Narcotic analgesics:morphine

Question 1

what are examples of morphine like alkaloids|

Answer 1

morphine
diamorphine= acetylated morphine
codeine- much less efficacious compared to morphine but it is less addictive

Question 2

what are examples of synthetic/semi-synthetic derivatives ?

Answer 2

phenylpiperidines = pethidine and fentanyl
methadones= methadone 
benzomorphans= pentazocine and cyclazocine 
thebaines= etorphine and buprenorphine

Question 3

what is hydrocodone ?

Answer 3

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

Question 4

what is tramadol ?

Answer 4

it is a synthetic opiate
opioid/SSRI
marketed as non-addictive but thats not true
it is less efficacious compared to strong opioids

Question 5

what are examples of full agonists ?

Answer 5

morphine and heroin (diamorphine)

Question 6

what are examples of partial agonists and agonist-antagonists ?

Answer 6

cyclazocine and pentazocine

Question 7

what are examples of antagonists?

Answer 7

naloxone and naltrexone - used clinically to prevent cardiac arrest in overdose

Question 8

describe heroin

Answer 8

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

Question 9

describe pethidine

Answer 9

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

Question 10

describe fentanyl

Answer 10

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

Question 11

describe methadone

Answer 11

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

Question 12

with opioids what is more important potency or efficacy ?

Answer 12

efficacy

Question 13

describe codeine and hydrocodone

Answer 13

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

Question 14

what is dextromethorphan ?

Answer 14

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

Question 15

describe tramadol

Answer 15

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

Question 16

what are the effects of the mixed agonist/antagonist pentazocine ?

Answer 16

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

Question 17

what is naloxone ?

Answer 17

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

Question 18

what research tools are used at mu receptors ?

Answer 18

agonists- synthetic opioid like peptides

• DAMGO
• DAG

Question 19

what research tools are used at delta receptors?

Answer 19

agonists

• DPDPE
• DADLE
• DSLET

Question 20

what research tools are used at kappa receptors ?

Answer 20

agonist- synthetic opiate

- U50488H

Question 21

what antagonist research tools can be used at opioid receptors ?

Answer 21

mu - CTOP
delta- naltrindole
kappa- nor-binaltorphimine

Question 22

what is the association betwen substance P and morphine ?

Answer 22

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

Question 23

what are the 2 forms of dependence ?

Answer 23

physical and psychological

Question 24

what are the physical problems associated with dependence ?

Answer 24

withdrawal
irritability 
weight loss 
shakes 
sweating 
piloerection "cold turkey"
effects wear off in 8-10 days

Question 25

what are the psychological problems associated with dependence ?

Answer 25

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

Question 26

what effect is caused by taking morphine actuely and what mechanism underlies this ?

Answer 26

reward

activation of mesolimbic dopamine pathway

Question 27

what effects are caused by taking morphine chronically and what mechanism underlies this ?

Answer 27

tolerance and dependence

adaptive changes in receptor, transporters and 2nd messengers

Question 28

what effects are caused by acutely withdrawing morphine and what is the mechanism of action?

Answer 28

withdrawal syndrome

uncompensated adaptive changes - decrease in dopmaine and increase in glutamate

Question 29

what are the effects caused by chronically withdrawing morphine ?

Answer 29

craving

Question 30

why are addicts give methodone to help to treat their heroin addiction ?

Answer 30

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

Question 31

what are the 2 groups that opioids can be divided into ?

Answer 31

morphine analogues- structure similar to morphine

synthetics- structure unrelated to morphine

both have multiple aromatic rings