Drugs of Abuse - Alcohol Flashcards
What is the formula for calculating Units of alcohol?
%ABV * Volume (ml)
1000
What is the Safe level of units per week?
What is considered Binge drinking?
< 14 Units/week
Binging: >8 units in one sitting
What are the Blood Alcohol levels of:
Safe Driving
Minimal effects
Legal Driving Limit
Gross Intoxication
Coma
Death
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
What proportions of alcohol drunk are absorbed where in the GI tract?
20% stomach
80% Intestines
What important factor is speed of onset of effects linked to?
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
How is alcohol metabolised?
Mainly in the Liver
75% Alcohol dehydrogenase
25% Mixed function oxidase
To Acetaldehyde
What proportion of Alcohol is metabolised?
90%
Remaining 10% is unmetabolised
Some is excreted via lungs (Breathalyser)
What is Mixed function oxidase?
An enzyme that is induced upon continuous exposure to alcohol
Partially responsible for increasing tolerance (Reversible)
What is the difference in taking one large dose or several small doses of alcohol?
The enzymes are saturable
Apart from the liver, where else is Alcohol metabolised?
What is the difference in males and females?
15% in stomach
Alcohol dehydrogenase found in the stomach
Women have <50% the amount of this
What is the difference in tolerance of Alcohol in men and women?
Why?
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
What is Acetaldehyde?
The primary metabolite of alcohol
It is toxic - causes many of the negative consequences associated with alcohol
What is disulfiram?
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
What causes Asian Flush?
Acetaldehyde acts as a vasodilator that causes the flush
A polymorphism in Aldehyde Dehydrogenase - It doesn’t work very well - causes a build up
What is the Pharmacological potency of alcohol?
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
What type of drug is alcohol?
A Depressant
What are the effects of Low dose alcohol?
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
What are the effects of High dose Alcohol?
Always a depressant
What are the three main CNS targets of Alcohol?
GABA receptors
NMDA receptors
Calcium channels
What is the effect of Alcohol on GABA receptors?
Enhances GABA function so has depressive effects
What is the effect of Alcohol on Allopregnenolone?
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
What is the effect of Alcohol on NMDA receptors?
Decreases NMDA receptor function which causes allosteric modulation
What is the effect of Alcohol on Calcium channels?
Decreases Calcium influx into pre-synaptic membrane reducing neurotransmitter exocytosis
What are the mechanisms of Alcohol’s action on the CNS?
We dont really know…
Alcohol has a low potency and selectivity and the CNS is soo complex
What are the main effects of Alcohol on the CVS?
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
How does Alcohol act as a Diuretic?
Acetaldehyde acts on Neurohypophysis and inhibits Vasopressin release - Powerful diuretic effect
What are the three main effects of Chronic alcohol on the CNS?
Dementia - Cortical atrophy - less white matter
Ataxia - Cerebellar cortex degeneration
Wernicke-Korsakoff Syndrome
What is Wernicke-Korsakoff syndrome?
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
How does alcohol cause fatty liver?
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
How does alcohol cause classic hepatitis?
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
How does alcohol cause Cirrhosis?
With persistent liver inflammation fibroblasts are recruited which lay down connective tissue - Cirrhosis
What are the Beneficial effects of alcohol?
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 🍷
What are the chronic effects of Alcohol on the GI tract?
Chronic presence of Acetaldehyde from stomach dehydrogenase metabolism damages the gastric mucosa
This can lead to ulcerations
What Endocrine symptoms may Chronic alcoholics present with?
Cushings symptoms - Alcohol causes an increase in ACTH secretion
