DOA 3 - Alcohol Flashcards
Epidemiology of Alcohol consumption?
HIGH consumption in Europe, Greenland & Russia
How can dosing be classified with alcohol?
Absolute amount (g alcohol/100ml) = %ABV x 0.78
Units = (%ABV x volume/ml) / 1000
• 1 unit = 10mls OR 8g of absolute alcohol
LOW-risk
• men & women <14units/week
• bing drinking >8units in one sitting
Explain the absorption of alcohol
20% from the STOMACH
• DIRECTLY
80% from the INTESTINE
What is the speed of onset of alcohol intoxication proprotional to?
GASTRIC EMPTYING
Post-prandial, the stomach does NOT empty as often as it needs to breakdown food
• SO alcohol is NOT absorbed very well
• i.e. eating a meal decreases speed of onset
General overview of alcohol metabolism
Only 90% is metabolised
• 10% is breathed off
85% of metabolism occurs in the LIVER
15% of metabolism occurs in the GIT
Explain the pharmacokinetics behind the metabolism of alcohol in the liver
Alcohol –> Acetaldehyde (toxic) via.
• 75% = alcohol dehydrogenase
• 25% = mixed function oxidase
- MFO is MOST significantly UPREGULATED in chronic alcoholics
- hence why do NOT get drunk as easily when drink MORE (reversible, so if drink less, less MFO so can get drunk again more easily)
ONE high-dose alcohol bolus will SATURATE the enzymatic system
• leads to a HIGHER intoxication as opposed to the same absolute amount of alcohol over say 4 seperate doses
Explain the pharmacokinetics behind the metabolism of alcohol in the GIT
Alcohol –> Acetaldehyde (toxic) via.
• 100% = alcohol dehydrogenase
- females have 50% LESS ADH than males in the GIT
A man and woman of similar height and weight share a bottle of wine.
Explain why the blood alcohol levels in the woman are likely to be higher
All to do with DISTRIBUTION
• Woman - body water = 50%
• Men - body water = 59%
MORE ADH = MORE BODY WATER
Men have a GREATER VOLUME of body water
• Women have MORE ADIPOSE TISSUE
• This allows alcohol to be MORE WIDELY DISTRIBUTED in men = at a [LOWER]
• Men also have MORE ADH so higher ability to metabolise
Once the alcohol is metabolised to acetaldehyde in both the liver and GIT, what happens next?
Acetaldehyde –> Acetic acid via.
• Aldehyde dehydrogenase
- polymorphisms can be found in this enzyme leading to Asian flush
Explain why disulfiram can be effective as alcohol aversion therapy
DISULFIRAM - inhibitor of aldehyde dehydrogenase
Effective as build-up of acetaldehyde makes you FEEL SICK & not want to drink alcohol
Relationship between alcohol & potency?
Alcohol has a LOW pharmacological potency
(as it a very general molecule)
• influences MANY receptors due to its uncomplicated shape BUT does NOT FIT a lot of receptors so NOT a lot of EFFICACY
Main acute effects on alcohol on CNS and what is it dependent on?
DEPRESSANT (CNS agitation may occur)
Dependant upon the
• ENVIRONMENT (non-social vs. social setting)
and
• PERSONALITY of the individual
Using pharmacodynamics, explain the acute effects of alcohol on the CNS
Alcohol DEPRESSES the system by:
• INCREASING INHIBITION
- pre- &post-synaptic
- via. release of ALLOPREGNENOLONE on pre-synaptic which binds to GABA receptors = stimulating it = increases Cl- influx
• REDUCING EXCITATION
- reducing stimulation at NMDA receptors
- reducing Ca2+ influx SO less NTs exocytosis
Is it easy/hard to assess the acute effects of alcohol on the CNS?
HARD as
- CNS is functionally complex
- Ethanol has LOW potency SO LOW selectivity
• so hard to know which target is being affected
Using pharmacodynamics, explain how alcohol leads to euphoria
Alcohol binds to U-receptor (mu)
• INHIBITS GABA release
LESS INHIBITORY GABA = LESS INHIBITION on DA release by VTA DA neurones into the NAcc
