Mechanisms of Analgesia Flashcards
These drugs modify transmission of nociceptive signals in the dorsal horn of the signal cord
Opioids
Anti-depressant drugs
These drugs activate descending inhibitory controls
Opioids
NSAIDS
Aspirin Diclofenac Ibuprofen Indomethacin Naproxen
Weak opiods
Codeine
Tramadol
Dextropropoxyphene
Strong opiod
Morphine
Hydromorphane
Fentanyl
Heroin
What does the nucleus raphne magnus release?
Serotonin (5-HT)
Enkephalins
What does the locus coruleus produce?
NA (noradrenergic neurones)
What stimulates the PAG (periaqueductal grey)
Electrical stimulation
Opiods
(Excitation by electrical stimulation produces PROFOUND analgesia)
Opiod drugs mimic the activity of what?
Enkaphalinergic interneurones
Which type of drug mimics the activity of enkaphalinergic interneurones?
Opioids
Opiod action is mediated by which type of receptor?
G protein coupled receptor
(couple to Gi/o to produce:
- inhibition of opening of voltage activated Ca2+ channels
- opening of K+ channels
Side effect of m opiod receptors
Respiratory depression Constipation Euphoria Sedation Dependence
Side effect of delta opiod receptors
Proconvulsant
These opiod receptors contribute to analgesia at the spinal and peripheral level
K opiod receptors
Side effect of k opiod receptors
Sedation
Dysphoria
Hallucinations
Activation of these receptors produces an anti-opiod effect
ORL-1 receptors
These opiod receptors are responsible for most of the analgesic action of opiods
m receptors
What inhibits COX-2?
Non-selective NSAIDs and COXIBs
What does PGE2 do?
Sensitises nociceptive neurones and causes hyperalgesia
Why is paracetemol not classes as an NSAID?
Lacks anti-inflammatory activity and only WEAKLY inhibits COX
What is acetaminophen?
Paracetemol
Why might paracetemol cause nephrotoxicity?
Because of inhibition of COX-2 which is constitutively expressed by the kidney and because of compromisation of renal haemodynamics)
Which COX-2 inhibitors are prothrombotic?
Rofecoxib, celecoxib (this limits their use)
COX-1 produced what which helps protect against the acid environment?
PGE2
Why do NSAIDS have limited analgesic effect?
NSAIDs have limited analgesic efficacy because multiple signalling pathways, several of which do not involve arachidonic acid metabolism, cause nociceptor sensitization
