APP Module (GTown) - Addiction, Alcoholism, and Drugs of Abuse (Hrs 1 and 2) Flashcards
All drugs of abuse interfere in some way with what?
ventral striatum
What is tolerance?
Decreased response to a repeated dose of substance over time; or the need to increase a dose to obtain a similar effect
What are some withdrawal symptoms of alcohol?
- tremor
- seizure
- DTs
What are the three factors which influence addiction?
- drug
- user (genetics)
- environment
Per statistics, which substance seems to be the “most” addictive?
nicotine
What is the typical human use pattern?
1) initial experimentation or use
2) repeated use
3) compulsive drug-seeking
4) abstinence
What properties does alcohol have?
anxiolytic, hypnotic, and anesthetic properties
How do you make beer?
1) Harvest some hops and barley.
2) Get some brewer’s yeast.
3) Get a container with some water and add the yeast with the barley and hops and then wait.
What is the affinity of ethanol for interactions?
millimolar range
What is the affinity of dopamine for its receptor?
nanomolar range
What do the differing affinities of dopamine and ethanol mean?
Lower affinities mean you mean much less of the substance to produce a response
What might be considered an intoxicating dose of ethanol?
Those above ~15mM (A moderately intoxicating blood alcohol level of 0.08% (80 mg/dl) is equivalent to an ethanol concentration of 17 mM.)
What are some molecular characteristics of ethanol?
amphipathicity and ability to readily cross lipid membranes
What are the main CNS effects of alcohol?
- inhibition of excitatory neurotransmission and enhancement of inhibitory neurotransmission
- DA release modulation
- disinhibition, ataxia, and sedation
- chronic use leads to tolerance, dependence, etc.
How does alcohol mediate its effect on plasma membranes?
Alcohol intercalates itself between lipid molecules in the plasma bilayer and affects both the membrane fluidity as well as protein function
What are the main brain regions affected by alcohol?
- mesolimbic DA system
- amygdala
- striatum
- hippocampus
- cortex/cerebellum
What changes do you see in the brain of a chronic alcohol user?
↓ brain mass
↑ ventricle size
larger gaps between gyri and sulci
What effect does alcohol have on the firing at a NMDA synapse?
Markedly attenuates the inward current usually seen with glutamate dosing
What are the main channels which alcohol affects?
1) NMDA and kainate
2) GABA-A
3) nACh
4) 5-HT3
What are the features of an NMDA receptor?
1) tetramer
2) binds glutamater and glycine as a co-agonist
3) voltage-dependent Mg2+ block
4) NR1 and NR2 subunits
What type of receptors does alcohol seem to affect?
“cys-loop” family which includes nAChRs, 5-HT3, GABA-A
How does alcohol affect GABA-A receptors?
potentiates flux of potassium ions
Where are 5-HT3 receptors primarily expressed?
emetic centers of the brain
What is Zofran?
Ondansetron is an anti-emetic which antagonizes 5-HT3 receptors
Why is Zofran being used for alcohol abuse?
Seems to reduce cravings in early-onset alcoholics
What are the six major receptor effects that alcohol has?
1) decrease in NMDAR activity
2) decrease in kainate receptor activity
3) decrease in voltage-sensitive calcium channels
4) increase in GABA-A activity
5) increase in 5-HT3 activity
6) increase in nAChR activity
What do you see in fMRI images of intoxicated patients while performing a task?
Global depression of brain activity
What are the four current pharmacological treatments for alcohol dependence?
1) disulfiram
2) naltrexone
3) acamprosate
4) long-acting naltrexone
What is disulfiram and how does it work?
Disulfiram blocks the action of acetaldehyde dehydrogenase leading to an accumulation of acetaldehyde in the body which has a lot of unpleasant effects
What is the treatment for acute methanol poisoning and how does it work?
Ethanol. Using ethanol actively competes for the alcohol dehydrogenase enzyme which in turn produces acetaldehyde instead of the far more toxic formaldehyde from methanol
What is naltrexone and how does it work to treat alcohol abuse?
Naltrexone is an opioid receptor antagonist which decreases DA release associated with alcohol expectancy and consumption
What is acamprosate and how does it work to treat alcohol abuse?
Acamprosate has complex effects on the glutamate-NMDA system and is also a GABA agonist. It seems to increase abstinence rates by working in opposition to the effects of alcohol