opioids - pharmacology Flashcards
where do opioids act
on opioid receptors (gpcrs)
endogenous opioid molecules released from vesicles from interneuron terminal
what happens in the neuron once the opioid receptor has bound (comment on the changes to the cell not changes to the receptor)
activate GPCRs>open K+ channels>membrane hyperpolarisation>inhibition of ACh = analgesia
effect of opioids in the gut
inhibition of parasympathetic contraction
(ileal smooth muscle)
which receptor do opioids interact with to produce analgesic effect? mu, delta, kappa or nociceptin
mu
mu receptors in periphery, spinal cord and brain
what happens to the g protein coupled receptor once it has been bound to
conformational change of receptor
exchange of GDP to GTP in receptor
G protein dissociates
alpha subunit inhibits adenylyl cyclase which is responsible for the conversion on ATP > CAMP = dec in cAMP levels
beta subunit stimulates an efflux of K+ and influx of Ca2+ which causes hyperpolarisation of membrane = inhibition of NT release
What happens when M3 receptors are activated
Once activated by ACh Gq proteins are activated, calcium is released and we get a ISM contraction
What is the effect of opioids in the gut
Inhibition of parasympathetic contraction
Release if endogenous opioid peptides = inhibition of parasympathetic contraction if ideal muscle
Where do opioid receptors derive from
Cleavage of larger proteins
What happens when adenylyl cyclase is activated
ATP —> cAMP
What is the role of the beta-gamma subunit of the G protein dissociates (effect on K+ and Ca2+ channels)
Stimulation of K+ channel = efflux of K+
Blocks Ca2+ VG channel
= hyperpolarisation
= inhibition of NT release
What happens when MOP receptors are activated
- inhibit adenylyl cyclase = red.cAMP
- GIRK channels open, hyperpolarosation neuronal membrane
- close VGVV = red ca2+ influx = inhibition of NT release
How do opioids produce their analgesic effect
Inhibit nociception
What are some side effects of opioids and why
Constipation and slow drug absorption - due to inhibition of GI motility
Histimine release from mast cells - opioid induced itch
