EXAM #3 OPIOIDS REVIEW Flashcards
Pain is transmitted via a______That originates where?
three-neuron system that originates
at the periphery and ends at the cerebral cortex.
At periphery tissues, noxious stimuli are mainly received and transmitted by
A beta, A delta, and C fiber neurons.
These first-order neurons synapse with
second-order neurons in the dorsal horn of the spinal cord level.
Second-order neurons
travel up the spinal cord via the
dorsal column and spinothalamic tract and synapse with third-order neurons at the thalamus, which then transmit signals to the cerebral cortex, the site of pain perception.
Opioids exert their effects at
receptors at all three levels of this system.
The major receptors activated by opioids are
mu, delta, and kappa
Opioids receptors are
These are G-coupled receptors, which carry the
mediator-induced signal in conjunction with a second messenger such as cyclic adenosine monophosphate (cAMP).
Opioids receptors are
G-coupled receptors, which carry the mediator-induced signal in conjunction with a second messenger such as cyclic adenosine monophosphate (cAMP).
Where are opioids receptors located? They are located at the
periphery, the dorsal horn of the spinal
cord, and finally the brainstem, thalamus, and cortex.
At the opioid receptor locations, the three major mechanisms of action are:
- Inhibition of presynaptic Ca2+ influx, which depolarizes the cell and inhibits the release of neurotransmitters at the synaptic cleft.
- Increasing postsynaptic K+ efflux, which depolarizes and inhibits cellular signal transmission.
- Activation of the descending inhibitory pain pathway
via inhibition of GABAergic receptors found in the
brainstem.
Opioid analgesia is primarily achieved at the brain, spinal
cord, and peripheral tissues via
mu1 and mu2 receptors.
In the spinal cord, opioids target
mu2 receptors
Supraspinal sites are
periaqueductal gray matter
locus coeruleus
nucleus raphe mmagnus) effects are achieved at mu1 receptor
Supraspinal effects are achieved at
Mu 1 receptor
Morphine on respiratory system
Morphine and other mu1 agonists decrease CO2 responsivity in the medullary respiratory center.
Morphine on ventilatory response
There is a right shift and decrease in the slope of the ventilatory response to CO2 curve
Remifentanil is most notably known for its short
context-sensitive half-life
Morphine : It is primarily metabolized by
hepatic phase II conjugation (3- glucuronidation) to form morphine-3-glucoronide
Methadone protein binding and metabolism
Methadone is 90% protein bound and
undergoes N-demethylation in the liver
Fentanyl metabolism and % excretion
in the liver by N-dealkylation to norfentanyl and only 6% is excreted unchanged by the kidneys.
How does meperidine reduces shivering?
Through kappa-opioid receptors,
Whereas all opioids and propofol in a dose-dependent manner,
suppress motor evoked potentials (MEPs)
Remifentanil and MEPs
suppresses MEPs to a lesser extent.
The partial agonists and mixed agonist–antagonists are have clinical effects at mu and kappa receptors
nalbuphine, butorphanol, and buprenorphine
The partial agonists and mixed agonist–antagonists are have clinical effects at what receptors?
mu and kappa receptors
What happens with an agonists and a partial antagonists?
When combined with low doses of a full agonist compound, the effects of the partial agonist are additive up to the maximum, or “ceiling” effect of the partial agonist. With increasing doses of a full agonist, the partial
agonist will behave as an antagonist.
Can cause hypotension from histamine release, 2 opioids
morphine and meperidine,
Methadone can cause
Prolonged QT syndrome
Urinary system and opioids
Inhibition of urethral sphincter relaxation causes urinary retention, and can be seen after systemic and neuraxial morphine
administration
High-dose morphine or fentanyl can
reduce abdominal muscle and thoracic wall compliance via supraspinal mu receptors
Hydromorphone vs morphine
High-dose morphine or fentanyl can reduce abdominal muscle and thoracic wall compliance via supraspinal mu receptors
Hydromorphone active metabolites are
dihydromorphine and dihydroisomorphine.
The inactive metabolite of hydromorphone :
hydromorphone-3-glucuronide can accumulate in renal failure patients and cause neuroexcitation and cognitive impairment.
Opioids site of action ; nociceptive pain
the dorsal horn (layer 4 and 5 of the substantia gelatinosa) of the spinal cord, which inhibits the transmission of nociceptive information;
Meperidine active metabolites is_______: What can it cause
Normeperidine; Accumulation such as seen with renal patients can lead to seizures./
How does opioids causes nausea and vomiting?
Opioids stimulate the chemoreceptor trigger zone located in the area postrema of the brain stem, which can result in nausea and vomiting.
Postoperative shivering can be attenuated with
meperidine, which may
act through a k-receptor mechanism.
Dose of meperidine for shivering?
Only 12.5 to 25 mg of meperidine, administered intravenously as a slow push,
Dependence refers to the presence of
withdrawal symptoms if a drug is withheld and can be either physical or psychological.
Psychological dependence refers to
craving for a drug and is synonymous
with addiction.
Tolerance is the need to
increase the dose of an opioid over time to maintain the desired analgesic effect, reflecting the desensitization of the antinociceptive pathways to opiates and the upregulation of opioid binding receptors.
The apnea threshold, defined as the highest Paco2 without ventilatory effort with opiods
increased with the use of opioids.
Opioid- receptor activation inhibits the
presynaptic release and postsynaptic
response to excitatory neurotransmitters (glutamate, acetylcholine, and substance P)
Opioid administration decreases minute ventilation by
decreasing the respiratory rate (as opposed to decreasing the tidal volume).
OPIOIDS administration muscle rigidity can be prevented by
decreasing the rate of opioid administration or by concomitantly administering a neuromuscular blocking agent and controlling ventilation.
The fentanyl family is known to produce
chest wall rigidity
Which analgesic or labor is not associated with significant respiratory depression affecting the mother or fetus?
(A) Mor
Nalbuphine
Your patient has a history of asthma. Which opioid
will you avoid?
(B) Morphine
Which narcotic will you avoid in patients taking MAO inhibitors?
Meperidine ( Demerol)
Those medications lead to metabolites accumulate in patients with renal disease and increase the likelihood o respiratory depression and/or seizures.
Meperidine and Morphine
Which common anesthetic medications should be
avoided during the induction of a patient diagnosed
with acute intermittent porphyria?
Barbiturates and etomidate should be
avoided.
Which o the ollowing has mainly analgesic and anytipyretic properties?
A) Acetaminophen
Which opioid causes the greatest respiration depression in newborns?
Morphine
Rank opioids from most to least lipid-soluble.
Sufentanil Fentanyl Alfentanil Meperidine Remifentanil Morphine
Most of the clinically used opioids arerelatively selective for what receptor: mu, kappa or delta?
Mu receptors
Contrast spinal and supraspinal analgesia.
With spinal analgesia perception of pain is decreased. With supraspinal analgesia the patient’s response to pain is altered
On what receptors do spinal opioids work to produce spinal analgesia?
mu-1, mu-2, kappa, and delta receptors of the spinal cord and brain to produce spinal anesthesia
Spinal anesthesia is mediated primarily by
mu-2 receptors.
On what receptors do intravenous opioids work to produce supraspinal analgesia?
Opioids work on mu-1, kappa, and delta receptors to produce supraspinal analgesia.
Stimulation of what opioid receptor does not produce supraspinal analgesia?
Supraspinal analgesia is mediated primarily by mu -1
receptors.
In addition to spinal and supraspinal analgesia, stimulation of mu-1 receptors elicits what six responses? Does stimulation of mu-1 receptors have high or low
abuse potential?
Stimulation of mu-1 receptors produces:
(l) euphoria
(2) miosis
(3) bradycardia
(4) hypothermia
(5) urinary retention and
(6) pruritus.
Which receptors have low abuse potential?
Mu-1
Supraspinal analgesia is mediated primarily by
mu -1 receptors.
In addition to spinal analgesia, stimulation
of mu-2 receptors elicits what three responses?
Stimulation of mu-2 receptors produces: (1) depression of ventilation, (2) marked constipation, and (3) physical dependence.
Does stimulation of mu-2 receptors have high or low abuse potential?
Mu-2 receptors have high abuse potential because of the physical dependence.
What opioid receptor promotes respiratory
depression?
Mu-2 receptors
At what anatomic locations do opioids work to produce spinal analgesia?
Opioids work in the substantia gelatinosa of the spinal cord and at several supraspinal sites including the periaqueductal and periventricular gray matter.
In what two ways do epidural and intrathecal
opioids produce spinal analgesia?
Opioids administered epidurally or intrathecally diffuse into the substantia gelatinosa and: (I) combine with presynaptic opioid receptors and inhibit the release of substance P, and (2) combine with postsynaptic opioid receptors and decrease activity in neurons ascending in the lateral spinothalamic tracts
An important target for opioids in the brainstem is the
periventricular and periaqueductal gray matter
Does electrical stimulation of the periventricular/periaqueductal gray produce supraspinal or spinal analgesia?
Yes; “
Stimulation of midbrain periaqueductal gray in humans produces _____why?
widespread analgesia:’ This analgesia occurs because the periventricular/ periaqueductal gray sends impulses via the dorsolateral tract down to the spinal cord to inhibit transmission of pain impulses through the
substantia gelatinosa.
What spinal cord tract modulates pain? Explain.
The descending dorsolateral funiculus modulates pain. Action potentials in this tract activate the enkephalin-containing neurons of the substantia gelatinosa, which diminish the transmission of pain impulses through the
spinal cord
What brainstem areas send action potentials to the substantia gelatinosa via the dorsolateral funiculus?
The periaqueductal gray and the periventricular gray.
Spinal cord gray matter was divided by Rexed into how many laminae?
The gray matter of the spinal cord was divided by Rexed into IO lamina (I- X).
Opioids work in which of these lamina?What is
another name for this lamina?
. Lamina II is also known as the substantia gelatinosa. Note: Some sources indicate the substantia gelatinosa is formed by Rexed’s lamina II and III.
What are seven responses to mu -1
receptor stimulation?
(I) Supraspinal analgesia
2) urinary retention
(3) miosis
(4) decreased heart rate
(5) hypothermia
(6) pruritus
(7) euphoria.
Which opioid can block voltage-dependent
sodium channels, in other words, which opioid has local anesthetic properties?
Meperidine is an agonist of both μ- and K-receptor and has been shown to block voltage-dependent sodium channels
Mediate opioid-induced bradycardia.
Mu receptors
Which opioid receptor(s) mediate bradycardia?
mu receptors mediate opioid-induced bradycardia