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
State the acute effects alcohol has on different parts of the brain
Corpus Callosum
• information from left –> right
Hypothalamus
• controls appetite, emotions, pain, oC
RAS
• consciousness
Hippocampus
• memory
Cerebellum
• movement & coordination
Basal ganglia
• perception of time
State the general acute effects alcohol has on the CVS/CNS/Endocrine
VasoDILATION
Increased HR
Diuresis (polyuria)
Using pharmacodynamics, explain the acute effect of vasodilation from alcohol consumption
Cutaneous vasodilation - flushing
• DECREASED Ca2+ influx = LESS VSM contraction
- so the capillary sphincters relax rather than remain contracted
• INCREASED prostaglandins (vasodilators)
Using pharmacodynamics, explain the acute effect of increased HR from alcohol consumption
Alcohol DIMINISHES the control of the brain on the ARTERIAL BARORECEPTORS
• SO the heart receives LESS INHIBITORY INPUT
• SNS becomes dominant
• HR increases
Using pharmacodynamics, explain the acute effect of diuresis from alcohol consumption
ADH SUPRESSES VP release
• Less VP = less water absorption = diuresis
Explain the CHRONIC effect on the CNS from alcohol consumption
Largerly due to THIAMINE deficiency
• drives production of enzymes used in energy metabolism = cerebral energy utilisation
• SO unsure if it even is acetaldehyde that is the issue (more due to chronic drinkers get most calories from alcohol do aren’t getting enough thiamine in)
What are some chronic effects seen on the CNS from alcohol consumption?
Dementia
• cortical atrophy = confusion (encephalopathy)
• decreased cerebral white matter = oculomotor symptoms
Ataxia
• cerebellar cortex degeneration = gait
Wernicke-Korsakoff Syndrome - due to THIAMINE deficiency
• Wernicke’s encephalopathy (affects 3rd ventricle & aqueduct)
- REVERSIBLE
• Korsakoff’s pyschosis (affects dorsomedial thalamus)
- impairs memory (makes memory up)
- IRREVERISBLE
Explain the CHRONIC effect on the liver from alcohol consumption
NAD+
• require NAD+ for a lot of liver function
BUT
• alcohol dominates the use of NAD+ SO not being used for other functions
Leads to a BUILD-UP of other dangerous toxic by-products
What are some chronic effects seen on the liver from alcohol consumption
Fatty liver
• the lack of NAD+ means that TAGs are deposited in the liver
Hepatitis
• mixed function oxidases are upregulated in chronic alcoholics and these generate free radicals which then generate an inflammatory response
- MFO –> free radicals –> inflammation
- Cytokines are then released – e.g. increased IL-6 and TNF-a
Cirrhosis
• fibroblasts lay down fibrin supportive structures that reduce regenerative capacity of liver
- decreased regeneration and active liver tissue
- increased fibroblasts
What are some POSITIVE effects on the CVS from alcohol consumption?
• Decreases mortality from coronary hear disease
- men with 2-4 units/day
• Increased HDLs
• Increased tPA levels
- decreases platelet aggregation levels
• Polyphenols (red wine) may reduce free radicals
Using pharmacodynamics, explain the GIT/Endocrine chronic effects of alcohol consumption
GIT
• Damages gastric mucosa (in proportion to dose)
- can lead to stomach cancer from acetaldehyde build-up
- Acetaldehyde is a carcinogenic
Endocrine
• Increased ACTH secretion –> Cushing’s-like syndrome
• Decreased testosterone –> gynecomastia
Why do people get hangovers?
Believe is because symptoms peak as BAC (blood [alcochol]) reaches 0
Nausea
• irritant –> vagus –> vomiting centre of medulla
Headache
• vasodilation
Fatigue
• sleep deprivation, ‘rebound’
Restlessness & muscle termors
• ‘rebound’ - rebound excitation as BAC = 0
Polyuria, polydipsia
• decreased VP secretion
Cure for hangover?
- SLEEP
- Drink water (not as much evidence)
• believe it’s because, drinking might help clear out toxins (acetaldehyde) via. excretion
