Pharm 15 - Drugs of Abuse - Alcohol

Question 1

What is considered low risk for alcohol drinking?

Answer 1

<14 units / week

Question 2

What is defined to be binge drinking?

Answer 2

> 8 units in one sitting

Question 3

How to calculate the absolute amount of alcohol?

Answer 3

%ABV x 0.78 = g alcohol/100ml

Question 4

How to calculate units of alcohol?

Answer 4

(%ABV x volume (ml) )/1000

Question 5

How much is 1 unit defined to be?

Answer 5

10ml or 8g of absolute alcohol

Question 6

How much alcohol is absorbed from the stomach and how much is absorbed from the gut?

Answer 6

20% stomach

80% SI

Question 7

Speed of onset of alcohol is proportional to?

Answer 7

Rate of gastric emptying

If stomach full of food - low rate of gastric emptying

Therefore blood alcohol levels higher on empty stomach

Question 8

How much alcohol do we metabolise?

Answer 8

90%

10% unmetabolised Is tested for in breath test (excreted via lungs)

Question 9

Which 2 enzymes are involved in converting alcohol to acetaldehyde

Answer 9

1. Alcohol dehydrogenase (75%)

2. Mixed function oxidase (25%)

Question 10

Which enzyme can be unregulated in chronic drinkers?

reversible

Answer 10

Mixed function oxidase

Question 11

The alcohol metabolic system is saturable. Why

Answer 11

All metabolic enzymes become saturated - leading to much higher blood alcohol levels

Taking smaller doses = less blood alcohol levels because allows enzymes to metabolise smaller doses at a time

Question 12

Aside from the liver, where else is alcohol dehydrogenase found?

Answer 12

Stomach

Question 13

Alcohol is very water soluble, yet can still diffuse through lipid membranes? Why

Answer 13

Because it is very small molecule

Question 14

Why is the capacity for women to metabolise alcohol less than men?

Answer 14

They have about 50% less alcohol dehydrogenase in the stomach wall than men

Question 15

Why would the average man have less plasma alcohol concentration than the average woman, therefore men are generally able to tolerate alcohol better than women

(Generally speaking)

Answer 15

1. Men have more body water than women
2. Men have 50% more stomach alcohol dehydrogenase than women
3. Alcohol is very water soluble - therefore greater volume of water = more dilute alcohol

Question 16

Acetaldehyde is toxic. What enzyme is present both in the liver and stomach that converts acetaldehyde into acetic acid?

Answer 16

Acetaldehyde dehydrogenase

Question 17

What is the genetic polymorphism common in Asian populations that cause Asian flush?

Answer 17

Aldehyde dehydrogenase not as effective

Question 18

What drug is used as alcohol aversion therapy and why?

Answer 18

Disulfiram - it is a aldehyde dehydrogenase inhibitor

It causes buildup of toxic acetaldehyde - causes unpleasant symptoms which persuades people not to drink again

Question 19

Why does alcohol have such a low pharmacological potency?

Answer 19

It is a very simple drug that has no obvious targets - lack of selectivity

Question 20

What are the 3 major CNS targets of alcohol

Answer 20

1. GABA
2. NMDA receptor
3. Ca channels

Question 21

What does alcohol do to GABA

Answer 21

Activates GABA - enhances its effect

makes sense as alcohol is a depressant

Question 22

Alcohol increases production of allopregnenolone presynaptically. What does this do

Answer 22

Allopregnenolone = allosteric Cl channel modulator

Facilitates Cl channel opening - causing Cl influx - causing depressant effects by positively modifying GABA

Question 23

What does alcohol do to the NMDA receptor?

Answer 23

Binds to NMDA receptor and decreases its activity - decreases an excitatory receptor

(allosteric modulation)

Question 24

What does alcohol do to Ca channels

Answer 24

Decreases Ca influx - decreases neurotransmitter exocytosis

Question 25

What is a proposed reason why alcohol may cause euphoria?

Answer 25

Binds to alcohol/opiate receptors (if alcohol in high doses)

Alcohol then inhibits GABA - which then allows central reward pathway to occur

Question 26

Why can alcohol cause cutaneous vasodilation?

Answer 26

1. Decreases Ca entry - less vasoconstriction
2. Upregulates prostaglandins - vasodilatory

(it is thought to be due to acetaldehyde)

Question 27

How does alcohol cause an increase in heart rate?

Answer 27

1. Decrease in baroreceptor sensitivity
2. Means less parasympathetic stimulation and less inhibition of SNS stimulation
3. This causes increased HR

There are associations with chronic drinking and high BP

Question 28

What is the diuretic effect of alcohol caused by?

Answer 28

(Probably caused by acetaldehyde)

Acts on neurohypohysis and decreases vasopressin secretion

Question 29

What are the chronic problems of alcohol

Answer 29

Thiamine deficiency - causes problems in energy metabolism - means that cerebral energy utilisation is compromised

can cause things like impaired metabolism, NMDA excitotoxicity, ROS

Question 30

What is Wernicke-Korsakoff syndrome?

Answer 30

Caused by thiamine deficiency

When impaired energy metabolism may cause cell death and decrease in cerebral white matter, oculomotor symptoms etc

Question 31

What is Wernickes encephalopathy

Answer 31

Problems with the hypothalamus/thalamus due to chronic alcohol drinking. It is REVERSIBLE - symptoms include confusion, oculomotor symptoms, gait, etc

Question 32

What is Korsakoff’s psychosis

Answer 32

Problems with the deep brain due to chronic alcohol drinking (e.g. hippocampus)

May cause cortical atrophy, ataxia, dementia due to significant loss of cortical white matter

IT IS IRREVERSIBLE - really shows when people start to get memory problems

Question 33

Alcohol can cause liver problems, by using up all the NAD+, meaning less NAD+ for other liver functions. What problems can this cause

Answer 33

1. Inhibition of beta oxidation of lipids - fat buildup in the liver
2. Impaired TCA cycle - causes pyruvate to be converted into lactic acid
3. Acetyl CoA can’t be put into TCA due to lack of NAD+ so converted into ketones

Question 34

Healthy liver to fatty liver can be caused by binge drinking. But the good news is?

Answer 34

Fatty liver is reversible

Question 35

How does one get hepatitis

Answer 35

Chronic alcohol drinking

1. CYP 450 metabolism of alcohol causes oxygen free radicals
2. Oxygen free radicals cause inflammatory changes and mitochondrial damage

Question 36

How does one get cirrhosis

Answer 36

1. Constant inflammation of the liver
2. Causes fibroblasts recruitment and infiltrates into the liver
3. The fibroblasts lay down connective tissue - replacing the active hepatocytes
4. Less hepatocyte regeneration too

Question 37

What are purported positive effects of alcohol?

Answer 37

Increased HDLS, decreased platelet aggregation, antiatherogenic effects are good for reducing mortality from CAD

It could be due to polyphenols - red wine contains lots of

Question 38

How can alcohol cause gastric ulcerations

Answer 38

Alcohol is partially metabolised in the stomach - meaning lots of acetaldehyde can build up here.

This damages gastric mucosa and may cause ulcerations

Question 39

How can alcohol affect the endocrine system?

Answer 39

1. Increases ACTH secretion - may cause Cushings-like symptoms
2. Chronic alcohol decreases testosterone secretion - feminine characteristics maybe

Question 40

Why does sleep quality suffer on alcohol?

Answer 40

Rebound excitation as blood alcohol conc reaches 0

Question 41

Why does alcohol cause nausea

Answer 41

Irritates stomach

Question 42

Why does alcohol cause headache

Answer 42

Profound vasodilation