Pain Flashcards
What are the 4 proposed mechanism of action for paracetamol?
Paracetamol usually acts more centrally then peripherally
- COX inhibition but better adverse effect profile than other COX inhibitors
- Paracetamol metabolites activate TRPA1 receptors in the spinal cord- thermoreceptors that have an analgesic effect
- Paracetamol metabolite (AM404) activate enhance the endocannabinoid system- known as pain relievers though CB1 and TRPV1 receptors
- Activation of descending 5-HT pathways
What are 5 main effects of opioids?
- Analgesia
- Sedation
- Respiratory depression
- Cough supression
- Constipation
What are some adverse effects of opioids?
Nausea and vomiting Constipation Dyspepsia Drowsiness Miosis Dependence
Use with caution with patients with epilepsy, biliary colic, respiratory depression, hepatic impairment and in the eldery
MOA of morphine
Metabolite M6G is a strong against at MOR
Also actives MOR in PAG
MOA codeine
Usually found in combination with other analgesics
Prodrug that needs to be metabolised by CYP2D6 into morphine
MOA buprenorphine
MOR partial agonist but very affinity and slowly dissociates hence long duration of action (has an active metabolite as well)
KOR antagonist
MOA fentanyl
Strong MOR agonist (100x more potent than morphine)
High lipid solubility: Transdermal and buccal routes prefered
Long half life and released in a linear manner over 72 hours (reason to why patches are applied every 3 days)
When is the use of fentanyl contraindicated?
For short term analgesic use- cannot titrate small dose
Can cause serotonin syndrome (Increases 5-HT) - causation with MAOIs
What other opioid is hydromorphone similar to?
Morphine- MOR agonist
Beside being a MOR agonist, what other effects does methadone have?
NMDA receptor antagonist - role in the reduction of tolerance
Interacts with K channel in myocardium = prolong QT
Long half life (long acting metabolites)
Does oxycodone have against activity on all 3 opioid receptors?
Yes
Which receptors do pethidine act on?
MOR and KOR agonist
Short onset than morphine
Why is pethidine used in labour?
Analgesic effect without reducing the force of contractions
What are 3 precautions with pethidine?
serotonin syndrome (it can weakly inhibit 5-HT reuptake) Toxic effects- convulsions and excitation Metabolised into norpethidine - hallucinogenic and convulsant effects
MOA of tramadol
- Weak affinity MOR agonist- its metabolite has higher affinity (O-demethyltramadol)
- Inhibits NA and 5-HT reuptake - antidepressant effects since similarity to antidepressant drugs