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Opioid & Non-opioid analgesics Flashcards

1
Q

What are the 4 steps of pain:

A

transduction
transmission
modulation
perception

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2
Q

What is transduction?

A

Noxious stimuli stimulates an action potential

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3
Q

What nerve fibers are involved in pain transduction?

A

C fibers: slow pain, dull, poorly localized from free nerve endings
A-delta fibers: fast pain, sharp, well localized from specialized receptors

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4
Q

How does inflammation contribute to pain?

A

Reduced threshold to pain stimulus (allodynia)
Increased reposed to pain stimulus (hyperalgesia)

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5
Q

What drugs target pain transduction?

A

NSAIDs
local anesthetics
steroids
antihistamines
opioids

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6
Q

What is pain transmission?

A

Pain signal is relayed via three-neuron pathway along the spinothalamic tract.

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7
Q

Where does the first order neuron originate and travel to? Where is the cell body?

A

periphery to dorsal horn
cell body in dorsal root ganglion

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8
Q

Where does the second order neuron originate and travel to? Where is the cell body?

A

dorsal horn to thalamus
cell body in dorsal horn

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9
Q

Where does the third order neuron originate and travel to? Where is the cell body?

A

thalamus to cerebral cortex
cell body in thalamus

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10
Q

What drugs target pain transmission?

A

local anesthetics

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11
Q

What is pain modulation?

A

Pain signal is modified (augmented or inhibited) as it travels to cerebral cortex.

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12
Q

What is the most important site of pain modulation?

A

Substantia gelatinosa in the dorsal horn, aka Rexed lamina 2 & 3

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13
Q

When is pain inhibited due to modulation?

A

spinal neurons release GABA and glycine (inhibitory ntms)
descending pain pathway releases NE, serotonin, endorphins

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14
Q

When is pain augmented by modulation?

A

central sensitization
wind-up

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15
Q

What drugs target pain modulation?

A

Neuraxial opioids
NMDA antagonists
Alpha 2 agonists
AchE inhibitors
SSRIs
SNRIs

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16
Q

What is pain perception?

A

describes feeling of pain due to afferent pain signals in the cerebral cortex and limbic system

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17
Q

What drugs target pain perception?

A

general anesthetics
Alpha 2 agonists
opioids

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18
Q

Discuss opioid receptor agonism:

A
  1. Opioid binds receptor
  2. G protein is activated
  3. Adenylate cyclase is inhibited
  4. cAMP production is decreased
  5. Ca conductance is decreased
  6. K conductance is increased
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19
Q

List opioid receptor types and their endogenous opioids:

A

Mu - endorphins
Delta - enkephalins
Kappa - dynorphins

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20
Q

What side effects do Delta receptors produce?

A

respiratory depression
urinary retention
pruritus

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21
Q

What side effects do Kappa receptors produce?

A

respiratory depression?
sedation, dysphoria, hallucinations, delirium
miosis
diuresis
anti shivering

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22
Q

What side effects do Mu 1 receptors produce

A

*analgesia (supra spinal and spinal)
*bradycardia
miosis
low abuse potential
euphoria
hypothermia
urinary retention

23
Q

What side effects do Mu 2 receptors produce?

A

*analgesia (only spinal)
*bradycardia
*respiratory depression
*constipation
*physical dependence

24
Q

What side effects do Mu 3 produce?

A

immune suppression

25
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
26
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
27
What pupil effects accompany opioid administration?
miosis due to PNS stimulation of ciliary ganglion and oculomotor nerve (CN3) tolerance to miosis does not develop
28
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
29
What SSEP effects accompany opioid administration?
minimal effect on evoked potentials
30
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
31
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
32
What GU effects accompany opioid administration?
urinary retention due to detrusor muscle relaxation (contraction needed to pass urine into ureters) urinary sphincter contraction
33
What immunologic effects accompany opioid administration?
histamine release: morphine, meperidine, codeine inhibition of cellular and humor immune function suppression of natural killer cell function
34
What thermoregulation effects accompany opioid administration?
hypothalamic temperature set point is reset -> decreased core body temperature
35
What gender differences occur with morphine administration?
in women: greater analgesic potency slower onset of action longer duration of action lower postoperative opioid consumption
36
Relative potency of opioids:
37
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
38
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
39
Discuss butorphanol
Mu antagonist (weak) Kappa agonist greater analgesia than morphine can be reversed by narcan useful for postop shivering available via intranasal route
40
Discuss the antagonism properties of naloxone:
antagonizes mu (greatest affinity), kappa, and delta opioid receptors
41
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
42
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)
43
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
44
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
45
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
46
Which partial agonists mechanism of action includes kappa agonism and mu antagonism?
nalbuphine butorphanol
47
Which partial agonists have greater potency than morphine?
butorphanol buprenorphine
48
Which partial agonists partially agonize mu receptors?
buprenorphine
49
Which partial agonists can be reversed by naloxone?
nalbuphine butorphanol (not buprenorphine due to strong affinity mu receptor)
50
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
51
Which partial agonist can be used for postoperative shivering?
butorphanol
52
Which partial agonist is available via transdermal route and has a long duration of action of 8 hours?
buprenorphine
53
Which partial agonist is available via intranasal route?
butorphanol

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