Alcohol Flashcards
What does ethanol look like at low doses?
A stimulant
Why does ethanol look like a stimulant at low doses?
GABAergic neurons are really sensitive to it
ethanol inhibits GABAergic neurons
What happens when you have a large dose of ethanol?
Ethanol inhibits most neurotransmitters in prefrontal cortex
What happens when you have a massive dose of ethanol?
Changes membrane fluidity for neurons
What is a sedative-hypnotic?
What is important about them?
Drugs that diminish awareness
most dangerous group of drugs
Drugs can kill you
withdrawal can kill you
Only group you can die from if you go cold-turkey
What drugs are in the sedative-hypnotic category?
ethanol
barbituates
You take two CNS depressants. What is the pharmacodynamic effect?
They can be additive with each other
Can CNS depressants be antagonized by stimulants?
Not directly. You just become a wide-awake drunk
Neural and behavioral disinhibition happens as the result of taking a CNS depressant. Why?
The drug is working at GABA synapses, antagonizing them. That means that inhibitory neurons are themselves inhibited, creating an excitatory effect
What is the most common drug used in the world?
Caffeine
Ethanol is second
Where in the body will alcohol generally be?
Aqueous compartments
Very small, so can get through BBB
Water-soluble, so doesn’t clump up in blood
Where is ethanol absorbed?
Small intestine. Significant 1st pass metabolism
What does carbonation do to ethanol?
Accelerates metabolism
Why do females metabolize alcohol more quickly?
More female body is fat
Fat has less water in it than muscle, and therefore tissue with more fat has more water in blood
So, ethanol is more concentrated in blood (water-soluble)
What are pylorospasms?
Spasm of the sphincter
Why does the stomach empty more slowly if ethanol is higher than 30%?
Because of pylorospasms
What are the two metabolites of alcohol?
Alcohol >(alcohol dehydrogenase) > acetaldehyde > (acetaldehyde dehydrogenases) > acetic acid > (oxidation) > CO2, H2O, energy
What two things almost always happen when drug tolerance occurs?
Alteration of liver enzymes
Alteration of nervous system (acute/functional tolerance)
What are hepatic enzymes?
liver enzymes
What does coffee drinking do to ethanol metabolism?
There’s cross-tolerance
Ethanol causes caffeine tolerance
Due to changes in hepatic enzymes
What is the righting reflex?
Makes the body go upright
Impaired with ethanol consumption
You lie down in bed and the room is spinning. Why?
bedspins
Differences in distribution of ethanol across vestibular apparatus
Makes neurons in inner ear more excitatory where ethanol is not active
This causes weird activation patterns resulting in bedspins
How do you get rid of bedspins?
Put your foot on the ground
Gives somatosensory feedback that overrides vestibular feedback
Where does neural activation pathway from vestibular apparatus go?
To cerebellum, then to motor/parietal cortex
What does alcohol do to NMDA receptors?
Fucks with them to prevent GLU binding
What are the two reasons alcohol effects learning and memory?
- NMDA receptor not taking in GLU as easy
2. Glutamate RELEASE inhibited in the HC
Why do cells die with regards to alcohol / glutamate?
Elevated glutamate activity during withdrawal
This causes excessive Ca2+ influx
Influx leads to cell death
What are the subunits of GABA receptors?
a, B, Y/theta subunits
How many classes of GABA receptors are there? What are they called?
2: GABA-A and GABA-B
‘endogenous’
naturally occurring (inside the body)
‘exogenous’
Comes from outside the body
How many GABA molecules do you need to open the GABA-A receptor?
Two
Where on the GABA-A receptor does ethanol effect?
Trick question: facilitates transmission at all three!
a1, B2, or delta
Which GABA subunit does GABA bind to?
B subunit
Which GABA subunit do barbituates bind to?
B subunit
What subunit does benzodiazepine attach to?
Y/Delta
What ion comes in when GABA-A receptors open?
Cl-, it’s ionotropic
What happens to GABA receptors over time when you have a bunch of ethanol?
less GABA-A receptors to compensate
What happens when you have less GABA-A receptors?
increased excitability in the nervous system (less inhibition)
What does EtOH do for glutamate?
antagonization
What receptors does ethanol’s glutamate antagonization affect?
both NMDA and AMPA
Why (molecularly) will unsupervised ethanol withdrawal cause seizures?
There’s a shitload of NMDA and AMPA receptors everywhere, which causes the seizures
What takes over as the principal neurotransmitter in the spinal cord?
Glycine
Chronic
Always there. Exposed to drug constantly. Different from ‘repeated’
Acute
Brief spike in drug concentration, with large periods of lack of drug. Once
Kainate
Think of it as the same as AMPA
Where in the brain do low concentrations of ethanol cause dopaminergic neurons to increase firing rate?
The VTA
Why do dopaminergic VTA neurons increase firing rate with low EtOH doses?
Inhibition of GABAergic neurons there increases activity of DAergic neurons
What is the rough rule of thumb for D1 and D2 DA receptors?
D1 = increase in excitability D2 = decrease in excitability
Why is an alcoholic’s stomach hard when you pat it?
Liver accumulation of fat
Perseveration
Continually engaging in the same sequence of behavior, even if it’s maladaptive
When would you see the accumulation of fat in the liver due to ethanol? What type of drinking?
Chronic drinkers. Constant exposure to ethanol with no letting-up
What is the name of the syndrome involving loss of memory/confabulation due to chronic ethanol exposure?
Wernicke-Korsakoff’s syndrome
What is the word for bullshit / huge intervals of time where memories are made up?
Confabulation
What area of the brain is damaged with wernicke-korsakoff’s syndrome?
Dorso-medial thalamus
What is the dorso-medial thalamus part of the circuitry doing?
Part of memory circuit
HC talks to mammilary bodies
mammilary bodies talk to dorsomedial thalamus
dorsomedial thalamus to cortex
Deficiency in what in the dorsomedial thalamus in wernicke-korsakoff’s?
Thiamine deficiency
What is the #1 cause of retardation in the US?
Fetal alcohol syndrome..
No safe EtOH when pregnant
What does fetal alcohol syndrome do cellularly?
GABA and GLU systems involved in apoptosis
Apoptosis enhanced by EtOH exposure
Why is apoptosis caused with ethanol?
more ethanol = more Ca2+ in the cell due to more NMDA
High concentrations of Ca2+ causes apoptosis
What does disulfuram do?
Blocks breakdown of acetaldehyde
Leads to flushing reaction / hangover
Where does EtOH enter the fluid of to cause bedspins?
endolymph, changes its density
Where does EtOH not enter the fluid of to cause bedspins?
perilymph (gel-like)
difference in density causes the bedspins
What happens to AMPA and NMDA receptors with repeated use?
upregulation of both receptor types
