Pharmacology of Opioids Flashcards
what are opioids?
Any substance (natural or synthetic) that mediate an analgesic effect through opioid receptors that can be blocked by naloxone
- natural
- semi synthetic
- synthetic
what are natural opioids?
isolated
0 Endogenous
0 Morphine, codeine (Papaver somniferum)
what are semi-synthetic opioids/
modelled on the structure of opioids
0 Derivatives of morphine
0 Diamorphine, dihydrocodeine, buprenorphine, naloxone
what are synthetic opioids?
separate classes of chemical structures name of series comes from that chemical structure 0 Phenylpiperidine series 0 Pethidine, fentanyl, alfentanyl, remifentanyl 0 Diphenylpropylamine series 0 Methodone, dextropropoxyphene 0 Benzomorphan series 0 Pentazocine 0 Thebaine derivatives 0 Buprenorphine
what are the clinical effects of opioids?
Help control pain and reduce pain.
what other effects om the body do opioids have?
But as opioids have effects on other systems, they have effects on GI, endocrine, autonomic and cognition. We cannot easily get away from the two. They come as one.
Different opioids will have different effect on different pathways.
what are endogenous opioids?
• Enkephalins Met-enkephalin Leu-enkaphalin • Endorphins a-neoendorphin b-neoendorphin g-neoendorphin • Dynorphins Dynorphin A Dynorphin B • Endomorphins Endomorphin 1 Endomorphin 2
what are the different opioids receptors?
MOP: m1; m2; m3
DOP: d1; d2
KOP: k1a; k1b; k2a; k2b; k3
which opioids bind to MOP?
B-endorphins
Endomorphin 1
Endomorphin 2
which opioids bind to KOP?
Dynorphin A
Dynorphin B
which opioids bind to DOP?
Met-enkephalin
Leu-enkephalin
which opioids bind to KOP?
nociceptin
what is the opioid receptor mechanism?
- G coupled receptors have 7 transmembrane structure. G protein is within the cytoplasm which associates with the pre and post synaptic membrane
- this inhibits adenlyate cylase which decreases production of cAMP and neurotransmitter release
- this activates the voltage-gated inward K+ channels
- hyperpolarisation of the cell (no more excitation)
- decreases the responsiveness of the stimuli
- reducing the neurotransmitter release
where are the opioid receptor locations?
- vagal centres
- chemoreceptors of area postrema
- antinociceptive system
- smooth muscle
- bladder
what is pain?
- naturla defence to response of a stimuli
- higher centre of processing signals which allow the body to minimise exposure to the damage of the stimuli
- psychological factors will influence the extent to which an individual will feel suffering and distress
what is nocicpetion?
- The sensory processing associated with firing of small diameter nociceptive afferents
- Activated by different stimuli
- Chemical
- Mechanical
- Thermal – could be cold or hot - C-fibres – unmyelinated; dull, diffuse burning pain
- Ad fibres – myelinated; sharp localised pain
what are nociceptive fibres?
0 The sensory processing associated with firing of small diameter nociceptive afferents
0 Activated by different stimuli
0 Chemical
0 Mechanical
0 Thermal – could be cold or hot
0 C-fibres – unmyelinated; dull, diffuse burning pain
0 Ad fibres – myelinated; sharp localised pain
what are nociceptors?
Nociceptors are out in the periphery, present In the skin, organs, muscles, EVERYWHERE. Why we feel pain when we damage a part of our body – nerve signal sent to the brain.
Peripherally, we can get lots of different stimulus that will cause pain.
what causes stimulation of nociceptors?
- Cancer cells, tissue injury, osteolysis, inflammatory cells will cause release of noxius factors which act on receptors on the free nerve endings on the nociceptors to then trigger the action potential which will travel to the cell body in the dorsal root and dorsal ganglion and then go up to the doral horn and transmitted up to the brain
- Can also get an exacerbation of the peripheral signal by release of certain neurotransmitters which can cause release of more inflammation which can then also trigger chemical stimuli
- Prostaglandins don’t tend to cause stimulus on their own, they tenf to bind to a nociceptor and sensitise it and make it more susceptible to detecting changes of other substances
what is the ascending pain pathway?
0 Nociceptor is stimulated
0 Action potential travels along axon to cell body in dorsal ganglion (first order afferent)
0 Action potential potentiated along to dorsal horn
0 Signal transferred to next nerve: crosses over to other side of spinal cord (second order afferent)
0 Action potential travels to thalamus
0 Signal transferred to next nerve (third order afferent) which terminates in somatosensory cortex
what happens when a signal is detected?
Once we get the signal in the periphery from the nociceptor, it travels up to the dorsal root ganglion which lies just beside the dorsal horn in the spinal chord. Then get the signal sending the signal up through thr brain stem and up to cortex – where it decides how to interpret brain signal. Pain back out with motor nerves.
Ascending pathway – signal from periphery in to brain
what is the descending pathway?
- Somatosensory cortex connects with brain regions which co-ordinate the response
- The amygdala, anterior cingulate cortex, insular cortex and hypothalamus send projections to the periaqueductal grey (integrates response)
- PAG sends signal to rostroventral medulla
- RVM sends signal to dorsal horn, where nerve interacts with the ascending pathway
- When it travels to other side of dorsal horn: e.g. if you have pain in your left finger, it will go up to spinal chord and signal will be sent up the right hand side of your body.
- Dorsal horn up to other regions of brain, there are second order afferents
