opioid pharmacology Flashcards
what are the naturally occurring opioids?
morphine
codeine (weak)
What are the drugs that were made from simple chemical modifications of the naturally occurring opioids?
diamorphine
oxycodone
dihydrocodeine
what are the synthetics opioids?
pethidine
fentanyl
alfentanil
remifentanil
What is a synthetic partial agonist of the opioids?
buprenorhine
Which drug is an antagonist of the opioids?
naloxone
What are the routes of administration of the opioids?
subcut IM IV IV (PCA - pt controlled analgesia) epidural/CSF transdermal patches for fentanyl
What percentage of oral (enteral) morphine is metabolised in first pass metabolism and what does this mean if giving the drug IV/subcut/IM ie via parenteral routes?
50% - half the dose if parenteral route used
How long dose a single dose of morphine last for?
3-4 hours
What are MST CONTINUS tablets and how often are they given?
slow release preparations of morphine given 12 hourly
What is diamorphine?
morphine that has been chemically transformed into diacetylmorphine
How does diamorphine compare to morphine?
more potent and faster acting, as crosses the BBB faster (called heroin) - so more addictive
What class are opioids?
class A
What drug is given to drug addicts?
bupromorphine - partial opioid agonist
Why is it important to titrate the amount of naloxone?
Because if all the morphine is blocked suddenly, the pt may wake up in pain, so give small increases in dose at a time
How fast does IV morphine take to work?
1 minute
How long does it take for subcut morphine to peak?
1 hour
What is the difference between potency and efficacy?
potency - how much do you need to give to get the effect
efficacy - how much of it that you give actually does the effect that you want
How do opioids work?
descending inhibition of pain - inhibit the release of pain transmitters at the spinal cord and midbrain and modulate perception of pain in higher centre giving euphoria and so changing the emotional perception of pain
Which is stronger dihydrocodeine or codeine?
dihydrocodeine is more potent
Which is stronger oxycodone or morphine?
oxycodone
Name some opioid receptors
MOP, kappa (KOP), delta (DOP) and nocioceptin opioid like receptor (NOP) - the drugs we use at the moment are all MOP
What is the current aim for making new opioid drugs?
analgesia without the side effects of resp depression and addiction
What dictates the potency of a drug?
how well the drug binds to the receptor ie affinity
What dictates efficacy?
whether the drug is a full or partial agonist
From most potent to least potent list morphine, pethidine and diamorphine
diamorphine
morphine
pethidine
For a 70kg male what dose would you give of:
diamorphine
morphine
pethidine
diamorphine 5mg
morphine 10mg
pethidine 100mg
Which direction does giving naloxone shift the morphine dose response curve?
to the right - as you have to give more morphine to get the same effect with naloxone
Will you get a maximal response from buprenorphine?
no - as it is a partial agonist of the opioid receptor
What is tolerance?
down regulation of the receptors with prolonged use, so need higher doses to achieve the same effect
What is dependence?
psychological - craving and euphoria, physical
how long does opioid withdrawal last?
72 hours
what are the side effects of opioids?
resp depression sedation nausea and vomiting constipation itching immune suppression endocrine effects
Why do we get side effects with opioids?
as opioid receptors exist outside the pain system - in the digestive tract, resp control centre
why do we need to titrate the dose with opioids?
as different people have a different sensitivity to opioids
What should you do if a pt has opioid induced resp depression?
call for help
ABC
naloxone - IV, titrate to effect
self inflating oxygen bag
What is co-codamol?
mixture of paracetamol and codeine can still get resp depression and addiction
How can we avoid resp depression with opioids?
titrate to effect - 1ml diluted in 10ml saline
What type of pain should opioids mainly be used for?
chronic cancer pain, as there are dangers of addiction and death from using opioids in non-chronic cancer pain
What is the significance of pharmacogenetics in codeine?
codeine is a prodrug - needs to be metabolised by CYP2D6, the activity of this cytochrome is decreased in 10-15% of the Caucasian population and is absent in 10%, so codeine will have a reduced or absent effect in these people
and in 5% CYP2D6 is overactive, so mire at risk of resp depression
How is morphine metabolised?
it is metabolised to morphine 6 glucoronide which is more potent than morphine and is renally excreted
What can happen if a pt with renal failure is given morphine?
morphine will build up and may cause resp depression
What should be done in pts with renal failure?
reduce the dose and increase timing intervals, can be dangerous to use morphine so can use oxycodone instead
What is tramadol?
it is a weak opioid agonist that is stronger than codeine
also a prodrug and requires CYP2D6 to become active
What can tramadol interact with and why?
SSRIs
tricyclic antidepressants
MAOIs
as it is a serotonin and noradrenaline re-uptake inhibitor, so take care when prescribing it to pts on antidepressants
