Alcohol

Question 1

What are the sites that alcohol can be absorbed from?

Answer 1

• Small intestines
• Stomach

Question 2

What is rate of absorption related to when it comes to the stomach

Answer 2

• Rate of alcohol absorption (if oral administration) is proportional to the rate of gastric emptying

Question 3

How does drinking on a full stomach influence blood alcohol levels?

Answer 3

• It lowers the rate of gastric emptying
• Thereby decreasing the rate of absorption because alcohol is held up in the stomach so it is absorbed via the stomach route more which is a slower route so slower rate of absorption

Question 4

What are the 3 enzymes that metabolise alcohol that are produced by the liver?

Answer 4

1. Alcohol dehydrogenase
2. Mixed function oxidase
3. Acetaldehyde dehydrogenase

Question 5

How and where is alcohol metabolised, and what is it metabolised into - i.e. outline the steps in the metabolism of alcohol?

Answer 5

STEP 1

• Alcohol dehydrogenase in the stomach metabolises alcohol into acetaldehyde first - but little effect and even less effect in women
• Then alcohol dehydrogenase and mixed function oxidases in the liver metabolise alcohol into acetaldehyde also, greater effect here

STEP 2

• Acetaldehyde is converted into acetic acid by acetaldehyde dehydrogenase in both the stomach and the small intestine
• Note acetaldehyde is toxic and it is important to clear it

Question 6

Why is the time basis for how you dose your alcohol intake important in terms of the effects you feel?

Answer 6

• If you have a high dose very quickly then you can saturate the enzymes that metabolise the alcohol so there’ll be inefficient metabolism and thus more alcohol will enter the systemic circulation

Question 7

Give 2 reasons why women have a lower tolerance for alcohol than men

Answer 7

1. They have less ADH (alcohol dehydrogenase) in the stomach than men - so the arm of metabolism within the stomach is less effective
2. They have a lower water content within their bodies so once it enters the systemic circulation, it is less diluted than in males

Question 8

What is the basis for development of tolerance to alcohol?

Answer 8

• Upregulation of…

1. Mixed function oxidases
2. ADH (alcohol dehydrogenase)

• So alcohol is metabolised better and faster so less enters the systemic circulation where it will have its effect

Question 9

Describe how you can be less tolerant to alcohol due to defects in one of the steps in the metabolism of alcohol and what phenomenon is this responsible for?

Answer 9

• Common polymorphism of the aldehyde dehydrogenase enzyme
• So less conversion of acetaldehyde into acetic acid, and remember that acetaldehyde is toxic, so you build up this toxic intermediate metabolite
• Phenomenon: Asian flush - this polymorphism is common in Asian populations

Question 10

What drug is used to prevent over consumption of alcohol in alcoholics and describe its physiological basis for its mechanism of action?

Answer 10

• Disulfiram
• Inhibits acetaldehyde dehydrogenase, thereby preventing the conversion of the toxic intermediate metabolite acetaldehyde into acetic acid
• Acetaldehyde is off-putting so having high levels of acetaldehyde will put off the alcoholic from drinking further

Question 11

What is the selectivity of alcohol like?

Answer 11

• Low selectivity - it has widespread effect due to simple molecular structure

Question 12

What is the affinity and efficacy of alcohol like?

Answer 12

• Low for both

Question 13

Outline the 4 physiological mechanisms behind how alcohol is a CNS depressant

Answer 13

• Direct effect to stimulate the GABA receptors
• Acts pre-synaptically to increase allepregnenolone which itself binds GABA receptors to increase its effect
• Alcohol also decrease NMDA receptor activation by allosteric modulation
• Alcohol may also impair VGCC opening, thereby preventing NT release

Question 14

Describe the physiological mechanism behind how alcohol can stimulate euphoria, particularly when administered by inhalation

Answer 14

• Binds opiod receptor to impair GABAergic dampening of the dopaminergic reward pathway from the ventral tegmental nucleus all the way to the nucleus accumbens within the ventral striatum
• Thereby stimulating euphoria by potentiating the reward pathway

Question 15

List some different brain areas that alcohol can have its depressant effects and thus cause some of the effects that it has

Answer 15

• Corpus callosum
• Hypothalamus - appetite, emotional, temperature regulation
• Cerebellum - impaired balance
• Hippocampus - impaired memory
• Reticular activating system - impaired consciousness
• Basal ganglia - impaired perception of time

Question 16

Outline the effect that alcohol can have on the CVS

Answer 16

1. CUTANEOUS VASODILATION

• You go red due to cutaneous vasodilation
• Due to increased acetaldehyde which…
• Interferes with smooth muscle function in the arterioles
• Impairs calcium entry and promotes prostaglandins, thereby causing vasodilation

2. TACHYCARDIA
   * Due to depression of baroreceptors which normally promote PNS and inhibit SNS in order to slow HR, so by depressing their function, the reverse happens and you get tachycardia

Question 17

Outline the 3 parts of the endocrine system that alcohol can effect (3 hormones) and thus the symptoms it can cause due to these

Answer 17

1. Acetaldehyde impairs VP synthesis and secretion - therefore causing polyuria
2. Alcohol increases cortisol production - Cushing’s like symptoms
3. Alcohol impairs testosterone secretion - feminisation symptoms

Question 18

Give 3 negative effects of chronic alcohol abuse in the CNS and the physiological basis for these

Answer 18

1. Ataxia - cerebellar cortex degeneration
2. Dementia - cortical atrophy
3. Wernicke-Korsakoff syndrome

• Due to THIAMINE DEFICIENCY
• Wernicke’s encephalopathy (3rd ventricle and aqueduct) - reversible
• Korsakoff’s psychosis (dorsomedial thalamus) - irreversible
• Acidosis and glutamate production

Question 19

Describe the negative consequences of chronic alcohol abuse in the liver (3 stages) and the psychological basis for everything

Answer 19

• ADH depletes NAD⁺ (essential component of aerobic metabolism), therefore…
• Pyruvate starts getting converted into lactate (acidosis)
• Acetyl CoA starts getting converted into ketones (ketosis)
• Acidosis and ketosis impairs the liver’s ability to metaobolise lipids
• Also the mixed function oxidase system is very active so you build up lots of damaging oxygen free-radicals
• All this also contributes to a pro-inflammatory environment
• There are 3 stages in the changes to the liver:

1. Fatty liver - due to fatty TAG depostits as poor lipid metabolism - reversible
2. Hepatitis - due to all of the above lactic acid, ketosis, oxygen free radicals, and you also see cytokine changes - IL-6 and TNF-alpha build up
   - reversible
3. Cirrhosis - long term - eventually all the damage results in lots of inflammatory recruitment invluding fibroblasts coming alon and depositing connective tissue in place of active liver tissue - liver dysfunction - irreversible - requires transplant eventually

Question 20

What negative consequences can you get in the stomach as a result of chronic alcohol abuse and what causes this?

Answer 20

• Due to stomach alcohol dehydrogenase, the stomach is exposed to acetaldehyde when alcohol is metabolised into acetaldehyde
• This is toxic and irritates the gastric mucosa
• This increases stomach ulceration
• Also increases stomach cancer risk - carcinogenic

Question 21

What beneficial effects might moderate alcohol use have?

Answer 21

• Protective effects against CAD
• Improves lipid profile as…
• Increased HDLs
• Increased tPA levels
• Decreased platelet aggregation

Question 22

List some signs / symptoms that occur during hangover and where possible the physiological basis behind this

Answer 22

• Nausea - alcohol is an irritant - irritates the vagus - vomiting centre
• Headache - vasodilation
• Fatigue - sleep deprivation
• Restlessness and muscle tremors
• Polyuria and polydipsia - reduced ADH

Question 23

Define binge drinking

Answer 23

• Drinking > 8 units in one sitting