1. Monohydroxyl Alcohols
Department of
Pharmacology

2. ALCOHOLS Methanol (CH3OH) Wood alcohol Ethanol (CH3CH2OH)
Grain alcohol
Ethylene Glycol (CH2OHCH2OH)
Polyhydric alcohol

3. Ethyl Alcohol The most commonly abused drug in the world
75% of adults drink alcohol regularly
In the United States, 18% of adults are classified as heavy drinkers
Approx. 10% are considered alcoholics
Cost attributed to alcohol abuse exceed 200 billion dollars annually
Traffic fatalities, homicides, rapes and suicides are all alcohol related
Moderate alcohol use protect against cardiovascular diseases in individuals
Alcoholism is a complex disorder with a genetic and environmental component

4. Pharmacokinetics
Ethanol is a small water soluble molecule rapidly absorbed from stomach and small intestine ( 75%) after oral ingestion
Rate of absorption from the stomach is reduced by the presence of food
Peak blood alcohol levels are achieved in 30 minutes
About 60% of inspired ethanol vapor is absorbed through the lungs and can lead to intoxication
Percutaneous absorption also occurs (in infants)
Distribution is rapid, with tissue levels approximating blood alcohol concentration (BAC)
BAC for a fixed amount of alcohol depends on sex, age and adipocity
Volume of distribution of ethanol is L/kg which is approximately total body water.
For the same oral dose of alcohol, women will have a higher peak concentration than men because of lower total body water and lower (50 %) gastric Alcohol dehydrogenase (ADH)

5. Pharmacokinetics
>90% of ingested ethanol is metabolized by oxidation in the liver
<10% is excreted by the lungs and kidneys
Ethanol in the alveolar air is in equilibrium with BAC and is measured in test for drunkeness
80 mg% (80 mg EtOH/100 ml of blood) is the BAC for legal intoxication in the US.
The concentration. of alcohol in expired air is 0.05% times the concentration of alcohol in blood
Metabolic oxidation of ethanol occurs by zero order kinetics (rate is independent of concentration and time)
A typical 70 kg adult can metabolize 10 g of ethanol (1 can of beer; 3.5 oz wine) per hour
Amount of alcohol oxidized per unit time is approximately proportional to body or liver weight

6. Estimates of Blood Alcohol Levels
A typical adult (70 kg/150 lb) can metabolize 7-10 g of alcohol/hour
Blood alcohol levels of a 70 kg male will increase by 20 mg% per drink
12 oz beer (3 % EtOH) = 9 g EtOH
3 oz wine (12 % EtOH) = 9 g EtOH
1 oz whisky(40 % EtOH)= 9 g EtOH
A 70 kg adult male will be legally intoxicated after 4 drinks in one hour
Total body water in lean males=68%
Total body water in females = 55 %
BAC = Amount of Ethanol
(Body weight)(% body water

7. Estimates of Blood Alcohol levels
A lean and healthy 90 kg man drank 4 (1oz) whisky in 1 hour
His BAC will be:
(10g EtOH/drink) (4 drinks) = 0.65mg
(90 kg) (0.68) or 65 mg%
If his lean and healthy 45 kg (100 lb)
female friend also dank same amount
Her BAC will be:
(10g EtOH/drink) (4 drinks) = 1.62 mg
(45 kg) (0.55)
Or 162 mg %
She is legally drunk

8. Metabolic Pathways ALCOHOL DEHYDROGENASE
Major Pathway for ethanol oxidation
Cytosolic enzyme containing zinc and sulfhydryl groups
Human alcohol dehydrogenase (ADH) also oxidizes methanol and ethylene glycol
Found mainly in liver, but there are gastric and brain ADH
Significant amount of ethanol is oxidized in the stomach by gastric ADH
Lower levels of gastric ADH present in women (50% lower than in men)
4-methylpyrazole (fomepizole), an orphan drug, is a potent ADH inhibitor
Polymorphic genotypes occur as ADH2 1, 2,3
There are 3 phases of hepatic oxidation of ethanol

9. MEOS PATHWAY
Microsomal enzyme-oxidation system (MEOS) or mixed function oxidase
An alternative oxidative pathway for ethanol metabolism
Metabolizes less than 5 % of alcohol in regular drinkers
Becomes important at BAC >100 mg%
Uses NADP+ instead of NAD+
Chronic alcoholism induces the MEOS pathway
Result is increased clearance of drugs handled by hepatic microsomal enzyme system or the cytochrome P450 enzyme multifamily.
Genetic polymorphism occurs in the EtOH-inducible cytochrome P450
(CYP2E1) enzyme family. Also varies with ethnic groups.

10. CNS EFFECTS OF ETHANOL Ethanol is a sedative-hypnotic agent
Membrane-active CNS depressant similar to anesthetic agents
Primarily affects the Reticular Activating system
Mechanism of CNS action involves the potentiation of GABA receptor and inhibition of Glutamate receptor neurotransmission
Ethanol may induce the release of endogenous opiates (basis for opiate antagonist Naltrexone treatment)

11. Ligand-gated ion channels: allosteric enhancement
Ion channel pore
Extracellular
barbiturates
GABA
Ethanol ?
benzodiazepines
Cl-
Cl-
Intracellular

12. Cardiovascular Effects of Ethanol
ACUTE EFFECTS:
Cutaneous vasodilation with increased blood flow to the skin
Increased coronary blood flow
Depressed myocardial contractility
Acetaldehyde induce cathecholamine
release result in tachycardia
Vasoconstriction in cerebral and renal
vascular beds
CHRONIC EFFECTS
Dilated cardiomyopathy
Ventricular hypertrophy
Atrial & Ventricular arrhythmias
Mild Anemia from Folate deficiency

13. Gastrointestinal Effects of Ethanol
Gastrin release and gastric acid secretion
Inflammation and bleeding by ulceration of the stomach linning
Retards intestinal absorption of glucose, amino acid, folic acid, thiamine & vitamin B12 (alcoholics)
Chronic CNS effects (Korsakoff Psychosis & Wernicke encephalopathy occurs from thiamine deficiency
Liver acidosis, hypoglycemia, increased fatty acid and lactate formation; steatosis
Alcoholic hepatitis; Liver Cirrhosis;
Liver failure (Alcoholism)

14. Cell & Organ damage by Ethanol

15. Facies in Fetal Alcohol Syndrome
Streissguth, 1994

16. Fetal Alcohol Syndrome
Specific pattern of facial features
Pre- ad/or postnatal growth deficiency
Evidence of central nervous system dysfunction
Photo courtesy of Teresa Kellerman

17. Acute Ethanol Intoxication
Occurs from consumption of large quantities by naiives individuals
Degree of intoxication depends on
Blood ethanol concentration (BAC)
How fast the blood ethanol level rises
How long the BAC is maintained
Other factors are: Drinking patterns, G.I.
Absorptive surface, other medications.
Acute Effects: Vasodilation, Tachycardia
G.I. Irritation, respiratory depression
Managemaent: Prevention of respiratory depression; aspiration of vomitus
Treatment of: Hypoglycemia & ketosis with glucose
Treatment of dehydration with electrolytes

18. Tolerance & Physical Dependence
Acute Tolerance: Occur in naiive & alcoholics after only a few drinks
Chronic tolerance: Occurs after high doses of EtOH for long periods
Can result in physical dependence
Tolerance and dependence results in
Metabolic increase in EtOH oxidation
Adaptation of CNS receptors
Changes in receptor-coupled signal transduction system. i.e. cAMP
Limited tolerance can result in death

19. 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, tremulousness 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

20. Therapeutic Uses TOPICAL To cleanse the skin (poison ivy)
To denature protein and toughen skin with % EtoH in bed sores.
To reduce body temperature during high fever
Antiseptic 70 % EtOH (needle puncture, cavity preparation)
SYSTEMIC
Mild Sedative, Digestive aid
Trigeminal neuralgia (to destroy painful facial nerves)
Pulmonary Edema (to collapse airway foam)

21. Methanol Industrial Solvent, Gasoline additive, home heating
Oxidized by the ADH enzyme system
Death from 2-8 oz methanol ingestion
Ethanol or 4-MP dosage may rescue poisoning

22. Ethylene Glycol Heat exchanger in antifreeze formulations
Industrial solvent more poisonous to humans than to animals
Metabolized by the ADH enzyme system
Acute renal failure from oxalate crystal deposition
Treatment with ethanol or 4-MP may treat acute poisoning

23. Antabuse Disulfiram De-addiction of alcohol Consent essential
Similar reactions

24. Must Read Treatment of Methanol poisoning Mechanism of action of ethyl
alcohol used in treatment of Methanol
poisoning
Therapeutic Uses of alcohol