pharmacology of alcohol
DESCRIPTION
Undergraduate MBBS level Power Point presentation of Theory ClassTRANSCRIPT
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ALCOHOLS
Dr. D. K. Brahma
Department of Pharmacology
NEIGRIHMS, SHILLONG
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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.
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What are they ?
Ethyl Alcohol
(Ethanol)
Methyl Alcohol
(Methanol)
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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 Maltose• Commercially - obtained from Mollases
Convertase
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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
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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
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1litre water1litre alcohol
+ =2 litres 50% (volume)
1 kilo water 1 kilo alcohol2 kilos 50% (weight)
+ =
40% alcohol by weight = 50% by volume
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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
5. No action on spores
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Effects of alcohol consumption - Acute
CNS: depressant – dose dependent mannerPlasma concentration Expected effects
30 – 100 mg/dl Anxiolytic, euphoria and excitationHesitation, restraint, caution are lostImpaired 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
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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
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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
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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
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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
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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
Absorption
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Uniformly distributed throughout tissues and body fluids
Readily crosses placenta, to exposure fetus Crosses BBB readily
Distribution
Elimination
Urinary ExcretionExhalationMetabolism
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Metabolism I
CH OH
Ethanol
H
H
C
H
H
CH
H
H
C O
H
=
Acetaldehyde
(ADH – Alcohol Dehydrogenase)
ADH
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Metabolism II
CH
H
H
C O
H
=
Acetaldehyde(ALDH – Acetaldehyde Dehydrogenase)
ALDH
Acetate
CH
H
H
C O
OH
=
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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
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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
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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
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Consequences of acute Alcohol intoxication - images
Vomiting Driving accidents Loss of inhibitions
Hangover
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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)
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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
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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
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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
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Fetal Alcohol Syndrome (FAS)
CharacteristicsGrowth retardationFacial malformationsSmall headGreatly reduce intelligence
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• 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)
Chronic Alcoholism - features
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Ethanol – Usefulness:
1. Local: antiseptic, rubefacient and counterirritant in sparins
and to prevent bedsores antiperspirant and aftershave Alcohol sponges – to reduce body temperature
2. Appetite stimulant and carminative: 30 – 60 ml of 7-10%
3. Neuralgias: severe cancer pain – injection round the nerve
4. Protection from cold5. Alcohol may have a protective effect from heart attack
and stroke - frugivores6. Methanol Poisoning
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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
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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
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
Methanol formaldehyde Formic acid
ADH ALDH
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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
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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
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Thank You