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40 Cards in this Set
- Front
- Back
- 3rd side (hint)
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What is the physical reward pathway?
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VTA --> nucleus accumben + prefrontal cortex
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What type of neurons are the key players in the reward pathway?
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dopaminergic neurons
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What do abused substances have in common?
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Increase the release of DA from the nucleus accumbens
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What is the basal release?
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% of compound which is released normally (when no drug present) this is 100%
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What did the mouse model prove about the D2 receptor?
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It is involved in the reward pathway but not with withdrawal symptoms
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Main cause of receptor down regulation?
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Increase stimulation of the receptor so receptor internalisation occurs/decrease in receptor expression may also lead to desensitisation
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Main cause of receptor up regulation?
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Under stimulation (eg due to antagonism) may also lead to sensitisation
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What does receptor desensitisation refer to?
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Uncoupling of 2nd messenger
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When heroin passes the BBB what is it converted to?
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Morphine
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MOA of morphine in reward pathway?
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Binds to MOP and inhibits release of GABA (by decreasing Ca influx) thus reducing inhibitory effects of GABA --> rush of DA release
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Describe cocaine MOA
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- Binds to DAT
- Prevents the degradation of DA by MAO |
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Why does combining heroin and morphine result in intense dopamine activation?
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They act on different pathways
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What is substitution therapy and give example
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Where the abused substance is replaced by a less harmful compound eg. methadone (subtitutes morpine binds to MOP but no euphoria)
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What is the active agent in tobacco?
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Nicotine
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Does nicotine stimulate the reward pathway?
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Yes (via nAchRs in the brain)
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In low doses nicotine has what kind of effects?
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Stimulatory
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In high doses nicotine has what kind of effects?
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relaxing
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Nictotine replacement strategy is as effective as...
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placebo (25% success)
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Name a nicotine replacement drug
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Buproprion
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What are 2 treatment methods of treating a nicotine addict?
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- Nicotine replacement therapy (path, gum etc)
- Buproprion |
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How does buproprion take effect?
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Weakly blocks DATs in the nucleu saccumbens
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What is the first priority after someone has OD on drugs?
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Pulmonary and cardiovascualr support
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What are the difference of withdrawing from long and short acting drugs?
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- Long acting drugs take longer to withdraw from but less withdrawal symptoms
- Short acting drugs are faster to withdraw from but stronger symptoms |
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What is precipitated withdrawal?
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Patient is given an antagonist to the drug, very fast withdrawal BUT severe symptoms and high chance of relapse
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What are some effects of withdrawal?
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anxiety, dysphoria, irratibilty. tachycardia, restlessness
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What enzyme does morphine inhibit?
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Adenylyl cyclase
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How does the brain readjust to the fact that morphine inhibits adenylyl cyclase?
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Increases adenyly cyclase expression so that enough cAMP can be produced
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What happens to adenylyl cyclase production after addict comes off morphine?
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[Adenylyl cyclase] and [cAMP] very high so expression of adenylyl cyclase is reduced
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Once withdrawal is successfully completed what is next?
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Behavioural therapy
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Describe the metabolism of alcohol
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Alcohol --> acetaldehyde (by Alcohol dehydrogenase and NAD+) --> Acetic acid (by aldehyde dehydrogenase)
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What is aversion therapy?
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When taking drug gives bad feelings... dont like dont do!
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Example of aversion therapy with ethanol
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disulfiram - inhibits metabolism of alocohol leads to tachcardia, flushing, hyperventilation
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What enzyme is often missing in asians?
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aldehyde dehydrogenase
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Methanol is metabolised to what? An d if consumed what can this cause?
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Formate - blindness
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reversed by giving ethanol (high affinity to the enzymes)
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What is the overall effect of ethanol on the CNS?
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CNS depression
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List the effects of ethanol on CNS
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- Enhances GABA inhibition
- Inhibition of NMDA, kainate receptors - Inhibition of opening of Ca channels - Increase of DA release in n. accumbens |
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Alcohol tolerance does what to GABAa and Ca channel and glutamate receptors receptor density?
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Decreases GABAa, increase the others
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What group does caffeine, theophylline adn theobromine come from?
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xanthides
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What are xanthides?
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CNS stimulants
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Caffeine is an antagonist of what at A2a receptor?
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Adenosine
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