Alcohols………

Dr. Rajesh
Ramwani
 Ethyl Alcohol
Alcohol is a general term for any
organic compound in which
(-OH ) is bound to a carbon atom

Refers to ethyl alcohol (ethanol) in

common usage
Types of ethyl alcohol
I) Malted Liquors:
Obtained by fermentation of germinating cereals:
eg: Beer
- Undistilled
- Alcoholic Contents is low : 3-6%
II) Wines
Obtained by fermentation of natural sugars from
grapes & other fruits. Undistilled

Light Wines :- cider, claret- (15%)-

Fortified Wines :-Port, Sherry- ( 16-22%)-

Effervescent Wines :- champagne- (12-16 %)-

III) Spirits:
These are distilled after fermentation
Eg: Whiskey, Rum, Brandy , Vodka- (40-50%)

( standardized to 42.8% v/v or 37% w/w)

In India percentage of most whiskey’s is

42.8% barring a few which have upto 50%
IV) Others :
Absolute alcohol: Dehydrated alcohol
(99%)
Rectified spirit: (90%)
The concentration of alcohol in an alcoholic beverage
may be specified

 in percent alcohol by volume (ABV) v/ v

 in percentage by weight ( w / w )

 in proof.

the “proof” of an alcoholic beverage is twice its

percentage of alcohol; ( e.g., 40% alcohol is 80 proof
100 proof ~ 50% ABV )
 Production
 Produced by fermentation, which is the metabolism of

carbohydrates (usually sugars) by certain species of yeast

in the absence of oxygen

Zymase
C6H12O6 → 2 CH3CH2OH + 2 CO2

 The process of culturing yeast under conditions that

produce alcohol is referred to as brewing

To produce ethanol from starch such as cereal grains, the starch
must first be broken down into sugars. This is accomplished
by allowing the grain to germinate or malt
During germination, the seed produces enzymes that can break
its starches into sugars like Maltose

Convertase Zymase
Starch Maltose Alcohol
A major source of commercial alcohol is molasses, a
byproduct of sugar industry
Most yeasts cannot grow when the concentration of alcohol
is higher than about 18% by volume, so that is a practical
limit for the strength of fermented beverages such as
wine, beer

Strains of yeast have been developed that can survive in

solutions of up to 25% alcohol by volume
 Pharmacological actions:
Local Actions:
 Rubefacient
 Counterirritant
 Applied to delicate skin- irritation , Burning
 Astringent
 Antiseptic action:
 - 20- 70% - increases
 - 70- 90 % - Remains constant
 - > 90% - decreases
BAC ( mg / dL ) Symptoms
50-100 Euphoria, talkativeness, Excitation.

100-200 Central nervous system depression,

mental clouding, disorganization of thought ,
impaired motor and sensory function, Alteration of gait,
impaired memory, Slurring of speech, impaired
cognition

200-300 Emesis, stupor

300-400 possible unconsciousness, coma

> 500 Resp. depression, Possible death

 Mechanism of Action
Cellular sites and mechanism(s) of action
 Receptor Modulation
- promotes GABAA mediated synaptic inhibition
- Inhibits Glutamate receptors ( NMDA )
- Augments 5-HT action on 5-HT3 (inhibitory
auto
receptor)
- Inhibits “voltage-gated Ca-channels”

 Enhances DA turnover in brain through beta

endorphin release. ( pleasurable reinforcing effects
 CVS
 Blood vessels: cutaneous (specially of face )
and gastric vasodilatation
 Heart: Tachycardia, rise in BP – moderate doses

depression of myocardial activity with

large amounts (due to acetaldehyde)
 Blood pressure: not affected with small doses
falls with large doses
(vasomotor centre
depression)
 Chronic use may lead to Hypertention,
cardiomyopathy. Cardiac arrhythmias may
occur.
GIT
Dilute alcohol stimulates gastric secretions

Stronger beverage inhibits gastric secretion and

causes vomiting and gastritis

Chronic use leads to chronic gastritis

 LES tone is reduced- accentuate reflux.

Chronic alcohol ingestion is by far the most

common cause of Chronic pancreatitis.


 Liver disease is the most common medical

complication of Chronic Alcoholism.

 Alcoholic fatty liver- may progress to

alcoholic hepatitis and finally to cirrhosis and

liver failure.
 Skeletal Muscle: Weakness and myopathy

occurs in chr. Alcoholism.

 Diuresis

 Hyperglycemia- moderate amount

 Hypoglycemia – Ac. Intoxication.

 Neuro toxicity: most common neurological

abnormality in chr. Alcoholism is generalized

symmetric peripheral nerve injury- paresthesias of the
hand and feet
 Wernicke-Korsakoff syndrome:

 Paralysis of extra ocular muscles

 Ataxia

 Confusion

 Associated with thiamin deficiency.

 Other actions
 Uterine relaxation

 Aggressive sexual behaviour (Aphrodisiac ?) due to loss

of inhibition, but impairment of sexual act

 Sympathetic over activity due to Adrenaline release

 Beneficial effect on lipid levels in moderation

 Body Temperature – sense of warmth due to cutaneous

Vasodilatation.
 Pharmacokinetics
Absorption
 Water soluble, Absorbed rapidly from intestines
 Ingested in fasting state - Peak B A Conc.
Reaches within 30 min.
 Food decreases rate of absorption
 Absorption from skin is minimal in adults

Distribution
 widely distributed
 Crosses blood-brain barrier efficiently
 Also crosses placental barrier freely
 Elimination
Metabolism Extensive metabolism in liver
(90%)
(1) Alcohol
NAD alcohol dehydrogenase
NADH

Acetaldehyde
disulfiram (-) aldehyde
dehydrogenase

Acetic acid
Kreb’s / Citric
Acid Cycle
 (2) Microsomal Ethanol Oxidizing
system (MEOS)
CYP2E1, CYP1A2, CYP3A4

Alcohol Acetaldehyde

NADPH NADP+ + H2O

Excretion of a small fraction occurs via lungs
(That’s the reason to carry out Breath test by
Police -by using Breath Analyzers) and kidneys

Elimination by metabolism exhibits

Zero order kinetics
(basically due to NAD cofactor saturation)
 The amount present in exhaled air can be

measured to indirectly detect the plasma

conc.

 35 µg/100 ml in exhaled air = 80mg/ 100 ml

in blood

 i.e. the concentration in blood is about

2000 time higher than the exhaled air.

 Clinical uses
 Methanol poisoning

 Chronic intractable pains Trigeminal neuralgia

Carcinomas
 Intractable pruritis – intradermal, subcutaneous

 Appetite stimulant orally

 Reflex stimulation in fainting - nasal drop

 As antiseptic

 Bedsores
Chronic Intractable pains

Dehydrated Alcohol Injection is indicated for

therapeutic neurolysis of nerves or ganglia
Relief of trigeminal neuralgia usually is only temporary

Alcohol produces injury to tissue cells by dehydration

and precipitation of protoplasm
Contraindications
 Hepatic disease

 Epilepsy

 Peptic ulcer

 Pregnancy – Fetal alcohol syndrome:

Retarded growth
low IQ
low birth weight
facial abnormalities
 Side Effects and Toxicity
 Acute toxicity

Nausea, vomiting, flushing, hangover,

Hypotension, gastritis,
hypoglycemia, Respiratory depression,
coma, death
Treatment is supportive
Gastric lavage, prevention of
aspiration
positive pressure respiration
 Chronic alcoholism
 Tolerance and dependence – withdrawal syndrome

 Wernicke’s encephalopathy Deficiency of

 Korsakoff’s psychosis Thiamine
 Cirrhosis liver - 15-30% of chronic heavy drinkers

 Fatty liver

 Impaired gluconeogenesis

 Cardiomyopathy

 Myopathies
 Chronic gastritis

 Megaloblastic anemia, vitamin deficiencies

 Testicular atrophy, gynaecomastia,

impotence

 Teratogenicity
Treatment
 Psychological support

 Benzodiazepines- for withdrawal symptoms-

Diazepam/ chlodiazepoxide, clonazepam.

 Three drugs are approved by FDA for the t/t of

alcohol dependence/ alcoholism:

 Naltrexone

 Acamprosate

 Disulfiram
Naltrexone: has been shown to reduce craving for

alcohol and to reduce the rate of relapse to either

drinking or alcohol dependence.
50 mg OD orally.

 Extended release formulation – IM inj-once every

month.
 hepatotoxic – dose dependent manner

 Naltrexone + disulfiram- avoided – hepatotoxic

Acamprosate: weak NMDA-receptor antagonist
and GABA-A receptor activator.
 used for maintenance therapy of alcohol abstinence.

 along with social and motivational therapy , it has been

found to reduce relapse of drinking behavior.

 Enteric coated tab.- 333 mg 1-2 tab TDS. Started soon

after withdrawing alcohol

 A/E: GI upset.
 Disulfiram:
Irreversible inhibitor of Aldehyde dehydrogenase.
 produce distressing symptoms: -
 Flushing, burning sensation, throbbing headache,
nausea vomiting, sweating, hypotension and
confusion – starts within few min. after ingestion of
alcohol.
 effects may last for 30 min. in mild cases and for
several hrs. in severe cases.
 tab. 1g- on day 1, 0.75g – on day 2, 0.5 g on day 3
 followed by 0.25 g subsequently.
 Other drugs have shown efficacy in

maintaining abstinence and reducing

craving in chr. Alcoholism: -
 Ondansetron

 Topiramate

 Balcofen
Drug interactions
 Disulfiram

 Disulfiram like reaction: Metronidazole,

sulfonylureas, cephalosporins
 Phenytoin – induction of metabolism

 Aspirin – gastric bleeding

 Insulin – enhanced hypoglycemia

Methanol poisoning
Methanol was formerly obtained by the distillation of

wood, and was called “wood alcohol”

Metabolized to formaldehyde and formic acid

Poisoning causes

 vomiting, headache, retinal damage, dyspnea,

bradycardia, hypotension, delirium, acidosis, coma,

death. (fatal dose = 75-100 ml)
Methanol poisoning -
Treatment
 Gastric Lavage- sod bicarbonate- if pt. is
brought early

 Ethanol – 100 mg/dl (10% in water) –

nasogastric tube . 0.7 ml/kg loading
dose
 Followed by 0.15ml/kg/ hr

 competitive inhibition of metabolism-

decreased formation of toxic metabolites.
Fomepizole: inhibitor of alcohol dehydrogenase

loading dose- 15 mg /kg IV

f/b – 10mg/ kg every 12 hrs till the serum level falls below 20
mg/ dl

 Leucovorin (folinic acid) - Ca leucovorin 50 mg inj 6 hrly---

reduces formic acid levels by increasing its oxidation.

 Haemodialysis
Thank You