Pharmacology lecture pdf

1. Alcohols
• History
• Forms
• Pharmacokinetics- ADME
• Pharmacodynamics including reinforcing mechanism, tolerance & fetal
effect.
• Treatment of alcoholism
• Methyl alcohol

2. Alcohol generally means ethyl alcohol,
ethanol
ETHYL ALCOHOL (ETOH)
Alcohol
An Arabic Word Meaning
“Something Subtle”

3. 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

4. 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

5. Alcohol: Forms
• Naturally Fermented (max 14%)
• Beer
• Wine
• Distilled (up to 95%)
• Whiskey (40%)
• Gin (40%)
• Vodka (40%)
• Tequila (40%)

6. 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

7. Metabolism
• Metabolism: 90-98% metabolized in liver
Alcohol Acetaldehyde 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%)
Alcohol
Dehydrogenase
Aldehyde
dehydrogenase

8. Limiting factor for ethanol metabolism
is a NAD+ availability

9. 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

10. 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)

11. 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

12. 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….

13. 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)

14. 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

15. 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

16. 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

17. Reinforcement: Neurochemical systems
Enkephalin
Inhibitory
Neuron
REWARD
Glutamate
Excitatory Input
Enkephalin or
Dynorphin
Inhibitory Neuron
GABA
Inhibitory
Neuron
GABA Inhibitory Feedback
Dopamine Neuron GABA
Neuron
Ventral Tegmental Area
(VTA)
Nucleus Accumbens
(NAc)
Dopamine Receptors
GABA-A Receptors
Presynaptic
Opioid
Receptors
(m, d?)
m Opioid
Receptors
k Opioid
Receptors

18. 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)

19. 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

20. 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

21. 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.

22. Acute Intoxication Tt
- Mostly supportive Tt
- Fluid & Electrolyte balance
- Thiamine Infusion (100mg in 500ml of glucose)

23. 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.

24. • 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).

25. 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

26. 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

27. 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.

28. 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

29. THANK YOU