This document discusses the effects of ethanol (alcohol) on various body systems. It begins by classifying alcoholic beverages and describing alcohol metabolism in the liver. It then summarizes ethanol's effects on the central nervous system, including its actions on various neurotransmitter systems. The document goes on to discuss ethanol's cardiovascular, gastrointestinal, and other organ-specific effects. It concludes by covering topics like alcohol tolerance, dependence and withdrawal, as well as pharmacological treatments for alcoholism.

1. Dr Chintan DOshi
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2. • A) Malted liquors:
– By fermentation of germinating cereals
– Undistilled
– Low alcohol content(3-6%)
• B) Wines:
– By fermentation of natural sugars e.g. Grapes & other
fruits
– Undistilled
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3. • C) Spirits:
 Distilled after fermentation
 40-55% alcohol (standardized to 42.8%v/v or
37%w/w)
 e.g. Rum, gin, whiskey, vodka, brandy
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4. Alcohol
dehydrogenase
CYP450
CYP2E1
NAD+ NADPH
Catalase
H2O2
Aldehyde
Dehydrogenase
Fomepizole
Disulfiram
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5. 5

6. Central Nervous System
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7. • Ethanol primarily is a CNS depressant
• Anti-anxiety actions & Behavioral Changes
• Uncontrolled mood swings and emotional outbursts
• The cortex & RAS are most sensitive
• With more severe intoxication → CNS function is
impaired, and ultimately a condition of general
anesthesia

8. Actions of Ethanol on Neurochemical
Pathways and Signaling
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9. Neurotransmitter
System
Effects
GABAA GABA release, ↑ receptor density
NMDA Inhibition of postsynaptic NMDA receptors;
with chronic use, up-regulation
DA ↑ Synaptic DA
ACTH ↑ CNS and blood levels of ACTH
Opioid Release of β endorphins, activation of μ
receptors
5-HT ↑ in synaptic 5-HT
Cannabinoid ↑ CB1 activity, changes in DA, GABA,
glutamate activity
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10. • GABA Boosting action :
– Feelings of sleepiness, muscle relaxation, and the
acute anticonvulsant properties
• Dopamine :
– Associated with feelings of euphoria, reward &
craving
• Alcoholic blackouts :
– Large doses of ethanol can interfere with encoding
of memories, producing Anterograde Amnesias
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11. • With heavy intake :
 Disturbances in sleep architecture, with frequent
awakenings and restless sleep
 Vivid and disturbing dreams, suppression of night
rapid eye movement
 Thiamine depletion - Wernicke-Korsakoff
syndromes (ataxia, opthalmoparesis, amnesia,
psychosis)
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12. • “Alcohol-induced" psychiatric syndromes :
 Caused by Heavy doses of ethanol over multiple days
or weeks
 Related to changes in CNS pathways
 Depressive symptoms, temporary suicidal thoughts
and behaviors
 Panic attacks and generalized anxiety
 Temporary auditory hallucinations and paranoid
delusions
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13. • Alcoholic dementia :
– Chronic heavy drinking increases the probability of
developing a more permanent cognitive deficit
• Hangover :
– The transient CNS effects of heavy ethanol
consumption
– “Next morning" syndrome
of headache, thirst, nausea
and cognitive impairment
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14. Cardiovascular System
• Greater than three standard drinks per day elevates the
risk for heart attacks and bleeding-related strokes
• Vascular-related diseases are among the leading causes
of early death in alcohol-dependent individuals
• 6-fold increased risk for coronary artery disease, cardiac
arrhythmias, and congestive heart failure
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15. Blood
• Regular intake of small to moderate amounts of alcohol(1-2
drinks) has been found to raise HDL cholesterol levels and
decrease LDL oxidation
• 15-35% lower incidence of CAD in such individuals
• Protection is lost if > 3 drinks are consumed daily
• Mild anaemia in chronic alcoholism
• Megaloblastic anaemia is due to interference with folate
metabolism
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16. Gastro Intestinal System
• ↑es gastric acid secretion cause vomiting, mucosal
congestion & gastritis
• Bowel movements are altered
• Acute pancreatitis → Complication of heavy drinking
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17. Liver
• If adequate nutrition is maintained → No significant
liver damage
• Increases fat synthesis in liver, proteins are also
accumulated
• Alcoholic cirrhosis :
– Chronic alcoholism → Oxidative stress
→ Cellular necrosis → Fibrosis
– Combined with vitamins &
other nutritional deficiencies
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18. • Body temperature :
 Warmth is produced due to cutaneous and gastric
vasodilatation
 High doses depress temperature regulating centre
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19. • Skeletal muscle :
 Muscle work is increased or decreased depending
on the predominating central effect
 Weakness and myopathy occurs in chronic
alcoholism
• Kidney :
 Diuresis
 Due to water ingested with the drink & alcohol
induced inhibition of ADH
 No significant renal damage
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20. Sexual function
• Alcohol is reputed as an aphrodisiac
• Aggressive sexual behaviour is due to loss of inhibition
• Performance of sexual act is often impaired
• Chronic alcoholism can produce impotence, testicular
atrophy, gynaecomastia and infertility in both sex
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21. Miscellaneous effects
• Chronic alcoholics → Predisposed to lung infection
• Ethanol not a carcinogen but chronic use → ↑ed
incidence of breast & liver carcinoma
• Alters uric acid metabolism → Gout precipitation
• Moderate blood ethanol levels → Uterine
contractions suppressed
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22. Clinical uses
• Medicinal uses of ethanol are restricted to external
application and as a vehicle for liquid preparations
used internally
1. As antiseptic
2. Rubefacient and counterirritant for sprains, joint
pains, etc
3. Rubbed into the skin to prevent bedsores
4. Astringent action used in antiperspirant and
aftershave lotions
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23. 5. Alcoholic sponges to reduce body temperature in fever
6. Intractable neuralgias (trigeminal and others), severe cancer
pain → Injection of alcohol round the nerve causes
permanent loss of transmission
7. To ward off cold → By causing vasodilatation of blanched
mucosa
8. As appetite stimulant
9. Reflex stimulation in fainting/hysteria: 1 drop in nose
10. To treat methanol poisoning
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24. Contraindications
1. Peptic ulcer, hyperacidity and gastroesophageal reflux
patients (alcohol increases gastric secretion and relaxes
LES).
2. Epileptics: seizures may be precipitated
3. Severe liver disease patients
4. Unstable personalities: they are likely to abuse it and
become excessive drinkers
5. Pregnant women: Moderate drinking during pregnancy
can produce foetal alcohol syndrome
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25. Guidelines for safe drinking
• 1 drink =
• 50 ml of spirits
• 150 ml of wines
• 400 ml of beer
• Guidelines :
 On an average 1-2 drinks per day is usually safe
 Not more than 3 drinks on any one occasion
 Consumption of >3 drinks per day is associated with
documented adverse health effects
16 gm alcohol & 30mg/dl Blood
Ethanol levels in adult male
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26. Contd …
• Do not drive or engage in hazardous activities after
drinking
• Do not drink if an interacting drug has been taken
• Subjects with any contraindication should not drink
• Safe limits are somewhat lower for women than for men,
because metabolism of alcohol is slower and its
bioavailability higher
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27. Drunk driving law
• The blood alcohol content (BAC) limits are fixed at
0.03% or 30 µl alcohol in 100 ml blood.
• Any person whose BAC values are detected more
than this limit is booked under the first offense.
• A person may be fined about 2000 andor he or she
may face a maximum of 6 months imprisonment.
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28. Toxicity
• Moderate drinking :
• Nausea
• Vomiting
• Flushing
• Hangover
• Traffic accidents
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29. • Acute Alcohol Intoxication :
 Unawareness
 Unresponsivenesas
 Stupor
 Hypotension
 Gastritis
 Hypoglycemia
 Respiratory depression
 Collapse
 Coma & death
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30. • Treatment :
 Gastric lavage – only if the patient is brought soon after
alcohol intake
 Maintain patent airway and prevent aspiration of vomitus
 Tracheal intubation and positive pressure respiration if
respiration depressed
 Maintenance of fluid and electrolyte balance
 Correction of hypoglycaemia by glucose infusion till
alcohol is metabolized
 Thiamine (100 mg in 500 ml glucose solution infused i.v.)
 Hemodialysis if needed
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32. • Tolerance :
 On chronic intake tolerance develops to the effects of
alcohol
 reduced behavioral or physiological response to the
same dose of ethanol
 Pharmacokinetic tolerance due to reduced absorption
& ↑ed metabolism
 Cellular tolerance also
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33. Dependence :
Physical dependence
• Elicitation of a withdrawal
syndrome when alcohol
consumption is terminated
• Symptoms and severity
depends on the amount and
duration of alcohol
consumption
• Sleep disruption,
sympathetic activation,
tremors, seizures & in
severe cases delirium
tremens
Psychological dependence
• Craving and drug-seeking
behavior
• With moderate drinking
• Depends on individual’s
likings & attitude
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34. Pharmacotherapy of Alcoholism
• 1. Naltrexone :Opioid antagonist
• M/A :
Blocks activation of dopaminergic pathways in the
brain
↓drinking through ↓ feelings of reward and/or ↓
craving
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• Nalmefene : Another opioid antagonist
• Adv: greater oral bio-availability,
» Longer duration of action,
• Lack of dose-dependent liver toxicity
• Appeared useful in clinical tests

36. • 2. Acamprosate :
– An analogue of GABA
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37. • 3. Disulfiram :
• Tetra ethyl thiuram disulfide
• M/A : Inhibits the enzyme Aldehyde Dehydrogenase
after conversion into active metabolites
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38. • Concentration of acetaldehyde in tissues and blood rises
and a number of highly distressing symptoms
E.g.
 Flushing, Burning sensation
 Throbbing headache, Perspiration
 Uneasiness, Tightness in chest
 Dizziness , Vomiting
 Visual disturbances, Mental confusion
 Postural fainting, Circulatory collapse
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39. • Use :
– As an aversion technique in chronic alcoholics who
are motivated to leave the habit
– should not be used in patients who are physically
dependent on alcohol
• Side effects
• rashes, metallic taste, nervousness, malaise
and abdominal upset
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40. Other drugs
• Varenicilin :
– Partial agonist at α4β2 of nicotinic Ach receptor
– ↓ed ethanol seeking behaviour & its consumption
in rodents
• Rimonabant :
– Antagonist of CB1 receptor
– Blocks the effect of ethanol on dopaminergic
system
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41. • Ondansetron:
 A 5-HT3-receptor antagonist and antiemetic drug
 Reduces alcohol consumption in laboratory animals and
currently is being tested in humans
 Lowers the amount of alcohol consumed & ↓es desire to drink
• Topiramate :
 A drug for seizures
 A new and unique approach to pharmacotherapy of alcoholism
 Useful for treating alcohol dependence
 Lowers craving
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42. Methanol
• Methyl alcohol or Wood alcohol
• One carbon alcohol (CH3OH)
• Only of toxicological importance
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43. • P/K :
– Rapidly absorbed via the oral route, inhalation,
and through the skin
– Metabolized by ADH and ALDH to Formaldehyde
& Formic acid respectively
– Methanol
– Zero order kinetics
Formaldehyde Formic acid
ADH ALDH
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44. Methanol Poisoning
• Toxic effects of poisoning due to formic acid as
further metabolism is slow & folate dependent
• Severe poisoning - >50 mg/dl blood methanol
• Fatal dose – 70-100 ml
• Even 15 ml caused blindness & 30 ml caused death
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45. • Manifestation :
 Vomiting
 Headache
 Epigastric pain
 Uneasiness
 Drunkenness
 Disorientation
 Dyspnoea
 Bradycardia
 Hypotension
 Delirium
 Seizure
 Coma
 Death due to respiratory failure
Toxicity of formic acid
- Retinal damage
- Blurring of vision
- Congestion of optic
disc
- Blindness
- Acidosis
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46. • Treatment :
• Keep the patient in a quiet, dark room; protect the eyes
from light
• Gastric lavage with sod. bicarbonate if the patient is
brought within 2hrs
• Treat acidosis by i.v. Sod.bicarbonate infusion
• Ethanol :
 l00 mg/dl in blood saturates alcohol dehydrogenase
and retards methanol metabolism
 Administered through a nasogastric tube
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47. • Haemodialysis:
 Clears methanol as well as formate & fastens recovery
• Fomepizole (4-methylpyrazole) :
 Specific inhibitor of alcohol dehydrogenase & retards
methanol metabolism
 A loading dose of 15 mg/kg i.v. followed by 70 mg/kg
every 12 hours till serum methanol falls below 2O mg/
dl
• Folate therapy:
 Calcium leucovorin 50 mg injected 6 hourly
 Decreases blood formate levels by enhancing its
oxidation
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