Pain Flashcards
Describe the different medications you would prescribe on this pain ladder.
Label this processes in this pain pathway
Describe the pain pathway in more detail
- starts w/ transduction of pain (stimulus)
- nociceptor nerve ending recognise painful stimuli and those nerve project into the spinal cord (A-delta, C fibres)
- within spinal cord, these nerve endings synapse w/ spinothalamic neurones
- they receive information and run that up to the thalamus
- thalamus is like a gatekeeper -> receives and distributes information
- cerebral cortex receives information and processes it (memory etc.)
- decided how to proceed
- stimulated descending inhibitory pathways
- brain decides how much it wants to suppress the painful stimuli
- they go down into spinal cord and as they enter the spinal cord, that can interfere with the transmission of the signal from the spinal cord to the spinothalamic neurones.
How do NSAIDs and paracetamol act as painkillers?
- NSAIDs inhibits COX and prevent arachadonic acid -> PG
- paracetamol inhibits peroxidase enzyme instead (also has some effect on cannabinoid system. anandamide is an endogenous cannabis. the systems are linked)
Why are NSAIDs anti-inflammatory as well as pain-killing?
because prostaglandins have an inflammatory element too
Why is paracetamol not anti-inflammatory as NSAIDs are?
peroxides are massively increased in inflammation
if there are loads of peroxides present, as there is in inflammation, the peroxides will compete with the paracetamol
Explain what effect morphine has at a cellular level using the diagram provided.
opioid binds to G-coupled protein receptor
- down regulates production of cAMP (reducing cell activity in general)
- stimulates K+ leaving cell, hyperpolarising it
- inhibits Ca2+ influx, preventing exocytosis of neurotransmitter
opioid effects on a cellular level are depressant…they slow everything down
opioids act at multiple points of the pain pathway
At what points do opioids work on the pain pathway?
In order for opioids (or any drugs) to produce effects within the brain, it needs to be able to access the brain tissue. The major route for drug permeation into the brain is via passive diffusion. Lipid solubility is the major determinant of passive diffusion.
Once inside the brain, opioids need to bind to opioid receptors in order to produce any effect. In this case, it is the chemical structure of the drug that determines the ability to bind to the receptor.
Discuss the ability of each of these opioids to produce opioid like effects in the brain.
the 3 opiods that can bind the receptor
- morphine
- 6-acetyl morphine
- morphine 6-glucuronide
6-acetyl morphine
(has the correct structure and has optimal oil-water partition coefficient)
all of the morphine metabolites have some kind of effect
heroine most lipid soluble and morphine not so lipid soluble
codeine and heroine are lacking the hydroxyl group
- they are converted in the body
Codeine is primarily a pro-drug for morphine.
Codeine can be metabolized to both norcodeine (inactive metabolite) AND morphine (active metabolite).
In the liver, cytochrome P450 enzymes are responsible for this metabolism.
- CYP3A4 is responsible for ‘fast’ metabolism of codeine to norcodeine
- CYP2A6 is responsible for ‘slow’ metabolism of codeine to morphine.
What do you think is the significance of this?
large proportion of codeine gets converted into norcodeine and 10-15% gets converted to morphine (which has the analgesic effects)
this is clinically important because the 2A6 enzyme has a lot of polymorphisms. your big worry is if you have several copies of the functional form. If someone is an ultra-fast metaboliser, they can overdose on codeine because of that genetic polymorphism,
What are some classical signs of opioid overdose?
pinpoint pupils
respiratory depression
Describe the affinity and efficacy of agonists and antagonists.
- agonists: affinity and efficacy
- antagonists: affinity, no efficacy
What drug can be used to treat opioid overdose and why?
Naloxone
it is an opioid receptor antagonist
In the liver, cytochrome ____ enzymes are responsible for the metabolism of codeine to norcodeine or morphoine.
_____ is responsible for ‘fast’ metabolism of codeine to norcodeine.
_____ is responsible for ‘slow’ metabolism of codeine to morphine.
P450 enzymes
CYP3A4
CYP2A6
In the liver, cytochrome ____ enzymes are responsible for the metabolism of codeine to norcodeine or morphoine.
_____ is responsible for ‘fast’ metabolism of codeine to norcodeine.
_____ is responsible for ‘slow’ metabolism of codeine to morphine.
P450 enzymes
CYP3A4 -> norcodeine
CYP2A6 -> morphine
