Alcohol

Beer
Cider
Wine


Whiskey
Brandy
Rum

Rectified spirit
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Ethyl alcohol
Alcohol is important in medicine -
misuse/abuse

Present in beverages/used as drug

Alcoholism is a complex disorder with a
genetic and environmental component

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Pharmacological actions -
Local
Mild rubefacient - Cutaneous vasodilation
Promotes heat loss
Astringent; antiseptic (20-70%=90%)
Injected to nerve permanent damage
(sclerosant)


24
William Shakespeare (15641616). The Tragedy of
Macbeth.

Lechery, sir, it provokes, and unprovokes;
It provokes the desire, but it takes away
the performance;
It makes him, and it mars him;
It sets him on, and it takes him off;
It persuades him, and disheartens him;
Giveth redness of nose, sleep and urine
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CNS effects

CNS depressant
Inhibition is lost
At higher concentrations - slurred speech, ataxia, impaired judgment, motor
incoordination, increased self-confidence & disinhibited behavior
Induces sleep-not dependable
Chronic: dementia, wernicks, cognition disorders
Mechanism of CNS action involves:
potentiation of GABA receptor
inhibition of Glutamate receptor neurotransmission
Enhances action at other ligand-gated ion channels like 5HT
3
, N
N
, glycine receptors
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CVS

Small doses cutaneous vasodilatation
Moderate dose - BP central sympathetic stimulation
High dose - BP Myocardial + vasomotor center depression
Chronic alcoholism cardiomyopathy,
conduction defect, ventricular hypertrophy,
atrial & ventricular arrhythmias
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Blood
Low doses- HDL & CHD risk
Do not advice non drinkers to drink
Body temperature
Combats cold??feeling of warmth
Heat loss is increased-vasodilation
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Gastric mucosa
disrupt the gastric mucosal barrier and cause acute and
chronic gastritis
Promotes the release of gastrin and histamine
gastric acid secretion
act synergistically with H. pylori to delay healing
Inflammation and bleeding by ulceration of the stomach
lining
Acute pancreatitis



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Liver
Small to moderate-safe
Chronic-Cirrhosis
Chronic alcohol consumption osteoporosis
reasons - unclear, impaired osteoblastic activity has
been implicated
Endocrine
Small doses-hyperglycemia-Adrenaline
release
Large- Hypoglycemia[gluconeogenesis is
inhibited]

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Kidney
Diuresis - Antidiuretic hormone

Uterus
Relaxant

17
Pharmacokinetics


Orally - rapidly absorbed from stomach and small intestine
Depends on the presence of food
Vol.of distribution wide
Metabolism-zero order [12ml/hr]
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Ethanol Metabolism
o Oxidation - Alcohol
dehydrogenase (Al.DH)
[Fomepizole inhibits]


o Ald.DH - mainly in liver,
stomach and brain
[Disulfiram inhibits]
[Sulfonylurea, cefoperazone,
metronidazole]


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Microsomal Ethanol-Oxidizing System (MEOS)
Another minor pathway of metabolism
Ethanol-metabolism
Genetic factors
In 50% of Asian people, an inactive genetic
variant of one of the aldehyde
dehydrogenase isoforms (ALDH-2) is
expressed;
These individuals experience a disulfiram-
like reaction after alcohol, and the incidence
of alcoholism in this group is extremely low
13
Adverse health effects

>3 drinks/day is associated with adverse health effects
1 drink =18 ml of alcohol
350ml of beer or 150 ml of wine or 45 ml of spirit

1. GIT peptic ulcer, hyperacidity, nutritional deficiency,
pancreatitis
2. Lowers seizure threshold
3. Liver disease
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Adverse health effects
Abuse

Fetal alcohol syndrome

HTN, cardiomyopathy

CNS impaired mental and physical
performance

Wernickes encephalopathy, Korsakoffs
psychosis
13


Teratogenic effects
Fetal alcohol syndrome
Characteristics of fetal alcohol syndrome include:
(1) intrauterine growth retardation,
(2) microcephaly,
(3) poor coordination,
(4) underdevelopment of mid-facial region
(appearing as a flattened face),
(5) minor joint anomalies
Severe cases - congenital heart defects and mental retardation
12
Interactions
Anxiolytics, antihistaminics, hypnotics-
marked CNS depression

Sulfonylurea, cefoperazone,
metronidazole-Disulfiram like reaction

Acute[Enzyme inhibitor][Chronic inducer-
Pmol?]
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Therapeutic Uses
TOPICAL

Antiseptic
Counterirritant
Prevent bedsores
To reduce body temp???
SYSTEMIC
Trigeminal neuralgia (to destroy painful nerves)
Carminative and appetizer
Treat Methanol poisoning
Fainting hysteria
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Contraindication

Peptic ulcer
Epileptics
Liver disease
Pregnancy-
a. Moderate drinking-fetal syndromes
b. Heavy-miscarriage, stillbirths
9
Acute Ethanol Intoxication

Occurs from consumption of large quantities by naive individuals
Degree of intoxication depends on:
1. Blood ethanol concentration (BAC)
2. How fast the blood ethanol level rises
3. How long the BAC is maintained
Other factors are:
Drinking patterns, Absorptive surface, other medications
8
Acute Ethanol Intoxication..
Acute Effects: Vasodilation, Tachycardia
G.I. Irritation, respiratory depression
Management: Prevention of respiratory depression;
aspiration of vomitus
Treatment of: Hypoglycemia & ketosis with glucose
Treatment of dehydration with electrolytes
Thiamine - to protect against Wernicke-Korsakoff
syndrome.
7
Alcoholism & Treatment


Chronic alcohol use (alcoholism) results in CNS adaptations called
Tolerance and Physical dependence
Withdrawal symptoms during abstinence from alcohol include
delirium tremens, convulsion, seizure, tremors and nausea
TREATMENT / DETOXIFICATION
Substitution of a long acting sedative/hypnotic drug for ethanol, i.e.
Benzodiazepine or Oxazepam
I.V. infusion of Phenytoin to stop Seizures
Disulfiram (250 mg daily)
Supplementary dietary thiamine to replace body vitamin loss
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Treatment of alcoholism
1.
Motivated alcoholic and complete abstinence

2. Disulfiram used as a aversion technique in chronic
alcoholics

3. Naltrexone long acting opioid antagonist - craving for
alcohol and prevent relapse
4. Acamprosate ; Complex receptor action[GABA & NMDA]
decreases drinking frequency and reduces relapse in abstinent
alcoholics

5
Disulfiram

Inhibits ALDH activity - blood acetaldehyde concentration rise to 5
to 10 times
Ingestion of alcohol by individuals pretreated with disulfiram - rise
to marked signs and symptoms of acetaldehyde poisoning.
Face feels hot , flushing
Throbbing ache in the head and neck, Respiratory difficulties,
nausea, copious vomiting, sweating, thirst, chest pain,
hypotension, marked uneasiness, weakness, vertigo, blurred
vision, and confusion
A/E Psychosis, hepatitis, rashes, metallic taste
4
Methyl alcohol
(Methanol/Wood alcohol)
Metabolized to formaldehyde and formic acid

CNS depressant

Formic acid is responsible for toxic effect

Manifestation vomiting, headache,
epigastric pain, dyspnoea, hypotension,
acidosis, retinal damage, death
3
Leucovorin
Methanol-poisoning
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Leucovorin
Treatment
Protect the eyes from light
Gastric lavage with sodium bicarbonate
IV sodium bicarbonate - retinal damage by
decreasing acidosis.
Ethanol to saturate alcohol dehydrogenase
enzyme
Fomepizole specific inhibitor of alcohol
dehydrogenase retards methanol metabolism
[Also used in ethylene glycol poisoning]
Folinic acid [promotes oxidation of formic acid]

2
Summary
Actions-CNS,CVS,LOCAL,
KIDNEY,STOMACH
PK-Zero order and metabolism
ADEs-peptic ulcer,
cirrhosis,CNS,cardiomyopathy, psychosis
DIs---Disulfiram like reactions
Uses
Methyl alcohol poisoning
last