THE ALCOHOLS

DEFINITION: Alcohols are hydroxyl (OH) derivatives of aliphatic

hydrocarbons. When unqualified alcohol refers to ethyl alcohol or
ethanol.

IMPORTANCE: Pharmacology of alcohol is important for its presence in

beverages and for alcohol intoxication, rather than as a drug.

PRODUCTION: Alcohol is manufactured by fermentation of sugars.

C6H1206 zymase 2CO2 + 2C2H5OH or CH3CH2OH

(Glucose) (in yeast) (ethanol)

Fermentation proceeds till alcohol content reaches 15%. Then the

reaction is inhibited by alcohol itself.

Distillation can further increase the alcohol concentration greatly, and

the law sets limit on the content which may be sold.

Examples: Ethanol (ethylalochol)

Methanol (methylalcohol)
Propanol etc

ETHANOL (ETHYLALCOHOL)
P-kinetics: Ethanol is water soluble and is rapidly and almost completely
absorbed in the GIT. The rate of absorption is determined by the
quantity of ethanol consumed,the concentration of ethanol in the
beverages, the rate of consumption and the composition of the gastric
content.

Absorption from an empty stomach occurs within 30 – 60mins.

Absorption from an adult skin is minimal, but may be significant in
infants given alcohol sponges.
Ethanol is well distributed, crosses the BBB (concn. in brain near blood
concn), and placenta freely. Test for drunkenness generally involve an
analysis of blood, the expired air, or urine for their alcohol content.

Metabolism takes place in the liver majorly (90-98% of ingested dose).

Most of the remaining 2 – 10% is excreted unchanged in the urine and
exhaled air.

METABOLISM OF ETHANOL
Ethanol

Metabolic P – W of ethanol oxidation

- Over 90% of the alcohol consumed is completely oxidized in the

liver.
- Rate of oxidation follows zero order kinetics, which means that a
constant amount of alcohol is metabolized irrespective of time and
concentration of the drug.
- The breakdown reaction in the liver consists of three (3) steps.
1. Hepatic oxidation of alcohol to acetaldehyde (alcohol
dehydrogenase pathway), using the hydrogen acceptor
nicotinamide adenine dinucletoide (NAD) as coenzyme. This
reaction is slow and determines the speed at which alcohol is
removed from the body, and is termed as rate limiting step.

In addition, alcohol is metabolized to acetaldehyde by the

microsomal enzymes using NADPH as cofactor and a minor
pathway involving catalase which oxidize ethanol in the presence
of a hydrogen peroxide generating system.

2. Conversion of acetaldehyde to acetate is catalyzed by the enzyme

aldehydedehydrogenase.

3. The acetate formed enters the Kreb’s tricarboxylic acid cycle

producing energy. (7Kcal per gram of ethanol). Later it is
converted to carbon dioxide and water. Co2 leaves the body in the
exhaled air.

An increase in alcohol oxidation is observed in chronic alcoholic

due to an induction of microsomal ethanol oxidation activity.

MODE OF ACTION
Ethanol auguments GABA – mediated synaptic inhibition and fluxes
of chloride.

PHARMACOLOGICAL EFFECTS OF ETHANOL

A. Local actions (topical application)
- Cools skin through evaporation
- Acts as an astringent (shrink or constricts body tissue eg.
alum)
- Counter irritant or rubifacient (produces erythema or mild
burning)
- Prevents bed sores or decubitus ulcers in bedridden patients
– serves as gen antibacterial agent.
- When injected around a nerve neuritis and nerve
degeneration (used to treat pain of trigeminal neuralgia).

B. Systemic Actions
- CNS – alcohol is primarily a CNS depressant. The
degree depression is directly proportional to quantity of
ethanol consumed.

- Increased and progressive depressant effect

euphoria, talkativeness, aggressiveness, loss of
behavioural control, sedation, anxiety, ataxia, slurred
speech, altered judgment, coma and death.

- Chronic ingestion may serious neurological disorders

like memory loss, reduced perceptual activity,
emotional and sleep disorders to psychotic behaviours.

- Can induce sleep, but not a dependable hypnotic.

CVS
- Vasodilatation of cutaneous vessels in moderate quantity.
- d myocardial contractility (from cardiomyopathy)
- Congestive heart failure (from excessive ingestion)
- Cardiotoxic effect (partly from nutritional def. +
acetaldehyde)
- Elevated triglyceride levels in chronic alcoholics, however
small to moderate amount may elevate HDL, which is
protective and enhances clearance of cholesterol.

GIS
- Stimulate secretion of gastric juice and HCL acid.
- High concentration (for a long time) inflammation of the
gastric mucosa gastritis
- Can provoke GI bleeding blood loss anaemia.
- Impaired absorption of nutrients and vitamins (especially
water soluble vitamins) malnutrition vitamin
deficiencies
- Megaloblastic anemia (due to interference with folate
metabolism).
- Chronic alcohol ingestion risk of pancreatitis
Fatty liver alcoholic hepatitis →
cirrhosis→Liver damage

Endocrine
- Gynaecomastia and testicular atrophy
- Aggressive sexual behaviour (from loss of inhibition and
restraint)
- Impotence and sterility (from prolonged consumption).

MSS
- Impairs psychomotor performance and blunts reflex motor
activity.
- As a smooth muscle relaxant of the uterus, it may be used to
suppress premature labour.

Renal system
- Has a diuretic effect proportional to blood alcohol level (due
to inhibition of ADH release from posterior pituitary).

Others
- Risk of certain cancers like oropharyrgeal, laryngeal,
oesophageal, hepatic and possibly pancreatic.
- Excess consumption during pregnancy (1st trimester) may
lead to fetal abnormalities (fetal alcohol syndrome)
 - Depression of temperature regulating centre (from high
dose)

THERAPEUTIC USES
A. External Uses
- As skin disinfectant prior to injection, phlebotomy and
surgery.
- Rubefacient and counter irritant for sprains and joint pain.
- Rubbed into skin to prevent bed sores. Not to be applied on
already formed sores.
- As an ingredient of anhidrotic and astringent lotions to
decrease sweating.
- Alcoholic sponges to reduce body temperature in case of
fever. However, cold water/ice may be better.

B. Local Uses
- Injection of dehydrated alcohol around the nerves or ganglia
is used for relief of chronic, intractable pain e.g pain of
trigeminal neuralgia or inoperable carcinoma.
- Inhalation of ethanol mist has been used as an antifoaming
agent to collapse the foam obstructing the tracheobronchial
tree in acute pulmonary oedema secondary to left heart
failure.

C. Systemic Uses
- As an appetite stimulant and carminative (30-50ml of 7-10%
alcohol may be taken as beverage or tincture before meal).
- Reflex stimulation in fainting/hysteria (1 drop in the nose).
- Methanol poisoning
- Has limited application as sedative, hypnotic,
analgesic/antipyretic.

DRUG INTERACTIONS
Ethanol can interact with other drugs in four distinct ways.
1. Produce additive pharmacological action of CNS depression.
2. Inhibit the metabolism of another coadministered drug.
3. Have its own metabolism inhibited by a coadministered compound.
4. Induce a cross tolerance with other drugs especially after chronic
use.

Drugs Effects of simultaneous use in alcohol

Anticoagulants Increase likelihood of bleeding
Anticonvulsants Decrease antaiconvulsant effectiveness
Antidepressants Decrease antidepressant action, increase BP
Antihistamines Increase drowsiness
Antihypertensives Increase BP lowering action, reduced drug
effectiveness in chronic alcoholics
Diuretics Increase hypotension and diuresis
CNS stimulants Reduced stimulatory effect
(e.g. caffein)
Hypoglycaemics Interference with control of diabetes, increased
hyperglycaemia
Narcotic anelgesics Increase drowsiness, respiratory depression, and
motor impairment
Sedative hypotics Increase CNS depression
Salicylate and other Increase GI distress and bleeding
anti inflammatory
drugs
Vitamins Decrease utilization of most vitamins

ADVERSE REACTIONS
This may manifest as acute or chronic ethanol intoxication.

A. ACUTE ETHANOL INTOXICATION

Clinical Features
- Disturbances in sensorium depending on blood alcohol level
- Residual hangovers.
- Hypothermia especially in the elderly.
 - Hypostatic pneumonia if coma continues for
- Increase intracranial pressure 8 – 10hrs
- Cold and clammy skin
- Pupils normal or dilated
- Respiration is depressed and noisy

Treatment
Is especially supportive and consists of maintaining respiration, BP,
and body temperature until the ethanol has been removed by
metabolism or haemodialysis. No effective remedy for hangover.

Pharmacological Intervention
- Administer hypertonic mannitol solution intravenously if
intracranial pressure is raised.
- Regulate fluid and electrolyte balance
- Phenothiazines or butyrophenones may be needed to control
psychotic behaviour.

B. CHRONIC ETHANOL ABUSE

Clinical Features
- Psychological and physical dependence.
- Withdrawal syndrome – begins 6 – 8hrs following sudden
ceasation of drinking or reduction in amount consumed

STAGES OF WITHDRAWAL SYNDROME

Stage 1: Onset of nausea, vomiting, sweating, tremors and
hyperactivity.

Stage 2: Increase severity of above + auditory or visual

hallucination + seizures (grand mal or non focal).
Stage 3:Delirum tremens (DTs) profound confusion,
disorientation and extreme autonomic hyperactivity.

A number of organs are affected adversely by chronic alcohol use,

a result of a direct cytotoxic action
- Hepatic fatty infiltration and cirrhosis.
- Cancer may develop in advanced stages of hepatic disease.
- Progressive malnutrition and vitamin deficiency.
- Alcoholic cardiomyopathy, cardiomegaly and heart failure
- Chronic gastritis and constipation.
- Pancreatitis, peripheral neuropathy and gonadal failure in
both men and women levels of sex hormones.
- Wernicke’s encephalopathy and korsakoff’s psychosis.
- Foetal alcohol syndrome with microcephaly, prenatal growth
deficiency and short palpebral fissures.

Treatment
The immediate concern is often detoxification and management of
the withdrawal syndrome.
- Complete abstinence.
- Psychiatric treatment and support from organization like the
Alcoholic Anonymous (AA)

Pharmacological Intervention
- Multivitamin supplements are helpful in combating dietary
deficiencies.
- Benzodiazepines are drug of choice for suppressing the
withdrawal symptoms.
- Use of alcohol deterrent drugs (for aversion therapy of
alcoholism).

1. Naltrexone – an inhibitor of opioid receptors. It alters the

responses to alcohol by decreasing the cravings of abstinent
alcoholics for alcohol or by blunting the pleasurable high that
 comes with renewed drinking. Dose 50mg dly for treatment
of alcoholism.

2. Disulfiram – Is an inhibitor of aldehydedehydrogenase

accumulation of acetaldehyde unpleasant
symptoms such as nausea, sweating, thirst, thrombing
headache, dyspnoea, weakness, vertigo, blurred vision,
confusion and syncope. With large amount of alcohol can
have congestive heart failure, arrhythmias, respiratory,
depression, convulsions and even death. This scenario is
called DISULFIRAM REACTION or ACETALDEHYDE
SYNDROME or MALROUGE.

Dose – 500mg daily x 1 – 2weeks then 125-500mg/daily

until appetite for alcohol disappears.

3. Citrate calcium carbimide – It is a mixture of 1 part

calcium carbimide and 2 parts of citric acid. It has similar
actions to disulfiram, although milder and of a short
duration.

Alcohol deterrents are dangerous drugs, and should be used

with extreme caution and under strict supervision.

METHANOL
- Methanol (methylalcohol, wood alcohol, CH 3OH) is the simple
aliphatic alcohol. It has no therapeutic use, but is widely used
commercially as an industrial solvent ,ethanol denaturant, and as a
fuel.

- Methanol has pharmacological properties similar to ethanol.

- Unscrupulous mixing of methylated spirit with alcohol beverages or

its inadvertent ingestion results in “METHANOL POISONING”.

- Methanol is readily absorbed and distributed throughout the body.

it is metabolized to formaldehyde and formic acid by alcohol and
 aldehydedehydrogenases respectively, but its rate is 1/7th that of
ethanol. It follows zero order kinetics with a t½ of 20-60hrs.

- Methanol toxicity appears to be primarily due to the formation of

formic acid and direct toxic action of formaldehyde.

- Blood concn. > 50mg/dl is associate with severe poisoning.

15ml of methanol has caused blindness.
30ml has resulted to death
75-100ml is regarded as fatal dose.

Clinical Features
Vomiting, headache, uneasiness, dyspnoea, bradycardia,
hypotension, delirium, coma, acidosis (due to production of formic
acid), retinal damage (specific toxicity of formic acid), blurring of
vision congestion of optic disc blindness, and death (due
to respiratory failure)

Treatment
- Keep the patient in a dark and quiet room. Protect the eye
from light.
- Gastric lavage with sodium bicarbonate, supportive measures
to maintain ventilation and BP.
- Combat acidosis by IV sodium bicarbonate infusion the most
important measure to prevent retinal damage and other
symptoms.
- Potassium chloride infusion is needed only when
hypokalemia occurs due to alkali therapy.
- Ethanol 100mg/dl in blood, saturated alcohol dehydrogenase
and retards methanol metabolism. This helps by reducing
the generation of toxic metabolites.
- Haemodialysis – clears methanol as well as formate and
hastens recovery.
- Formepizole (4-methylpyrazole) is a specific inhibitor of
alcohol dehydrogenase. It retards methanol metabolism.
- Folate therapy – calcium leucovorin injected repeatedly has
been shown to reduce blood levels by enhancing its
metabolism.

Other Alcohols
- Isopropanol (isopropylalcohol) – used as rubbing alcohol
- Butanols and pentanols – are more toxic than ethanol, but
are rarely involved in poisoning.
- Dihydroxyalcohol (glycol) – like propylene glycol, are used as
solvents for many drugs and cosmetics.
- Ethylene glycol – was formerly used as a solvent for drugs
but caused deaths. Hence it is not employed medicinally.
Death has occurred from ingestion of anti freeze mixture
containing ethylene glycol.