Pharmacology: Opoid Analgesics Flashcards
What is intractable pain?
Pain that doesnt respond to any analgesics, patients good candidates for pain management courses.
What are the general actions of opoids?
Centrally - feelings of euphoria, dissociation of the pain
Peripherally - blocks pain sensation at the level of the spinal cord.
What is the gate theory of pain?
The pain signal goes through the substantia gelatinosa in the spinal cord, and in this region can be modified.
The neurotransmitter is substance P - opoids inhibit release of substance P from nerve terminals.
Inhibitory descending pathways from higher centres in the brain can reduce the pain.
Outline the pain pathway
The pain is picked up by nocioceptors (nerve sensitive to pain)
The signal is transmitted either by type A (myelinated) or type B (nonmyelinated) to the dorsal root of spinal cord.
- if gate is open signal is sent to the thalamus and primary sensory cortex
- interneurones use GABA to close the gate to stop the pain signal (mechanoreceptors can also close the gate)
What are the 3 classes of opioids?
- Enkephalins (cleaved from proenkephalin)
- Endorphins (cleaved from POMC)
- Dynorphins (cleaved from prodynorphin)
All peptide molecules
What are the 3 types of opioid receptors?
Where is each type found and what is the function?
Mu: found supraspinally eg in the brain, very important analgesic effects
Delta: widely distributed eg brain, spinal cord, neuromuscular junction, enkephalins have their effects on delta receptors
Kappa: found in spinal cord, analgesic effects
What is the mechanism of action of opioid receptors?
They are all GPCRs
- K+ efflux, moves RMP more negative and further from threshold so decreases excitability.
- Decreased Ca2+ influx, stops processes inside cell so inhibitory effect eg vesicles of substance P dont migrate t membrane.
- Decreased cAMP synthesis - inhibitory action inside the cell.
What are the adverse drug reactions of opioids?
Most side effects are via the Mu receptor which is the most important.
- stimulates vomiting centre in brain so nausea and vomiting
- inhibits nerve plexus in gut so constipation
- sedatives so drowsiness
- miosis (pin-point pupils - sign of abuse)
- build up dependence esp if IV
- respiratory depression, needs monitoring
- relax smooth muscle so can cause hypotension
- kappa receptor can cause dysphoria
How are the actions of opioids such as morphine reversed?
Morphine is an opioid receptor agonist, however if there has been an OD or respiratory depression an antagonist such as naloxone can be given to reverse the effects.
What is the half life of morphine? Why is it not usually given orally?
T1/2 of ~4 hours.
Morphine isnt very lipid soluble so has an oral availability of 25% so much more effective if given IV.
What about the pharmacokinetics of methadone makes it a good drug for treating opioid dependence?
Has a long half life of 24hrs so is long acting
Has an oral availability of 90% so given orally, aim is to try to stop injecting.
What method is commonly used to screen for opioid abuse?
Measure the metabolites of morphine in the urine
What are some clinical uses of opioids?
- analgesics: relief of moderate-severe pain, particularly of visceral origin, not as good for sharp stabbing type pain
- morphine commonly given in palliative care, kaolin and morphine (morphine and clay) used to stop diarrhoea
- diamorphine used in terminal illness
- diamorphine can be used in epidurals but not licensed
- methadone to treat opioid dependence
- tramadol for analgesia, also inhibits reuptake of 5HT and NA so anti-depressant effects
- tapentadol is a specific Mu agonist, also inhibits reuptake of NA
- fentanyl (really potent) used in anaesthetics
- pethidine used IM for labour analgesia
How is codeine metabolised?
Via CYP - some people (esp chinese) lack this enzyme so respond less to codeine
Converted to morphine which is the active compound
