Alcohol

Question 1

How is an alcohol produced?

Area of absorption?

How are behavioural effects described on ethanol levels within the blood?

Answer 1

• Fermentation of:
  
  • sugar by yeast.

Area of absorption:

• GI tract, readily enters the tissue of the brain.

Blood alcohol concentration:

*

Question 2

The effect of oral administration and alcohol absorption?

Movement of alcohol to the blood?

Answer 2

• Food in stomach slows down the absorption of alcohol:
  
  • from the GI tract(high) to blood(low concentration).

as alcohol moves via passive diffusion the GI tract to blood.

Question 3

Gender differences in alcohol consumption effect?

Use of aspirin?

The difference in concentration between genders?

Answer 3

Alcohol dehydrogenase:

• More active in men(by 60%), therefore leaving a higher concentration of alcohol that will be absorbed more rapidly in females.

Aspirin:

• . gastric alcohol dehydrogenase, but in a greater extent in women then men.

Furthermore:

• Alcohol is generally more concentrated in women, as fluid volume is much smaller.
  *

Question 4

Metabolism of alcohol?

• areas where it is metabolized?
• enzymes involved in the conversion of alcohol to other products?
  
  • Overall process of alcohol —> C02 + H20 and energy.
• Case that occurs in 10% of asians in the metabolism of alcohol?
  
  • what is the problem with this?

Answer 4

Areas of metabolism:

• 95% is metabolized in the liver.
• 5% excreted by the lungs:
  
  • can be detected via Breathalyzer.

Synthesis of alcohol:

• Alcohol——->Acetaldehyde:
  
  • via Alcohol dehydrogenase.
• Acetaldehyde——-> acetic acid:
  
  • via Acetaldehyde dehydrogenase(ALDH)

10% of asians:

• Have a gene that encode for a inactive form of Acetaldehyde dehydrogenase, causing a buildup of acetaldehyde as a result of drinking alcohol.
  
  • causes flush, nausea, tachycardia, headache and dizziness.

Question 5

Relevance of the cytochrome P450 family to alcohol?

And its relevance with the joint intake of alcohol and other drugs?

Answer 5

• Converts alcohol to acetaldehyde.

The danger with other drugs:

• alcohol + drugs:
  
  • = buildup of drugs will increase as they are also competing for the same enzymes of alcohol.

Question 6

What is induction and its role in metabolic tolerance of alcohol?

• Its effects on the liver?

Answer 6

• Induction:
  
  • regular alcohol consumption——> ++ levels of enzymes and rate of metabolism of alcohol and other drugs.
    
    • Being the basis for metabolic tolerance.
  • However, the build-up will damage the liverand impair the metabolism of alcohol and other drugs.

Question 7

Describe the 4 types of tolerance in relation to alcohol:

• Acute?
• Metabolic?
• Pharmacodynamic?
• Behavioural?

Answer 7

Acute:

• Single exposure, drug effects are greater when alcohol levels are higher.
  
  • feeling less intoxicated on the declining limb of the blood alcohol curve.

Metabolic:

• Higher levels of P450 to metabolize alcohol.

Pharmacodynamic:

• neurons adapt to the constant presence of alcohol by making compensatory changes.

Behavioural:

• practicing behaviours whilst under the influence of alcohol.

Question 8

What drugs are involved with the cross tolerance of alcohol?

Answer 8

• Barbiturates and Benzodiazepines:
  
  • sedative hypnotic class.

Question 9

What are Delirium tremens(DTs)?

Answer 9

• convulsions, hallucinations, disorientation, panic attacks, unstable blood pressure:
  
  • experience of withdrawal symptoms of alcohol.

Question 10

Effects of different doses of alcohol and cultural effect?

Answer 10

Cultural factors:

• Alcohol increases sociability, reducing anxiety, and enhances sexual responses.

Low doses:

• Acute effects on memory,loss of social inhibition and more talkative.
  
  • High doses:
    
    • experiencing blackout and total amnesia for events.

Question 11

How does alcohol lead to death?

Answer 11

• Depression of the respiratory control center in the brain.

Question 12

How is brain damage due to alcohol consumption achieved?

Describe the pathophysiology of Wernicke-Korsakoff syndrome?

Answer 12

• Elevated acetaldehyde, liver deficiency and inadequate nutrients:
  
  • Deficiency of Thiamine(B1), which is involved in glucose metabolism, leading to cell death,

Deficiency of Thiamine(B1) leads to Korsakoff syndrome:

• confusion, poor co-ordination, tremors and ataxia.
  
  • causing brain tissue shrinks and ventricles to enlarge.

Question 13

The effects of chronic use of alcohol on the liver?[3]

• 3 levels?

Answer 13

Fatty liver:

• Triglycerides accumulate in liver cells.
  
  • Alcohol leaving the fats for storage.

Alcoholic hepatitis:

• Liver cell damage ,caused by high-level accumulation of high levels of acetaldehyde, via liver cell damage.

Alcohol cirrhosis:

• death of liver cells stimulates scar formation and blood vessels carrying oxygen are cut off.

Question 14

Fetal alcohol syndrome(FAS)?

• Symptoms?
• result of the fetus?

Answer 14

• Damaging development effects of prenatal alcohol exposure.
  
  • As BAC passes the placental barrier and to the fetus.

Symptoms:

• mental retardation.
• Low birthweight; failure to thrive and grow.
• Neurological problems: some infants born with high alcohol levels experience.
• Distinctive craniofacial malformations.
• Other physical abnormalities:
  
  • cardiac defects, failure of kidney development and undescended testes.

Question 15

Effects of alcohol on neuronal membranes?

• Non-specific interaction of alcohol
• The specific action of alcohol?

Answer 15

Non-specific:

• alcohol interacting with the polar heads of the membrane, which alters lipid composition, disturbing the relationship of proteins in th membrane.

Specific:

• interacting with certain proteins:
  
  • influencing ligand-gated and altering second-messenger systems.

Question 16

Effects of alcohol on glutamate:??

• ions and receptors involved?
• Result of withdrawal?
  
  • contribution to symptoms?
  • leading to cell death?
• Effects on the fetus?

Answer 16

Glutamate antagonist:

• reduces glutamate in brain regions,e.g. hippocampus.
  
  • Repeated use causes upregulation of NMDA receptors.

Withdrawal:

• increase in Glutamate , correlating with CNS hyperexcitability and seizures(after 10 hrs).
  
  • as this causes increase in Ca2+ influx, leading to cell death,

Fetus:

• reduced in NMDA receptors as an adult as inhibition of glutametergic system occurs.

Question 17

Effects of alcohol on GABA:

• Receptors?
• Consequence?
• repeated exposure?
  
  • leading to tolerance?

Answer 17

GABA agonist:

• acts on GABA_{<strong>A</strong>} receptors, allowing influx of Cl^-, causing hyperpolarization.
  
  • only a few receptors are stimulated.

Repeated exposure:

• leads to a reduction in GABA_A mediated Cl influx.
  
  • seizure inducing antagonistic doses due to increase sensitivity of prolonged exposure.

leading to tolerance.

Question 18

Alcohol and the effects of Dopamine:

• Area of reinforcement?
• pathways involved?
• withdrawal effects and mechanism?

Answer 18

Increase in the dopaminergic mesolimbic pathway:

• VTA——-> NAc:
  
  • NAc, is associated with drug motivation and primary reinforcement.

Withdrawal:

• As a decrease in firing of the mesolimbic pathway:
  
  • =rebound depression, as a reinforcement mechanism.

Question 19

Effects of alcohol on Opioids(endorphins):

• Difference between acute and chronic administration of alcohol on opioids?
• Ways of reducing alcohol self-administration?
  
  • names?
• Baseline levels of µ-opioid receptors with individuals with alcohol preferences?

Answer 19

Acute:

• increases in endorphins and enkephalin( endogenous opioid) production and release.

Chronic:

• reduces the production of endorphins, contributing to dysphoria, and accompanies withdrawal.

Reduction of self-administration: opioid receptor antagonist( naloxone and naltrexone).

Alcohol users:

• higher levels of µ-opioid present in alcoholics leading to withdrawal.