Drugs of Abuse Flashcards
what pathway do all drugs of abuse affect? what are its components?
- mesolimbic pathway
- ventral tegmental area + nucleus accumbens
how do opioids work?
- inhibit the inhibitor
- GABA interneurons normally inhibit neurons going to the NA; opioids inhibit this inhibition = increased DA release to neurons in the end
deaths related to opioids are a result of …
respiratory depression/arrest
do benzos or barbiturates have a narrower therapeutic window? which has worse withdrawal symptoms?
- barbiturates = narrower therapeutic window
- barbiturates also have worse withdrawal
where do barbiturates and benzos act? what’s the difference b/w the 2 drug classes/
- barbiturates have more widespread effects and less specificity; they act on both GABA A & GABA B
- benzos only work on GABA A
alcohol is the liquid version of ???
what receptors does alcohol work on?
- benzos
- GABA A, NMDA glutamate, & cannabinoid receptors
tx for alcohol withdrawal?
benzos
what things combined explain the high addiction potential of cigarettes?
strong direct mesolimbic effects + inhalation route + nicotine’s short half-life
how does cocaine & amphetamine work?
- block reuptake of NTs = DA, norepi, & 5HT
- specific targets = locus ceruleus (pons) and nucleus accumbens
5 approaches to addiction therapy
- administer agent that causes AE if drug abused again
- block effect of drug of abuse
- use long-acting agonists for med maintenance
- use meds to prevent long-term dysphoria & dysfunctional reward mechanisms
- tx co-occurring psych symptoms
what do you tx w/ disulfiram? how does it work? aversive symptoms when drug abused again?
- tx alcoholism
- inhibits aldehyde dehydrogenase
- AS = facial flushing, headache, N/V, weakness, orthostatic hypotension, resp. difficulty
what does naltrexone tx? how does it work?
- tx for opioid abuse
- opioid antagonist = competitively blocks binding of opioids
- can also be used for alcohol abuse b/c EtOH causes release of endogenous opioids
why is naltrexone more prone to non-adherence?
- prevents the “high” from opioids but DOES NOT prevent the cravings or withdrawal symptoms
what does methadone tx? how does it work?
- tx for heroine addiction
- long-acting opioid agonist
risks associated w/ methadone?
- cross-tolerance to other opioids = very dangerous when combined w/ multiple opioids
- high risk of abuse and overdose when combined w/ another opioid or CNS depressant
nicotine replacement: what forms, how it works
- gum, lozenge, transdermal patch, inhaler
- curbs cravings & w/drawal
- all forms more effective than placebo w/ added benefit = avoiding toxicity assoc w/ tobacco
buprenorphine: what receptors does it act on
- mu-opioid receptor PARTIAL agonist
benefits to buprenorphine
- not a full agonist & long half-life = low risk of overdose
- only mild w/drawal upon cessation
- antagonizes full agonist & subsequent reinforcing effect responsible for relapse
suboxone components?
- combo of buprenorphine & naloxone (Narcan)
why can’t you inject suboxone?
- the antagonist (naloxone) will antagonize everything including the partial agonist (buprenorphine) if you inject it = pt will feel awful
- when you take it orally as directed the antagonist is destroyed by first pass so the partial agonist can still work
varenicline
- nicotinic receptor partial agonist = outcompetes nicotine
- s/e = neuropsych symptoms (emotional lability, acute psychosis) = FDA warning for use in pts w/ psych disorders
acamprosate
- modulates glutamate hyperactivity
- tx for alcohol dependence
- only NALTREXONE has been proven significantly better than placebo
topiramate
- anti-epileptic drug = inhibits AMPA glutamate receptors
- being studied as tx for alcoholism but NOT YET approved
bupropion
- anti-depressant = inhibits reuptake of DA and norepi
- can help in smoking cessation
- buffers nicotine w/drawal induced cravings
- s/e = lowers seizure threshold = don’t use for pts w/ seizure disorders
anti-depressants in clinical trials for …
- not many tx options for cocaine & amphetamine abuse –> NONE approved by FDA
- both desipramine & fluoxetine have been shown to reduce cravings BUT NOT prevent use
