Drug Withdrawal Flashcards
What is the action of disulfiram?
Blocks aldehyde dehydrogenase, preventing acetaldehyde breakdown and increasing the physiological effects of alcohol (feel sicker when you drink BUT doesn’t reduce cravings)
What are the 3 ways alcohol decreases thiamine levels?
- Decreased in diet due to poor nutrition
- Decreases thiamine phosphorylation in the brain
- Decreases absorption from GIT
What macroscopic changes do we see in the brain in alcoholism?
Thinning of cortical gyri (reduction in white matter + some grey matter), enlargement of ventricles
What is the mechanism for brain matter shrinkage in alcoholism and binge drinking?
NOT glutamate excitotoxicity! Ethanol intoxication activates pro-inflammatory enzymes and causes oxidative stress. Also CREB family transcription factors are reduced and these usually promote neuronal survival by preventing apoptosis. In addition high alcohol levels prevent neurogenesis.
Short-term alcohol effect on NTs?
Enhances GABA function (by increasing Cl flux, facilitating GABAa receptors and inhibiting NMDA glutamate receptors)
In the VTA inhibits GABA interneurons to disinhibit dopamine neurons.
GABA ions channels and alcohol (channel, main ions, effect of alcohol)
GABA has GABAa channels
Cl is the main ion
Alcohol enhances action
Glutamate ion channels and alcohol
NMDA channels Ca and Na are the main ions Alcohol inhibits Non-NMDA channels do Ca and Na also Alcohol inhibits
Which areas of the brain do drugs affect?
Ventral striatum, specifically the dopamine networks therein.
We think dopamine is possibly more important in the pursuit of what we have learned to be a pleasurable sensation rather than the experience of the sensation itself.
Effect and mechanism of cocaine and amphetamines
Both increase monoamine effect.
Cocaine: inhibits reuptake by blocking dopamine transporters.
Amphetamines: cause release by displacing monoamines in the pre-synaptic terminal.
How does alcohol increase dopamine release?
Usually we have an inhibitory GABA interneuron, alcohol releases inhibitory endorphins (beta-endorphins) to inhibit GABA release, removing inhibitory tone from dopamine cells and triggering its release.
What is the mechanism of action of naltrexone?
Blocks alcohol’s inhibition of GABA interneurons so inhibitory tone is maintained. Acts as a mu opioid antagonist.
Why are alcohol and some inhalant drugs considered “messy drugs”?
They have multiple targets including GABA and glutamate receptors rather than a single effect
What factors cause relapse from a drug withdrawal?
Stress, withdrawal effects (physiological), anxiety and depression, stimulus response habits.
Which part of the brain is involved in setting negative habits such as drug addiction?
Dorsal striatum
What are the mechanisms of tolerance (innate and acquired)
Innate: genetic factors
Acquired: pharmacokinetic (eg. too much drinking, changes absorption and metabolism), pharmacodynamic (receptor desensitisation), learned tolerance (behavioural and conditioning)
