opioids pt 1 Flashcards
how do opioid agonists work
blocks the ascending pathway via 1st and 2nd order neuron and engages the descending pathway via agonizing GABA (increasing cl)
what are the two main chemical classification groups of opoids
- benzylisoquinoline alkaloid
- phenanthrenes
what is the key structure of an opoid
the phenanthrene ring (3 benzene rings fused together)
papaverine is a ____________________ that is a non, analgesic antispasmodic
benzylisoquinoline alkaloid
_________________ is a naturally occuring phenanthrene and is the principle active compound from opium
morphine
if you substitute an ether for an alcohol of the phenanthrene nucleus of morphine you get _______________
codeine
_________________ was the first synthetic opioid
meperidine
___________ is the prototype phenylpiperidine
meperidine
if you take morphine and split it between the 12th and 13th carbon to get a benzene connected to a 5 ring structure you get ____________ class of opioids
phenylpiperidine
T/F: synthetic opoids only have 2 of the original 5 rings of the basic morphine molecule
TRUE
which drugs are your natural opioid agonists
- morphine
- thebaine
- codeine
which drugs are your semi-synthetic opioid agonists
- hydromorphone
- heroine
- oxymorphone
- oxycodone
what are your synthetic opioid agonists
- methadone
- fentanyl
- remifentanil
- alfentanil
- meperidine
- sufentanil
- tramadol
what are your semi-synthetic partial agonist opoids
buprenorphine
what meds are your synthetic partial agonists opioids
butorphanol
which meds are your synthetic agonist-antagonist opioids
nalbuphine
which meds are your semi-synthetic opioid anatagonists
naloxone & naltrexone
which meds are your synthetic opoid antagonists
nalmefene
which semi-synthetics are “morphine derivatives” (i.e. synthesized by making small changes to morphine molecule)
heroine, oxymorphone, and hydromorphone
if something is a “synthetic” opioid that means it contains the _______________ of morphine
phenanthrene nucleus
(generally) opioids are largely _________________ at physiologic pH
ionized (pKa > 7.45)
(generally) opioids are highly lipid ______________, weak _____________, and ______________ protein bound
soluble; bases; highly
what are the 3 opioid receptor classes
- Mu
- kappa
- delta
what are your endogenous opioid agonists
- enkephalins
- endorphins
- dynorphins
- nociceptin
- endomorphin 1
- endomorphin 2
opioid receptors are what type of receptors
G-coupled protein receptors
________________ are individual peptides that have their own specific precursors and share a common amino acid terminal sequence with a small variation
opioid agonists (endogenous & exogenous)
what is the amino acid terminal sequence all opioid agonists share
try-gly-gly-phe-met or leu
what is the terminal amino acid sequence of all opioid agonists called
the opioid motif or the opioid message
the specific amino acid sequence of the opioid agonist is necessary for what?
the endogenous agonists action with the receptor
describe the steps/effects at the cellular level of when a opioid agonist binds with a receptor
- binding of opioid agonist with receptor
- activation of the G-protein (alpha, beta, and gamma subunit)
- produces inhibitory effects: (alpha) inhibits adenyl cyclase –> cAMP –> relaxes smooth muscle; (beta & gamma) –> decreased Ca influx –> decreased neuronal excitation; (beta and gamma) –> increased K efflux –> hyperpolarization
- results in membrane hyperpolarization and reduction of neuron excitability
abrupt withdrawal of opioid agonist can cause rebound disinhibition of __________________
cAMP
abrupt withdrawal of opioid receptor agonist –> disinhibition of cAMP –> what s/sx
- increased irritability
- restlessness
- tremors
- chills
- muscle cramps
- sweating
- mydriasis
- abdominal pain
- diarrhea
- increased HR
opioid receptor locations
- brain
- spine
- GI
- vasculature
- heart
- lung
- immune systems
where are the opioid receptor locations in the brain
- periaquaductal gray
- limbic system
- area postrema
- cerebral cortex
- thalamus
where are the opioid receptor locations in the spine
substantia geletanosa of the dorsal horn
where are the opioid receptors located in the GI system
in the intestines
_______________ analgesia occurs through activation of the opioid receptors in the brian that cause inhibition of the nerves involved in pain pathways
supraspinal
_______________ analgesia occurs via activation of the presynaptic opioid receptors in the spine decreasing release of the neurotransmitters of the nociception
spinal
supraspinal analgesia + spinal analgesia =
synergistic pain relief
brainstem modulates nociceptive transmission via ________________ pathways of the spinal cord
inhibitory
opioid receptors in the _______________ inhibits the release of substance P and blocks the ascending pathways
spine
opioid receptors in the GI –> __________________; and in the GU –> ________________
constipation/post-op ileus; increased urinary sphincter tone –> urinary retention
mu will cause ____________________ analgesia and kappa will cause _______________ analagesia
supraspinal & spinal; supraspinal & spinal
mu receptors cause what CV effects? kappa causes what CV effects
mu = bradycardia
respiratory effects of mu? kappa?
mu = respiratory depression
CNS effects of mu
- euphoria
CNS effects of kappa
- sedation
effect of mu and kappa on the pupil
miosis
which opioid receptor if activated will inhibit peristalsis, and cause N/V?
mu
which opoid receptor when agonized causes urinary retention? which causes diuresis
mu; kappa
which opioid receptor if activated causes pruritus
mu
_________ opioid receptors have high risk of physical dependence, and _______ receptors have a low abuse potential
mu; kappa
which endogenous opioid ligands agonize the mu receptor
- B-endorphin
which naturally occurring opioid ligand agonizes the kappa receptor
dynorphin
what are the different routes of opioid administration?
- oral
opioids absorption is _____________ orally, due to extensive _________________
modest; first pass
the more _________________ an opioid is the __________ the absorption
lipophillic; increased
opioids are distributed throughout the body via the _________ compartment model
2 (VRG)
metabolism of opioids
liver via cyp450 into active metabolites except remifentanil
generally primary excretion of opioids = ______________ and secondary = _______________
kidney; bile
differences in use of opioids r/t anesthesia practice
- higher analgesic requirement
small dose opioids will have a termination of DOA by ________________
redistribution into peripheral compartments
larger doses/multiple doses/continuous infusions of opioids DOA is more dependent on __________________
metabolism
________________ is a key factor in if the effect of an opioid is therapeutic or adverse
clinical setting (ex: respiratory depression is therapeutic in the OR but detrimental in the ER)
considerations with the pharmacokinetics of opoids
- they have a narrow therapeutic index
what are the therapeutic effects of mu agonists
- pain relief (spinal and supraspinal)
mu agonists are good for txing ___________ pain sensations, but less effective for ___________ pain sensations
secondary (c-fibers); primary (A-delta)
T/F: opioids can be used as a sole anesthetic
false; they do not reliably produce unresponsiveness and are not an anesthetic
there is a risk for _____________________ reaction of increase in _______________ with bolus dosing opioids
paradoxical; coughing
what are the adverse effects of opioid agonists
- euphoria –> abuse
opioid CNS effects
- sedation and eupohoria
opoids are most effective for continuous ____________ dull pain
visceral
analgesic MOA of opioid within the CNS
- inhibit ascending transmission of nociceptive stimuli from the dorsal horn of SC
_______________ to opoids begins with a decrease in DOA followed by decrease in effect
tolerance
undesired CNS effects of opioids
- dependence
what is the most significant adverse effect of opioids
depression of ventilation
who is at increased risk of respiratory depression with use of opioids
- if use high dose opioids
T/F: respiratory depression 2/2 opioid use is not an issue intraoperatively when the airway is secured and ventilation is controlled
TRUE
opoids will depress the response to ____________ and ____________ which results in a _____________ shift of the oxyhgb dissocation curve
increased CO2; decreased O2; right
respiratory depression 2/2 opioids intraopertively is potentially life threatening in the postoperative period in those that are _____________ or ___________________
morbidly obese; have OSA
T/F: tolerance to opioids will decrease the miosis pupillary response
false; tolerance does not effect miosis with use
what is though to cause miosis with opioid use
- opiate depression of GABA –>
T/F: miosis with opioid use is reversible with narcan
TRUE
what are the best opioids for cough suppression
- codeine
opioids will depress the ______________ in the medulla, but preserves _______________ reflexes
cough center; glottic protective
what benefit does the antitussive effect of opioids have to us as anesthesia providers?
increases tolerance to intubation and ETTS
what are the 5 receptors that cause PONV
- H1/2
T/F: patients would rather have pain than have N/V
TRUE
PONV 2/2 opioid use is higher in _____________ patients
ambulatory
opioids cause N/V by acting where?
CTZ which is in the area postrema in the floor of the 4th ventricle
T/F: Anesthesia + opioids increases incidence of PONV
TRUE
T/F: opioid analgesia is not safe for patients with cardiovascular compromise
FALSE
CV effects of opioids
- decrease HR 2/2 medullary vagal stimulation
which opioids cause histamine release
- morphine
T/F: fentanyl congeners do not release histamine
TRUE
opioid use will cause venous and arterial vasodilation which results in ______________ & _____________
decreased preload; decreased afterload
what can you use to inhibit the vasodilation, tachycardia, and hypotension seen with morphine, meperidine, and codeine?
H1 and H2 antagonists
generalized hypertonus 2/2 to opioid use is most common with large doses of ________________
IV opioid agonists (primarily phenylpipridines)
muscle rigidity 2/2 to opioid use occurs more frequently if they are used concurrently with ___________
N20
how do you tx muscle rigidity caused by opioids
narcan or muscle relaxant
muscle rigidity effects of opioids
- no effect on nerve conduction
if you give remifentanil, and truncal rigidity ensues, if this happens near induction you should give ________________, and if it happens near the end you should give __________________
muscle relaxant; narcan
feeling of warmth in the face, upper chest and arms after opioid administration = ________________
pruruitus
pruritus with opioid administration is most common via what administration route
neuraxial (d/t central mu receptors)
how do you tx pruritus caused by opioid administration?
- naloxone / naltrexone
which opioid causes sphincter of oddi spasm the most
meperidine
GI effects of opioids
- constipation/post op ileus 2/2 decreased gastric motility and decreased secretory activity
what meds can be given to tx the GI s/e of opioids
- alvimopan (entereg)
how do alvimopan & methylnaltreone tx the GI s/e of opioids
they antagonize (locally) on mu receptors in the GI tract, BUT they do not reverse the analgesia
which opioid causes immunosuppression the MOST
morphine
endocrine effects of opioids
- reduces the stress response
chronic use of opioids will __________ temperature byt resetting equilibrium point of temp regulation in the brain
decrease
administration of opioids via the ________________ route causes urinary retention the most
neuraxial
why do opioids cause urinary retention?
- decreases detrusor muscle tone
primary use of morphine is for __________________ pain
moderate to severe
which opioid is the LEAST lipophillic
morphine
IV onset of morphine
20 min
peak of morphine
30-60 min
morphine is ____________% protein bound
35
DOA of morphine
4-5 hours
Vd of morphine
2.8 L/kg
metabolism of morphine
- occurs in the liver via phase II biotransformation
what is the active metabolite produce from morphine metabolism
morphine - 6 - glucuronide
T/F: the active metabolite of morphine metabolism is more potent than morphine in the CNS but has a higher lipophillicity
false; is more potent in the CNS but has a higher hydrophillicity
the decreased lipophillicity of morphine compared to the other opioids –> ______________ onset of action, and _______________ DOA due to ___________ absorption
delayed; longer; slow
what is the cause of a prolonged effect/excessive sedation of morphine in patients with renal failure
the active metabolite Morphine-6-glucuronide
1/2 life of morphine in adults
3-5 hours
1/2 life of morphine in peds
4-13 hours
dose of morphine
1-4 mg
effects of morphine
- sedation THEN analgesia
routes of morphine administration
- PO
T/F: sedation is an appropriate indicator of analgesia
FALSE
why is morphine less commonly use intraoperatively compared to fentanyls
slow onset and peak effects + large patient variablility
MOA of morphine
- causes inhibition of the ascending pain pathways
hydromorphone is ___________x more potent than morphine
7-8
IV onset of hydromorphone
15-30 min
peak of hydromorphone
30-90 min
hydromorphone is _______% protein bound
20
Vd of hydromorphone = ___________
4 L/kg
DOA of hydromorphone
4-5 hours
metabolism of hydromorphone
- liver
1/2 life of hydromorphone
1-3 hours
dose of hydromorphone
0.2 - 2 mg
hydromorphone is used in the management of __________________ pain
moderate to severe
effects of hydromorphone
- generalized CNS depression
routes of administration for hydromorphone
PO, PR, IV
__________________ is the most widely used opioid in anesthesia
fentanyl
fentanyl is _________________x more potent than morphine
80 - 100
IV onset of fentanyl
2-5 min
peak of fentanyl
20-30 min
fentanyl is highly _______________ (lipophillic or hydrophillic)
lipophillic
fentanyl is ___________% protein bound
84
Vd of fentanyl
4 L/kg
DOA of fentanyl
30 min - 1 hr
metabolism of fentanyl
- first pass uptake in lungs with temporary accumulation before release to the periphery
clearance of fentanyl is dependent on
hepatic flow
fentanyl is eliminated via
kidneys and bile
1/2 life of fentanyl
2-4 hours
single dose actions of fentanyl is terminated via ___________________, and continuous infusion actions are terminated via ___________________
redistribution; elimination
induction dose of fentanyl
1-2 mcg/kg
maintenance dose of fentanyl
25-100 mcg
elimination of fentanyl is prolonged is who?
- elderly
MOA of fentanyl
increases the pain threshold & inhibits ascending pain pathways
effects of fentanyl
- profound dose dep analgesia and sedation
routes of administration of fentanyl
- IV
IV onset of remifentanil
1 min
peak of remifentanil
1 min
remifentanil is _________% protein bound
58
Vd of of remifentanil
0.39 L/kg (smallest of all we have discussed)
DOA of remifentanil
5-10 min
metabolism of remifentanil
rapidly metabolized in blood via tissue esterases then catalyzed further by general esterases via hydrolysis to less active compound
1/2 life of remifentanil
9 min
dose of remifentanil
0.2-2 mcg/kg/min
T/F: if use remifentanil for intraop pain management, you need a plan for post op management
TRUE
MOA of remifentanil
- increases pain threshold and alters pain perception
__________________ is a phenylpiperidine with an ester link
remifentanil
effects of remifentanil
- dizziness
due to this drug being powder that contains free base + glycine, this drug has a huge risk for glycine neurotoxicity
remifentail
why is remifentanil not to be used via neuraxial routes
risk for glycine neurotoxicity
what is the onset of sufentanil
1-3 minutes
sufentanil is __________% protein bound
93
Vd of sufentanil
2L / kg
DOA of sufentanil
dose depdendent
metabolism of sufentanil
hepatic via O-demethylation and N-dealkylation
1/2 life of sufentanil
6 hours (longest of the opioids)
infusion dose of sufentanil
0.05 - 0.5 mcg/kg/hr
bolus dose of sufentanil
0.1 - 2 mcg/kg
sufentanil gtt should be d/c’d _____________ min prior to emergence
30-60
MOA of sufentanil
increases the pain threshold & inhibits ascending pain pathways
effects of sufentanil
- dose dep CNS sedation/depression
routes of sufentanil
IV and intrathecal
what drug would be used in situations where profound and often long term anesthesia/analgesia required (cardiac cases, chronic pain, &/or free tissue transfers/flaps)
sufentanil
what is context sensitive 1/2 time
time required for plasma concentrations of a drug to decrease by 50% after discontinuation of an infusion
T/F: context sensitive 1/2 time can be predicted by elimination 1/2 life
FALSE
context sensitive half-time is dependent on the __________________ of the drug
distribution
what drug has a short, stable context sensitive 1/2 time
remifentanil
what drug has a variable context sensitive half time and less predictable
fentanyl
MOA of nalbuphine
- kappa agonist
IV onset of nalbuphine
2-3 minutes
peak of nalbuphine
20 min
nalbuphine is _________% protein bound
0
DOA of nalbuphine
2-3 hours or 3-6
Vd of nalbuphine
4.8 L/kg
metabolism of nalbuphine
via liver
nalbuphine should be cautioned in those with ________________ impairment and dose should be reduced
hepatic
dose of nalbuphine
10mg / 70 kg every 3-6 hours ; max single dose = 20 mg
gtt of nalbuphine
0.3-3mg/kg over 10 min; max = 20 mg
effects of nalbuphine
- generalized CNS depression
routes of nalbuphine
SQ, IM, IV
what opioid OD effects are NOT reversible with narcan?
- shakiness
IV onset of naloxone
2 min
peak of IV naloxone
5-15 min
T/F: naloxone crosses the placenta
TRUE
DOA of naloxone
20-60 min (note this is less than most opioid agonists, so may have to repeat dose)
metabolism of naloxone
hepatic metabolism via glucoronidation via biotransformation (needs glucuronic acid in phase II)
1/2 life of naloxone
10 hours
dose of naloxone
1 mcg/kg repeat as needed
how should you mix naloxone?
0.4 mg with 9 mL = 40 mcg in 10 mL
MOA of naloxone
competitive antagonism of mu, kappa, and delta receptors
effects of naloxone
- reverses analgesia
routes of naloxone
IM, IV, intranasal
what is the goal of administering naloxone in anesthesia
to reverse respiratory depression but maintain the analgesia
fentanyl patches reach peak plasma concentration in ______________
18 hours
the delivery of fentanyl patches is done in ____________
mcg/hr
elimination half life of fentanyl transdermal patch
17 hours
what is the dose range of fentanyl transdermal patches
25-100 mcg
T/F: transdermal fentanyl not recommended for postop pain
TRUE
what is the name transdermal fentanyl
duragesic
which opioid has the highest absorption sublingually
fentanyl
what is a common s/e of sublingual opioids
pruritus
transmucosal fentanyl uses
- lollipop for peds
transmucosal fentanyl is dissolved in a _____________ solution and placed in a lozenge
sucrose
which opioids are minimally absorbed sublingually
- hydromorphone
