2. Ch 10 Alcohol Flashcards
3 types of alc
methyl alcohol - used in labs, toxic
ethyl alcohol - drinks, drunk
isopropyl alcohol - rubbing alcohol
Alc absorption
readily crosses BBB
even on empty stomach, absoroption takes at least 20 mins
continues for 3-4 hrs (0 order kinetics)
90% absoroption from small intestine
cabronated absorp faster
1st-pass metab. by ADH in stomach (greater in males so higher BAC in women)
Alchohol Metabolism
Alcohol -> Acetaldehyde (by ADH, toxic) -> Acetic Acid (by ALDH) -> CO2
ADH/ALDH liver enzymes but not CYP family, ADH in stomach too
Asians don’t have ALDH (higher toxic acetaldehyde causes flushing/nausea)
two other enzymes in alc metab.
MEOS - CYP2E1, only active after large amts alc, can be induced (higher enzyme after repeat alc), metab’s other drugs too
Catalase - metab’s small % alc in body
4 types tolerance with alc.
Acute tolerance - occurs with single exposure. drug effects greater when BAC rising, smaller when falling
Metabolic - increases in CYP450 enzymes
Pharmacodynamic - neurons adapt/compensatory changes with receptors
Behavioral - adjust beh’r to adapt from drug effects
Withdrawl from alc and dependence
2-4 days
symptoms - tremor, anxiety, rapid BPM
Delirium Tremens - rare, convulsions/hallucination/disorient
motivates with neg. reinforcement to do drug again
Alc has cross-dependence with similar sedatives (Barbs/BDZs). eliminate withdrawal symptoms by taking those drugs too
Thiamine Deficiency and Wernicke Korsakoff
heavy alc use causes thiamine deficiency = no glucose metablism = cell death
ethanol interferes with thiamine uptake in GI too (animals with no thiamine have brain lesion/learning memory deficits
Wernicke - confusion/disorient/amneisa in late (cell loss in mammillary bodies and thalamus). can stop degen with thiamine treatment but can’t reverse (thiamine deficiency = neurodegen)
Brain damage from alc
ventricle enlargement
frontal lobe loss - personality
hippocampal/MTL loss - memory dysfunction
cerebellar loss - ataxia
Systemic effects of alc
dilation of periphery blood vessels (flushing/warmth, vasodilation might help cog)
Cirrhosis
death of liver/scarring, blood cut off
takes a while to develop
damage caused by too much actyladlehyde
Fetal Alc Syndrome
low IQ/birthweight
neurological problems
craniofacial malformations
physical abnormalities - cardiac/kidney/skeletal
Glutamate and Alc
acutely - NMDA/AMPA antagonist. mGluR autoreceptor agonist in hippo (less glut in hippo) = impair LTP = blackout
chronically - upregulate NMDA receptors bc less glut, NMDAR # higher in alcoholics, rebound increase in glut release during withdrawal = rebound hyperexcitability/seizures during withdrawal
GABA and alc
acute - binds GABAa receptors and opens channel = Cl- enterss to hyperpol. Delta subunit is sensitive to alc, Delta KO = reduce preference to alc
Chronic - reduces GABAa-mediated l-flux, more sensitive to seizures from GABA antags -> decrease in GABA function, not receptor #
Dopamine and alc acutely
acute - increased DA in mesolimbic, self admin to VTA. DA antag in NAcc and destruction of DA nerves reduces self admin (but not abolish) = DA independent mechs of reinforcement
Dopamine and alc chronically
Chronic - withdrawal of alc reduces firing rate of mesolimbic and decreases DA release in NAcc (higher withdrawl beh’r when low DA)
Rebound depression - neg. reinforcement, elevated threshold of ICSS, reinforcement is less rewarding in withdrawl bc reward system damaged
Endogenous Opioids (endorphin) and alc effects
Acute - increases endogenous opioid production and release
Chronic - reduces endorphin production
Opioids and alc network
release of DA regulated by opioids in VTA
Endorphins inhibit GABA in VTA which inhibit Mesolimbic to release DA in NAcc (so inhibit the inihibitor = more DA)
alc induced opioid release = reinforcement bc DA
Opioids and alc reinforcement
opioid receptor antags (naloxone/naltrexone) reduce alc self admin
mu-opioid receptor KO = fail to self admin alc
Rats that prefer alc (gene edit them) have more mu-opioid receptors in NAcc/amygdala, more responsive to alc
Alcohol use disorder and MAT
chronic relapsing disease, compulsive alc use, neg. emotions when not using
biopsychosocial factors
less than 10% get treatment
Medication-assisted treatment (pharmacotherapeutic, make drinking unpleasant/reduce alc’s reinforcement/reduce withdrawal
Disulfiram
inhibits ALDH = more acetaldehyde so more nausea/flushing/heart pound
make drinking unpleasant but doesnt help with craving
Naltrexone
mu-opioid receptor antagonist
reduces high of alc, no reward effects less reinforcing
Good for absitence
helps with craving
Acamprosate
partial antagonist of NMDA receptor
blocks Glutamate release during withdrawal (restore GABA levels, restore inhibition)
reduces hyperexcitability associated with alc withdrawal
only helps with rebound excitation
Future therapy and carcinogen
Psilocybin - reduces heavy drinking days
Senaglutide (GLP-1 agonists, ozempic) - suppresses motivating beh’rs/alc use
5% cancer traces to alc (acetaldehyde causes DNA mutations)
ALDH KO mice = 4x as much DNA damage (asians have higher esophagal cancer)
