L8 Ethanol Flashcards
What does ethanol act on?
CNS
What are the general effects of ethanol?
general depressant of CNS
anxiety relief (at low doses)
disinhibition
sedation
hypnosis (sleepiness)
general anesthesia (passing out)
coma
death
What are the 5 concepts of CNS depressants
- additive effects when combined
- can’t be reversed using CNS stimulants
- not totally general (varying effects on different people)
- chronic use leads to rebound excitation upon stopping
- result in some degree of tolerance, frequent cross-tolerance
ARGET (additive, stimulants, general, excitation, tolerance)
What is rebound excitation and why does it occur
rebound excitation is when a neuron becomes more excitable and fires action potentials at a higher rate than its baseline level following a period of inhibition.
It occurs when inhibitory inputs to a neuron are removed or reduced
What are some consequences of alcohol consumption
Emotional changes
Impaired judgement
Impaired motor skills
Impaired involuntary system
Passing out
death
amnesia
*impaired brain activity in memory/learning tests
What is disinhibition
brief excitation due to depression in inhibitory pathways (inhibiting inhibition)
What is the difference between partial amnesia and total amnesia
partial = fragmentary loss of memory, universal and dose-related
total (blackout) = total loss of memory, susceptibility varies per person
At what blood alcohol concentration does alcohol consumption start showing effects
0.03-0.05% (emotional changes)
On which parts of the brain can ethanol act on?
cortex (judgement)
hippocampus (memory)
cerebellum (coordination)
other (vision, movement, sensation, reward pathway)
Which receptors and ion channels does ethanol act on
Na, K, Ca ion channels
5HT (serotonin) and ACh receptors
GABA, glycine (inhibitory)
glutamate (excitatory)
Describe GABA_A receptors
1) inhibitory receptor + chloride ion channel made up of 5 constituents (main inhibitory receptor of the brain)
2) prominent in CNS
3) varying types
4) causes Cl- influx which has inhibitory potential
5) inducible by ethanol
6) extrasynaptic and synaptic
TF: ethanol has presynaptic and postsynaptic effects?
True
What happens when ethanol binds to a postsynaptic receptor?
Cl ion channels open and causes influx of Cl into postsynaptic neuron resulting in GABAminergic inhibition
How many binding sides are there for ethanol on GABA_A alpha subunits
3 (usually 2 for normal GABA)
Which is the main receptor activated by ethanol
GABA-A alpha-beta-gamma
TF: ethanol causes the release of glycine
True
acts pre-synaptically to release glycine, which acts on post-synaptic glycine receptors to cause inhibition
What is the effect of ethanol on NMDA receptors
ethanol blocks NMDA receptors (that release glutamate which is excitatory)
What is the effect of chronic ethanol use on glutamate receptors
the CNS will produce excess glutamate receptors to increase excitation
Summarize which neurotransmitters are affected by ethanol and how
1) glutamate releasing receptors are blocked (decrease excitation)
2) GABA and glycine receptors are activated (GABA can further activate glycine release) - (increase inhibition)
3) ACh and 5HT release is lowered
4) dopamine and opiate neuropeptide release is facilitated
5) voltage-gated Ca2+ ion channels are blocked (decreased neurotransmission)
Decrease in 5HT causes what in alcohol users?
impulsiveness and aggression
Decrease in ACh causes what in alcohol users?
cognitive impairment and amnesia
TF: ethanol acts on the dopamine-reward pathway
True
What makes ethanol addictive?
lowers GABA inhibition of dopaminergic neurons in VTA of brain (still being researched)
Endorphin released by ethanol acts on opiate receptors which are linked to dependence
Describe properties of ethanol that affect its absorption
small, lipid-soluble
Describe the absorption of ethanol
1) rapid detection in blood and brain
2) 30-90 min after consumption = peak
3) absorbed in stomach (less absorption in the presence of food) but mostly absorbed in small intestine
4) peak blood level higher on an empty stomach
5) carbonation increases absorption rate
6) some alcohol is broken down in stomach by alcohol dehydrogenase in gastric mucosa
7) can cause gastritis
Where is ethanol distributed
in total body water (it goes everywhere due to being small and lipid-soluble)
TF: the apparent volume of distribution (AVD) of ethanol is equal to total body water
True
What is apparent volume of distribution
the amount of drug in body/concentration of drug in circulation
TF: ethanol concentration in the body of a female and a male of the same size will be the same when consuming the same amount of alcohol
False
woman have higher total body water resulting in higher concentration of drug in body
TF: women have lower thresholds of alcohol intoxication than men
true
TF: alcohol can pass the blood-brain barrier
True!
TF: alcohol does not trigger the CTZ
false
alcohol causes nausea and vomiting
What is the drug metabolism order for alcohol at low doses? and high doses?
first order (directly proportional) for low doses
zero order for high doses
What order of drug metabolism occurs when binge drinking?
zero order (due to high blood alcohol concentrations)
Describe the 2 step metabolism of alcohol
step 1: ethanol -> acetaldehyde
- liver and gastric mucosa
- enzyme alcohol dehydrogenase (higher in males)
- enzyme has polymorphisms (variability due to genes)
step 2: acetaldehyde -> acetate (-> water + CO2)
- enzyme acetaldehyde dehydrogenase
Why are asians less tolerant to drinking?
genetic variation causing a less active form of acetaldehyde dehydrogenase resulting in increased acetaldehyde (toxic) which causes flushing, nausea, vomiting, etc.
Which enzymes can metabolize ethanol?
alcohol dehydrogenase
CYP450 enzymes (CYP2E1)
TF: alcohol can be eliminated through direct elimination
True
elimination can occur through breath, sweat, and urine
it is dose-dependent
What are the effects of alcohol on kidney function
alcohol blocks water reabsorption by inhibiting ADH hormone (resulting in increase diuresis)
anti anti-diuretic = diuretic
What does it mean when a therapeutic index value is of 4?
that means that the lethal level/recreational level = 4, meaning that the lethal level is only 4 times greater than the recreational level
e.g. benzodiazepine therapeutic index is of 500
What is a teratogen
substance that causes congenital abnormalities or birth defects in a developing fetus
TF: alcohol is a teratogen
True
How can alcohol reach the fetus?
it passes through the placenta
what are effects of fetal alcohol syndrome
damage to CNS, heart, deformities, irreversible neuronal destruction particularly in the hypothalamus, mental retardation
which organs are most vulnerable to alcohol
liver and brain
what is it called when the liver is permanently scarred and damaged
cirrhosis
TF: liver damage impedes on blood flow
true
what are some cardiovascular consequences of alcohol consumption
arrythmia, hypertension, stroke, cardiomyopathy
what is neurodegeneration due to alcohol abuse potentiated by
vitamin b deficiency
TF: alcohol abuse can cause pancreastitis
true
TF: brain damage from alcohol abuse is reversible
false
TF: alcohol is a carcinogen
true
e.g. esophageal cancer
what is the predominant aldehyde for ethanol-derived acetaldehyde and what does it cause
ALDH2
mitochondrial damage, DNA damage, other cellular components damage
In what ways does alcohol affect:
1. liver
2. pancreas
liver: cirrhosis, fat accumulation - fatty liver, hepatitis (liver inflammation) which leads to fibrosis (scar tissue accumulation)
pancreas: pancreatitis (inflammation)
what can cirrhosis lead to
fluid leakage to the abdomen (ascites)
what is hepatic encephalopathy and what is it caused by
impaired blood flow to liver = non-detoxified blood flows to brain (alcohol in blood) = brain damage
caused by necrosis of liver (tissue death) = impaired metabolism & cirrhosis (portal vein impairment)
What is the role of the portal vein
Its primary role is to transport blood from the digestive organs to the liver, where it undergoes extensive processing and filtration.
What happens during acute tolerance for ethanol
brain counters CNS depression by increasing excitation -hyperexcitable phase
Why is chronic tolerance to ethanol dangerous
rebound excitation as a consequence of withdrawal which can be fatal due to its intensity
What are symptoms of alcohol withdrawal syndrome
anxiety, insomnia, tremor, palpitations, nausea, anorexia, seizures, hallucinations, delirium tremens
Which neuronal systems (neurotransmitters) does ethanol have an effect on and what kinds of effects
GABA and glutamate (inhibitory and excitatory)
enhance GABA, inhibit glutamate (enhance inhibition, decrease excitation)
This increase in excitation due to alcohol is due to what?
increase in glutamate receptors and increase in glutamate levels in presynaptic terminal (increase binding chance)
TF: ethanol binds to NMDA receptors which are GABA receptors
False, NMDA receptors are glutamate receptors (though true that ethanol binds to NMDA receptors)
What kind of tolerance is receptor upregulation? (pharmacodynamic or pharmacokinetic)
pharmacodynamic
TF: intensity of withdrawal reaction is directly proportional to the amount the person was drinking every day
true
TF: acute withdrawal of alcohol is treated with CNS stimulants
False, treated with CNS depressants
What does Disulfiram do? What is it used for?
it blocks acetaldehyde dehydrogenase thus causing acetaldehyde accumulation resulting in unpleasant symptoms like nausea, vomiting and headaches
it used to help people stop drinking
recall: ethanol -> acetaldehyde -> acetate (-> water + CO2)
alcohol dehydrogenase, acetaldehyde dehydrogenase
what are some possible treatments for alcoholics?
disulfiram
NMDA receptor antagonists
opioid receptor antagonist
TF: alcoholism is in major part due to genetics
false, it is largely environmental
