Opioid Agonist/Antagonist Flashcards
List the 4 components of pain
Transduction
Transmission
Modulation
Perception
Describe the process of pain signal transduction
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
Describe the process of pain signal transmission
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
Which classes of drugs target pain transduction?
NSAIDs
local anesthetics
steroids
antihistamines
opioids
capsaicin
anticonvulsants
ASA
acetaminophen
nitrate
Which classes of drugs target pain transmission?
local anesthetics
opioids
alpha-2 agonists
Describe the process of pain signal modulation
pain signal is modified (inhibited or augmented) as it advances toward the cerebral cortex
What is the most important site of pain modulation?
substantia gelatinosa in the dorsal horn (rexed lamina 2 & 3)
Where does the descending inhibitory pain pathway originate?
in the periaqueductal gray and the rostroventral medulla - it then projects to the substantia gelatinosa
What are the 2 methods by which pain is inhibited?
- spinal neurons release GABA and glycine (inhibitor NT)
- descending pain pathway releases NE, serotonin, and endorphins
Which classes of drugs target pain modulation?
neuraxial opioids
NDMA antagonists
alpha-2 agonists
acetylcholinesterase inhibitors
SSRIs
SNRIs
TCAs
Describe the process of pain perception
processing of afferent pain signals in the cerebral cortex and limbic system
Where does the brain itself feel pain?
it doesn’t - there are no nociceptors in the brain
Which classes of drugs affect pain perception?
general anesthetics
opioids
alpha-2 agonists
TCAs
SSRIs
SNRIs
Define opioid/opiate
all exogenous substances, natural and synthetic, that bind specifically to any of the several opioid receptors and produce some agonist or morphine-like effects
List the steps of opioid receptor activation
- opioid binds to receptor
- G protein is activated
- adenylate cyclase is inhibited
- less cAMP is produced
- Ca++ conductance is DEcreased
- K+ conductance is INcreased
(hyperpolarizes the membrane and makes the impulse less likely to fire after stimulation)
What two classes do we divide the alkaloids of opium into?
phenanthrenes
benzylisoquinolines
What are the phenanthrenes?
morphine
hydromorphone
oxymorphone
levorphanol
codeine
hydrocodone
oxycodone
buprenorphine
butorphanol
nalbuphine
pentazocine
dezocine
thebaine
What are the benzylisoquinolines?
papaverine
noscapine
What are the two semisynthetic opioids?
codeine
heroin
List the phenylpiperidines
meperidine
fentanyl
sufentanil
alfentanil
remifentanil
List the phenylheptanones
methadone
propoxyphene
levomethadyl
What are the endogenous opioids and their precursors?
pre-proopiomelanocortin –> endorphins (mu)
pre-enkephalin –> enkephalins (delta)
pre-dynorphin –> dynorphins (kappa)
What type of analgesia results from stimulation of the mu-1 receptors? What are some effects of that stimulation?
supraspinal analgesia
effects: euphoria, miosis, hypothermia, bradycardia, urinary retention, pruritis
What type of analgesia results from stimulation of the mu-2 receptors? What are some effects of stimulation?
spinal analgesia
effects: hypoventilation, physical dependence, ileus, constipation
What effect do opioid agonists have on the cardiovascular system?
minimal effect on BP (healthy pts)
vasodilation (dose-dependent)
bradycardia
potential histamine release (dose-dependent)
What effect do opioid agonists have on ventilation?
shift CO2 curve to the right
bradypnea
increased Vt
increased ICP (d/t increased PaCO2)
blunted hypoxic threshold
What effect to opioid agonists have on the nervous system?
analgesia
drowsiness
euphoria
skeletal muscle rigidity (esp in chest wall)
miosis
N/V
cerebral vasoconstriction
depression of cough reflex (esp codeine)
What effect do opioids have on the GI system?
spasm of biliary smooth muscle (increased biliary pressure)
decreased GI motility and delayed gastric emptying
What effect do opioids have on the GU system?
increased genitourinary tone (retention)
What effects can co-administration of opioid agonists and MAOIs produce?
exaggerated CNS depression
hyperpyrexia
hypertension
hyperthermia
seizures
How long does physical dependence on opioids take to develop?
25 days or
2-3 weeks of continual usage
Define hyperalgesia
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)
List the common opioids from most to least lipid soluble
sufentanil
fentanyl
alfentanyl
meperidine
remifentanil
morphine
Compare morphine to other opioids when it comes to ionization, protein binding, lipid solubility, and potency.
mostly ionized (77%)
low protein binding (35%)
least lipid soluble
not very potent (only more potent than meperidine)
What is a critical side effect of morphine?
histamine release (can lead to N/V, itching, broncho/laryngospasm)
What side effects is oxymorphone (numorphan) known for?
more N/V than other opioids and higher degree of physical dependence
