Opiod Analgesics And Pain Processing Flashcards Preview

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Flashcards in Opiod Analgesics And Pain Processing Deck (13)


Opium extracted from poopy juice contains alkaloids-> morphine etc
Endogenous endorphins and encephalins produce a similar effect and are blocked by naloxane
Can cause resp depression and death


u, d, and k receptors

7 transmembrane spanning receptors coupled to G protiens-> Gi's-> inhibitory effect when activated
Inhibit adenyl cyclase and reduce cAMP
Open K+ channels, close Ca channels-> hyper polarised-> harder to create and action potential


Pre synaptic u receptor

Ligand binds and activates GI-> decreased AC-> decreased cAMP-> decrased activation of protein kinases-> K open Ca closed-> decreased excitability-> decreased neurotransmitter release


Post synaptic u receptor

Ligand binds-> causes K channels to open on post synaptic membrane-> post synoptic membrane hyper polarised



Acts via u receptors
Tolerance-> major issue-> decreased response to same amount of drug-> receptor desensitisation-> receptor becomes uncoupled from its G protein -> can't activate downstream signalling
Constipation which you don't develop tolerance to
Anti tussive


Spinal effects of opiods

Opiods receptors are found on noiciceptors, especially c fibres
-> effect pain but not touch transmission
70% presynaptic


Descending inhibitory control of pain

Spinal cord receives pain transmission from periphery-> travels up to NRPG and thalamus
Cortex, thalamus and hypothalamus activate PAG
PAG, NRPG, locus coerulus activate NRM
NRM and locus coerulus inhibitory on spinal pain detection -> decreased pain messages sent to brain
Normally short acting to escape from pain
u receptor activation at PAG and NRM-> prolong pathway action by increasing output ->pain relief
Morphine binding-> increased out out of PAG-> increased pain messages to NRM-> increased inhibitory transmitters release into spinal cord-> decreased pain transmission to brain


Two neurone networks

1st GABAergic 2nd glutamate
1st not activated-> 2nd is disinhibited-> glutamate-> excitation
1st is activate-> inhibitory GABA-> 2nd is inhibited
Activation of u receptor on 1st-> 1st is inhibited-> 2nd is disinhibited-> excitation
-> produce an excitatory effect by inhibiting an inhibitory neurone


Plasticity in chronic pain

Reduced effectiveness of opiods
Opiod receptors involved in the acute pain and chronic pain C fibre pathways as well as nerve damage
In tissue damage causing chronic pain-> hyperalgesia
Nerve damage c-fibre hyperalgesia and Ad fibre Allodynia


Avoiding/counteracting tollerance

Change drug or route
Switch to subcutaneous or epidural morphine-> changes metabolism
Spinal opiod-> epidural/intra thecal-> little benefit over subcutaneous but good for combination therapy-> no mental clouding



High lipophilicity -> rapid brain penetration
Broken down to morphine in CNS
More potent and additive than morphine



Weak opiate
Les resp depression
Good anti tussive


Synthetic opiods

Penthidine-> orally active, less potent! short duration, labour
Fentanyl-> orally active-> highly potent, short duration, anaesthesia
Methadone-> plasma half life >24h-> used to reduce opiod abuse-> physical abstinence syndrome is reduced -> psychological dependence similar-> morphine etc doesn't produce euphoria with methadone