Opioids Flashcards
(43 cards)
The nociceptors are what?
A delta and C fibers
Which fibers mediate the first response to pain, sharp pain?
A delta
C fibers are responsible for what kind of pain?
Dull, aching, or burning pain
Are there more C and A delta fibers?
More C fibers
What are some things that can turn on a nociceptor?
Heat, cold, mechanical perturbations, or protons
T/F pain and inflammation go hand in hand?
True
What are some ways that we can diminish pain?
We can inhibit signaling to the CNS- stop signal transmission to the brain.
We can inhibit CNS activity
We can have inhibition at the periphery- (anti-inflammatories)
What drugs inhibit signaling to the CNS?
Local anesthetics
What drugs inhibit CNS activity?
Opioids
What are the three opioid receptors? and what kind of receptors are they?
Mu (sign for micro)
Kappa (k) and
Delta
They are all G protein coupled receptors that activate the Gai protein
b-endorphin is the natural agonist of what?
The mu-opiod receptor
The dynorphin’s A, B and alpha/beta net-endorphin are the agonists for which opioid receptor?
k-opioid receptor
What happens when you activate the opioid receptors?
The opioid receptor activates the Gai and GbetaGgamma subunits of the G protein.
Activation of Gi leads to the inhibition of adenylate cyclase activity, which ends up decreasing the cAMP levels as well as a reduction in the PKA activity. If there isn’t PKA activity then there is a reduction of Ca++ entry from voltage gated channels.
Also, a particular potassium channel is going to be opened and this hyper polarizes the cell, making it more difficult to get an action potential
Let’s look at the synapse- the presynaptic terminal, the synaptic cleft and the post synaptic terminal. What effects will a reduction of Ca++ and hyper polarization produce at the synapse?
Presynaptically, Ca++ is required for transmitter release. Inhibition of the voltage sensitive Ca++ channel and hyper polarization will both diminish Ca++ entry. Presynaptically, opioids will reduce transmitter release.
Postsynaptically, hyper polarization will make it more difficult to generate an action potential.
There are 3 mu receptors. Which ones are most important?
mu1 and mu2 are physiologically important.
What do mu receptors in the GI tract do?
They inhibit peristaltic action in the GI tract- this causes constipation
What is the natural agonist of the mu-opioid receptor?
Beta-endorphin
Where are mu receptors found?
GI tract, periqueductal gray, superficial horn of the spinal cord, nucleus accumbins, amygdala, cerebral cortex
The majority of the analgesic drugs act where?
The majority of analgesic drugs primarily acts at mu receptors
Do opioids modulate the response to pain? If endogenous opioids were weakening the response to pain, you would think that inhibition of those receptors would increase pain sensitivity.
Opioids don’t seem to modulate the baseline response to pain. (see slide 24)
T/F opioids inhibit GABA release? Then what happens?
True, GABA is inhibited. Remember that GABA is inhibitory itself, so if you inhibit the inhibitor then you are basically activating something. The something in this case is activating the pathway that produces the CNS mediated inhibition of pain.
What are the two components that influence pain?
- sensory-discriminative component
2. emotional components (your brain processing what’s going on)
All opioid analgesics produce the following:
analgesia, respiratory depression, constipation, gastrointestinal spasm, and physical dependence
Which drug is your prototypical full agonist of the mu (u) receptor?
Morphine
