Opioid & Non-opioid analgesics Flashcards
What are the 4 steps of pain:
transduction
transmission
modulation
perception
What is transduction?
Noxious stimuli stimulates an action potential
What nerve fibers are involved in pain transduction?
C fibers: slow pain, dull, poorly localized from free nerve endings
A-delta fibers: fast pain, sharp, well localized from specialized receptors
How does inflammation contribute to pain?
Reduced threshold to pain stimulus (allodynia)
Increased reposed to pain stimulus (hyperalgesia)
What drugs target pain transduction?
NSAIDs
local anesthetics
steroids
antihistamines
opioids
What is pain transmission?
Pain signal is relayed via three-neuron pathway along the spinothalamic tract.
Where does the first order neuron originate and travel to? Where is the cell body?
periphery to dorsal horn
cell body in dorsal root ganglion
Where does the second order neuron originate and travel to? Where is the cell body?
dorsal horn to thalamus
cell body in dorsal horn
Where does the third order neuron originate and travel to? Where is the cell body?
thalamus to cerebral cortex
cell body in thalamus
What drugs target pain transmission?
local anesthetics
What is pain modulation?
Pain signal is modified (augmented or inhibited) as it travels to cerebral cortex.
What is the most important site of pain modulation?
Substantia gelatinosa in the dorsal horn, aka Rexed lamina 2 & 3
When is pain inhibited due to modulation?
spinal neurons release GABA and glycine (inhibitory ntms)
descending pain pathway releases NE, serotonin, endorphins
When is pain augmented by modulation?
central sensitization
wind-up
What drugs target pain modulation?
Neuraxial opioids
NMDA antagonists
Alpha 2 agonists
AchE inhibitors
SSRIs
SNRIs
What is pain perception?
describes feeling of pain due to afferent pain signals in the cerebral cortex and limbic system
What drugs target pain perception?
general anesthetics
Alpha 2 agonists
opioids
Discuss opioid receptor agonism:
- Opioid binds receptor
- G protein is activated
- Adenylate cyclase is inhibited
- cAMP production is decreased
- Ca conductance is decreased
- K conductance is increased
List opioid receptor types and their endogenous opioids:
Mu - endorphins
Delta - enkephalins
Kappa - dynorphins
What side effects do Delta receptors produce?
respiratory depression
urinary retention
pruritus
What side effects do Kappa receptors produce?
respiratory depression?
sedation, dysphoria, hallucinations, delirium
miosis
diuresis
anti shivering
What side effects do Mu 1 receptors produce
*analgesia (supra spinal and spinal)
*bradycardia
miosis
low abuse potential
euphoria
hypothermia
urinary retention
What side effects do Mu 2 receptors produce?
*analgesia (only spinal)
*bradycardia
*respiratory depression
*constipation
*physical dependence
What side effects do Mu 3 produce?
immune suppression
Where are opioid receptors located?
Brain: periaquaductal gray, locus coeruleus, rostral ventral medulla
Spinal cord: primary afferent neurons in dorsal horn and interneurons
Peripheral: sensory neurons and immune cells
What ventilation effects accompany opioid administration?
CO2 curve shifts right
decreased response to CO2
decreased RR
increased Vt
increased PaCO2 -> increased ICP if ventilation not maintained
What pupil effects accompany opioid administration?
miosis due to PNS stimulation of ciliary ganglion and oculomotor nerve (CN3)
tolerance to miosis does not develop
What N/V effects accompany opioid administration?
increased stimulation of the chemoreceptor trigger zone of the area postrema in medulla
possible interaction with the vestibular apparatus
What SSEP effects accompany opioid administration?
minimal effect on evoked potentials
What CV effects accompany opioid administration?
bradycardia
minimal BP reduction in healthy patient
dose dependent vasodilation
baroreceptor reflex NOT affected
contractility NOT affected
depression can occur if given with N2O
What GI effects accompany opioid administration?
increased biliary pressure due to Sphincter of Oddi contraction (reverse: naloxone or glucagon)
(meperidine affects least)
prolonged gastric emptying
slowed peristalsis -> constipation
What GU effects accompany opioid administration?
urinary retention due to detrusor muscle relaxation (contraction needed to pass urine into ureters)
urinary sphincter contraction
What immunologic effects accompany opioid administration?
histamine release: morphine, meperidine, codeine
inhibition of cellular and humor immune function
suppression of natural killer cell function
What thermoregulation effects accompany opioid administration?
hypothalamic temperature set point is reset -> decreased core body temperature
What gender differences occur with morphine administration?
in women:
greater analgesic potency
slower onset of action
longer duration of action
lower postoperative opioid consumption
Relative potency of opioids:
Discuss Buprenorphine
partial Mu agonist
greater analgesia than morphine
narcan reversal difficult due to high affinity for mu receptor
long duration - 8 hours
available via transdermal route
Discuss Nalbuphine
Mu antagonist
Kappa agonist
similar analgesia to morphine
can be reversed by narcan
doesn’t increase HR, BP, PAP, or RAP
useful with history of heart disease
Discuss butorphanol
Mu antagonist (weak)
Kappa agonist
greater analgesia than morphine
can be reversed by narcan
useful for postop shivering
available via intranasal route
Discuss the antagonism properties of naloxone:
antagonizes mu (greatest affinity), kappa, and delta opioid receptors
What is naloxone used for?
prototype opioid antagonist used to reverse opioid-induced respiratory depression
treatment of opioid overdose
reversal of respiratory depression in the neonate whose mother received an opioid
What is the dose and duration of action of naloxone?
1-4 mcg/kg
duration 30-45 minutes
titrate 20-40 mcg at a time to prevent overshoot
liver metabolism (significant first-pass metabolism)
What opioid antagonist is a quaternary amino group? What does this prevent?
Methylnaltrexone. Cannot pass BBB, so cannot reverse respiratory depression. Useful in peripheral effects of opioids, such as opioid-induced bowel dysfunction
Discuss the opioid antagonist that is similar to naloxone but has a much longer duration of action:
Nalmefene
0.1-0.5 mcg/kg
Duration 10 hours
Used to maintain recovering opioid abusers
What is the benefit of naltrexone vs naloxone?
Naltrexone does not undergo significant first-pass metabolism
Can be given orally
Duration up to 24 hours
Use extended release for alcohol withdrawal treatment
Use to maintain recovering opioid abusers
Which partial agonists mechanism of action includes kappa agonism and mu antagonism?
nalbuphine
butorphanol
Which partial agonists have greater potency than morphine?
butorphanol
buprenorphine
Which partial agonists partially agonize mu receptors?
buprenorphine
Which partial agonists can be reversed by naloxone?
nalbuphine
butorphanol
(not buprenorphine due to strong affinity mu receptor)
Which partial agonist does not increase BP, HR, PAP, or RAP? What patient population are these useful in?
nalbuphine
useful in patients with heart disease
Which partial agonist can be used for postoperative shivering?
butorphanol
Which partial agonist is available via transdermal route and has a long duration of action of 8 hours?
buprenorphine
Which partial agonist is available via intranasal route?
butorphanol
