ETHANOL

History

Alcohol has held a level of importance in a lot of cultures. Whisky means Water of life in Gaelic(go figure). Also Gin has two diuretics in it, Ethanol and Juniper.

Ethanol affects the CNS, GI, Hormonal, Liver, Cardiovascular system, and Kidney. Alcohol also affects fetal life and cross reacts with many drugs.

CNS Effects

Alcohol causes a release of inhibition. So why does it also cause euphoria? It stimulates inhibitor pathways:

1.      Potentiates the specific g-2L subunit of the GABA receptor, which activates the protein kinase C and causes sedation.

2.      Inhibits the release of neurotransmitters - glutamate, and acetylcholine(ACH)

a.       Glutamate is the main excitatory neuron

b.      ACH is responsible for conversion of short term to long term memory à results in blackouts

1.      Inhibits voltage gated Ca+ ion flux, which results in decreased endorphin release.

2.      D2 Dopamine receptors are stimulated and endorphins are released, resulting in Euphoria. The exact mechanism of endorphin release is unknown.

Concentration response:

o        >30mg% à impairment of fine motor control

o        80 - 100mg% à is the legal limit of DWI

o        150mg% à is gross intoxication

o        >400mg% à is lethal, although people have survived at levels of 1300mg%

Cardiovascular effects

If one were to drink 1-3 drinks per day, this would decrease mortality from CAD (coronary Artery Disease), increase HDL levels, and decrease platelet aggregation. However, larger amounts cause vasodilatation, increased Blood pressure, and alcoholic cardiomyopathy.

Gastrointestinal effects

Stomach Secretion is:

o        Stimulated at <20%

o        Inhibited from 20-30%

o        Stomach irritation followed by gastritis occurs at levels >40%.

o        The incidence of Stomach cancer is also increased by ETOH.

Liver

ETOH causes fatty change in liver. This change is reversible, and caused by impairment in lipid metabolism and mobilization of peripheral fat. Prolonged excessive ETOH insult causes damage throughout the liver resulting diffuse fibrous scar formation that compresses neighboring cells resulting in Cirrhosis. Liver Cirrhosis results in esophageal varices, jaundice and ascites. Acites is the collection of fluid in the peritoneal cavity due to increased blood pressure as a result of portal blockage.

Kidney

Alcohol causes diuresis via the inhibition of ADH ( Antidiuretic Hormone) secretion.

Impotence

Alcohol decreases the production of testosterone resulting in impotence.

Other effects of Alcohol

Labor is inhibited via decrease in oxytocin secretion.

Absorption of ETOH

Depends on Concentration, is decreased by food(especially fat. Absorption is increased by vasodilation. The CO₂ in Champagne causes vasodilatation, which is why the buzz hits you faster. ETOH is absorbed by mouth and stomach, but mostly from intestine. So decreased GI motility results in increased absorption. But delayed gastric emptying will cause a decreased absorption.

Distribution

ETOH is distributed to total body water. (60% of body weight)

1 drink equals 1.5 oz = 45ml of 86 proof whisky = 20ml of ETOH = 16g of ETOH = 16,000mg

BLOOD ALCOHOL CONCENTRATION

BAC = 16,000mg / 420dl = 40mg%

In reality though the peak Blood alcohol is ½ the theoretical one.

METABOLISM

……………. a……      …………………. b

Ethanol à Acetaldehyde à Acetate

    …………..c

a - Alcohol dehydrogenase b - Acetaldehyde Dehydrogenase c - MEOS(Microsomal ethanol oxidizing System)
 

Acetaldehyde Dehydrogenase

High capacity enzyme, that is inhibited, by hypoglycemic sulfonyl ureas (Chlorpropamide), and Metronidazole. Inactive variant in 50% of asiams.

Excretion of ETOH

Expired air has .05% of blood concentration, and the urine has 135% of blood concentration.

The effects of alcohol can be divided into the following categories and we should avoid certain medications so as not to exacerbate these effects.
 

Alcohol Abuse

25 - 40% of the general hospital admissions are for ETOH related complications.

Treatment of Alcohol abuse can be divided between acute and chronic measures.

The first thing to do is maintain respiration. Do not use stimulants.

Also make sure to differentiate from Diabetic Coma, drug intoxication, head trauma and cardiovascular incident.

Chronic use

Acute Stimulant Effects due to Dopamine sensitization. Physical dependance is caused by GABA downregulation, Glutamate upregulation, increased Norepinephrine activity and upregulation of Ca+ channels. Craving is due to DA, 5-HT, opioids, GABA, NE and Glutamate. The Metabolic tolerance is due to MEOS induction. Also learned behaviors increase persons tolerance.

Neuropathic Changes

Atrophy of neuronal connections is a reversible change. Irreversible Mamillary body damage caused by Thiamin deficiency causes Wernicke’s Encephalopathy and Korsakoff’s psychosis, which results in short term memory impairment. Fetal alcohol syndrome results in facial malformations, retardation, increased susceptibility to infections, and abortion or stillbirth. At risk women have 3 or more drinks a day, although the timing is unclear. Do not use the 3 drinks as a cut and dry number.

Alcohol Withdrawal

There are three signs of alcohol withdrawal: Tremulous syndrome, seizures and Delirium Tremens. Tremulous Syndrome results in shakes, cramps and nausea. Seizures are contraindicated in epilepsy. Confusion, hyperthermia and tremors denote Delirium Tremens, which can be lethal. All of these are due to physical dependance.

Genetic types of Alcoholism
 

Treatment

Psychosocial

Indirect Therapy

Group

Residential

Self Help (AA)
 
 

Pharacological

Disulfuram - Inhibits Acetaldehyde dehydrogenase à results in Acetaldehyde poisoning. It is not very effective in double blind studies, and inhibits metabolism of Warfarin, phenytoin, isoniazide, toxic to liver and teratogenic.

Naltrexone - Blocks ETOH induced release of dopamine which results in decreased Euphoria. Effective in double blind studies. Side Effects are nausea, Headache and hepatotoxicity.

Acamproset - Glutamate antagonist, and agonist of GABA receptors. It is used for withdrawal and abstinence. Effective 60%. Side effects include Diarrhea and headache. It is renally cleared.

Tiapride - Dopamine 2 antagonist (atypical neuroleptic and anxiolytic. Used in Europe only for both withdrawal and abstinence.
 

METHANOL

Methanol is in many industrial solvents, and causes similar effects as Ethanol.

It causes less CNS depression than ethanol, however it can cause toxic effects of metabolic acidosis, and Blindness. The acidosis is the result of the production of formic acid by ADH (alcohol dehydrogenase - note that antidiuretic hormone is also abbreviated ADH) and acetaldehyde dehydrogenase. The Blindness is the result of formaldehyde’s toxic effects on the retina.

Treatment is 2 fold:

1.      Sodium bicarbonate is given to offset the metabolic acidosis,

2.      Ethanol and fomepizole are given to prevent the formation of formaldehyde.

METABOLISM

………………a……………………..b

Methanol à Formaldehyde à Formic Acid

…………...c

a - Alcohol dehydrogenase b - Acetaldehyde Dehydrogenase c - MEOS(Microsomal ethanol oxidizing System)