Opiod Analgesics And Pain Processing

Question 0

u, d, and k receptors

Answer 0

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

Question 1

Opiods

Answer 1

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

Question 2

Pre synaptic u receptor

Answer 2

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

Question 3

Post synaptic u receptor

Answer 3

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

Question 4

Morphine

Answer 4

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

Question 5

Spinal effects of opiods

Answer 5

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

Question 6

Descending inhibitory control of pain

Answer 6

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

Question 7

Two neurone networks

Answer 7

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

Question 8

Plasticity in chronic pain

Answer 8

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

Question 9

Avoiding/counteracting tollerance

Answer 9

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

Question 10

Diamorphine

Answer 10

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

Question 11

Codeine

Answer 11

Weak opiate
Les resp depression
Good anti tussive

Question 12

Synthetic opiods

Answer 12

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