Pharm Opioid Pain Mgmt Flashcards
Peripherial pain neurons (primary nociceptors) are what types of sensory neurons?
Which are responsible for ‘fast’ pain response? What is that characterized as?
- Adelta fibers - fast -sharp stabbing
- C fibers - slow - dull aching
Where does the first synaptic connection for primary nociceptors occur?
What do the primary nociceptors release as an excitatory NT?
dorsal horn of SC in lamina I, II, and V
release glutamate to the secondary nociceptors
Secondary nociceptors send their axons across midline to ascend in what tract?
spinothalamic tract
A pt is rx’d a capsaicin patch for chronic pain. The burning sensation that the pt feels when first applying the patch is from activation of… channels.
TRPV1
What receptor does PGE2 bind to in order to produce pain?
GPCR
A 67 yo female presents to her PCP c/o mild chronic knee pain. Pt is dx’d with osteoarthritis. Which analgesic is best for this pt?
acetaminophen
A pt brought to the ED with a dislocated L shoulder a/w severe pain. Which IV analgesic is given?
morphine
Pt is taking acetominophen for chronic pain, what is the CDC guideline for the max daily acetominaphen dose?
2.5 gm
What receptor is thought to be responsible for peripheral, spinal, and supraspinal analgesia along with euphoria, respiratory depression, physical dependence, and constipation?
MOR
mu receptor
What receptor may induce some spinal and supraspinal analgesia, constipation, respiratory depression, and modulate motor function?
DOR
delta receptor
What receptor is thought to be involved in peripheral and spinal analgesia along with dysphoria, miosis, and sedation?
Kappa receptor
MOR are the targets of endogenous opioid peptides like…
endorphins and enkephalins
All opioid receptors are GPCRs. MOR activation will…
- decrease syn of cAMP
- inhibit pre-synaptic Cav channels
- decreasing glutamate release
- activate GIRK channel
- hyperpolarize the post-synaptic neuron
- inhibit pre-synaptic Cav channels
Descending pain inhibitory pathway gets disinhibited to induce pain relief. Where do these pathways originate?
PAG - periaqueductal gray
RVM - rostral ventromedial medulla
Opioid drugs increase activity of the pain (Off/On) cells and inhibit activity of the pain (Off/On) cells.
- increase activity of Off cells
- inhibit activity of On cells
What other opioid receptor is in the DH of the spinal cord and uses the same mechanisms as MOR?
KOR - kappa receptor
How does codeine cause antitussive effects?
What is D-isomer of the codeine analog that has no analgesic effect but is an effective antitussive?
- binds to non-opioid receptors, effective dose is much lower than needed for analgesia
- Dextromethorphan
What is given in a small one time dose to alleviate postoperative shivering?
merperidine
Antidiarrheal opioids include what?
diphenoxylate and loperamide
What opioid can relieve ssx of acute pulmonary edema?
IV morphine
Morphine enhances the release of opioid peptides in the dorsal horn by…
inhibiting GABA release
Activation of MOR leads to the activation of pain “Off”-cells in RVM by..
blocking the release of GABA onto the Off-cells
Approximately 10% of morphine is metabolized into what?
morphine-6-glucuronide (6x more potent but does not cross BBB)
This drug is often formulated with NSAIDs or acetominaphen; is an MOR agonist with half life of 4-6 hours.
It can be demethylated into what?
If it is formulated with NSAIDs, it may produce an opioid sparing effect. What does this do?
hydrocodone
hydromorphone (10x> morphine)
allows for reduced opioid doses to achieve the same analgesic level as with the opioid used alone
What drug is a synthetic modifcation of morphine with higher potentcy?
What can it be metabolized into and what does this do?
hydromorphone
hydromorphone-3-glucruonide - neuroexcitatory and may generate AE of myclonus, allodynia, and rarely seizures in pts
What drug is 100x more potent than morphine and very lipophilic? What is it used for and why is it great for this use?
What forms is it available in?
fentanyl
perioperative pain mgmt - rapid onset and short duration
IV and transdermal (72 h, for chronic pain)
Oxycodone is often formulated with NSAIDs and acetominaphen and is a moderately potent MOR agonist. This drug may be better tolerated by some pts who are sensitive to…
sedation and mental status changes induced by morphine
Why is meperidine not recommended for long term treatment?
AE of tachycardia from a cholinergic effect
major metabolite is normeperidine which is toxic
What drug is a partial MOR agonist and a kappa receptor antagonist?
What is a result of this?
Which is the worst route to take this drug?
Buprenorphine
partial MOR agonist - reduced incidents of resp depression and constipation
Not great taken orally d/t very strong first pass liver metabolism
What opioid drug may be preferred in pts with renal failure?
buprenorphine
What drug is a full MOR agonist but can also block glutamate NMDA receptor?
This NMDA block could help to tx…
Methadone
neuropathic pain
What opioid drug is more likely to cause OD? Why?
methadone
very long excretion half life (24 h), 4-6x longer than its analgesic half-life
What drug can block the placebo effect?
naloxone
mu opioid receptor antagonist
What drugs are weak activators of MOR but also act as NE reuptake inhibitors?
tramadol and tapentadol
What drug is a synthetic codeine analog with weak MOR agonist and NE and 5-HT reuptake inhibitors?
What CYP is metabolizing this drug?
How is it excreted?
tramadol
CYP2D6
primarily via kidneys
What are primary AEs of tramadol?
- seizures (contraindicated)
- dizziness, HA, somnolence
- nausea
- increased suicide risk
Codeine is contraindicated and not recommended in who? (per FDA warnings)
- children under 12
- children under 18 s/p tonsillectomy or adenoidectomy
- breastfeeding women
- children 12-18 who are obese or have increased risk of breathing problems
What CYP enzyme metabolizes codeine?
What is the pathway to toxic metabolites from this CYP enzyme working on codeine and other opioids?
CYP2D6
CYP3A4
What kind of metabolizer might experience a morphine OD from taking a typical codeine dose?
UM - ultrametabolizer
What opioid drug produces significantly less constipation than others?
buprenorphine
How do you tx opioid induced constipation?
includes MOR antagonists and stool softeners
- Lubiprostone activates GI Cl- channels, increasing fluid in intestines
MOR antagonists cannot penetrate BBB so must work only peripherially and not lose analgesia -
- methylnaltrexone
- naloxegol
- alvimopan
- naloxone (does cross BBB)
How do opioids cause N/V?
disinhibit neurons in the chemoreceptor trigger zone (CTZ)
How do opioids cause respiratory depression?
MOR-induced decreased responsiveness of brain stem respiratory neurons to CO2
MOR agonists also depress the pontine centers that regulate rhythmicity of breathing, leading to irregular breathing and cessation at high doses
increased dosage of drug in order to receive the same benefit
tolerance
What drugs are FDA approved for tx of opioid addiction?
methadone and buprenorphine
How do you tx an opioid OD?
naloxone (short half life) and naltrexone (approved for decreasing etoh cravings) - MOR antagonists
low dose naloxone can also alleviate some minor AEs
AEs in non-analgesic opioid drugs like loperamide include…
cardiac arrhythmias
weak blocker of cardiac Ikr channel (same as target for class III antiarrhythmic drugs like dofetilide)
cause torsades de pointe
What are major concerns for drug drug interactions and opioids?
- MAOIs and morphine
- increase plasma concentration of morphine to the point of OD
- serotonin modulators
- some opioids block serotonin uptake and are CI in pts taking drugs increasing serotonin concentration (SSRIs, TCAs, SNRIs, and MAOIs)
- CI opioids: meperidine, methadone, fentanyl, tramadol
- would cause serotonin syndrome
