Alcohol Flashcards
What are the basics of alcohol?
2nd most commonly used drug, most abused
2/3 consumed, 10% addicted.
Ethanol from fermnetation by sugars and yeasts (grapes, rice, grains)
Methyl and isopropyl are toxic to ingest
Easily absorbed from GI tract and goes into tissues (brain too)
Behavioral effects on BAC (mg/100ml blood) not amount ingested cause there are different drink [ ].
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What happens at different doses of alcohol?
Biphasic:
Lower doses: disinhibition, eurphoria, relaxation, impaired judgement, increased risk taking
- depresses neural activity, suppresses inhibitory GABAergic interneurons, causes a “stimulant” like effect even tho its a depressor.
Higher doses: slurred speech, impaired motor co-ordination, memory, sedation, black-out.
- suppression of cortical pyramidal neuron activity
Effects of alcohol influenced by environmental factors (alcohol occurs under placebo too!)
how does alcohol diffuse? what effects absorption?
From gastro tract into blood (stomach and intestines-faster in Intestine)
- greater concentration of alcohol, more rapid, larger increase.
- contents of stomach (more food in tummy means less gets to small intestine cause sphincter is closed, since small intest does it faster there will be slower absorption. it also just takes longer to get through the cheeseburger to the stomach walls).
How is alcohol metabolized?
Alcohol dehydrogenase (in liver and gastric fluid)
- more active in men 60%
- 95% metabolized by liver, the rest by lungs
Turns to acetaldehyde (makes you feel bad) then acetic acid by acetaldyhyde dehydrogenase (ALDH)
- polymorphisms exist (asian people)
- Cytochrome P450 also convert alcohol to acetaldehyde
- CYP 2E1: metabolizes ethanol, but also other drugs (Can be interactions that lead to too much competition for enzyme molecules = dangerous)
What happens when asian people drink?
inactive ALDH. buildup of toxic acetaldyhyde (flushing nausea, vomiting, tachycardia, headache, dizziness, etc)
What are the types of alcohol tolerance?
Acute: single exposure. Drug effects greater when levels are INCREASING but even if they are higher, if plateaued you feel sober even if you aren’t
Metabolic: incrase in CP450 liver enzymes (body gets better at metabolizing it, you have less BAL content)
Pharmacodynamic: neurons adapt via compensatory changes
Behavioral: get better at performing tasks while drunk (allows for adjustment and compensation)
What is acute toxicity?
HIgh doses: unconsiousness/death (at 0.45 BAC) because of depression of respiratory centers. but this is hard to get to cause of vomiting at 0.15 and unconciousness at 0.35. but alcoholics can become tolerant to this and teenagers can drink a lot all at once (mickey chug) and cause issues
- alcohol poisining, slow and irregular breathing, cold, clammy, bluish skin
What are the effects chronic toxicity?
- Liver death
- Korsakoff’s syndrome (diet related)
- Enlarged ventricles and thin gyri (glutamate exitotoxicity during withdrawal, too much withdrawal leads to this)
What is karsakoff’s syndrome?
confusion, disorientation, tremors, poor coordination, ataxia
- make up stories why they can’t remember something
- severe anterograde amnesia because of medial thalamus (b1 deficiency)
- related to poor diet
What are types of neurobiological actions alcohol has?
Tiny molecules that can cross BBB
nonspecific: polar heads of membrane lipids, alters compositoin, disturps relationships of proteins.
- can make them leaky, more ions flow in/out, disrupts receptor function
specific: specific sites on specific proteins resulting in specific actions
- ligand gated channels and second messenger symptoms.
Describe alcohol and GABA transmission.
Alcohol acts as positive allosteric modulator on GABA A receptors. (similar to benzodiazapines)
- ionotropic receptors
- works on many subtypes
- on wired and extrasynaptic transmission.
- extrasynaptics are usually only activated at large concentrations, but these are supersensitive to alcohol! (delta, alpha 4, alpha 6 units)
What do GABA -A antagonists
block inhibitory effects of alcohol and reduce its intoxicating effects.
GABA A receptor extrasynaptic receptors: what happens to animals with delta, alpha 4, alpha 6 receptor subunits knockouts?
consume less alcohol. may mediate reinforcing effects
what happens to gaba a receptors if you have repeated alcohol exposure
reduced GABA A receptor mediated inhibition (less Cl- flux than normal)
- pharmacodynapic tolerance and withdrawal symptoms (cortical hyperactivity, convulsions, hallucinations)
what are the acute effects of alcohol on glutamate transmission?
- reduces NMDA receptor effectiveness (which is what alcohol acts on to impair learning and memory) -negative allosteric modulator
- repeated alcohol exposure up-regulates NMDA receptors to deal with reduced activation
- reduce glutamate release
IN WITHDRAWAL
leads to rebound hyperactivity (glutamate release can increase causing seizure)
