What are the 3 major groups of endogenous opioids?
Enkephalins, endorphins, dynorphins
What are the 3 classes of opioid receptor? Where are they found? Which receptor causes the majority of therapeutic effects?
MOP (Mu) - spuraspinally. Causes majority of effects.
KOP (Kappa) - spinally.
DOP (delta) - widely distributed
How do opioid receptors exert their effects?
GPCRs that increase outward flux of K, decrease influx of Ca by inhibiting ion channels, reduce cAMP synthesis that indirectly reduces influx of calcium.
All results in reduction of calcium conc which results in decreaesd release of neurotransmitter at synapse.
Name the opioids that can be considered agonists
morphine, codein, methadone
Name the opioids that can be considered partial agonists
Name the opioids that can be considered agonist/antagonist
nalbuphine - antagonist at MOP, partial agonist at KOP, and agonist at DOP.
Name the opioids that can be considered antagonist
naloxone. Used to treat OD.
Why is diamorphine much more effective than morphine?
Diamorphine is lipid soluble and therefore crosses BBB before breaking down. Also diffuses through tissues locally much more quickly.
Morphine is hydrophilic
What is the bioavailability, protein bound percentage, and half life of methadone?
Bio - 90%
Protein bound - 90%
half life - 15-30 hrs.
What ADRs are associated with opioids?
Resp depression, euphoria, constipation (mu receptors in gut inhibit motility), hypotension, vomiting, coma,
What other things can opioids be used to treat?
diarrhoea, heroin addiction, following an MI (vasodilatory and bronchodilatory effects), antitussive.