Opioid Agonist/Antagonist

Question 1

List the 4 components of pain

Answer 1

Transduction
Transmission
Modulation
Perception

Question 2

Describe the process of pain signal transduction

Answer 2

injured tissue releases chemicals that activate peripheral nerves and immune cells - peripheral nerves transduce the chemicals into an action potential to be interpreted by the brain

Question 3

Describe the process of pain signal transmission

Answer 3

electrical signal is relayed through 3 neurons in the afferent pain pathway along the spinothalamic tract
1st order: periphery to dorsal horn
2nd order: dorsal horn to thalamus
3rd order: thalamus to cerebral cortex

Question 4

Which classes of drugs target pain transduction?

Answer 4

NSAIDs
local anesthetics
steroids
antihistamines
opioids
capsaicin
anticonvulsants
ASA
acetaminophen
nitrate

Question 5

Which classes of drugs target pain transmission?

Answer 5

local anesthetics
opioids
alpha-2 agonists

Question 6

Describe the process of pain signal modulation

Answer 6

pain signal is modified (inhibited or augmented) as it advances toward the cerebral cortex

Question 7

What is the most important site of pain modulation?

Answer 7

substantia gelatinosa in the dorsal horn (rexed lamina 2 & 3)

Question 8

Where does the descending inhibitory pain pathway originate?

Answer 8

in the periaqueductal gray and the rostroventral medulla - it then projects to the substantia gelatinosa

Question 9

What are the 2 methods by which pain is inhibited?

Answer 9

1. spinal neurons release GABA and glycine (inhibitor NT)
2. descending pain pathway releases NE, serotonin, and endorphins

Question 10

Which classes of drugs target pain modulation?

Answer 10

neuraxial opioids
NDMA antagonists
alpha-2 agonists
acetylcholinesterase inhibitors
SSRIs
SNRIs
TCAs

Question 11

Describe the process of pain perception

Answer 11

processing of afferent pain signals in the cerebral cortex and limbic system

Question 12

Where does the brain itself feel pain?

Answer 12

it doesn’t - there are no nociceptors in the brain

Question 13

Which classes of drugs affect pain perception?

Answer 13

general anesthetics
opioids
alpha-2 agonists
TCAs
SSRIs
SNRIs

Question 14

Define opioid/opiate

Answer 14

all exogenous substances, natural and synthetic, that bind specifically to any of the several opioid receptors and produce some agonist or morphine-like effects

Question 15

List the steps of opioid receptor activation

Answer 15

1. opioid binds to receptor
2. G protein is activated
3. adenylate cyclase is inhibited
4. less cAMP is produced
5. Ca++ conductance is DEcreased
6. K+ conductance is INcreased
   (hyperpolarizes the membrane and makes the impulse less likely to fire after stimulation)

Question 16

What two classes do we divide the alkaloids of opium into?

Answer 16

phenanthrenes
benzylisoquinolines

Question 17

What are the phenanthrenes?

Answer 17

morphine
hydromorphone
oxymorphone
levorphanol
codeine
hydrocodone
oxycodone
buprenorphine
butorphanol
nalbuphine
pentazocine
dezocine
thebaine

Question 18

What are the benzylisoquinolines?

Answer 18

papaverine
noscapine

Question 19

What are the two semisynthetic opioids?

Answer 19

codeine
heroin

Question 20

List the phenylpiperidines

Answer 20

meperidine
fentanyl
sufentanil
alfentanil
remifentanil

Question 21

List the phenylheptanones

Answer 21

methadone
propoxyphene
levomethadyl

Question 22

What are the endogenous opioids and their precursors?

Answer 22

pre-proopiomelanocortin –> endorphins (mu)
pre-enkephalin –> enkephalins (delta)
pre-dynorphin –> dynorphins (kappa)

Question 23

What type of analgesia results from stimulation of the mu-1 receptors? What are some effects of that stimulation?

Answer 23

supraspinal analgesia
effects: euphoria, miosis, hypothermia, bradycardia, urinary retention, pruritis

Question 24

What type of analgesia results from stimulation of the mu-2 receptors? What are some effects of stimulation?

Answer 24

spinal analgesia
effects: hypoventilation, physical dependence, ileus, constipation

Question 25

What effect do opioid agonists have on the cardiovascular system?

Answer 25

minimal effect on BP (healthy pts)
vasodilation (dose-dependent)
bradycardia
potential histamine release (dose-dependent)

Question 26

What effect do opioid agonists have on ventilation?

Answer 26

shift CO2 curve to the right
bradypnea
increased Vt
increased ICP (d/t increased PaCO2)
blunted hypoxic threshold

Question 27

What effect to opioid agonists have on the nervous system?

Answer 27

analgesia
drowsiness
euphoria
skeletal muscle rigidity (esp in chest wall)
miosis
N/V
cerebral vasoconstriction
depression of cough reflex (esp codeine)

Question 28

What effect do opioids have on the GI system?

Answer 28

spasm of biliary smooth muscle (increased biliary pressure)
decreased GI motility and delayed gastric emptying

Question 29

What effect do opioids have on the GU system?

Answer 29

increased genitourinary tone (retention)

Question 30

What effects can co-administration of opioid agonists and MAOIs produce?

Answer 30

exaggerated CNS depression
hyperpyrexia
hypertension
hyperthermia
seizures

Question 31

How long does physical dependence on opioids take to develop?

Answer 31

25 days or
2-3 weeks of continual usage

Question 32

Define hyperalgesia

Answer 32

a decrease in pain threshold in an area of inflammation; a trivial stimuli may cause pain; release of chemical mediators sensitize pain receptors (esp in PNS)
(many hypotheses about how it happens)

Question 33

List the common opioids from most to least lipid soluble

Answer 33

sufentanil
fentanyl
alfentanyl
meperidine
remifentanil
morphine

Question 34

Compare morphine to other opioids when it comes to ionization, protein binding, lipid solubility, and potency.

Answer 34

mostly ionized (77%)
low protein binding (35%)
least lipid soluble
not very potent (only more potent than meperidine)

Question 35

What is a critical side effect of morphine?

Answer 35

histamine release (can lead to N/V, itching, broncho/laryngospasm)

Question 36

What side effects is oxymorphone (numorphan) known for?

Answer 36

more N/V than other opioids and higher degree of physical dependence