Pharmacology of Alcohol

Pharmacology Of Alcohol

What is Alcohol?
Alcohol is a sedative
It’s is primarily used for recreation not medicine
2nd Largest used psychoactive drug in the world (first is caffeine)

Alcohol’s chemical composition

CH3 CH2OH
Yellow – H Black – C Red – O

The Phamacokinetics of Alcohol - Absorption

Alcohol is both soluble in fat and water
This means alcohol is absorbed though the gastrointestinal tract and through the Blood Brain barrier
20% is absorbed through the stomach the other 80% through the upper intestine


The Phamacokinetics of Alcohol - Distribution
Alcohol easily crosses the Blood-Brain barrier because it is lipid soluble
Alcohol can even cross the placental barrier where there can be an occurrence of fetal alcohol syndrome (FAS). FAS occurs in 30% to 50% of all alcoholic mothers

The Phamacokinetics of Alcohol – Metabolism and Excrection

95% of all alcohol is digested (metabolized) by an enzyme called alcohol dehydrogenase
85% via the liver
15% via the stomach – a full stomach can metabolize more
Alcohol is exposed to first-pass metabolism
5% is excreted via the lungs

Metabolism of Alcohol by Men and Women

Since men have naturally less fat than woman and bigger blood vesicles, men have a lower Blood Alcohol Concentration (BAC) then woman
Also, woman have 50% less enzyme than men, thus the metabolism rate is slower
Remember – Alcohol metabolism is zero order

How the Liver Metabolizes Alcohol

1. NAD+ + Ethanol  NADH + Acetaldehyde
Enzyme: Alcohol Dehydrogenase
2. NAD+ + Acetaldehyde  NADH + Acetic acid
Enzyme: Aldehyde Dehydrogenase
3. Acetic acid  Water + CO2
Uses ATP ATP  AMP
Disulfiram inhibits Aldehyde Dehydrogenase
Step 2 is the rate limiting step


More on Metabolism
BAC is measured in grams of alcohol per liter
0.08 is the legal limit in New York
More than that, not legally in USA
Weight is a big determiner in the concentration of alcohol

Glutamate Receptors

Acoamprosate an anti-craving drug to alcohol .
Glutamate Antagonist to alcohol

GABA Receptors

Ethanol is a GABA agonist, binds to a subunit of the GABAA receptor
Low doses of alcohol can reduce panic and anxiety

Other pharmacodynamic effects

Chronic use of Alcohol changes mRNA of the Neuron
As a result, Ach, DA, opioid and serotnin systems are effected
Alcohol-Abuse potentiated maybe due to increase in dopamine

Pharmacological Effects

Alcohol effects many different functions of the brain
Alertness, motor functions, and intellectual abilities are decreasing.
Combined with other sedatives (benzodiapines), this increase the sedative effects of alcohol


Pharmacological Effects – Cont.
Alcohol dilates blood vessels, thus releasing more body heat and decreasing blood temp.
Large doses of Alcohol increases the risk of heart failure
Small Doses decrease the risk of coronary disease
Alcohol is a diuretic – it decrease the amount of diuretic hormone thus increasing the excretion of water

Psychological Effects

Low amounts of Alcohol have minimal Change in behavior < 0.04 BAC
From 0.04 - 0.10 BAC, increasing by 4x more likely to get into an accident
0.12-0.18 Likelihood increases to 25x
0.23-0.29 your in a stupor
0.30 - 0.33 your in a coma
0.39 and greater, your dead

Psychological Effects – Cont.

50% of all highway crimes and accidents are alcohol related

Health Effects

Alcohol is highly caloric but has little nutritional value
Vitamin and trace element deficiencies are linked to alcohol
Liver and stomach cancers


Tolerance
Metabolic Tolerance – Increase of alcohol digesting enzyme by the liver
Behavioral Tolerance – Brain adapts to amount of drug present. A tolerant person can have a BAC 2x the amount of a non-tolerant and act the same

Dependence

Many be do to either increase in dopamine and/or the effect of decreased anxiety
Withdrawal and alcohol seizures may occur in 10% of people who stop taking alcohol
This is due to the neuron producing more glutamate to counteract the effects of increased GABA

Dependence – Cont.

Other effect of withdrawal include hallucinations, psychomotor, agitation, confusion
This syndrome is also known as delirium tremens (DT)

Side effects and Toxicity

Liver damage – 75% of all deaths due to alcoholism are caused by cirrhosis of the liver, the 7th most common cause of death in the US
Other effects are Panreatitis and chronic gastritis causing peptic ulcers

Side effects and Toxicity – Cont.

The metabolizing of alcohol produces free radicals, causing cancer in the liver and some hypothesis breast cancer also
Alcohol has immunosuppressive effects thus promoting tumor growth


Teratogenic Effects
FAS – Fetal Alcohol Syndrome is accountable for 3 to 5 birth defects in 1000
Causes low intelligence, mental retardation, behavioral abnormalities
There is retard body growth
Facial Abnormailities

Teratogenic Effects – Cont.

Adolescents engage in anti-social behavior
These people are slow learners
Congenital heart defects

Alcoholism & It’s Pharmacological Treatment

1950s : American Medical Association recognized the syndrome of alcoholism as an “ILLNESS”
Ø 1970s : Alcoholism redefined as a “CHRONIC, PROGRESSIVE, AND POTENTIALLY FATAL DISEASE.”

Alcoholism & It’s Pharmacological Treatment – Cont.

Denial is nearly always the major obstacle (integral part)
إن الحرمان هو دائما العقبة الرئيسية عند المدمنين (جزء لا يتجزأ)
Environmental Factors seem to be less important than Genetic Factors
Alcoholism is used as a “self-medication” of psychological distress.


Alcoholism & It’s Pharmacological Treatment – Cont.
Often times alcoholism is associated with addiction to other drugs, depression, manic-depressive illness, anxiety disorder, or antisocial personality .
Now a day the alcohol replaced by drug misuse and drug addiction in IRAQ or both alcoloh and drugs together….

Goals of Pharmacotherapy for Alcohol Dependence & Abuse

Reversal of the severe pharmacological effects of alcohol
Treatment & prevention of withdrawal symptoms & complications
Maintaining abstinence & preventing relapse by :
-using agents that decrease craving for alcohol
-stop the loss of control over drinking
-make it unpleasant to ingest alcohol

Goals of Pharmacotherapy for Alcohol Dependence & Abuse – Cont.

Treatment of coexisting psychiatric disorders that complicate recovery
Note:
No agent can reverse the acute pharmacologic effects of alcohol
Pharmacotherapies are available for the treatment & prevention of withdrawal symptoms & complications in alcohol-dependent people who are decreasing or discontinuing alcohol

Pharmacotherapies for Alcohol Withdrawal

Benzodiazepines are the drug of choice for acute alcohol withdrawal
Improve symptoms
Prevent seizures & DTs
Substituting this long-acting drug prevents or suppresses w/drawal symptoms


Drugs to Help Maintain Abstinence
Alcohol-sensitizing drugs (including: disulfiram & calcium carbimide) :
Used to prevent the patient from drinking by producing an aversive reaction when consuming alcohol
The drug alters the metabolism of alcohol

Drugs to Help Maintain Abstinence – Cont.

- Allows acetaldehyde to accumulate which in turn causes acetaldehyde syndrome (characterized by throbbing headache, nausea, vomiting, chest pain ect.)

Drugs to Help Maintain Abstinence – Cont.

Opioid Antagonist including: Naltrexone, Nalmefene, Acamprosate are used in European Countries
Naltrexone:
Used to reduce craving for alcohol
The hypothesis is that the reinforcing properties of alcohol involve the opioid system

Drugs to Help Maintain Abstinence – Cont.

- The blockade of the system by use of naltrexone should reduce cravings by reducing the positive reinforcement associated w/ alcohol use

Drugs to Help Maintain Abstinence – Cont.

Dopaminergic drugs: use in maintaining abstinence

Drugs to Help Maintain Abstinence – Cont.

Serotoninergic Drugs (used to treat alcohol dependence)
- Serotonin-specific reuptake inhibitors (SSRIs) (e.g. fluoxetine) : used for treating depression & anxiety.
- Serotonin 5-HT1a agonist (e.g. buspirone): used for treating anxiety. Effective in treating comorbid anxiety in alcoholics but less effective at reducing alcohol consumption.


Drugs to Help Maintain Abstinence – Cont.
Serotonin 5-HT3 antagonist (e.g. ondansetron) : used for treating nausea.