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Neuro B2 - WLB > Opioid Analgesics - Slattery > Flashcards

Opioid Analgesics - Slattery Flashcards

1
Q

What are the four steps to pain?

A
  1. Initiation by local stimulus
  2. Transmission to brain
  3. Perception as pain
  4. Reaction of individual
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2
Q

What types of treatment eliminate the cause of pain?

A
  • Anti-inflammatory (NSAIDs)
  • Chemotherapy (including antimicrobials)
  • Antiulcer
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3
Q

What types of treatment prevent transmission of pain?

A

Local anesthetics

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4
Q

What kind of treatments affect the way pain is perceived?

A
  • General anesthetics
  • OPIOIDS
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5
Q

What types of treatment affect a patient’s reaction to pain?

A
  • OPIOIDS
  • Anxiolytics
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6
Q

In the case of a bear attack, is the descending pain pathway inhibitory/excitatory to the normal ascending pain pathway?

A

Inhibitory!

(“survival mode” ultimately inhibits transmission of signal between 1° and 2° ascending (afferent) neurons)

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7
Q

What neurotransmitters are released by the descending pathway to inhibit the transmission of signal between 1° and 2° afferent neurons?

A
  • Endogenous opioids
    • endorphins
    • enkephalins
  • 5HT
  • NE
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8
Q

What is the difference between “opiate” and “opioid”?

A
  • Opiate = drug derived from opium poppy
    • Opium
    • Morphine
    • Codeine
  • Opioid = more generic term, all substances (endogenous and exogenous) that bind opioid receptors
    • Endorphins (endogenous)
    • Morphine, etc.
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9
Q

The word “narcotic” is now a legal term encompassing what?

A

Illicit drug use:

-opioids, cannabinoids, stimulants, etc.

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10
Q

What are the four types of opioid receptors?

A
  • Mu
  • Kappa
  • Delta
  • ORL1 - Orphanin opioid receptor-like 1
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11
Q

What opioid receptor is related to analgesia, respiratory depression, decreased gastrointestinal motility, and physical dependence?

A

Mu receptor

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12
Q

What opioid receptor is related to analgesia, sedation, and decreased gastrointestinal motility?

A

Kappa

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13
Q

What opioid receptor modulates Mu receptor activity?

A

Delta

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14
Q

What opioid receptor is structurally similar to Mu, but insensitive to opioid ligands?

A

ORL1

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15
Q

What kind of receptors are involved in opioid signal transduction?

A

G-protein coupled receptors (GPCRs)

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16
Q

What action do G-protein coupled receptors have on pre-synaptic and post-synaptic transmission?

A
  • Pre-synaptic:
    • inhibit Ca2+ channels
    • stop transmission
  • Post-synaptic:
    • activate K+ channels
    • stop transmission
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17
Q

In pre-synaptic inhibition of afferent neurons, opioid receptor activation blocks voltage-gated Ca2+ channels, reducing the release of what?

A

Glutamate and Substance P

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18
Q

What three potential sites of action could opioid receptors interfere with signal transduction of the afferent (ascending) pathway?

A
  • Peripheral tissues (afferent nociceptor)
  • Spinal cord (substantia gelatinosa)
  • Thalamus (ventral caudal)
19
Q

What are the four steps of the descending inhibitory pathway?

A
  1. Cortex
  2. Periaqueductal gray (midbrain)
  3. Rostral ventral medulla
  4. Dorsal horn spinal cord
20
Q

What are four examples of opioid agonists that produce an effect when bound to receptor?

A
  1. ​Morphine (Mu/Kappa agonist)
  2. Methadone
  3. Oxycodone
  4. Heroin
21
Q

What are two opioid receptor antagonists that produce no effect when bound to the receptor or has a reverse effect of morphine-like opioids?

A
  1. Naloxone
  2. Naltrexone
22
Q

What opioid is a partial agonist that has less efficacy than full agonists, lower abuse potential, and effects on Mu receptors?

A

Codeine

23
Q

What are two examples of opioid mixed agonist-antagonist drugs?

A
  • Pentazocine
    • Agonist = Kappa receptors
    • Antagonist = Mu receptors
  • Buprenorphine
    • Agonist (partial) = Mu receptors
    • Antagonist = Kappa, Delta, ORL1
24
Q

What is the clinical relevance of giving opioid mixed agonist-antagonists?

A

Precipitate withdrawal symptoms if effect shifts at one receptor.

(narcotic abuse tx)

25
Q

Why does heroin enter the brain more rapidly than morphine?

A

More lipid soluble

(rapidly crosses BBB)

26
Q

What route of administration is convenient, but has a high first pass metabolism that can be limiting, slower onset, delayed peak effect, longer duration (relative to parenteral routes), and is better for chronic treatment?

A

Oral

27
Q

What route of administration is precise, has accurate dosing, rapid onset, but increased risk of adverse effects, can be bolus or continuous, and can be patient controlled?

A

Intravenous

28
Q

What route of administration has rapid onset and a duration in between oral and IV adminstered opioids?

A

IM/SubQ

29
Q

What route of administration has longer duration at lower doses than systemic and can avoid some brain-mediated adverse effects such as respiratory depression?

A

Spinal

(effect opioid receptors in CNS without brain causing respiratory depression)

30
Q

What route of administration may be easily discontinued?

A

Rectal suppository

31
Q

What route of administration has a faster onset than oral, avoids first pass metabolism and is convenient (no injection)?

A

Buccal/Sublingual

ex. Fentanyl “lollipop”

32
Q

What route of administration is convenient, avoids first pass metabolism, and is better for chronic treatment?

A

Transdermal

(e.x. Fentanyl, Buprenorphine)

33
Q

Why does oral morphine require 3-6x higher dose relative to parenteral administration?

A

First pass metabolism

(drugs absorbed from GI tract go to liver, then rapidly and efficiently metabolized)

34
Q

Why does oral methadone only need 1.5-2x higher dose compared to oral morphine?

A

Less impacted by first pass metabolism

35
Q

What pharmacologically active opioid metabolite is excreted in the urine, so it can impact morphine’s effect and duration if renal function is compromised?

A

Morphine-6-glucoronide

(morphine metabolite)

36
Q

What toxic opioid metabolite can cause excitotoxicity and result in tremor, twitching, and convulsions?

A

Normeperidine

(a metabolite of meperidine)

37
Q

Where are opioid metabolites primarily excreted?

A

Urine

(some glucoronides excreted in feces)

38
Q

What are five potential therapeutic uses for opioids?

A
  1. Analgesia
  2. Obstetric labor
  3. Anesthesia
  4. Cough
  5. Diarrhea
39
Q

Why would you use opioids in obstetric labor?

A
  • Crosses placenal barrier
    • potential neonatal respiratory depression
  • Slows progress of labor
40
Q

How are opioids used for anesthesia purposes?

A
  • Pre- and post-surgery
    • sedative
    • anxiolytic
    • analgesic
  • Cardiovascular surgery
    • minimizes cardiovascular depression
41
Q

What opioid is used for cough suppression?

A

Codeine

42
Q

Describe treatment of diarrhea with opioids.

A
  • All opioids effective
    • GI effect = constipation
  • Loperamide (Imodium)
    • opioid that is not able to cross BBB
  • Diphenoxylate + Atropine (Lotomil)
    • Atropine added to discourage abuse (anticholinergic)
43
Q

What is Naloxone used for?

A
  • Acute overdose
    • short duration of action
    • injection to avoid first pass metabolism
    • single dose - could relap

Neuro B2 - WLB (13 decks)

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