2.09 Analgesic drugs Flashcards
What class of drugs affects pain at the site of injury by decreasing inflammation?
NSAIDS
What group of drugs block nerve condition?
Local anaesthetics
What 2 groups of drugs modify the transmission of nociceptive signals in the dorsal horn of the spinal cord?
Opioids
antidepressant drugs
What activates or potentiates descending inhibitory controls on pain sensation?
Opioids
Are the following weak or strong opioids? morphine hydromorphone fentanyl heroin
Strong
Are the following weak or strong opioids?
codeine
tramadol
dextropropoxyphene
Weak opioid
What group of drugs do these belong to?
diclofenac
indomethacin
naproxen
NSAID
What are the 3 mechanisms involved in descending tracts and suppression of nociceptive transmission in the dorsal horn?
- Direct presynaptic inhibition of neurotransmitter release
- Direct postsynaptic inhibition
- Indirect inhibition
How does direct presynaptic inhibition of neurotransmitter release on nociceptors work?
There is GPCR activity that suppresses the opening of Voltage activated calcium channels
(calcium is required for exocytosis, so this is dampened)
How does direct postsynaptic inhibition work in nociceptive transmission at the dorsal horn?
There is GPCR mediated K+ channel opening; this hyperpolaises the cell;
more stimulus is required before an action potential is sent
How does indirect inhibition work in nociceptive transmission at the dorsal horne?
Activation of the inhibitory interneurons
-enkephalinergic and GABAergic
suppress transmission of pre and post-synaptic mechanisms.
Which mechanism of dorsal horn nociceptive neurotransmission do opioid drugs mimic?
Indirect inhibition- activation of inhibitory interneurones.
Which 3 sites can opioid receptors be found?
pons/midbrain: periacqueductal grey matter, nucleus raphe magnus
spinal cord
What is the cellular action of opioids?
Opioids bind GPCR coupled opioid receptors.
These are all coupled to Gi or Go.
This causes:
-Inhibition of voltage activated Ca channels (pre-synaptic)
-Opening of K+ channels (post-synaptic)
What are mu opioid receptors responsible for?
analgesic action
se: respiratory depression, constipation, euphoria, sedation, dependence
What are delta opioid receptors responsible for?
contributes to analgesia
se: pro-convulsant
What are kappa opioid receptors resopnsible for?
analgesia at spinal and peripheral level
SE: sedation, dysphoria, hallucinations
What are ORL1 opioid receptors responsible for?
anti-opioid effect
What is the main indication for NSAIDS?
mild to moderate inflammatory pain
What is the mechanism of action for NSAIDS (non-specific)
They inhibit COX1 and 2.
These enzymes act on arachadonic acid to make endoperoxides.
Both PGE2 and PGI2 are reduced.
Which is always active? COX 1 or 2?
COX1 is constituatively active.
COX2 is induced by inflammation.
Benefits of NSAIDS come from inhibiting COX2
What prostaglandin is generated in response to mechanical, thermal or chemical injury?
PGE2
this is made by prostaglandin isomerase
What is the action of PGE2?
PGE2 sensitises nociceptive neurones and causes hyperalgesia.
How does paracetamol work?
weak inhibitor of COX 2 and 3
main action due to metabolites- N-Acetyl-p-benzoquinoneimine
TRPA1 may be a new target of these metabolites
What is a side effect of long term administration of NSAIDS?
gastric ulceration - due to PGE2 inhibition that protects gastric mucosa
Nephrotoxicity- compromised renal haemodynamics
Why is the use of rofecoxib and celecoxib limited?
They are prothrombotic by only inhibiting COX2
