opioid agonists Flashcards
name some morphine derivatives
dilaudid (morphine with a hydroxyl group added)
heroin (morphine with two acetyl groups added)
how do opioid agonists produce miosis?
opioids cause miosis (pupillary constriction) by acting on mu and kappa receptors to stimulate the Edinger Westphal nucleus of the oculomotor cranial nerve (CN3) to constrict pupils
“The Edinger–Westphal nucleus is the accessory parasympathetic cranial nerve nucleus of the oculomotor nerve (cranial nerve III), supplying the constricting muscles of the Iris.” - wikipedia
name some phenylpiperidine derivatives
demerol
anything with fentanyl like sufenta, remi, etc.
most commonly used opioid agonists in anesthesia
why can’t you use opioids as the sole anesthetic?
two reasons
respiratory depression
not reliable as anesthetics
phenylpiperidines vary widely in potency, from the least potent __ to the most potent __
least - demerol (50mg to stop shivering)
most - sufenta (0.4 mcg/kg/min as an infusion)
where do opioid agonists work?
STEREOSPECIFIC receptors sites at pre and post synaptic sites in the CNS, also outside the CNS in peripheral tissues
NON-ionized and LEVOrotary
what is the prototypical opioid agonist?
morphine
where do neuraxial opioids exert their effect?
mu receptors of the substantia gelatinosa in the spinal cord
the epidural dose is usually __x greater than the subarachnoid dose
5-10x
remember, neuraxial opioids are specific for __, not somatic pain
visceral
epidural opioids work via mu spinal cord receptors AND __
systemic action
which way do neuraxial opioids move?
is the movement greater with more or less lipid soluble opioids?
they move cephalad
movement is greater with LESS lipid solubles like morphine
what’s the most common side effect of neuraxial opioids?
pruritis
what is poikothermia?
when the body temp equilibrates with room temp
is pruritis from histamine release?
NOPE, it’s due to cephalad migration in the CSF to trigeminal nucleus
treatment is narcan, antihistamines
four main side effects of neuraxial opioids
pruritis, urinary retention, ventilatory depression, sedation
how do neuraxial opioids cause urinary retention and what is the treatment?
opioid receptor activation in sacral spinal cord inhibits sacral parasympathetic outflow causing detrusor muscle relaxation and greater bladder capacity
reversed with narcan
what is the MOST SERIOUS side effect of neuraxial opioids?
respiratory depression, 2 hours think cephalad migration in CSF interacting with ventral medulla
occurs most often with morphine, coughing, ongoing use
sedation after neuraxial opioid is most common with __
sufentanil
should you use morphine WITH preservatives in epidural/SAB?
no
how do neuraxial opioids cause water retention?
release vasopressin
since neuraxial opioids delay gastric emptying, if your epidural patient becomes a crash c-section, besides the fact they are a full stomach, hold ___ !
cricoid
analgesia with morphine is best when given __ pain starts
before
morphine has a slower peak than fentanyl due to slower penetration of the __
BBB
morphine has poor CNS penetration due to high ionization, poor lipid solubility, and rapid conjugation via __ acid
glucuronic acid
where and how is morphine metabolized?
glucuronic acid conjugation in liver and kidney, 75% changed to morphine-3 which is INACTIVE, 25% changed to morphine-6 which is GREATER analgesic than morphine
morphine is eliminated in the __ so it has a cumulative effect in end stage renal patients
urine
how does morphine drop your BP?
- decreased SNS tone to capacitance vessels = decr venous return
- bradycardia from stimulation of vagal nuclei in medulla = decr cardiac output
- histamine release
give morphine no faster than __ mg/min
5 mg/min
how do people breathe on morphine?
like a hibernating bear, big tidal but slow rate, net increased PaCO2
could be bad for neuro patients d/t incr ICP from incr CO2
how to correct angina like pain caused by morphine induced spasm of biliary smooth muscle?
narcan, glucagon, ntg
signs your CRNA friend may be going through morphine withdrawal
yawning, sweating, can’t sleep, restless, cramps, N/V, diarrhea
what was the first synthetic opioid agonist? what receptors does it work on?
synthesized by Nazi chemists using cyanide and methylamine
meperidine/demerol
where and how is meperidine metabolized? any metabolites?
hepatic metabolism, urine excretion, metabolite = nor-meperidine, has half the potency
you’re not allergic to meperidine, you’re allergic to __-meperidine
nor-meperidine
meperidine is 60% protein bound so has greater effects in __, __, and __ failure patients
elderly, malnourished, liver failure
what opioid has the narrowest therapeutic index of all?
meperidine
how does meperidine decrease post-op shivering?
kappa agonism
meperidine for cough? diarrhea? cardiac?
no, no, no
has similar structure to atropine so increases HR and heart O2 req’s
produces MYDRIASIS, not miosis
fentanyl can rapidly redistribute to inactive tissues like fat and muscle, but the __ can store up to 75% of the initial dose
lungs
fentanyl metabolism and metabolite
metabolized to nor-fentanyl - minimally analgesic
urine excretion
fentanyl dosages and responses
1-2 mcg/kg
2-20 mcg/kg
50-150 mcg/kg
1-2 analgesia
2-20 adjuvant to inhaled
50-150 sole anesthetic
what are the disadvantages to using fentanyl as the sole anesthetic?
not reliable amnesia, post op ventilatory depression, sympathetic breakthrough, absorbed by CPB circuit
what are the advantages to fentanyl?
not a myocardial depressant (but does cause bradycardia by depressing carotid sinus - could be dangerous to neonates)
no histamine release
supression of stress response
it comes in a lollypop
fentanyl and ICP
increased ICP
sufenta is __ to __ more potent than fentanyl
5-10x
sufenta metabolism and metabolite
dealkylation into inactive metabolites
sufenta excretion
equal urine and GI
sufenta can cause prolonged vent depression in __
ESRD
how is sufenta better than fentanyl?
greater analgesia and less vent depression, more rapid induction, earlier emergence and extubation, minimal hemodynamic changes
sufenta is NOT better than fentanyl in these areas
not perfect in blunting BP and stress response to surg, may cause chest wall rigidity, bradycardia
remifentanyl is unique due to its __ linkage
ester
how is remi metabolized?
ester hydrolysis
which is more potent, remi or fentanyl?
equal
how fast can steady state be reached with a remi infusion?
10 minutes
does remi have active metabolites?
no, otherwise it would not have such a short action
does remi last longer in pt’s with liver or kidney failure?
nope, go ahead and use it.
what receptor for remi?
mu
what if your patient has a plasma cholinesterase difficiency, should you use remi??
not a problem, use it.
your patient may develop chest wall rigidity and be unable to ventilate with remi. what should you do?
hypnotics or NMB
does remi cause histamine release?
any problems with giving remi to a ESRD or liver?
no
no
narcan is a pure antagonist
reverses opioids
