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
What are some adverse effects of tramadol? (6)
Nausea Constipation Dizziness Autonomic nervous effects: dry mouth, perspiration, sweating Itch/ rash
What are some adverse effect of aspirin?
GI effects- nausea, epigastric pain, ulceration with chronic use
Tinnitus
Rashes, bronchospasm
Reye’s syndrome
What is the main MOA of diclofenac and what other 3 may contribute to its activity?
- non competitive inhibitor of COX 1 and COX 2
- Blocks arachidonic acid release and uptake
- Inhibit lipoxygenase enzymes
- Inhibit substance P
Why does inhibition of COX 2 produce cardio side effects?
COX 2 inhibitors lower PGI2 and hence increase platelet activity (risk of arterial thrombosis)
Decreases the regulation of oxidant stress
PGI usually has cardioprotective effects- if blocked then can lea to risk of thrombosis, MI, PE, stroke
Hepatic toxicity cause by paracetamol can be fatal- which metabolite causes this and who would you treat?
NAPQI
Treatment:
Induce vomiting to give gastric lavage
N-acetylcysteine (increases conjugating of reactive metabolite)
Methionine (increases conjugating of reactive metabolite)
What are 2 examples of inhalation agents used for pain?
Nitrous oxide- widely used in anaesthesia
Methoxyflurane- used in ambulances
How does capsaicin relieve pain?
Applied topically and acts on TRPV1
Causes pain due to release of substance P
But prolong exposure desensitises the nociceptive terminals and elevates pain threshold
List 7 non drug treatments for pain
- Heat
- Ice
- Massage/ exercise/ relaxation techniques
- Cognitive behavioural therapies
- Surgery
- Accupuncture
- TENS
List 5 locations where opioids can relieve pain
- Supraspinal
- Midbrain- PAG
- Brainstem- reticular formation and locus coeruleus
- Spinal- dorsal horn
- Peripheral- inflammatory cells, sensory afferent neurons
Cannabinoids also work in all these areas EXCEPT BRAINSTEM
Which adenosine receptor has anti-nociceptive effects?
A1
