Opioids (Exam V) Flashcards
What is a Hierarchical System in the CNS?
NT Examples
A chain of neurons that activates the next subsequent neurons. They are referred to as relay neurons, a multi-neuron web in the nervous system.
Glutamate (Excitatory NT)
GABA, Glycine (Inhibitory NTs)
What is the Nonspecific (Diffuse) System in the CNS?
NT Examples
NT diffused slowly through the nervous system either through the CSF, small unmyelinated fibers, or en-passant synapses. Slower conduction. Non-hierarchical, no-relay.
Monoamines, Dopamine, NE, 5-HT.
The diffuse system means that these NT can activate wide stretches of the CNS all at once.
Name 4 diffuse systems mentioned in lecture.
- Raphe Nuclei - 5HT
- Substantia Nigra/Ventral Tegmental Area- Dopamine
- Locus Coeruleus - NE
- Pontine Nuclei - ACh
What are Aβ fibers associated with?
What are Aδ fibers associated with?
What are C fibers associated with?
Aβ fibers are myelinated fibers involved with touch and non-noxious mechanical stimuli.
Aδ fibers are fast myelinated fibers involved with noxious heat, mechanical stimuli, sharp pain, produces initial reflex response.
C fibers are slow thin non-myelinated fibers involved with noxious chemical, heat, mechanical stimuli. Slow burning pain. Also has a prolonged response.
What is the Gate Control Theory of Pain?
What can be used to suppress pain?
There are “gates” in the spinal cord that allow pain signals through. These gates can be adjusted to increase/decrease pain sensation.
Opioids (blocks signaling) and anti-inflammatory agents (suppress nociceptor signaling)
How will Aβ fibers suppress pain signaling (close gate).
What would this be an example of activating Aβ fibers to suppress pain signaling.
Aβ fibers will activate the inhibitory neuron which will close the pain signaling of the interneuron.
Rubbing you arm knee after falling (Peter Griffin).
What will activate bradykinin release?
What two receptors does bradykinin bind to?
What do these receptors do?
Tissue damage
B1 receptors (inflammatory)
B2 receptors (constitutive)
Both receptors will activate PKA and PKC, which will send an action potential in the free nerve ending to release glutamate and substance P.
What three tracts are involved with pain transmission in the CNS?
Spinothalmic Tract (Affective Sensation)
Spinoreticular Tracts (Affective Sensation)
Spinomesencephalic Tract
Where is the signal sent in the spinomesencephalic tract?
What kind of receptors are at this location?
Periaqueductal gray matter (PAG).
Lots of opioid (mu) receptors that will suppress the spinothalmic and spinoreticular signaling.
The spinothalmic and spinoreticular tract will also send signals to the PAG to release more endogenous opioids.
Differentiate full agonist, partial agonists, & antagonists of the opioid receptors. Give examples for each.
- Full Agonists (strong to moderate effect) morphine, fentanyl
- Partial Agonists (moderate to mild effect) codeine, oxycodone, etc.
- Antagonists (Reversal) Naloxone
Name the 3 opioid receptors, which one is the the primary receptor?
Mu Receptor (Primary Opioid Receptor) - most responsive to endorphins/endogenous ligand
Delta Receptor- Analgesia
Kappa Receptor- Analgesia (May have negative analgesia effects mediated by dynorphins)
Pharmacokinetics of Opioids:
Absorption:
Distribution:
Metabolism: Morphine, Heroin, Other.
Elimination:
Pharmacokinetics of Opioids:
A: Well absorbed (IM, SQ, Oral- only with demerol or codeine)
D: Opioids can accumulate in the tissues
M: Morphine - metabolized by Phase II
M: Heroin - metabolized by tissue esterases to morphine
M: Other: Phase 1 (CYP3A4, CYP2D6)
E: Urine
Opioids will bind to the receptors in the brain and spinal cord. What type of receptor are opioid receptors?
How do μ(mu) opioid receptors suppress pain?
Where are three locations in the neuron where Mu receptors can suppress pain signaling?
Gᵢ GPCRs
Gᵢ = ↓AC → ↓cAMP = ↑pK⁺, ↓pCa⁺⁺ = Hyperpolarized neuron. This will reduce NT release: glutamate, ACh, NE, serotonin, Substance P.
Mu receptors are located in the:
1. Free nerve endings
2. Presynaptic Neuron
3. Postsynaptic Neuron
What are the CNS effects of opioids (9 items).
- Cough Suppression
- Hyperthermia (mu receptors)/ Hypothermia (kappa receptors)
- Analgesia- sensory/emotional
- Increase muscle tone (trunk)
- Respiratory Depression (brainstem)
- Miosis (always a marker, pinpoint)
- Euphoria (Dysphoria sometimes)
- N/V
- Sedation
CHAIRMENS
People who take opioids will develop a tolerance to what factors (8)?
Cough Suppression
Analgesia
Mental clouding
Euphoria/Dysphoria
Respiratory Depression
Antidiuresis
Sedation
N/V
CAMERAS N
