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
