Opioids

Question 1

3 types of opioid receptors; are they coupled to inhibitory or stimulatory GPCR?

Answer 1

mu
kappa
delta
“inhibitory”

Question 2

4 major effects of opioid receptor activation

Answer 2

1. Stimulation of K+ efflux (hyperpolarization of cells)
2. Reduced neurotransmission by inhibition of adenylyl cyclase and cAMP
3. Inhibition of voltage-gated Ca2+ channels (prevents vesicles from fusing, prevents NT release)
4. Phosphorylation and internalization of OPRs (desensitization)

Question 3

What are the normal functions of K+ channels and voltage-gated Ca2+ channels, and how do opioids alter their normal function?

Answer 3

1. K channels – allow repolarization after action potential – opioids cause them to leak K+ out of cell
2. VGCC (voltage-gated Ca2+ channels) – allow vesicles to fuse during an AP – opioids stop them from working

Question 4

Does opioid receptor activation increase or decrease neurotransmitter release?

Answer 4

decreases it

Question 5

4 major therapeutic uses for opioids

Answer 5

Analgesia
Antitussant
Antidiarrheal
Treating substance use disorders

Question 6

2 potent opioids recommended in the WHO (World Health Organization) analgesic ladder for moderate-severe pain:

Answer 6

morphine and fentanyl

Question 7

2 less potent opioids recommended in the WHO analgesic ladder for mild-moderate pain:

Answer 7

codeine and tramadol

Question 8

4 very short-acting opioids that are useful as surgical adjuncts

Answer 8

Sufentanil, alfentanil, remifentanil, fentanyl

Question 9

Opioids produce analgesic effects via synergistic actions at what 3 levels of the nervous system?

Answer 9

supraspinal, spinal, peripheral

Question 10

Which level is responsible for reducing the affective component of pain (perception and emotional response)?

Answer 10

supraspinal

Question 11

Which level reduces excitability of spinal cord neurons?

Answer 11

spinal

Question 12

Which level interferes directly with transduction (nociceptor ability to convert stimuli into electrical signals)?

Answer 12

peripheral

Question 13

Opioid Antitussant activity results from opioid effects on brain or lungs?

Answer 13

Brain - cough center in medulla

Question 14

Name 1 opioid commonly used as an Antitussant

Answer 14

Codeine

Question 15

What are the 2 major effects of nearly all opioids on the GI tract?

Answer 15

reduce GI motility and inhibit GI secretions

Question 16

Why is loperamide relatively free of analgesic and euphoric effects?

Answer 16

excluded from brain by BBB

Question 17

Name 1 opioid used to prevent relapse of alcohol / opiate use disorders.

Answer 17

naltrexone

Question 18

Name 2 opioids used for opioid replacement therapy?

Answer 18

methadone and buprenorphine

Question 19

In addition to risk of addiction and withdrawal / dependence, what are 3 other adverse effects of opioid analgesia therapy?

Answer 19

Respiratory depression
Nausea/vomiting
Constipation

Question 20

What agent can reverse opioid respiratory depression and how does it work?

Answer 20

naloxone…it’s an opioid receptor antagonist

Question 21

At what anatomical target do opioids act to produce nausea / vomiting?

Answer 21

MOR (mu opioid receptor) in area postrema

Question 22

What are two ways that opioid-induced nausea/vomiting can be reduced?

Answer 22

anti-emetics
tolerance development

Question 23

At what pathway do opiates act to produce rewarding effects associated with addiction?

Answer 23

DA reward pathway (VTA - NAc)

Question 24

What are some approaches for managing opioid tolerance development?

Answer 24

Drug holidays, interrupted dosing schedules, drug rotation