Opioid Analgesics Flashcards
Where do opioids exert their effect?
The CNS, but also in the periphery.
What is Gate theory?
Opites act as a gate between dorsal root of spinal cord and the thalamus and primary sensory cortex, to prevent the signal from the sesory receptor being noticed
What endogenous opioids does the body produce?
Enkephalins
Endorphins
Dynorphins
Where do endogenous opioids come from?
Cleaved from precursors - proenkephalin, POMC, and prodynorphin
What opioid receptors are present through the body?
M (mu) receptors
Delta receptors
K (kappa) receptors
What binds to delta receptors?
Enkephalins in the brain, CNS, and at the NMJ.
Where are K receptors found?
The spinal cord
Where are M receptors found?
Supraspinally.
Also in lymphocytes which is why opiates long term have an immunosuppressive effect.
What kind of receptors are opioid receptors?
GPCRs
What is the general effect that activating a opioid receptor has?
Increased efflux of K+ causing decreased excitability
Also decreased Ca2+ influx and cAMP synthesis
What effect does decreasing Ca2+ influx have?
Decreased release of neurotransmitter into the synaptic cleft
Which receptor are most opiate ADRs associated with?
M receptors
What ADRs are associated with M receptors?
N&V Constipation Drowsiness Miosis Dependance Tolerance
What ADRs are generally associated with all opioid receptors?
Respiratory depression
Hypotension
What ADRs are associated with K receptors?
Dysphoria (esp. with pentazocine)
How do opiate drugs work?
All fairly differently to each other
How does morphine work?
As a receptor agonist
How does bupranorphine work?
As a partial agonist
How does nalbuphine work?
As an agonist at some receptors, and an antagonist at others
How does naloxone work?
As an antagonist - used to reverse respiratory depression.
Tell me about morphines pharmacokinetics?
T1/2 ~ 4.5 hours
Oral bioavailability 25% so more effective if given IV.
What is the half life of diamorphine?
0.08 hours = about 5 minutes
What is methadone used for?
Maintenance in opiate dependancy
Tell me about the pharmacokinetics of methadone?
T1/2 = 1.9-3.9 hours
90% oral bioavailability if given as a syrup.
What is the t1/2 of bupranorphine?
2-4 hours
Tell me about codeine.
T1/2 = 2-4 hours.
90% oral bioavailability.
What is the gold standard opiate?
Morphine!
How is morphine metabolised?
Phase 2 glucuronidation in th liver to its also active metabolite which prolongs the effective t1/2.
How are the metabolites of morphine excreted? Why is this important?
Via urine. A urine screen can be used to look for morphine use.
Compare the structure of morphine and diamorphine.
Morphine is tricyclic with 2 polar groups, so is water soluble.
Diamorphine has 2 acetyl groups so is much more lipid soluble.
What is good about diamorphine?
It crosses the BBB rapidly and effectively, so gives you a big ol hit of morphine straight to the brain.
What is diamorphine metabolised to?
Morphine!
What do we use opiates for generally?
Analgesia for moderate to severe pain
What are opiates bette for, visceral pain or sharp stabby pains?
stabby stabby 🔪
Visceral pain
Did i catch you out with that lil ol knife?
🔪 stabby stabby
What kind of pain setting is morphine used in often?
Terminal illness and palliative care
When is tramadol used?
Analgesia, with slight antidepressant effect
What kind of analgesic is codeine?
Mild but metabolises to morphine
Why do people respond differently to codeine?
Metabolised to morphine by CYP2D6 which is highly polymorphic.
Which population tends to have a less effective CYP2D6 and therefore respond poorly to codeine?
Chinese populations
What are fentanyl, afentanil, and remifentanil?
Anaesthetics ~100-1000 times more potent than morphine
What is pethidine used for?
IM pain relief if labour
Can you give pethidine over and over?
Noop, because its metabolite can cause convulsions.
What are the agonist-antagonists?
Pentazocine Nalbuphine Butorphanol Buprenorphine Meptazinol
What are the antagonists to opioid receptors?
Naloxone
Naltrexone
What is the medicolegal aspect to opiates?
Some are controlled drugs under the 1971 and 2001 acts.
Which are the main controlled opiates?
Diamorphine Morphine Remifentanil Pethidine Certain preparations of codeine
