opiods Flashcards
what are the 4 basic parts to the pathophys of pain
- transduction
- transmission
- modulation
- perception
what are the 3 receptor families that opiod receptors elicit effects on?
mu, kappa and delta
what does agonizing mu (u) receptors do?
Agonizing leads to analgesia, bradycardia, sedation, respiratory depression, euphoria, and physical dependence
what does agonizing kappa (k) receptors do?
Agonizing leads to analgesia and respiratory depression
what does agonizing delta (d) receptors do?
Agonizing leads to analgesia, respiratory depression, and sedation
Analgesia is produced when agents act as agonist on the three opioid receptors to inhibit the transmission of what?
nociceptive input and the perception of pain
what is the main MOA of opiods in regards to the mu opiod receptor?
Bind to mu opioid receptors in the
-CNS, GI TRACT and BLADDER causing inhibition of ascending pain pathway altering the perception of and response to pain
what are opiod receptors MOA in regards to kappa and delta receptors (less important that mu receptor MOA) ?
kappa- act in dorsal horn of spinal cord, inhibit substance P release
delta- inhibit release of excitatory neurotransmitters from nerve terminal
what is the benefit/downsides of transdermal patch preparation of opiod?
better longterm pain control but takes longer to work
benefit of using intranasal prep of opiod?
avoid 1st pass and dont need as high of a dose
what is the difference between a full and partial opiod agonist ?
full: no clinically relevant max response (no ceiling effect) - as dose is raised, analgesia effects increase until analgesia is achieved OR dose-limiting side effects occur
partial: produces less than a max response when fully-occupying receptors (ceiling effect)
what is a mixed agonist/antagonist?
Drug acts as a full agonist, but antagonist component binds to receptor without activating it to prevent increased binding of agonist. (ceiling effect)
what is a Naturally occurring opioid that is weak analgesic compared to morphine?
codeine
what is codeine used for?
use low for anti-tussive, then at higher doses for mild-moderate pain
codeine is contraindicated in children under age ____ or undergoing what procedures?
18
tonsillectomy/adenoidectomy
what do we need to worry about with the metabolism of codeine?
codeine is converted to morphine by CYP2D6…
rapid metabolizers: convert codeine to higher than usual levels of morphine causing toxicity
poor metabolizers: who when taking CYP2D6 inhibitors (ex. Fluoxetine) the cannot convert codeine to morphine and may not experience analgesic effect
what is a Semi-Synthetic opioid (means we tweaked a naturally occuring one and manufactured it) that is metabolized by CYP2D6 to hydromorphone?
hydrocodone (loratab)
what is the absorption and metabolism of morphine?
good abs, extensive 1st pass metabolism
what patient population do you need to be careful prescribing morphine for?
patients with renal insufficiency because of accumulation of toxic metabolite
(Patients have agitation, confusion, & delirium)
what are “abuse deterrent formulations” of morphine and oxycodone?
formulations that, when crushed/dissolved for injection either illicit NO EUPHORIC effects or illicit ADVERSE effects
what kind of drug is hydromorphone? strength compared to morphine?
semi-synthetic opiod, several times more potent than morphine (more lipophilic = faster abs)
what are the different formulations of hydromorphone?
IV, rectal, PO (short and long acting)
what would be a safer choice than morphine for someone with renal insufficiency?
hydromorphone
fentanyl is ___ times more powerful than morphine
100
Transdermal fentanyl should only be started after what?
Transdermal should only be started after initial titration with a short-acting opioid
exposing the fentanyl patch to heat (heating pad, exertion - exercise, or high fever) could increase risk for what?
increase release of drug and risk for respiratory depression
what is the proper disposal of fentanyl patch?
fold in half and flush
what formulations are there for oxycodone?
only oral
what kind of drug is oxycodone? compared to morphine?
semi-synthetic derivative of morphine, 1.5 times more powerful than morphine
hydrocodone and oxycodone are both often combined with what for acute pain?
acetaminophen
oxycodone for chronic pain?
extended release formulation
what kind of drug is oxymorphone? strength compared for morphine?
semi-synthetic opiod, metabolite of oxycodone
- orally: 3 times more potent than morphine
- IV : 10 times more potent than morphine
what is the 1/2 life of methadone? why is this significant?
very long, up to 5 days.
- Repeated doses can lead to accumulation of CNS depression without close monitoring during titration period
what do we need to know about switching from another opioid agonist to methadone?
NEEDs to be done by specialist b/c equianalgesic dose of methadone is not well established in opioid-tolerant patients
in addition to the accumulation –> CNS depression, what else might be a concern with dose-related effects of methadone?
dose-related QT prolongation
how often do you give methadone for chronic pain? for drug abuse withdrawal?
chronic pain: every 8 hours (great 1st line for cancer pain)
drug abuse: once daily
why is meperidine a “least favorite” drug of Dr. Cleveland?
Has metabolite, normeperidine (VERY TOXIC), with a 15-30 hour ½ life
extra info:
- CNS effects (if renal failure, elderly or on for a long time)
-antimuscarinic effects (pupils dilate & tachycardia)
- encephalopathy and death: If recent use of MAOI
meperidine should ONLY (if at all) be used when?
short term (24-48 hrs), moderate-severe acute pain - (rapid onset of axn and short acting)
what are the 2 natural opiods?
- codeine converted to morphine
- morphine
what are the 4 semi-synthetic opiods?
- hydrocodone converted to hydromorphone
- hydromorphone
- oxycodone converted to oxymorphone
- oxymorphone
what are our two mixed-mechanism opiod drugs?
what does this mean?
- tramadol
- tapentadol
- these both target mu receptor and norepi and/or serotonin receptors as well.
what is the MOA of tramadol?
mixed mechanism: Synthetic codeine analog
Weak morphine receptor agonist with NET and SERT activity
what are the ADRs of tramadol? what are the upsides?
- exacerbate seizures
- BUT less respiratory depression and constipation than other opiods
what drugs lower seizure threshold? (maybe weeds)
TCAs (i.e. amytriptyline), SSRI, MAOI
anti-depressants
what is the MOA of tapentadol?
mixed mechanism: Opioid receptor agonist and a norepinephrine reuptake inhibitor
whats the one ADR we need to worry about with tapentadol?
serotonin syndrome (dont use with or w/on 14 day use of MAOI)
what is the one partial agonist opioid drug?
buprenorphine : Drug binds to and activates opioid receptor to produce less than a full response when fully occupying their receptors
what are the two uses of buprenorphine?
chronic pain and opiod use disorder
opioid dosing, which will generally have higher dose- IV or oral?
oral
30mg of oral morphine = ___ mg of hydrocodone = ___ mg of oral codeine = ____ (bl/buccal) of fentanyl
30mg hydrocodone
200mg - codeine
0.2 (sl/buccal) -fentanyl
how do you calculate the total daily dose of an opioid? what is the goal to keep it under?
- determine total daily amount of each opioid the person takes
- you convert each drug to the MME (morphine mg equivalent) ( multiple each by the conversion factor)
- add together
GOAL: under 50 total
definitely keep under 120 (dangerous level!)
opiods: all formulations have good abs, but which has significant first pass metabolism? why is this important to know?
abs well in all forms: IM, SQ or PO
1st pass: oral
- oral dose may need to be much higher than parenteral
- but amount of 1st pass varies from individual to individual
what is the distribution like for opiods?
LARGE volume of distribution
( they rapidly leave the blood compartment and localize in high concentrations in highly perfused tissue (brain, lungs, liver, kidneys & spleen)
Morphine is metabolized to ____ and ____
Hydromorphone is metabolized to ___
morphine: M3G & M6G
hydromorphone: H3G
morphine metabolite- M3G and hydromorphone metabolist H3G can both accumulate and cause what ADRs? what patients do we need to worry about this with?
neuroexcitatory & potential to cause seizures
(renal failure patients)
morphine metabolite M6G can accumulate and cause what?
oversedation & respiratory depression
the metabolite of merpiridine, normepiridine can cause what major ADR?
Can cause seizures in patients with renal failure , elderly or on a high dose for a long time
what is the only opiod that doesnt go through phase 1 CYP450? what does it go through? (maybe weeds)
oxymorphone: only goes through phase 2 (gluconization)
dose-related respiratory depression with opioids, why is this a major concern if someone has had head trauma?
Dose related respiratory depression leading to increased PCO2 (when you have this buildup = vasodilation. if head trauma… increase in cerebral pressure)
what are the 6 CNS effects of opioid-receptor stimulation?
- euphoria
- sedation w/out amnesia
- respiratory depression
- cough suppression (codeine)
- miosis
- N/V activation of chemoreceptor trigger zone
possible peripheral effects of opioid receptor activation
first 2 important, last 4 less important
- cardiovascular - possible HYPOtension
- GI- mu receptor- constipation
- gallbladder - smooth muscle contraction- pain with GB disease
- GU- urine retation
- Uterus- potentially prolong labor
- skin- urticaria, pruritis, flushing & warm skin (histamine release)
what are the possible cardiovascular effects of opioids? what is the one outlier for these effects?
usually well tolerated unless someone has CV stress
- if CV disease or is hypovolemic narcotics –> blood vessel dilatation & hypotension
- outlier : Meperidine (anticholinergic effects) –> tachycardia
tolerance usually begins to develop after ___ - ___ wks of chronic therapeutic narcotics
2-3 weeks
what is the progression of tolerance? (maybe weeds)
reduced ADRs –> shorter duration of analgesia –> decrease effectiveness with each dose
Tolerance occurs to analgesic effects and all other effects EXCEPT ____, _____ , and ______
miosis, seizures & constipation
- these effects will ALWAYS be there
4 opioid-induced constipation txts (weeds)
Methylnaltrexone (Relistor)
Naloxegol (Movantik)
Naldemedine (Symproic)
Alvimopan (Entereg)
what is opioid rotation?
if experiencing decreasing effectiveness of one opioid analgesic regimen they are “rotated” to a different opioid analgesic (to prevent tolerance and dose escalation)
=significantly improved analgesia at a reduced over-all equivalent dosage
-changed drugs = change receptor types and therefore get greater affect from the new receptors
physical dependence with opiods: phase 1 (timeline- hours without the drug, and effects)
up to 8 hrs
-anxiety and drug craving
physical dependence with opiods: phase 2 (hours without the drug and effects)
8-24 hours
- anxiety & insomnia
- GI upset
- rhinorrhea & diaphoresis
- mydriasis (dilation of pupil)
physical dependence with opiods: phase 3 (timeline- hours without the drug and effects)
up to 3 days
- tachycardia, hypertension
- N/V, diarrhea
- fever, chills
- seizure, tremors, muscle spasm
taking someone off an opioid you want to taper __% at a time (maybe weeds)
10%
All opioids are controlled (scheduled) drugs…
full vs partial agonist (which is more addictive, what is the correlating schedule) ?
Full agonists tend to be more addictive (higher schedule, lower number, 2) partial agonists (lower schedule, high number 3 or 4)
Pregnant women dependent on opioids should switch to
______ or ______
buprenorphine or methadone
increased risk of respiratory depression with opioids + what other drugs? (maybe weeds)
Alcohol, general anesthetics, phenothiazines (anti-emetic promethazine), benzodiazepines (xanax, adivan, etc), TCA
opioid withdrawal for mothers/newborns is associated with what?
spontaneous abortion and premature labor… better to taper them both off.
which 5 drugs have increased risk of serotonin syndrome with MAOIs ? (maybe weeds)
tramadol, tapentadol, methadone, meperidine, and fentanyl
which 7 drugs have CYP34A metabolism substrate? (maybe weeds)
Buprenorphine, fentanyl, hydrocodone, meperidine, methadone, oxycodone, and tramadol
which 3 drugs have CYP2D6 metabolism substrate? (maybe weeds)
Codeine, methadone, hydrocodone
WHO analgesic ladder: mild pain
non-opiod (acteaminophen (i.e. paracetamol), ASA, NSAID)
+/- adjuvant
WHO analgesic ladder: mild to moderate pain
opioid (codeine, tramadol, etc,)
+/- non-opiod
+/-adjuvant
WHO analgesic ladder: moderate to severe pain
opioid (morphine, fentanyl, etc,)
+/- non-opiod
+/-adjuvant
what agents may you use for localized pain? (maybe weeds)
Topical agents – diclofenac gel/patch or lidocaine creams/patch
what kind of opioids are you using for severe pain? what dose for how long?
Immediate release opioids
Lowest effective dose for shortest duration of time
Preferred less than 7 days
when would you use opioids for neuropathic pain?
only if antiepileptics (“gabas and carbas” , antidepressants and topicals dont work
why might you use morphine for pulmonary edema? what would you try first?
IV morphine decreases SOB by decreasing anxiety, dyspnea, preload and afterload
Works well if having an MI with chest pain & pulmonary edema
*try loops (furosemide) first, but if they still have pain then add morphine
if a patient HAS to have MME over 50, what else might you do to prevent ADRs? (maybe weeds)
add opioid antagonist
txt of diarrhea, diphenoxylate combined with ______ to prevent addiction (weeds)
atropine
what is naloxone (narcan) used for?
to save someone who ODed. Bind to but do not stimulate the narcotic receptor and end up blocking effects of other agonists
what if you give narcan to someone who doesnt have an opioid in the system?
nothing happens, it just sits on the opiod receptor and does nothing
how long does it take narcan to work?
1-2 minutes (fast acting)
what is the half life of narcan? why is this significant?
Half life - 2 hours
May wear off before all opioids metabolized – patient may relapse
what are the formulations for narcan? why?
naloxone- undergoes 1st pass metabolism so it NEEDS to be intranasal or IV
what is the difference between naloxone (narcan) and naltrexone?
naltrexone: longer DOA, up to 48 hours. used for maintenance programs to block heroine effects
