Opioid Analgesics

Question 1

In terms of neurotransmitters, endogenous opioids such as kephalin and endorphins are unique chemically: they are ______________.

Answer 1

pentapeptides–not small molecules like acetylcholine

Question 2

What is the “opioid motif”?

Answer 2

Tyr-Gly-Gly-Phe-X

Question 3

Endogenous opioids only affect nearby targets. Why?

Answer 3

Because they are rapidly broken down by peptidases

Question 4

Endorphans can act as neurohormones. Why can they do so and enkephalin can’t?

Answer 4

Because endorphins are larger–roughly 30 amino acids–and aren’t broken down as quickly.

Question 5

What two categories of endogenous opioids are least understood?

Answer 5

Dynorphins and endomorphins

Question 6

Nociceptin does not bind to _____________.

Answer 6

opioid receptors

Question 7

What type of G-protein are opioid receptors?

Answer 7

Gi/Go

Question 8

So far there are no drugs that are selective for the delta-opioid receptor. Why would it be desirable to have a drug that did so?

Answer 8

Because the delta receptors do not induce respiratory depression

Question 9

At what two sites do opioids inhibit pain?

Answer 9

At the first synapse of the pain pathway (in the posteromarginal nucleus of the dorsal horn) which prevents pain signals from ascending, and at the PAG.

Question 10

Opioids do not cause ___________, like local anesthetics do; and they do not cause __________, like general anesthetic.

Answer 10

block of all sensation; unconsciousness

Question 11

Opiates are not able to treat __________ pain very well.

Answer 11

neuropathic

Question 12

What opiate causes hallucinations?

Answer 12

Salvinorin A

Question 13

Respiratory depression is present even at ________ doses.

Answer 13

normal analgesic

Question 14

Opiates are contraindicated in cases of ______________.

Answer 14

head injury or respiratory dysfunction (because of their ability to suppress respiratory function); the only exception to the no-pulm disorder rule is with pulmonary edema (the reason is not understood)

Question 15

What is the weird relationship between opiates and vomiting?

Answer 15

They cause vomiting at low doses but suppress it at high doses.

Question 16

What descriptive category is dextromethorphan in?

Answer 16

Non-analgesic antitussive.

It still has abuse potential because it blocks NMDA receptors (like ketamine).

Question 17

What is the brandname of loperamide?

Answer 17

Imodium

Question 18

What opiate does not induce histamine release?

Answer 18

Fentanyl

Question 19

Opiate-induced histamine release usually manifests as ______________.

Answer 19

itching, hives, or asthma exacerbation

Question 20

The main cardiovascular effect of opiates is _________.

Answer 20

indirect because of histamine-induced vasodilation (resulting in hypotension)

Question 21

While some opioids are readily absorbed from the GI tract (like codeine and methadone), they work better __________.

Answer 21

intravenously (because of first pass metabolism)

Question 22

Pharmacokinetically, how are morphine and heroin different?

Answer 22

They have the same efficacy, but heroin has greater potency.

Question 23

10% of Caucasians have a deficiency of CYP2D6 and thus codeine is __________.

Answer 23

less effective, because metabolism activates it

Question 24

Percocet is ____________.

Answer 24

oxycodone and tylenol

Question 25

The brand name of meperidine is __________. What is its main advantage?

Answer 25

Demerol; fast on, fast off

Question 26

Fentanyl, aside from not having as much histamine release, is great because ____________.

Answer 26

it is fast acting and wears off quickly (1 hr vs. 6 hrs for morphine)

Question 27

What is the main clinical difference between naloxone and naltrexone?

Answer 27

Naltrexone is orally available while naloxone is not.

Question 28

Tolerance usually takes _____________.

Answer 28

at least 3 weeks

Question 29

Tolerance is at the __________ level.

Answer 29

receptor level (this is important, because any drug that stimulates mu-opioid receptors will develop cross-tolerance)

Question 30

What is the difference between physical and psychological dependence?

Answer 30

Physical dependence is needing the drug to maintain a normal physiologic state (i.e., avoiding withdrawal symptoms), while psychological dependence is the continued craving of a drug.

Question 31

What can be used to treat withdrawal symptoms without stimulating mu receptors?

Answer 31

Clonidine (suppressing sympathetic outflow)

Question 32

All endogenous opioids are derived from _______________.

Answer 32

proopiomelanocortin (POMC)

Question 33

What drug stimulates kappa-opioid receptors?

Answer 33

Pentazocine (spinal analgesia)

Question 34

Inhibitory interneurons (in the spinal cord) are activated by ______________.

Answer 34

serotonin secreted from cells that originate in the PAG and descend to the level of the posteromarginal nucleus in the dorsal horn)

Question 35

Opioids can induce constriction of the sphincter of Oddi. Where is that?

Answer 35

The biliary tract

Question 36

Opioids have been known to inhibit the __________ reflex.

Answer 36

baroreceptor (hypovolemia)

Question 37

Which antagonist can reverse the effect of endogenous opioids?

Answer 37

Naltrexone

Question 38

The major metabolic path of morphine is through ____________.

Answer 38

glucuronidation in the liver

Question 39

The drug ____________ is not absorbed from the GI tract but can act locally to block constipation.

Answer 39

alvimopam (similar to naloxone)