15: Drugs of Abuse: Alcohol

Question 1

What is one unit of Alcohol?

Answer 1

1 unit = 10ml or 8g of absolute alcohol

Question 2

How would you calculate one unit of alcohol?

Answer 2

(%Alcohol x V(ml))1000

Question 3

What is currently considered the “safe level” of alcohol consumption per week?

What is binge drinking?

Answer 3

Men & Women; = 14 units/week LOW RISK

Binge drinking i.e. > 8 units in one sitting)

Question 4

What is the ROA of Alcohol?

Answer 4

Oral

Question 5

Explain the effects of a full/ empty stomach on the pharmacokinetics of Alcohol

Answer 5

• 20% of alcohol is absorbed in the stomach
• 80% in the small intestine

With full stomach: gastric emptiing is slow –> slower absorbtion on the stomach and small intestine

Question 6

How much of the total alcohol in the body gets metabolised?

What happens to the rest?

Answer 6

90% gets metabolised in body, 10% gets directly excreted

Question 7

Where does phase 1 of Metabolism of Alcohol happen?

Answer 7

85% in the liver

15% directly in GI tract

Question 8

Explain Step 1 in Alcohol metabolism

Answer 8

In the liver (85%)

• Alcohol dehydrogenase (75%)
• Mixed function oxidases (25%)

In the GI tract (15%)

• Alcoholdehydrogenase

Into: Acetaldehyde

Question 9

Why do women have a lower alcohol tolerance than men?

Answer 9

Mainly 2 reasons

1. less Alcoholdehydrogenase (in GI tract)
2. Less total body water –> same amount is more concentrated in women

Question 10

Explaint Step 2 in the Metabolism of Alcohol

Answer 10

Acetaldehyde – Aldehydedehydrogenase –> Acetic Acid

Question 11

Name a drug that can be used in alcohol conversion therapy

Explain why it might work

Answer 11

Disulfiram can be used –> inhibits Aldehydedehydrogenase and therefore causes a buid up of Acetaldehyde

• Acetaldehyde is the toxic component that makes you feel bad from drinking –> feel effects from drinking

Question 12

What is the concept behind the “Asian Flush”?

Answer 12

There are genetic polymophisms in the enzxme Aldehydedehydrogenase that cause an build up of Acetaldehyde in some popoulation groups

Question 13

Explain the potency of alcohol

Answer 13

It is a small, simple molecule –>

• low potency
• but binds weakly to many targets

High dose required to see effects!

Question 14

What is the pharmacological use of alcohol?

Why?

Answer 14

Ther is no use for it–> because it is very very unspecific

Question 15

What are the primary effects of Alcohol on the body?

Answer 15

Overally: it has a depressant effect (but CNS agitation might occur at low doses –> increased CNS exitability)

• +ve on GABA
• -ve on NMDA receptors

Question 16

Why do people get talkative with alcohol, though its overall effects are depressant?

Which factors influence this?

Answer 16

• It can cause CNS agitation + increased exitability at low doses, dependant on
  
  • personaltiy
  • environment
    
    • social/ non-social setting

Question 17

What are the effects of Alcohol on GABA ?

Answer 17

It has a pre+post synaptic increasing effects on GABA

• Pre-synaptic: Increase Neuro-active steroids that enhance GABA function (Allopregnelone)
• Post-synatpit: interacts with GABA receptors (Cl-influx when binding to it)

Question 18

What are the effects of Alcohol on NMDA receptors?

Answer 18

It binds to NMDA receptors and inhibits them

–> Decrease

Question 19

What are the effects of Alcohol on Calcium channels?

Answer 19

Decreasing effect on Calcium influx –> decreased neurotransmitter efflux

–> inhibitory

Question 20

Explain how Alcohol can induce Euphoria

Answer 20

• It binds to opioid receptors
• Endogenous opioids switch off GABA–>
  
  • causing disinhibiton of the reward system
    
    • Euphoria

Question 21

Summaris the effects Alcohol has on the CNS

Answer 21

Slowing down of:

• Corpus Collosum - decreased rules and logic+ impulse retardation
• Hypothalamus - Controls appetite, emotions, temperature, and pain sensation.
• Reticular Activating System –Consciousness
• Hippocampus - Memory
• Cerebellum - Movement and coordination
• Basal Ganglia – Perception of time

Question 22

What are the effects of Alcohol on the vasculature

Answer 22

• Causes Vasodilation
  
  • decreased Ca2+ influx –> SM relaxation –> cutaneous vasodilation
  • increase in prostaglandins (possibly due to Acetaldehyde)

Question 23

Explain the effects of Alcohol on HR

Answer 23

It increases HR due to an decrease in Baroreceptor fiering

Question 24

Explain the endocrine effects of Alcohol

Answer 24

It Supresses the secretion of ADH – >polyuria

Question 25

Explain the effects of chronic alcohol abuse on the CNS

Answer 25

Main issue: Thiamine reduce (due to lack of thiamine in diet, because many calories got from Alcohol) Mainly damaging things build up in regions with high metabolic demand in brain * Dementia – Cortical atrophy/¯ volume cerebral white matter * confusion (encephalopathy), oculomotor symptoms * Ataxia – Cerebellar cortex degeneration - gait

Question 26

What is Wernicke-Korsakoff syndrome? Explain its backround

Answer 26

Associated with Thiamine defficiency due to chroinic alcohol abuse --\> 1. Wernicke’s encephalopathy – (hypothalamus/thalamus) (acute+ reversible) * agitation, ataxia and ophtalmoplegia 2. Korsakoff’s psychosis – (deep brain e.g. hippocampus (irreversible) * Anterograde+ Retrograde amnesia * might lead to confabulation (filling memory gaps with stories) Via Neurological injury due to cellular energy deficienty * oxidative damage, * mitochondrial injury leading to apoptosis, * and directly stimulating a pro-apoptotic pathway

Question 27

Explain the effects of chronic alcohol abuse on the liver

Answer 27

1. Alcohol metabilism required NAD+ for metabolism --\> used up and not there for other processes like * Triglyceride metabolism (increased NADH leads to production of fatty acids, low NAD+ leads to reduced fatty acid acitvation) * **Fatty liver (reversible)** * Other liver metabolism (e.g. lack of pyruvate in Krebs cycle) * Acidosis * Ketocis * Induces: **Oxidative stress** 2. **Hepatitis** 1. ​due to accumulation of free radicals and cytokine changes 2. Acetaldehyde --\> Forms acetaldehyde adducts --\> immunogenic and can upregulate transcription of **collagen I** directly + transforming growth factor-beta 1 (TGF-beta1). 3. **Cirrhosis (due to fibroblast repari of damaged hepatocytes)**

Question 28

What is Liver Cirrhosis? How is it connected to chronic alchol abuse?

Answer 28

In cirrhosis: fibroblasts replace hepatocyted and causes a * decrease in active liver tissue * decrease in heüatpcyte regeneration

Question 29

What are the beneficial effects of alcohol on the CVS?

Answer 29

Only in low doses : 2-4 units/day --\> * increase in HDL * decreased risk of mortality from coronary artery disease * tPA levels/¯ platelet aggregation Thought to be mediated via Polyphenols

Question 30

What are the effects of Alcohol on the GI tract?

Answer 30

**Carciogenic:** * Damage to the Mucusa via metabolism in GI tract--\> Acetaldehyde in mucosal wall of GI tract

Question 31

What are the damaging effects of Alcohol on the Endocrine system?

Answer 31

It * increases ACTH * Decreases Testosterone

Question 32

Explain the Symptoms of a Hangover

Answer 32

1. Nausea 1. Acetaldehyde --\> Irritant --\> Vagus --\> Vomiting center 2. Headache 1. Acetaldehyde --\> Vasodilation 3. Fatigue 1. 1. Sleep deprivation, 2. 2. ‘Rebound’ 4. Restlessness and muscle tremors ‘Rebound’ 5. Polyuria and polydipsia ↓ ADH secretion