Opioid & non-opioid analgesics Flashcards
Identify the process by which a nociceptor converts a chemical stimulus into an action potential.
a. transmission
b. transduction
c. perception
d. modulation
b. transduction
Transduction occurs when a
chemical, mechanical, or thermal stimulus is sensed by a nociceptor and converted into an action potential
Transmission occurs when
the afferent pain signal travels from the peripheral nervous system to the central nervous system via a 3-neuron pathway
Modulation is when the
pain signal is modified (inhibited or augmented) as it advances towards the cerebral cortex
Perception is when the
pain signal is processed and “perceived” in the cerebral cortex and limbic system
Nociception is divided into four processes including
transmission
transduction
modulation
perception
A-delta fibers transmit
“fast pain” that is sharp and well-localized
C-fibers transmit
“slow pain” that is dull and poorly localized
Inflammation also contributes to
reduced threshold to pain stimulus (allodynia)
increased response to pain stimulus (hyperalgesia)
Drugs that target transduction include
NSAIDs
LAs
steroids
antihistamines
opioids
What is a first order neuron
periphery to dorsal horn
what is a second-order neuron?
dorsal horn to thalamus
What is a third-order neuron?
thalamus to cerebral cortex
Drugs that target transmission include
local anesthetics
Perception means
how we “feel” about pain
Drugs that target perception include
general anesthetics
opioids
alpha-2 agonists
The most important site of modulation is
the substantia gelatinosa in the dorsal horn (rexed lamina 2 & 3)
Pain is inhibited when
spinal neurons release GABA & glycine (inhibitor neurotransmitters)
2. the descending pain pathway release NE, serotonin, and endorphins
Pain is augmented by
wind-up
central sensitization
Drugs that target modulation include
neuraxial opioids
NMDA antagonists
alpha 2 agonists
AchE inhibitors
SSRIs
SNRIs
Molecular mechanisms of opioid receptor stimulation include: (select 2)
a. decreased cAMP production
b. increased calcium conductance
c. increased adenylate cyclase activity
d. increased potassium conductance
a. decreased cAMP production
d. increased potassium conductance
Opioid receptor stimulation reduces
neurotransmitter release from presynaptic neurons and hyperpolarizes postsynaptic neurons
Where are opioid receptors located?
brain
spinal cord
peripheral
Where in the brain are opioid receptors located?
periaqueductal gray
locus coeruleus
rostral ventral medulla
Where in the spinal cord are opioid receptors located?
primary afferent neurons in the dorsal horn
interneurons
Where in the periphery are opioid receptors located?
sensory neurons
immune cells
What are the four types of opioid receptors?
all are G-proteins
-Mu
-Delta
-Kappa
-ORL1
The existence of ______________ has yet to be proven
mu receptor subtypes
Stimulation of kappa receptors helps _________ but can also ____________
quell shivering; but can also cause dysphoria, delirium, and hallucinations
Key physiologic effects of Mu receptor stimulation include
analgesia, bradycardia, respiratory depression, euphoria, physical dependence, and constipation
Describe how opioids work at the receptor level.
- opioid binds to a receptor
- G protein is activated
- adenylate cyclase is inhibited
- less cAMP is produced
- Ca+2 conductance is decreased
- K+ conductance is increased
What is the precursor of the Mu receptor?
pre-proopiomelanocrtin–> endorphins
What is the precursor of the Delta receptor?
Pre-enkephalin–> enkephalins
What is the precursor of the kappa receptor?
pre-dynorphin–> dynorphins
What is the only opioid receptor that causes bradycardia?
Mu
What opioid receptors cause miosis?
Mu &kappa
What opioid receptors cause urinary retention?
Mu & delta
What opioid receptor causes diuresis?
kappa
What opioid receptor has antishivering properties?
kappa
What opioid receptors cause pruritus?
Mu & delta
What opioid receptors lead to nausea & vomiting?
Mu
What are the effects of Mu1?
analgesia (suraspinal & spinal)
bradycardia
What are the effects of Mu2?
analgesic (spinal only)
respiratory depression
constipation
physical dependence
What are the effects of Mu3?
immune suppression
Cardiovascular consequences of opioid administration in healthy patients include:
a. bradycardia
b. myocardial depression
c. hypotension
d. impaired baroreceptor reflex
a. bradycardia
Do opioids effect blood pressure?
Nope- only minimal effect
Opioids cause nausea and vomiting by
stimulating the chemoreceptor trigger zone in the medulla and possible interaction with the vestibular apparatus
Opioids produce respiratory depression by
shifting the CO2 response curve to the right
Agents that produce histamine release include
morphine, meperidine, and codeine
Opioids may be implicated in _______________ through inhibition of cellular and humoral immune function.
cancer recurrence
Opioids cause _________________________ which can be reversed with ___________ or _____________
contraction of the sphincter of Oddi; naloxone or glucagon
In women, morphine is associated with a:
greater analgesic potency
slower onset of action
longer duration of action
lower postoperative opioid consumption
