Chapter 20: Opioid Analgesics Flashcards
opioids act at several points throughout the pain pathway, what is a disadvantage of this?
can cause a wide variety of ADRs
t/f opioids have been used as analgesics for thousands of years
t
what is an example of a naturally occurring opioid?
morphine
codeine is isolated from the ___
opium poppy
oxycodone, buprenorphine and heroin are all ____ forms of opioids
semi-synthetic
___ is the prototypic opioid
morphine
fentanyl and methadone are ___ type opioids
fully synthetic
what are the 3 types of opioid receptors?
mu, delta, and kappa
all opioid receptors are coupled to either ___ or ___ g proteins
Gi/Go
what are the endogenous agonists of opioid receptors?
endorphins, enkephalins, and dynorphins
endorphins act primarily on ___ opioid receptors
Mu
enkephalins act primarily on ___ opioid receptors
delta
dynorphins act primarily on ___ opioid receptors
kappa
the ___ opioid receptor is the most clinically targeted for pain relief
mu
peripheral nerves sense pain, carries it to the spinal cord, where ___ and ___ are released
glutamate and neuropeptides
release of glutamate from the presynaptic neuron causes __ in the postsynaptic neuron
depolarization by opininf Na channels and AP to be carried to the brain
what happens when mu opioid receptors are activated in the periphery?
opens K channels, causing hyper polarization, helping to stop the AP that would cause the brain to recognize the pain
in the spinal cord, mu receptors are located on the ___ neuron and their activation prevents the opening of ___ channels with results in a decrease in ___ release
presynaptic; Ca; NT
activation of mu receptors on postsynaptic neurons causes the ____ channels to be open longer, causing the neuron to become ___ and require a stronger stimulus to activate
K; hyperplarize
opioids cause the closing of ___ channels and the opening of ___ channels
ca; K
outline the anatomical pathway of ascending pathways
primary afferent neurons receives pain stimuli, spinal cord, brain stem, cortex for processing
opioids cause an increase in the DA ____ pathway
reward
opioid modulation of mu receptors in the cortex likely plays a role in dampening the perception of ____ attached to painful stimuli
emotion
pain stimuli are transmitted to the ___ horn of the spinal cord
dorsal
t/f in the descending pathway, stimuli are processed in the cortex and signal is sent back to the periphery
t
stimulation of mu receptors enhances the descending inhibitory signals by reducing ___ release into the inhibitory circuit
GABA
t/f inhibiting signals from moving from the spinal cord helps prevent pain
true
stimulation of mu receptors in the ___ enhances inhibition of signal in the spinal cord
midbrain
mu receptors in the __ are responsible for autonomic function
midbrain
mu receptors in the ___ are responsible for baroreceptor reflex and respiration
medulla
bc mu receptors are present in many brain regions, opioids can have systemic effects such as :
sedation, respiratory suppression, nausea, decreased GI motility, CV (bradycardia and hypotension)
t/f sedative effects of opioids are significant and shouldn’t be mixed with other drugs that have sedative effects
t
should benzodiazepams / alcohol be used when using opioids?
no, too much sedative
what is the most serious and life threatening effect of opioids that occurs in OD?
respiratory suppression
Naloxone MOA
competitive antagonist of mu opioid receptor, removing opioid during overdose to restore respiration (available as nasal spray)
Naloxone reverses the effects of opioid OD within ___ (time)
2-3 minutes
what is the duration action for naloxone?
short, 1-2 hours (important to monitor pt incase opioid still present after this time)
naltrexone has a half life of ___ and onset time of ___
10 hrs; 30 min-1hr
what is the role of naltrexone in OD treatment?
used once respiratory suppression has been reversed by naloxone and acts to prevent reoccurrence should naloxone be cleared before the opioid
the full agonists: ___, ___ , ___, and ___ all have high potency at the mu receptor and strong analgesic activity
morphine, oxycodone, fentanyl, methadone
fantanyl is approximately ____ x more potent than morphine
100
oxycodone and methadone have similar potency to morphine, but have higher ___
oral bioavailability
buprenorphine is a agonist at ___opioid receptors and an antagonist at __ and ___ opioid receptors, making it a mixed opioid receptors
mu; kappa; delta
it is not well known, but it is thought that blocking kappa and delta opioid channels reduces risk of ___
opioid dependence / abuse
codeine is known as a ___mu receptor opioid ___ agonist
weak; partial
the majority of the analgesic effects of codeine come from its biotransformation to ___
morphine
what is the benefit of administering codeine with caffeine and acetaminophen?
al these together have a synergistic effect on pain lowering, so less opioid is needed
how does caffeine in Tylenol 3 help reduce risk of addiction?
offsets sedative effect
a small amount of codeine is metabolized by the ___ enzyme to morphine in the liver
CYP 2d6
codeine has __% oral bioavialbility and ___% is metabolized to morphine
50, 10
t/f there is a popular polymorphism of the CYP2d6 enzyme, so different groups of people may turn codeine to morphine to a greater or lesser extent than expected
t
give 2 examples of opioids that rely less on CYP2D6 metabolism
morphine and oxycodon
which is more potent and has a higher oral bioavailability, morphine or oxycondone?
oxycondone
oxycodone is primarily metabolized by the ___ enzyme
CYP3A4
oxycodone is indicated for what pain level?
severe (7-10)
small doses of oxycodone in combination w/ non-opioid analgesics are indicated for what level of pain?
moderate
___ is the brand name for the combination of oxycodone and acetaminophen
percocets
t/f Percocet was discontinued in Canada (still exists as endocet etc)
t
___ is the most well known brand name of oxycodone
oxycontin
oxycontin is in a ___ type formulation which allows for __
controlled release; longer action
what is the duration of action for oxycontin?
12hrs
t/f their is a lot of controversy around oxycontin and possibly paying prescribers
t
what is the issue with the CR formulation of oxycontin by Perdue pharma?
easily crushed which causes immediate high, especially if dissolved and injected
if crushed oxycontin is injected, it has a similar effect as __
heroin
explain the formulation of Oxyneo form of oxycodone
difficult to crush and not water soluble, making it harder to abuse
t/f very little (micrograms) of fentanyl is needed to achieve analgesic
t
what is the indication for fentanyl?
severe pain in patients tolerant to other opioids (ex: cancer pain)
what is opioid tolerance?
loss of effectiveness even with repeated dosing when used for extended period of time
t/f opioid tolerant patients are also more resistant to respiratory suppression
t
t/f the exact mechanism of opioid tolerance is unknown
treu
what altered pharmacokinetics may be involved in opioid tolerance?
altered metabolism, increased clearance
how might altered opioid receptor signalling be involved in opioid tolerance>
receptor desensitization, altered downstream signalling pathways
how might altered neuronal circuitry be involved in opioid tolerance?
increased depression of NMDA receptors
fentanyl is often given as a ___ formulation because it has poor oral bioavailability
parenteral
for rapid onset of analgesic, ___ and __ formulations of fentanyl may be used
SL and IV
___ formulations of fentanyl are useful to allow slow absorption over many hours to get stable long-lasting analgesic effect
transdermal patch
t/f fentanyl is contraindicated in patients who do nat have opioid tolerance / are opioid naive
t
when opioids are abused, it is typically the ___ at the inset of the dose that is desired by the patient
euphoric high
the rapid decrease in opioids that have a quick onset and short duration can cause a ____ that leads to drug-seeking behaviour
“crash”
drugs that have a wearing off effect where a patient may experience pain between dosing can lead to ___
overuse and drug seeking and tolerance
what types of drugs are best for management of opioid use disorder>
opioid agonists with long duration of action and slower onset to reduce addictive qualities while also helping prevent severe withdrawal
what is a downside of methadone?
it is a full agonist of mu and can itself be abused
a specific formulation of buprenorphine called ___ includes a small dose of naloxone to discourage abuse
suboxone
how does the addition of naloxone in suboxone discourage abuse?
if excess is taken in an attempt to get high, the naloxone will antagonize these effects
buprenophine is a ___ of the mu receptor that may help its taper off opioids while reducing withdrawal symptoms
partal agonsit
