Opioid Agonists Flashcards
MOA of opioids
increase K conductance, inhibition of ca channels, decreased neurotransmission, and pain modulators
location of opioid receptors
BRAIN: PAG, RVM, locus ceruleus, and hypothalamus; SPINAL CORD: substantia gelatinosa (L2+3); OUTSIDE CNS: sensory neurons and immune cells
Direct application of opioids to the dorsal horn (substantia gelatinosa) causes? what is usually given
intense analgesia; LA + opioid
example of administration of opioid to pain receptors outside the cns
intraarticular morphine
name the mu 1 agonists
morphine, endorphins, synthetic opioids
name the mu 2 agonists
endorphins, morphine, sythetic opioids
name the kappa agonists
Dynorphins
name the delta agonists
Enkephalins
what drugs antagonize mu1, mu2, kappa, and delta receptors?
naltrexone, naloxone, and nalmefene
list the effects of mu1 receptor agonism
supraspinal and spinal analgesia, euphoria, low abuse potential, miosis, bradycardia, hypothermia, and urinary retention
list the effects of mu2 receptor agonism
spinal analgesia, depression of ventilation, physical dependence, marked constipation
list the effects of kappa receptor agonism
spinal and supraspinal analgesia, dysphoria, and sedation, low abuse potential, miosis, diuresis
list the effects of delta receptor agonism
spinal and supraspinal analgesia, depression of ventilation, physical dependence, minimal constipation, urinary retention
list the cv effects of opioids
decreased sns tone in peripheral veins causing decrease in vr, co, and bp; ortho hypo and syncope
one potential cardiac benefit of opioids
cardioprotective; may help prevent MIs
list pulm effects of opioids
decreased responsiveness of ventilation centers to co2; increases paco2 causing a shift to the right
what is the drug of choice to antagonize ventilatory depression? how does it work and what other benefit does it have
physostigmine; increases cns levels of ach; does not antagonize analgesic effect
mu2 and kappa receptors cause this; which would eventually lead to __________ in opioid OD
respiratory depression; apnea, miosis, hypoventilation, coma
list the cns effects of opioids
decreased cbf and possibly icp; myoclonus with large doses; chest wall and abdominal muscle rigidity
treatment of chest wall and abdominal rigidity associated with opioids
muscle relaxant or naloxone
caution with opioids in head injuries because
decreased wakefulness, miosis, paco2
list gi effects of opioids
sphincter of oddi spasms (spasm of biliary smooth muscle); delayed gastric emptying and constipation; n/v
least drugs from most likely to least likely to cause oddi spasms
fentanyl, morphine, meperidine
least treatment drugs for oddi spasms
glucagon, naloxone, atropine, nalbuphine, ntg
most common gu s/e of opiods
urinary urgency
cutaneous effects of opioids
flushing d/t histamine release in face, neck, and chest
how long does it typically take tolerance to develop
2-3 weeks
how long does it typically take morphine tolerance to build up
25 days
downregulation occurs when
opioid receptors become desensitized by reduced transcription and subsequently have a reduced number of receptors
meperidine and fentanyl onset of withdrawals; peak intensity; duration
2-6 hours; 6-12 hours; 4-5 days
morphine and heroin onset of withdrawals; peak intensity; duration
6-18 hours; 36-72 hours; 7-10 days
methadone onset of withdrawals; peak intensity; duration
24-48 hours; 3-21 days; 6-7 weeks
morphine onset, peak, and duration
onset 15-30 minutes; peak ivp 30-35 mins; peak im 45-90 mins; duration 4-5 hours
PO morphine first pass
25%
morphine accumulates rapidly in the
kidneys, liver, and skeletal muscle
gold standard opioid
morphine
morphine effects which kind of fibers the most
c fibers
what kind of pain is morphine good for
dull, visceral, skeletal muscle, or joint pain; intermittent pain
morphine metabolites
morphine 3 glucoronide (inactive); morphine 6 glucoronide (active)
how is morphine metabolized
glucoronic acid conjugation in hepatic and extrahepatic sites
with renal patients, we worry about giving them morphine because
they can have prolonged respiratory depression
morphine has an increased e 1/2 time because
of active metabolite morphine 3 glucoronide
morphine has a higher analgesic potency and slower offset in
women
meperidine is an agonist at
mu, kappa, a2 opioid receptors
list the analogues of meperidine
the fentanyls: fentanyl, alfentanil, sufentanil, remifentanil
meperidines have similar structures to
lidocaine and atropine
duration of meperidine
2 to 4 hours
hepatic first pass of meperidine
80%
metabolism of meperidine
hepatic
what percent of meperidine is protein bound
60%
elimination of meperidine
kidneys
e 1/2 time of meperidine
3-5 hours
with renal failure e 1/2 time of meperidine may be
35 hours
meperdine toxicity
delirium, myoclonus, seizures
uses for meperidine
post op shivering, intrathecal, post op analgesia
besides meperidine, what else might we use for post op shivering
clonidine
fentanyl is ___x more potent than morphine
75-125 x
peak time of fent in the brain
6.4 mins
lung first pass of fent
75%
fent is metabolized by
cyp3a
principal metabolite of fent
norfentanyl
excretion of fentanyl
kidneys
do we need to alter the dose of fent for elderly or liver patients
no
compared to the other meperidine derivatives, fentanyl’s context sensitive half time is
much much higher
when giving fent to someone on bypass, we worry about
not enough fent getting to blood - it sticks to the machine
fentanyl uses
solo surgical anesthesia, intrathecal. transmucosal. transdermal
1 mg of PO fentanyl is equivalent to
5 mg iV morphine
cv effects of opioids
depressed carotid sinus baroreceptor reflex causing bradycardia, decreased bp and CO
most prominent s/e of fent
sz like activity, modest increase in icp
sufentanil is __x more potent han fentanyl
5-12x
sufentanil is 92.5% bound to
alpha 1 acid glycoprotein
excretion of sufentanil
renal and fecal
main s/e of sufentanil
chest wall and abdominal muscle rigidity; bradycardia leading to decreased CO
alfentanil is ___ less potent than fentanyl
1/5th less
alfentanil 1/2 time is prolonged in these patients
cirrhosis
alfentanil is high protein bound
no right answer, just a reminder - like sufentanil
metabolite of alfentanil
noralfentanil
what drug has a quicker onset than fentanyl and sufentanil
alfentanil
remi is dosed by
ibw
remi has a quick peak effect at
1.1 min
remi + prop will cause
synergistic depression of ventilation
clearance of remi is faster than
alfentanil
plasma steady state of remi is
10 mins
remi is excretion is unaffected by
renal or hepatic disease
e 1/2 of remi
6.3 mins
remi is not recommended for
spinal or epidurals
before stopping remi, you should consider
longer acting opioid or supplementation with multimodal
main s/e of remi
sz like activity, n/v, depression of ventilation, decreased bp and hr, hyperalgesia from previous exposure to large opioid doses and tolerance
hydromorphone is _x more potent than morphine
5
redose dilaudid q
4 hours
uses, s/e, and metabolites are the same as
morphine
unlike morphine these drugs do not release histamine
fent and dilaudid
codeine can be given
PO or IM
codeine e 1/2 time
3-3.5 hours
codeine metabolism
liver
120 mgs of codeine equals
10 mgs of morphine
main s/e of codeine
physical dependence, minimal sedation, n/v, constipation, dizziness
tramadol is less potent than morphine by
5-10x
tramadol mostly affects which receptors
mu
worrisome tramadol interaction
warfarin
unlike fentanyl, ____ does not build up in tissues
remi
