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Neuro Round 2 wk 1 > Pharm Opioid Pain Mgmt > Flashcards

Pharm Opioid Pain Mgmt Flashcards

1
Q

Peripherial pain neurons (primary nociceptors) are what types of sensory neurons?

Which are responsible for ‘fast’ pain response? What is that characterized as?

A
  • Adelta fibers - fast -sharp stabbing
  • C fibers - slow - dull aching
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2
Q

Where does the first synaptic connection for primary nociceptors occur?

What do the primary nociceptors release as an excitatory NT?

A

dorsal horn of SC in lamina I, II, and V

release glutamate to the secondary nociceptors

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3
Q

Secondary nociceptors send their axons across midline to ascend in what tract?

A

spinothalamic tract

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4
Q

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.

A

TRPV1

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5
Q

What receptor does PGE2 bind to in order to produce pain?

A

GPCR

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6
Q

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?

A

acetaminophen

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7
Q

A pt brought to the ED with a dislocated L shoulder a/w severe pain. Which IV analgesic is given?

A

morphine

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8
Q

Pt is taking acetominophen for chronic pain, what is the CDC guideline for the max daily acetominaphen dose?

A

2.5 gm

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9
Q

What receptor is thought to be responsible for peripheral, spinal, and supraspinal analgesia along with euphoria, respiratory depression, physical dependence, and constipation?

A

MOR

mu receptor

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10
Q

What receptor may induce some spinal and supraspinal analgesia, constipation, respiratory depression, and modulate motor function?

A

DOR

delta receptor

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11
Q

What receptor is thought to be involved in peripheral and spinal analgesia along with dysphoria, miosis, and sedation?

A

Kappa receptor

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12
Q

MOR are the targets of endogenous opioid peptides like…

A

endorphins and enkephalins

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13
Q

All opioid receptors are GPCRs. MOR activation will…

A
  • decrease syn of cAMP
    • inhibit pre-synaptic Cav channels
      • decreasing glutamate release
    • activate GIRK channel
      • hyperpolarize the post-synaptic neuron
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14
Q

Descending pain inhibitory pathway gets disinhibited to induce pain relief. Where do these pathways originate?

A

PAG - periaqueductal gray

RVM - rostral ventromedial medulla

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15
Q

Opioid drugs increase activity of the pain (Off/On) cells and inhibit activity of the pain (Off/On) cells.

A
  • increase activity of Off cells
  • inhibit activity of On cells
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16
Q

What other opioid receptor is in the DH of the spinal cord and uses the same mechanisms as MOR?

A

KOR - kappa receptor

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17
Q

How does codeine cause antitussive effects?

What is D-isomer of the codeine analog that has no analgesic effect but is an effective antitussive?

A
  • binds to non-opioid receptors, effective dose is much lower than needed for analgesia
  • Dextromethorphan
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18
Q

What is given in a small one time dose to alleviate postoperative shivering?

A

merperidine

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19
Q

Antidiarrheal opioids include what?

A

diphenoxylate and loperamide

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20
Q

What opioid can relieve ssx of acute pulmonary edema?

A

IV morphine

21
Q

Morphine enhances the release of opioid peptides in the dorsal horn by…

A

inhibiting GABA release

22
Q

Activation of MOR leads to the activation of pain “Off”-cells in RVM by..

A

blocking the release of GABA onto the Off-cells

23
Q

Approximately 10% of morphine is metabolized into what?

A

morphine-6-glucuronide (6x more potent but does not cross BBB)

24
Q

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?

A

hydrocodone

hydromorphone (10x> morphine)

allows for reduced opioid doses to achieve the same analgesic level as with the opioid used alone

25
Q

What drug is a synthetic modifcation of morphine with higher potentcy?

What can it be metabolized into and what does this do?

A

hydromorphone

hydromorphone-3-glucruonide - neuroexcitatory and may generate AE of myclonus, allodynia, and rarely seizures in pts

26
Q

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?

A

fentanyl

perioperative pain mgmt - rapid onset and short duration

IV and transdermal (72 h, for chronic pain)

27
Q

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…

A

sedation and mental status changes induced by morphine

28
Q

Why is meperidine not recommended for long term treatment?

A

AE of tachycardia from a cholinergic effect

major metabolite is normeperidine which is toxic

29
Q

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?

A

Buprenorphine

partial MOR agonist - reduced incidents of resp depression and constipation

Not great taken orally d/t very strong first pass liver metabolism

30
Q

What opioid drug may be preferred in pts with renal failure?

A

buprenorphine

31
Q

What drug is a full MOR agonist but can also block glutamate NMDA receptor?

This NMDA block could help to tx…

A

Methadone

neuropathic pain

32
Q

What opioid drug is more likely to cause OD? Why?

A

methadone

very long excretion half life (24 h), 4-6x longer than its analgesic half-life

33
Q

What drug can block the placebo effect?

A

naloxone

mu opioid receptor antagonist

34
Q

What drugs are weak activators of MOR but also act as NE reuptake inhibitors?

A

tramadol and tapentadol

35
Q

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?

A

tramadol

CYP2D6

primarily via kidneys

36
Q

What are primary AEs of tramadol?

A
  • seizures (contraindicated)
  • dizziness, HA, somnolence
  • nausea
  • increased suicide risk
37
Q

Codeine is contraindicated and not recommended in who? (per FDA warnings)

A
  • 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
38
Q

What CYP enzyme metabolizes codeine?

What is the pathway to toxic metabolites from this CYP enzyme working on codeine and other opioids?

A

CYP2D6

CYP3A4

39
Q

What kind of metabolizer might experience a morphine OD from taking a typical codeine dose?

A

UM - ultrametabolizer

40
Q

What opioid drug produces significantly less constipation than others?

A

buprenorphine

41
Q

How do you tx opioid induced constipation?

A

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)
42
Q

How do opioids cause N/V?

A

disinhibit neurons in the chemoreceptor trigger zone (CTZ)

43
Q

How do opioids cause respiratory depression?

A

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

44
Q

increased dosage of drug in order to receive the same benefit

A

tolerance

45
Q

What drugs are FDA approved for tx of opioid addiction?

A

methadone and buprenorphine

46
Q

How do you tx an opioid OD?

A

naloxone (short half life) and naltrexone (approved for decreasing etoh cravings) - MOR antagonists

low dose naloxone can also alleviate some minor AEs

47
Q

AEs in non-analgesic opioid drugs like loperamide include…

A

cardiac arrhythmias

weak blocker of cardiac Ikr channel (same as target for class III antiarrhythmic drugs like dofetilide)

cause torsades de pointe

48
Q

What are major concerns for drug drug interactions and opioids?

A
  • 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

Neuro Round 2 wk 1 (15 decks)

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