Alcohols

• History

• Forms

• Pharmacokinetics- ADME

• Pharmacodynamics including reinforcing mechanism, tolerance & fetal

effect.

• Treatment of alcoholism

• Methyl alcohol
Alcohol generally means ethyl alcohol,
ethanol

ETHYL ALCOHOL (ETOH)

Alcohol
An Arabic Word Meaning
“Something Subtle”
 Alcohol

• Made from the fermentation of carbohydrates

• Fermented in every culture on earth at some point in time
• Animals (monkeys and birds) consume fermented fruit
 History
• Beers & wines since about 6400 BC: Berries, apples and honey

• Early use for spiritual ceremonies

• First brewery in Egypt 3700 BC

• Only natural fermentation until 800-900 BC

• Process of distillation in Arabia

 Alcohol: Forms
• Naturally Fermented (max 14%)
• Beer
• Wine

• Distilled (up to 95%)

• Whiskey (40%)
• Gin (40%)
• Vodka (40%)
• Tequila (40%)
 Pharmacokinetics
Absorption
• Oral is by far the route of choice

• Absorption based on many factors, primarily from small intestine

• 20% stomach, 80% small intestine

• Peak blood alcohol concentration (BAC) depends on:

• Amount and alcohol concentration of beverage
• Rate of drinking
• Food consumption and composition
• Gastric emptying and gastric metabolism
• Hepatic (liver) first pass
 Metabolism

• Metabolism: 90-98% metabolized in liver

Alcohol Aldehyde
Alcohol Dehydrogenase Acetaldehyde dehydrogenase Acetate

Constant 0.015% (8-12ml of Absolute alcohol) per hr. metabolized

• Accumulation of acetaldehyde associated with headache,
gastritis, nausea, dizziness (hangover)
• Those of certain Asian descent lack a gene that codes for ADH
(50%)
Limiting factor for ethanol metabolism
is a NAD+ availability
 Excretion

• Follow ZERO order Kinetics

• Kidney & Lungs routes of excretion

• Conc. in exhaled air is 0.05% of Blood concentration

• This is used for assessing medicolegal drunken state

Pharmacodynamics
Local actions

➢Rubefacient, counterirritant - Increases warmth on the skin, relieves

pain (in pain balms)

➢Astringent- Precipitates surface proteins and forms a coating on the

skin (in sunscreens)

➢Antiseptic - Precipitates bacterial proteins (in surgical spirit)

 CNS Effects
• Alcohol is a CNS depressant

• Apparent stimulatory effects result from depression of inhibitory

control mechanisms in the brain

• Characteristic response: euphoria, impaired thought processes,

decreased mechanical efficiency, sedation
Ethanol plasma concentrations vs. CNS effects

Ethanol plasma concentration (per mL) Effect

0.2 Feeling of relaxation

0.3 Slight euphoria

0.5 Slight motor incoordination
1 ataxia
3 stupor
>4 Coma, death due to the respiratory
failure

!!!! alcohol potentiate the effects of other drugs with central depressant effects –
barbiturates, benzodiazepines, H1-anithistamines….
 Effects on other systems
- Cutaneous vasodilatation ‘warm feeling’, sweating → heat loss
- Moderate Dose: Tachycardia, mild ↑ in blood pressure
- Large Doses: Fall in BP, ↑ BP in chronic use
- Moderate consumption ↑ HDL & ↓ LDL Oxidation
- ↑Diuresis (due to ↓ADH secretion)
- ↑Salivatory and Gastric secretion
- Liver: Moderate amount Fatty Liver, Heavy Drinking: Cirrhosis
-  Oxytocin secretion (delay in parturition at the term)
 Ethanol & fetal development
FAS (fetal alcohol syndrome)
typical of anatomical, mental and behavioural abnormalities:
- facial development, reduced cranium size
- retarded growth
- mental retardation and behavioural abnormalities

ARND (alcohol-related neurodevelopmental disorder):

- less serious than FAS (3x more common),
- behavioural, cognitive and motor deficits
 Harmful effects of chronic alcohol abuse

• Behavioural defects: loss of self-control, reliability and productivity, disrupted social and
family network

• Neurological disorders: dementia, peripheral neuropathies (thiamine deficiency).

• GIT disturbances: gastritis, peptic ulcers and GIT bleeding, hematemesis.

• Liver damage: fatty liver, progression to hepatitis and eventually to irreversible hepatic
necrosis and fibrosis

• Pancreatitis: ↑secretin production, ↑pancreatic enzyme, Oddi sphincter oedema

Alcohol as a Reinforcer

• Reinforcer: a substance whose pharmacological effects drive the user

to continue to use it

• Positive reinforcing effects:

• Gain pleasure
• Altered consciousness
• Conform to behavior of peers
• Negative reinforcing effects:
• Relief of stress and negative emotions
• Relief of withdrawal symptoms
Reinforcement: Neurochemical systems
Glutamate
Enkephalin or Excitatory Input
Dynorphin
Inhibitory Neuron

k Opioid Dopamine Receptors

Enkephalin Receptors
Inhibitory Dopamine Neuron GABA
Neuron Neuron

m Opioid REWARD
Receptors

GABA-A Receptors

GABA Inhibitory Feedback

GABA Presynaptic
Inhibitory Opioid
Neuron Receptors
(m, d?)

Ventral Tegmental Area Nucleus Accumbens

(VTA) (NAc)
Neuropharmacology: Summary

Experience Transmitter/Receptor
euphoria/pleasure Dopamine, Opioids
anxiolysis/ataxia  GABA
sedation/amnesia  GABA +  NMDA
nausea 5HT3
neuroadaptation NMDA, 5HT
stress CRF
withdrawal GABA, NMDA ( Ca, Mg)
 Tolerance: Definitions

• Acute Tolerance: during the time-course of a single exposure to drug

• Chronic Tolerance: over repeated use of drug

• Cross Tolerance: Tolerance to one drug leads to tolerance to other drugs

in a class:
• Benzodiazepines
• Barbiturates
• General Anesthesia
Tolerance: Significance

• Why is tolerance to alcohol important?

• One of the determinants of increased alcohol
consumption: Tolerance is one of the diagnostic
criteria for alcoholism
• Cross-tolerance to other depressant drugs
• Genetic determinants exist
 Withdrawal
• Tremors, sweating, anxiety, perspiration, headache, nausea, vomiting

• As withdrawal continues, one can have grand mal seizures

• Delirium tremens: over few following days: confusion, agitation,

aggression, unpleasant hallucinations.
Acute Intoxication Tt
- Mostly supportive Tt
- Fluid & Electrolyte balance
- Thiamine Infusion (100mg in 500ml of glucose)
Treatment of chronic alcoholism
• Disulfiram – blockade of aldehyde dehydrogenase → cumulation of
acetaldehyde - nausea, flushing, tachycardia, hyperventilation, sinking
sensation. Also called Antabuse

• Aim: to make alcohol consumption unpleasant and intolerable.

disulfiram
Ethyl alcohol Acetaldehyde Acetate
Alc.dehydrogenase Ald.dehydrogenase

So disulfiram is used in patients who are motivated and sincerely

desire to quit drinking.
• Naltrexone – reduces alcohol-induced reward (unclear mechanism)

• Acamprosate – Weak NMDA receptor antagonist. Anti-craving

effects.

• The drugs used to alleviate the acute abstinence syndrome:

Benzodiazepines, Clonidine (inhibits exaggerated neurotransmitter
release) and Propranolol (blocks excessive sympathetic activity).
Methyl Alcohol Poisoning
• Methyl alcohol is added to rectified spirit to render it unfit for
drinking.
• Accidental poisoning
• Methyl Alcohol formaldehyde formic acid
• Symptoms are due to formic acid-
vomiting, headache, epigastric pain

hypotension, bradycardia, acidosis-retinal

damage-congestion of disc and blurring of vision
 Methyl Alcohol Poisoning
Treatment

• Keep the patient in a dark room and protect from light

• Gastric lavage with sodium bicarbonate

• Sodium bicarbonate i/v to treat acidosis and thus retinal damage.

• Ethanol is given through a nasogastric tube. ETHANOL IS

PREFERENTIALLY METABOLISED BY ALC. DEHYDROGENASE OVER
METHANOL
Methyl Alcohol Poisoning-contd

• Hemodialys is to remove methanol and formic acid.

• Fomepizole (4 methyl pyrazole) given i/v
Methyl Alc formaldehyde formic acid
alcohol dehydrogenase.
• Folate therapy : ↓ Blood Formate levels
Induces oxidation of formic acid to CO2 and water.
LEARNING OBJECTIVES

• At the end of this topic the student must be able to describe about:
1. The mechanism of action of drugs
2. classification,
3. doses,
4. report the side effects,
5. the indications vs. contraindications,
6. Poisonings of alcohals
THANK YOU