Opioid Analgesics - Slattery

Question 1

What are the four steps to pain?

Answer 1

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

Question 2

What types of treatment eliminate the cause of pain?

Answer 2

• Anti-inflammatory (NSAIDs)
• Chemotherapy (including antimicrobials)
• Antiulcer

Question 3

What types of treatment prevent transmission of pain?

Answer 3

Local anesthetics

Question 4

What kind of treatments affect the way pain is perceived?

Answer 4

• General anesthetics
• OPIOIDS

Question 5

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

Answer 5

• OPIOIDS
• Anxiolytics

Question 6

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

Answer 6

Inhibitory!

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

Question 7

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

Answer 7

• Endogenous opioids
  
  • endorphins
  • enkephalins
• 5HT
• NE

Question 8

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

Answer 8

• 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.

Question 9

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

Answer 9

Illicit drug use:

-opioids, cannabinoids, stimulants, etc.

Question 10

What are the four types of opioid receptors?

Answer 10

• Mu
• Kappa
• Delta
• ORL1 - Orphanin opioid receptor-like 1

Question 11

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

Answer 11

Mu receptor

Question 12

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

Answer 12

Kappa

Question 13

What opioid receptor modulates Mu receptor activity?

Answer 13

Delta

Question 14

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

Answer 14

ORL1

Question 15

What kind of receptors are involved in opioid signal transduction?

Answer 15

G-protein coupled receptors (GPCRs)

Question 16

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

Answer 16

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

Question 17

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

Answer 17

Glutamate and Substance P

Question 18

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

Answer 18

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

Question 19

What are the four steps of the descending inhibitory pathway?

Answer 19

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

Question 20

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

Answer 20

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

Question 21

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

Answer 21

1. Naloxone
2. Naltrexone

Question 22

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

Answer 22

Codeine

Question 23

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

Answer 23

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

Question 24

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

Answer 24

Precipitate withdrawal symptoms if effect shifts at one receptor.

(narcotic abuse tx)

Question 25

Why does heroin enter the brain more rapidly than morphine?

Answer 25

More lipid soluble | (rapidly crosses BBB)

Question 26

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?

Answer 26

Oral

Question 27

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?

Answer 27

Intravenous

Question 28

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

Answer 28

IM/SubQ

Question 29

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

Answer 29

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

Question 30

What route of administration may be easily discontinued?

Answer 30

Rectal suppository

Question 31

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

Answer 31

Buccal/Sublingual ex. Fentanyl "lollipop"

Question 32

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

Answer 32

Transdermal | (e.x. Fentanyl, Buprenorphine)

Question 33

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

Answer 33

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

Question 34

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

Answer 34

Less impacted by first pass metabolism

Question 35

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

Answer 35

Morphine-6-glucoronide | (morphine metabolite)

Question 36

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

Answer 36

Normeperidine | (a metabolite of meperidine)

Question 37

Where are opioid metabolites primarily excreted?

Answer 37

Urine _{(some glucoronides excreted in feces)}

Question 38

What are five potential therapeutic uses for opioids?

Answer 38

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

Question 39

Why would you use opioids in obstetric labor?

Answer 39

* Crosses placenal barrier * potential neonatal respiratory depression * Slows progress of labor

Question 40

How are opioids used for anesthesia purposes?

Answer 40

* Pre- and post-surgery * sedative * anxiolytic * analgesic * Cardiovascular surgery * minimizes cardiovascular depression

Question 41

What opioid is used for cough suppression?

Answer 41

Codeine

Question 42

Describe treatment of diarrhea with opioids.

Answer 42

* 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)

Question 43

What is Naloxone used for?

Answer 43

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