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Pharmacology of Alcohol
1. ALCOHOLS
Dr. D. K. Brahma
Department of Pharmacology
NEIGRIHMS, SHILLONG
2. Why and What to Learn on
Alcohol ?
The pharmacodynamics of alcohol actions in the body and
brain, that is the pharmacological effects that produce the
biological actions of the drug. (e.g. intoxication, organ
damage etc.)
The pharmacokinetics of alcohol, that is the timing of alcohol
distribution and metabolism within the body and brain, as well
as the pathways involved in metabolism of ethanol and its
major metabolites.
3. What are they ?
Ethyl Alcohol
(Ethanol)
Methyl Alcohol
(Methanol)
4. How Manufactured ?
• Fermentation – Sugar to Alcohol and Carbon
dioxide
C6H12O6→ 2(CH3-CH2-OH) + 2CO2
(Yeasts +sugar + water = CO2 + ethanol)
• Yeasts are living micro-organisms which die in
concentrations of alcohol greater than 10 to 15%
Starch Convertase
Maltose
• Commercially - obtained from Mollases
5. Alcoholic Beverages
Malted Liquors: Fermentation of germinating cereals (malts) –
mostly Barley – Beers (3-6%)
Wines: fermentation of Natural Sugars – grapes, apples and
other fruits
No distillation, <15%
Fortified (port) – up to 22%
Champagne – 12-16% (effervescent wine)
Spirits – Rum, Whisky, Brandy and Gin
40 - 55% v/v
Standard 42.8% v/v or 37% w/w
Sources:
Whiskey - distilled grain
Rum - distilled molasses
Gin – any sugar source
Brandy – Distilled wine (Grapes)
Vodka – fermentation of any of grain, rye, wheat, potatoes, grapes, sugar beet or mollases
6. Alcohol – Percentage Calculations
Alcohol content of beverages:
specific gravity of alcohol is 79
Therefore, 1 litre alcohol weighs 790g
Percent may be by weight or by volume
By volume:
1 litre alcohol add 1 litre water = 50% (vol)
By weight:
1 litre alcohol (790g), add 790g water = 50%
(weight)
40% alcohol by weight = 50% by volume
7. 1litre water
+ =
1litre alcohol
2 litres 50% (volume)
1 kilo water 1 kilo alcohol
2 kilos 50% (weight)
+ =
40% alcohol by weight = 50% by volume
8. Pharmacological actions of
alcohol - Local
1. Rubefacient and counterirritant to skin
2. Irritant – soft skin and mucus
membrane
3. Pain, inflammation and necrosis –
injection
4. Astringent: Antiseptic (20 – 90%)
100% is dehydrating
1. No action on spores
9. Effects of alcohol consumption -
Acute
CNS:
depressant – dose dependent manner
Plasma concentration Expected effects
30 – 100 mg/dl Anxiolytic, euphoria and excitation
Hesitation, restraint, caution are lost
Impaired coordination – mood and feelings are
altered
100 -150 mg/dl Mental clouding, ataxia, disorganization of thought
and impairment of memory and drowsiness
150 – 200 mg/dl Sloppy, ataxia and drunkenness
- Slurring of speech, loss of judgment and inhibition
200 – 300 mg/dl Stupor and unconsciousness
10. Effects of alcohol consumption
(acute) - contd.
Impaired performance, slowing of reflexes and
fine discrimination impaired
Induces sleep – but not ideal hypnotic
Analgesic – but no ideal analgesic
Anticonvulsant action – but not ideal
anticonvulsant
Mechanism:
GABAA receptor mediated synaptic inhibition by
chloride channel opening
Inhibition of NMDA excitatory amino acid receptor
Stimulates 5-HT3 receptors
11. Effects of alcohol consumption
(acute) - contd.
CVS:
Small doses – cutaneous vasodilatation, flushing
Medium dose – tachycardia and mild rise in BP
Large dose - Vasodilatation due to direct vascular
smooth muscle dilatation and vasomotor centre
depression (clinical implication)
Respiration:
Stimulation of Respiration – by irritation of
pharyngeal and buccal mucosa
Central action – depression
Blood:
Moderate drinking increases HDL-cholesterol
level
Decrease in LDL oxidation
12. Effects of alcohol consumption
(acute) - contd.
GIT:
Dilute alcohol at low
doses - stimulate GI
secretion – flavour,
aroma or direct
action on gastrin
secretion
Higher doses inhibit
GI secretion
Acute consumption
– pylorospasm,
gastritis, vomiting,
reflux etc
Mallory-Weiss lesion
13. Effects of alcohol consumption –
(acute) - contd.
Kidney: Diuresis – increased water
ingestion and inhibition of ADH
Uterus: Relaxation of uterine muscles
Endocrine:
Low dose – Adrenaline release and
hyperglycemia
High dose – Hypoglycemia
Sex - Aphrodisiac
14. Absorption
Rapidly absorbed from small intestine,
and colon but slowly from stomach
First pass metabolism in stomach and
liver
Maximal blood concentration within 30 to
90 minutes
Can be absorbed through the lungs
Can be absorbed through skin
15. Distribution
Uniformly distributed throughout tissues and body
fluids
Readily crosses placenta, to exposure fetus
Crosses BBB readily
Elimination
Urinary Excretion
Exhalation
Metabolism
16. Metabolism I
H
H
H C OH
H
C
H
Ethanol
H
H C
H
=
C O
H
Acetaldehyde
ADH
(ADH – Alcohol Dehydrogenase)
17. Metabolism II
H
H C
H
=
C O
H
ALDH
H
H C
H
=
C O
OH
Acetaldehyde
Acetate
(ALDH – Acetaldehyde Dehydrogenase)
18. Metabolism III
80-90% Metabolized
Also metabolized in small amounts by hepatic
microsomal enzyme
Rate is constant (not increased by
concentrations in the blood) – zero order (8-12
ml/H of absolute alcohol)
About 30 ml (1 oz) in 3 hours
Concentration in exhaled air is 0.05% of blood
concentration – used in medico legal purposes
19. Adverse Effects of Alcohol
Acute Effects
Nausea, Vomiting, hangover and traffic accidents
CNS Depressant
Depression of inhibitory control
Vasodilatation, warm, flushed, reddish skin
Emotional outbursts
Decreased memory & concentration
Poor judgment
Decreased reflexes
Decreased sexual response
20. Adverse Effects of Alcohol –
contd.
Acute Alcohol Intoxication:
Estimated ED50: 150 mg/100 ml and LD50 = 500
mg/100ml
Therapeutic index about 3.5
Hypotension, hypoglycemia, respiratory depression
coma and death
Death due to respiratory depression or inhaled vomit
Treatment:
Gastric lavage
Endotracheal intubations
Fluid and electrolyte balance
Glucose infusion
Thiamine injection 100 mg in 500 ml of glucose IV
Haemodialysis
21. Consequences of acute
Alcohol intoxication - images
Vomiting Driving accidents Loss of inhibitions
Hangover
22. Toxic Effects - Chronic
Alcoholism
GIT:
Gastritis and damage to the mucosa –
anaemia
Intestinal damage: Lack of absorption -
Deficiency of water soluble vitamins and
amino acids (protein deficiency)
Less or no food intake (enough calorie) -
Vitamin and Protein deficiency
(Q. Is Alcohol a total food ? Answer: No -
Lacking in total food value)
23. Chronic Alcoholism – contd.
Liver cirrhosis – scarring of
liver
Usually fatal if drinking
is not stopped
Fatty infiltration
(excess in NADH)
Oxidative stress and
cellular necrosis
Damage to
hepatocytes and
inflammation –
aldehyde
Glutathione
depletion
Microsomal enzyme
induction
24. Chronic Alcoholism – contd.
Neurological: Polyneuritis, pellagra,
tremors, seizures, loss of brain mass,
Korsakoff`s psychosis and Warnicke`s
encephalopathy
CVS: Hypertension, cardiomyopathy,
CHF arrhythmias and stroke
Hormonal: Impotence, gynaecomastia
and infertility
Acute pancreatitis
25. Chronic Alcoholism – contd.
Reproduction
Alcohol is a teratogen, it causes birth
defects.
Fetal Alcohol Syndrome (FAS) or Fetal
Alcohol Effects (FAE), or Alcohol-Related
Birth Defects (ARBD)
Symptoms include retardation, poor
coordination, loss of muscle tone, low birth
weight, slow growth, malformation of internal
organs and peculiar facial characteristics
26. Fetal Alcohol Syndrome (FAS)
Characteristics
Growth retardation
Facial malformations
Small head
Greatly reduce
intelligence
27. Chronic Alcoholism - features
• Craving: A strong need, or compulsion, to drink
• Loss of control: The inability to limit one’s drinking on any given
occasion
• Tolerance: The need to drink greater amounts of alcohol in order to
“get high” – pharmacokinetic or cellular tolerance
• Physical dependence: Withdrawal symptoms, such as nausea,
sweating, shakiness, sleep impairment, hallucinations, delirium
tremens and anxiety, occur when alcohol use is stopped after a
period of heavy drinking
• Withdrawal syndromes: long acting BZDs like chlordizepoxide
and diazepam
• Naltrexone (50 mg)
28. Ethanol – Usefulness:
1. Local:
antiseptic, rubefacient and counterirritant in sparins
and to prevent bedsores
antiperspirant and aftershave
Alcohol sponges – to reduce body temperature
1. Appetite stimulant and carminative: 30 – 60 ml of 7-
10%
2. Neuralgias: severe cancer pain – injection round the
nerve
3. Protection from cold
4. Alcohol may have a protective effect from heart attack
and stroke - frugivores
5. Methanol Poisoning
29. Disulfiram (Antabuse)
Internationally marketed as antabuse
ALDH enzyme inhibitor
Alcohol + disulfiram rise in concentration of aldehyde in
blood and tissue distressing aldehyde syndrome
Symptoms: flushing, burning sensation, throbbing headache,
perspiration, dizziness, vomiting, visual disturbance, mental
confusion, fainting and circulatory collapse
Uses: aversion technique in chronic alcoholics: only to
motivated persons
Technique: abstain alcohol overnight and start with 1 gm on
day 1 followed by 0.75 gm next day and 0.50 gm next day and
so on. Effects start within few hrs of 1st dose and lasts for 2
weeks
Mechanism: irreversible inhibition of ALDH and synthesis of
new enzyme takes time and thus person resolves not to drink
for distressing symptoms
Available as 250 mg tablets
30. Ethanol as Antidote
Methanol, Ethylene glycol, Diethylene glycol
Methanol poisoning – toxicological importance –
unscrupulous mixing with alcoholic beverages
Formic acid is toxic: above 50 mg/dl, lethal dose 75 – 100
ml, even 15 ml can cause blindness
ADH ALDH
Methanol formaldehyde Formic acid
Methanol poisoning: vomiting, epigastric pain dyspnoea,
bradycardia, acidosis – permanent retinal damage and
Death
Mechanism: Ethanol saturates alcohol dehydrogenase
enzyme - no metabolism of Methanol to form Formic acid
31. Methanol Poisoning
treatment
Patient in dark room, Ventilation and BP supportive measures
Gastric lavage with sodibicarb if brought immediately
IV sodibicarb to combat acidosis – large quantity may be
required
Ethanol 10% in water – nasogastric tube with loading dose of
0.7 ml/kg followed by 15 ml/kg/hr by infusion – continue
treatment for several days (methanol is oxidized slowly)
Potassium chloride if hypokalemia occurs
Folinic acid or Calcium leucovorin ijection 50 mg IV every 6 Hrly
– to enhance oxidation of formic acid
4-methylpyrazole – specific inhibitor of ALD – 15 mg/kg IV and
10 mg/kg 12 Hrly. till methanol level is <20 mg/dl
Haemodialysis
32. Summary
Alcohol is a neuronal depressant
Long term exposure to alcohol brings about
adaptive changes in the neuronal system
Chronic alcoholism causes toxic effects on all
the organs especially liver
Withdrawal syndrome in alcoholics are treated
by BZDs and Naltrexone
Antbuse/disulfiram is the drug is use as
aversion technique in chronic alcoholics
Ethanol is used as antidote in Methanol
Poisoning
The drunkometer collected a motorist&apos;s breath sample directly into a balloon inside the machine. The breath sample was then pumped through an acidified potassium permanganate solution. If there was alcohol in the breath sample, the solution changed colour. The greater the colour change, the more alcohol there was present in the breath.