Narcotic analgesics:morphine Flashcards
what are examples of morphine like alkaloids|
morphine
diamorphine= acetylated morphine
codeine- much less efficacious compared to morphine but it is less addictive
what are examples of synthetic/semi-synthetic derivatives ?
phenylpiperidines = pethidine and fentanyl methadones= methadone benzomorphans= pentazocine and cyclazocine thebaines= etorphine and buprenorphine
what is hydrocodone ?
it is a popular analgesic in the US
quite addictive
it is mixed with ibuprofen or aspirin to make it less addictive but these can irritate the stomach
what is tramadol ?
it is a synthetic opiate
opioid/SSRI
marketed as non-addictive but thats not true
it is less efficacious compared to strong opioids
what are examples of full agonists ?
morphine and heroin (diamorphine)
what are examples of partial agonists and agonist-antagonists ?
cyclazocine and pentazocine
what are examples of antagonists?
naloxone and naltrexone - used clinically to prevent cardiac arrest in overdose
describe heroin
similar actions to morphine
it is more lipid soluble and crosses the BBB faster to give a greater rush
shorter duration of action than morphine
it is one of the most powerful opioids- used medically because it acts rapidly
produces strong euphoric effects
describe pethidine
close to morphiine
tends to cause restlessness instead of sedation
antimuscarinic: dry mouth and blurred vision
less antitussive
shorter duration of action- it is preferred for labour
describe fentanyl
actions similar to morphine
cheap to produce
80-100 times more potent than morphine in analgesia
rapid onset
short duration - 15-30 mins
main use is in anaesthesia, used in conjucion with droperidol a neuroleptic producing neuroleptanalgesia
describe methadone
similar actions to morphine taken orally rather than iv slow acting opioid longer duration of action less withdrawal can be used to wean morphine and heroin addicts off the drug
with opioids what is more important potency or efficacy ?
efficacy
describe codeine and hydrocodone
these are much less potent analgesics than morphine - even if you give maximal dose it will still not cause same euphoric effects of morphine
codeine is mostly used in europe whereas hydrocodone is mostly used in the US
often used in combo with NSAID
antitussive at subanalgesic dose
what is dextromethorphan ?
it often replaces codeine and hydrocodone for its antitussive action
it is a synthetic antitussive
has very little analgesic effects and has a low poential for abuse
describe tramadol
it is a weak agonist at mu receptors but does not act at delta or kappa receptors
it is also a serotonin and noradrenaline reabsorption inhibitor- activity of antidepressant- this explains its emotional component
use is similar to that of codeine– moderate to severe pain
what are the effects of the mixed agonist/antagonist pentazocine ?
agonist= kappa receptor and weak antagonist = mu and delta receptors at low dosees it is similar to morphine higher doses it causes: - respiratory depression - decreases GIT activity - increases BP - dysphoria rather than euphoria - - nightmaers and hallucinations - tolerance and dependence on repeated use
what is naloxone ?
competitive antagonist at mu kappa and delta receptors
10 fold higher affinity for mu compared to kappa
used to reverse coma and respiratory depression caused by overdose of opioids
fast acting- signs in 30 seconds after iv admin
short duration- 60-100mins
it has no effect on normal individuals - therefore it is a true antagonist to opioid agonists
what research tools are used at mu receptors ?
agonists- synthetic opioid like peptides
- DAMGO
- DAG
what research tools are used at delta receptors?
agonists
- DPDPE
- DADLE
- DSLET
what research tools are used at kappa receptors ?
agonist- synthetic opiate
- U50488H
what antagonist research tools can be used at opioid receptors ?
mu - CTOP
delta- naltrindole
kappa- nor-binaltorphimine
what is the association betwen substance P and morphine ?
at high intensity stimulation lots of substance P is released from A delta and c fibres, however once morphine is applied the substance P release is inhibited however once nalxone is applied the release of substance P occurs agains
what are the 2 forms of dependence ?
physical and psychological
what are the physical problems associated with dependence ?
withdrawal irritability weight loss shakes sweating piloerection "cold turkey" effects wear off in 8-10 days
what are the psychological problems associated with dependence ?
desire for the drug
want to experience the “RUSH”
dont want the withdrawal
some opioids such as codeine and pentazocine are much less likely to cause dependence
what effect is caused by taking morphine actuely and what mechanism underlies this ?
reward
activation of mesolimbic dopamine pathway
what effects are caused by taking morphine chronically and what mechanism underlies this ?
tolerance and dependence
adaptive changes in receptor, transporters and 2nd messengers
what effects are caused by acutely withdrawing morphine and what is the mechanism of action?
withdrawal syndrome
uncompensated adaptive changes - decrease in dopmaine and increase in glutamate
what are the effects caused by chronically withdrawing morphine ?
craving
why are addicts give methodone to help to treat their heroin addiction ?
methadone is metabolised and acts much more slowly and therefore it maintains the patient in the therapeutic range for longer whereas heroin is rapdily and fast acting so its therapeutic effects are not long lasting
- the addict is given 1 tablet of methadone a day to keep them in the stable range
what are the 2 groups that opioids can be divided into ?
morphine analogues- structure similar to morphine
synthetics- structure unrelated to morphine
both have multiple aromatic rings
