Opiods and Nonopioids Flashcards
What are the four opioid receptors?
Mu (MOR)
Kappa (KOR)
Delta (DOR)
Nociceptive (NOR)
_____ fibers cause dull burning pain
_____ fibers cause sharp pain
Unmyelinated C cause dull
A delta cause sharp, pricking pain
Afferent fibers enter the spinal cord at the ______
dorsal horn, terminating in lamina I-II
There are three examples of analgesia driven by endogenous opioid systems:
- Stress-induced Analgesia (delayed onset of pain in stressful situation)
- Placebo-induced analgesia
- Conditioned Pain Modulation (CPM) (Pain arising from noxious stimuli in one part of the body is reduced if a second application of noxious stimuli is introduced)
What causes the pain associated with diabetic polyneuropathy?
Damage to the descending pain inhibition pathway
How does the inflammatory cascade balance the pain caused by its mediators?
Leukocytes release opioid peptides
The inflammatory process stimulates opioid receptor upregulation, increasing the action of those peptides
A patient who is taking carbamazepine may have (Increased/decreased) clinical effects from opioids
decreased
carbamazepine is a CYP3A inducer, meaning metabolism of morphine will be increased
Which morphine metabolite is a full MOR agonist?
M6G
M3G (which accounts for 60% of metabolites) has no analgesic or anesthetic action
If morphine is metabolized in the liver, why does severe renal failure sometimes prolong the action of opioids?
Because of M6G. It’s already been metabolized, but the substrate isn’t being excreted and it’s active on the MOR
List the piperidines
Fentanyl
Alfentanil
Sufentanil
Remifentanil
Morphine is metabolized by a Phase ____ reaction
Fentanyl is metabolized by a Phase _____ reaction
Phase 2 (UGT2B7, not CYP450 dependent)
Phase 1 (CYP450 system)
Why doesn’t oral naloxone effect the pain control of patients?
It has a 95% first pass effect, so it really only reaches the intestinal cells
During surgery opioids are titrated to ______
Postoperatively, opioids are titrated to ______
during surgery, they’re titrated to dampen and prevent hemodynamic response to painful surgical stimuli
Postoperatively they’re given for perceived pain
Fentanyl is _____ times more potent that morphine
100
How potent is sufentanil?
10x more potent than FENTANYL
Why do opioids cause reduced RR and Vt?
RR: activate MORs on respiratory neurons
Vt: opioid-induced decreased afferent input into the brainstem from peripheral chemosensors
Why does speed of administration impact the respiratory effects of opioids?
When it’s given slowly, the increased CO2 from depression of the respiratory neurons has a chance to stimulate peripheral and chemoreceptors before they’re blunted by the opioid
If given slowly the arterial CO2 will still be higher, but the patient will continue to breathe
How do opioids impact sleep apnea?
Most patients who receive opioids will develop sleep apnea while taking them
opioids suppress the neurons in the brainstem that are involved in maintaining upper airway muscle tone, causing collapse
Besides decreased RR and Vt, what is another effect of opioids on respiratory sufficiency?
Strong, high dose opioids given rapidly cause skeletal muscle rigidity in thoracic, abdominal, and pharyngeal muscles
Bad news
A patient who is dependent on opioids and smoke 2 ppd suddenly stops smoking. What may happen?
They may be exposed to high opioid concentrations in the blood
tobacco smoke induces the CYP system
Why does morphine cause the most cardiovascular effects?
it mediates histamine release
What are the central cardiovascular effects of opioids?
activation of vagal nuclei
depression of vasomotor centers in the brainstem
What are the peripheral cardiovascular effects of opioids?
Direct myocardial depression
Arterial and venous dilation
Describe the cellular signaling pathway of opioids
G protein-coupled receptor activation causes cAMP and Adenyl cyclase production
OR
direct interaction with ion channels on presynaptic neurons
Stimulation of the mu receptor produces:
supraspinal analgesia, euphoria, decreased ventilation
Kappa receptor stimulation causes
spinal analgesia, sedation, and miosis
Delta receptor stimulation causes
spinal analgesia and modulation of mu receptors
Which opioids are associated with histamine release?
Morphine, codeine, and meperidine
What causes facial flushing from opioids?
Interestingly, not histamine release, but mu receptor activation
Also, most common with neuraxial administration
What can be done to relieve pruritis in the patient receiving neuraxial opioids?
Nalbuphine, droperidol, antihistamines, ondansetron
Which opiate is least likely to cause sphincter of Oddi spasms?
Meperidine
Tolerance develops to all of the side effects of opioids EXCEPT
miosis and constipation
Which opioid has anticholinergic effects?
Meperidine
It is structurally related to Atropine
Which A2 adrenergic Agonist is most selective for Alpha 2 receptors?
Precedex
What happens when Neostigmine is administered intrathecally?
Stimulates muscarinic cholinergic receptors, resulting in anti-nociceptive activity
Decreases the amount of drug needed and prolongs duration
What is the biggest downside to using spinal neostigmine?
VERY high instance of PONV
but this is NOT true with epidural administration
How do COX inhibitors prevent prostaglandin synthesis?
They prevent arachidonic acid from binding with the COX enzyme
What is the most COX-1 selective NSAID?
Ketoralac
Why do COX-2 inhibitors cause so many CV issues?
Prostaglandins formed from Arachidonic acid include both Prostaglandin I2 (made from COX-2) which is a potent vasodilator, AND Thromboxanes (made from COX1) which are vasoconstrictive
Ordinarily this ensures balance: anytime constrictive thromboxanes are developed, so are vasodilatory prostaglandins
BUT when you just inhibit COX 2, you knock out the vasodilatory prostaglandin synthesis and leave the vasoconstrictive synthesis intact, leading to cardiovascular distress
