Drugs of Abuse - Alcohol Flashcards

1
Q

What is the formula for calculating Units of alcohol?

A

%ABV * Volume (ml)
1000

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2
Q

What is the Safe level of units per week?

What is considered Binge drinking?

A

< 14 Units/week

Binging: >8 units in one sitting

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3
Q

What are the Blood Alcohol levels of:

Safe Driving
Minimal effects
Legal Driving Limit
Gross Intoxication
Coma
Death

A

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

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4
Q

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

A

20% stomach

80% Intestines

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5
Q

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

A

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

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6
Q

How is alcohol metabolised?

A

Mainly in the Liver

75% Alcohol dehydrogenase

25% Mixed function oxidase

To Acetaldehyde

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7
Q

What proportion of Alcohol is metabolised?

A

90%

Remaining 10% is unmetabolised

Some is excreted via lungs (Breathalyser)

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8
Q

What is Mixed function oxidase?

A

An enzyme that is induced upon continuous exposure to alcohol

Partially responsible for increasing tolerance (Reversible)

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9
Q

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

A

The enzymes are saturable

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10
Q

Apart from the liver, where else is Alcohol metabolised?

What is the difference in males and females?

A

15% in stomach

Alcohol dehydrogenase found in the stomach

Women have <50% the amount of this

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11
Q

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

A

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

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12
Q

What is Acetaldehyde?

A

The primary metabolite of alcohol

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

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13
Q

What is disulfiram?

A

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

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14
Q

What causes Asian Flush?

A

Acetaldehyde acts as a vasodilator that causes the flush

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

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15
Q

What is the Pharmacological potency of alcohol?

A

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

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16
Q

What type of drug is alcohol?

A

A Depressant

17
Q

What are the effects of Low dose alcohol?

A

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

18
Q

What are the effects of High dose Alcohol?

A

Always a depressant

19
Q

What are the three main CNS targets of Alcohol?

A

GABA receptors

NMDA receptors

Calcium channels

20
Q

What is the effect of Alcohol on GABA receptors?

A

Enhances GABA function so has depressive effects

21
Q

What is the effect of Alcohol on Allopregnenolone?

A

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

22
Q

What is the effect of Alcohol on NMDA receptors?

A

Decreases NMDA receptor function which causes allosteric modulation

23
Q

What is the effect of Alcohol on Calcium channels?

A

Decreases Calcium influx into pre-synaptic membrane reducing neurotransmitter exocytosis

24
Q

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

A

We dont really know…

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

25
Q

What are the main effects of Alcohol on the CVS?

A

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

26
Q

How does Alcohol act as a Diuretic?

A

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

27
Q

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

A

Dementia - Cortical atrophy - less white matter

Ataxia - Cerebellar cortex degeneration

Wernicke-Korsakoff Syndrome

28
Q

What is Wernicke-Korsakoff syndrome?

A

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

29
Q

How does alcohol cause fatty liver?

A

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

30
Q

How does alcohol cause classic hepatitis?

A

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

31
Q

How does alcohol cause Cirrhosis?

A

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

32
Q

What are the Beneficial effects of alcohol?

A

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 🍷

33
Q

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

A

Chronic presence of Acetaldehyde from stomach dehydrogenase metabolism damages the gastric mucosa

This can lead to ulcerations

34
Q

What Endocrine symptoms may Chronic alcoholics present with?

A

Cushings symptoms - Alcohol causes an increase in ACTH secretion