Drugs of Abuse - Alcohol

Question 1

What is the formula for calculating Units of alcohol?

Answer 1

%ABV * Volume (ml)
1000

Question 2

What is the Safe level of units per week?

What is considered Binge drinking?

Answer 2

< 14 Units/week

Binging: >8 units in one sitting

Question 3

What are the Blood Alcohol levels of:

Safe Driving
Minimal effects
Legal Driving Limit
Gross Intoxication
Coma
Death

Answer 3

Safe: 0

Minimal effects: 20-40mg/100ml

Legal Driving Limit: 80mg/100ml

Gross Intoxication: Up to 150mg/100ml

Coma: 300mg/100ml

Death: 4-500mg/ml

Question 4

What proportions of alcohol drunk are absorbed where in the GI tract?

Answer 4

20% stomach

80% Intestines

Question 5

What important factor is speed of onset of effects linked to?

Answer 5

Speed of gastric emptying

If full then emptying from the stomach is reduced

Alcohol is absorbed more readily in the intestines so drinking on an empty stomach means more alcohol will hit you at once

Question 6

How is alcohol metabolised?

Answer 6

Mainly in the Liver

75% Alcohol dehydrogenase

25% Mixed function oxidase

To Acetaldehyde

Question 7

What proportion of Alcohol is metabolised?

Answer 7

90%

Remaining 10% is unmetabolised

Some is excreted via lungs (Breathalyser)

Question 8

What is Mixed function oxidase?

Answer 8

An enzyme that is induced upon continuous exposure to alcohol

Partially responsible for increasing tolerance (Reversible)

Question 9

What is the difference in taking one large dose or several small doses of alcohol?

Answer 9

The enzymes are saturable

Question 10

Apart from the liver, where else is Alcohol metabolised?

What is the difference in males and females?

Answer 10

15% in stomach

Alcohol dehydrogenase found in the stomach

Women have <50% the amount of this

Question 11

What is the difference in tolerance of Alcohol in men and women?
Why?

Answer 11

Men have a higher innate tolerance:

Men have a higher body water % so there is more water for alcohol to be dissolved in - lower blood alcohol level

Women have less stomach dehydrogenase

Question 12

What is Acetaldehyde?

Answer 12

The primary metabolite of alcohol

It is toxic - causes many of the negative consequences associated with alcohol

Question 13

What is disulfiram?

Answer 13

An aldehyde dehydrogenase inhibitor - used as an alcohol aversion therapy

It causes a build-up of Acetaldehyde which makes you feel bad and less keen to drink again

Question 14

What causes Asian Flush?

Answer 14

Acetaldehyde acts as a vasodilator that causes the flush

A polymorphism in Aldehyde Dehydrogenase - It doesn’t work very well - causes a build up

Question 15

What is the Pharmacological potency of alcohol?

Answer 15

Very low - you need a lot more compared to other drugs to get an effect

It is a small molecule and therefore binds to many different target sites so you basically have to throw it in huge quantities to get it to stick to the right places

Question 16

What type of drug is alcohol?

Answer 16

A Depressant

Question 17

What are the effects of Low dose alcohol?

Answer 17

The degree of CNS excitability at that moment is dependent on your environment and personality

A very social setting with lots of sensory information will lead to excitation

Question 18

What are the effects of High dose Alcohol?

Answer 18

Always a depressant

Question 19

What are the three main CNS targets of Alcohol?

Answer 19

GABA receptors

NMDA receptors

Calcium channels

Question 20

What is the effect of Alcohol on GABA receptors?

Answer 20

Enhances GABA function so has depressive effects

Question 21

What is the effect of Alcohol on Allopregnenolone?

Answer 21

Increase Allopregenonolone production - allosteric steroid modulator of chloride channels

Facilitates Chloride channel opening increasing the Chloride influx increasing the actions of GABA - acting as a depressant

Question 22

What is the effect of Alcohol on NMDA receptors?

Answer 22

Decreases NMDA receptor function which causes allosteric modulation

Question 23

What is the effect of Alcohol on Calcium channels?

Answer 23

Decreases Calcium influx into pre-synaptic membrane reducing neurotransmitter exocytosis

Question 24

What are the mechanisms of Alcohol’s action on the CNS?

Answer 24

We dont really know…

Alcohol has a low potency and selectivity and the CNS is soo complex

Question 25

What are the main effects of Alcohol on the CVS?

Answer 25

Cutaneous **Vasodilation** (associated with reduced Calcium entry and increased prostaglandins) Vasodilatory effects thought to be due to Acetaldehyde Decrease in centrally medicated baroreceptor sensitivity - **acute increase in HR** Chronic use associated with **HPT**

Question 26

How does Alcohol act as a Diuretic?

Answer 26

Acetaldehyde acts on Neurohypophysis and inhibits Vasopressin release - Powerful diuretic effect

Question 27

What are the three main effects of Chronic alcohol on the CNS?

Answer 27

Dementia - Cortical atrophy - less white matter Ataxia - Cerebellar cortex degeneration Wernicke-Korsakoff Syndrome

Question 28

What is Wernicke-Korsakoff syndrome?

Answer 28

Caused by Thiamine Deficiency Chronic alcoholics get most calories from alcohol so have poor diet Thiamine is an important co-factor and ATP formation in cells is dependent on this As the Krebs cycle is impaired Oxidative stress builds up in the cell and leads to mitochondrial injury and eventually apoptosis Wernicke's Encephalopathy - mitochondrial injury (3rd ventricle & aquaduct) Korsakoff's Psychosis - Irreversible injury leading to apoptosis (Death) - Associated with hippocamus and dorsomedial thalamus - leads to memory problems

Question 29

How does alcohol cause fatty liver?

Answer 29

Metabolism uses NAD+, so stores of liver NAD+ are used up and there is excessive NADH NADH will inhibit beta-oxidation of lipids so fat builds up

Question 30

How does alcohol cause classic hepatitis?

Answer 30

If there is not enough NAD+ you use Cytochrome P450 to metabolise Alcohol Chronic use of CP450 generates oxygen free radicals These damage the cell causing mitochondrial injury and inflammatory changes - Hepatitis

Question 31

How does alcohol cause Cirrhosis?

Answer 31

With persistent liver inflammation fibroblasts are recruited which lay down connective tissue - Cirrhosis

Question 32

What are the Beneficial effects of alcohol?

Answer 32

Supposedly increases HDLs and decrease in platelet aggregation Anti-atherogenic effects Not definitive whether alcohol is causing this, could be the polyphenols in Red Wine 🍷

Question 33

What are the chronic effects of Alcohol on the GI tract?

Answer 33

Chronic presence of Acetaldehyde from stomach dehydrogenase metabolism damages the gastric mucosa This can lead to ulcerations

Question 34

What Endocrine symptoms may Chronic alcoholics present with?

Answer 34

Cushings symptoms - Alcohol causes an increase in ACTH secretion