Pain & Opioids Flashcards
acute pain that is not treated promptly and properly transitions into ____ that causes _____
persistent pain; irreversible changes to nervous system
eudynia
symptomatic or normal pain
maldynia
pathophysiologic disease of the nervous system, “abnormal” pain
3 dimensions of pain
1) sensory-discriminative (sensation, location, quality)
2) motivational-effective (unpleasantness)
3) cognitive-evaluative (past experiences modify other 2 dimensions; negative or positively affect outcome and pain experience; based on patient beliefs, cultural background, past experience)
opioids affect which dimension of pain
motivational-effective
Which cells initiates the motor, sensory, and ANS responses of pain? which is inhibitory?
T cell; SG neuron
which NT release allows pain transmission?
Substance P (blocked by intrathecal opioids) and glutamate
opioid receptors on ____ are probably on Substance P terminals and block it’s release
substantia gelatinosa
non-opioid inhibitory NT
Endorphins (are excitatory for the descending p/ways that inhibit pain)
Serotonin (inhib in brain)
Norepi (RAS & hypothalamus)
glycine (inhibs at spinal chord by increasing Cl-)
GABA (cerebral cortex, basal ganglia, cerebellum, SC (increases cl- and hyperpolarizes)
Glutamate
excitatory NT in hippocampus, outer layer of cerebral cortex, and substantia gelatinosa (learning & memory recall, central pain transduction, excitotoxic neuronal injury)
-there are also inotropic glutamate receptors (ligand-gated channel opens, influx of cation (na+) and depolarization
opioids
- have receptor agonist activity with morphine-like effects at mu receptors throughout body, but also at kappa and delta receptors
- mu receptors produce analgesic and SE
- inhib NT, block Ca influx and increase K efflux
analgesia
absence of pain without loss of consciousness
Which endogenous opioids affect mu receptors
endomorphins and endorphins
Which endogenous opioids affect delta receptors
endorphins and enkephalins
Which endogenous opioids affect kappa receptors
dynorphins
mu receptors
brain: sedation, analgesia, physical dependence
spinal cord (SG): resp depression, miosis
peripheral sensory neurons: euphoria
GI tract: reduced GI motility, vasodilation
kappa receptors
brain: analgesia, anticonvulsant effects, delirium
SC: diuresis
Peripheral: dysphoria, miosis, sedation, reduces shivering
delta
location: brain
action: analgesia, antidepressent effects, convulsant, dependence
generalized opioid SE
sedation & resp depression, N/V, CV effects (vasodilation d/t histamine release), euphoria (esp meperidine), antitussive, miosis, pruritis, biliary spasm, myoclonus/seizures with high dosage, chest wall rigidity
morphine
-classic mu receptor agonist
-influences the motivational-effective aspect of pain
-analgesia in the brain mu-1 and spinal mu-2
-only 23% unionized and able to cross BBB
-lipid solubility low (1.4) slow onset
1/2 life 2-3 hours
DOA 4-6
morphine SE
- resp depression (shift to right of the CO2 response curve)
- vent response to hypoxia decreased
- N/V
- large doses or rapid admin cause skeletal muscle rigidity (eliminated with GABA agonists and paralytics)
- miosis
- pruritis (not histamine related, but rx with antihistamines)
- hyperalgesia with prolonged use
- decreased cough reflex
- decreased GI motility
- increased biliary pressure by increasing phasic wave frequency of the sphincter of oddi
- release of histamine
- reduces centrally mediated SNS –> vasodilation
morphine metabolism
70% metabolized in liver via glucuronidation (liver disease has minimal effect, but reduced liver blood flow reduces clearance [very old and young])
excretion of metabolites by kidney (renal disease affects)
-m3 glucuronide (75-85%) inactive metabolite, no analgesia
-m6 (5-10%) active, 10x more potent than morphine
codeine
3-methyl-morphine
- 10% converted to morphine which causes analgesia
- less 1st pass metabolism when taken orally
hydromorphone
5x more potent than morphine
onset : 5 min, peaks 10-20 min
1-2 mg dilaudid = 10-20 mg morphine
oxycodone
-less first pass metabolism
oxycontin
SR oxycodone, bolus high when crushed or chewed
meperidine
1/10th potency of morphine but more lipid soluble –> faster onset
-less bradycardia/resp depression than equianalgesic morphine
-some local anesthetic activity
-has dysphoric and psychotomimetic effects (K receptor)
-less biliar pressure effect
-> histamine release than morphine
-liver metabolism
-active metabolite: normeperidine
T1/2 14-21 hours, can build to toxic levels–seizures/coma
-useful for post op shivering
meperidine and serotonin syndrome
meperidine inhibits reuptake of serotonin, when given in conjunction with MAOI or SSRI can lead to serotonin syndrome (delirium, fever, convulsions)
fentanyl
-50-100x more potent than morphine
-SE similiar at equianalgesic dose
-almost completely mu receptor agonist
-onset: 3-5 min (rapid resp depression)
context sensitive 1/2 life depends on length of admin
(1 min = 5 min; 1 hr = 20 min; 8 hour = 250 min)
-100% hepatic extraction to inactive metabolites
-clearance correlated to liver blood flow
-decreased with P450 inhibitors (cimetidine, erythromycin)
-transdermal patches
alfentanil
10x more potent than morphine (1/10th -1/4 as potent as fentanyl)
-effects similar at equianalgesic dose
-mu receptor agonist
-very rapid onset (1-2 min; 90% unbound unionized at 7.4; crosses BBB)
-metabolized in the liver 30-50% (inactive metab)
context sensitive 1/2 life depends on length of admin, but less than fentanyl (1 min = 1 min; 1 hour = 30 mins, 8 hour = 50 mins)
remifentanil
- equipotent to fentanyl
- v. rapid onset, 1 min (cannot be bolus)
- mu receptor agonist
- metabolism by non-specific plasma esterases
- clearance is constant, not affected by liver flow, renal failure, length of infusion
- great option for neurosurg
- t1/2= 3 mins
spinal opioids
preservative free
-less drug intrathecal than epidural
-spinal mu receptors are present in dorsal form
-morphine or fent admin spinally is analgesic
epidural : acute; intrathecal: acute and chronic
Morphine controls pain well, less sedation and resp depression than IV; SE: resp depression, N/V, itching
-d/t lipid solubility, morphine hangs around longer
-NO MOTOR BLOCKADE
hydromorphone
IV or Po
-more lipid soluble than morphine, faster onset
-5x more potent
glucuronid metabolism (hydromorphone 6G less agonist act than morphine 6 G; 3 G inactive)
hydrocodone
metabolized by CYP2D to hydromorphone
oxycodone
metabolized by CYP2D6 to oxymorphone
codeine
prodrug converted to morphine via demethylation by CYP2D6
methadone
-ultra long active
1/2 life: 15-60 hr
-useful for addicted patient’s maintenance
-chronic pain management
acute opioid overdose
sedation leads to stupor leads to coma leads to death
-rx with opioid antagonist naloxone
-abrupt reversal of all opioid effects
-may require multiple redosing due to opioid t 1/2
resp and cv support
naloxone
competetive antagonist at mu, kappa, delta receptors
-given IV, IM, SQ
-onset: 1-2 mins
T1/2 60 mins (3 hours in infants)
met in liver by glucuronidation
0.4 mg per ampule
0.04 mg increments for slow/partial reversal
naltrexone
oral opioid antangonist= slow active
-used for maintenance of opioid dependence
Which effects do we not dev opioid tolerance to
Gi/ocular
signs/symptoms of opioid withdrawl
restlessness, insomnia, perspiration, abd cramps, N/V/D, tachycardia, tachypnea, Hypertension/hypotension, hot/cold flashes
tramadol
partial mu agonist (also inhibits MAO reuptake, adds to analgesic effect)
- metabolized by CYP2D6
- good for mild to moderate acute pain (not severe)
tapentadol
- partial mu agonist
- less pharmacogenomic variability than tramadol
- metabolized by CYP2C19, C19, D6
- > mu receptor efficacy
- good for mild to moderate acute pain (not severe)
nalbuphine/butorphanol
kappa agonist; partial mu agonists; mu antagonists
nalbuphine 10x as potent as butorphanol
-chemically related to naloxone and oxymorphone
Good for ST, Acute moderate to severe pain (often L&D)
no chronic
receive benefits of opioids with fewer unwanted side effects
petazocine
two isomers
+ has affinity for kappa; - does not
-often mixed with naloxone
-has ceiling effct
buprenorphine
- partial mu receptor agonist and kappa agonist
- high affinity for mu: hard to reverse
- useful to rx opioid addiction at higher doses
- available as 7 day transdermal patch
