase- retards methanol

metabolism

 It is not available commercially in India

 But it has several advantages over ethanol, like longer t 1/2

 Folate therapy: Leucovorin Calcium 50 mg injected 6

hourly reduce blood formate levels by enhancing its
oxidation
 Synergises with anxiolytics, antidepressant, antihistaminics,
hypnotics, opioids

 Acute alcohol ingestion inhibits, while chronic intake induces

metabolism of tolbutamide, phenytoin & many other drugs

 Insulin & sulphonylureas: alcohol increases hypoglycaemia acutely

 Aspirin & other NSAIDs cause more gastric bleeding when taken
with alcohol

 Alcoholics are more prone to paracetamol toxicity due to increased

formation of its toxic metabolites