531 - Med Chem I - Exam Iii - Opioids

Front 1

Define endorphin.

Back 1

Broad term describing any endogenous peptide opioid.

Front 2

Define analgesic.

Back 2

An agent that decreases pain, generally by a state of decreased awareness

Front 3

Define antinociceptive.

Back 3

Any pain relieving agents.

Front 4

Define opiate.

Back 4

Any agents derived from morphine.

Front 5

Define protease/peptidase.

Back 5

An enzyme that hydrolyzes amine bonds between amino acids in a peptide/protein.

Front 6

What are the three classes of opioid receptors?

Back 6

Mu, kappa and delta

Front 7

What are the two subtypes of mu receptor and what are they associated with?

Back 7

Mu1: mediates pain neurotransmission; mu2: controls respiratory depression

Front 8

What pharmacologic actions are associated with mu receptors?

Back 8

analgesia, respiratory depression, tolerance, withdrawal symptoms, decreased gastric motility, emesis

Front 9

What are some endogenous ligands that bind to mu receptors?

Back 9

beta-endorphin, enkephalins, endomorphin-1&-2

Front 10

What pharmacologic actions are associated with kappa receptors?

Back 10

analgesia, sedation, dysphoria and diuresis

Front 11

What are some endogenous ligands that bind at kappa receptors?

Back 11

dynorphin A & B, alpha-neoendorphin

Front 12

What are pharmacologic actions associated with delta receptors?

Back 12

analgesia, antidepressant effects, physical dependence

Front 13

What are some endogenous ligands that bind at delta receptors?

Back 13

enkephalins and beta-endorphin

Front 14

What is the general formula for endorphins?

Back 14

Tyr-Gly-Gly-Phe-X (where X=Leu, Met)

Front 15

What amino acid is found in the first five peptides of Endomorphin 1 and 2 that is not other endorphins?

Back 15

Proline

Front 16

Where is the main difference in amino acid sequence between the different types of opioid receptors?

Back 16

The 2nd and 3rd extracellular loops, the extracellular NH2-terminus and the intracellular COOH terminus.

Front 17

What amino acid represents a key pharmacophore for potent binding to opioid receptors?

Back 17

Tyrosine

Front 18

What type of analog to Tyr does morphine represent?

Back 18

Conformationally restrained

Front 19

What type of receptor are opioid receptors?

Back 19

GCPR

Front 20

What is the rationale for using semi-synthetic opioid?

Back 20

Plants provide a renewable source of morphine, morphine has a low bioavailability and thus a better analog could be developed, an analog with fewer side effects could be developed.

Front 21

What are some of the main side effects of morphine?

Back 21

Tolerance, physical dependence, constipation

Front 22

What semi-synthetic opioids is thebaine used as a starting material for?

Back 22

Oxycodone/oxymorphone, naloxaone, natrexone, nalbuphine, etorphine, buprenorphine

Front 23

Why is codeine less potent than morphine?

Back 23

3-OCH3 substitution decreases its potency

Front 24

What is the major product of morphine metabolism and does it cross the BBB?

Back 24

3-glucuronide metabolite; does NOT cross BBB

Front 25

What are the three main class of synthetic opioid analgesics?

Back 25

Phenylpiperidines, 4-analidopiperidiens, and diphenylheptanones

Front 26

Why is demerol such a short-acting analgesic?

Back 26

It is rapidly hydrolyzed by serum esterases

Front 27

Why is Alfentanil found mostly in its neutral form?

Back 27

It has a pka of 6.5.

Front 28

Why is Ultiva (Remifentanil) such a short-acting drug? Why is this desirable?

Back 28

It is rapidly hydrolyzed by serum esterases; this is desirable because it's metabolism is independent of renal/liver function

Front 29

What advantage does sufentanil citrate have because it is 600-800x more potent than morphine?

Back 29

It can be used in smaller doses and thus less respiratory depression is seen.

Front 30

What are some pitfalls of opioids?

Back 30

tolerance, addiction/withdrawal, respiratory depression and constipation

Front 31

What would be the advantage of having a mu agonist and delat antagonist?

Back 31

Suppress tolerance, physical dependence and relaxed side effects of mu agonists

Front 32

What receptors does buprenorphine act on and how does it work at each of those receptors?

Back 32

Mu receptors: partial agonist
Kappa receptors: partial agonist
Delta receptors: antagonist

Front 33

Is buprenorphine more or less potent than morphine?

Back 33

20-50x more potent at producing an ED50, but doesn't reach ED100 of morphine.

Front 34

What is the problem with the 3-OH found on many opioid analogs?

Back 34

It undergoes extensive glucuronidation and thus first pass metabolism.

Front 35

What happens to diphenoxylate when it is administered?

Back 35

Serum esterates cleave ester bonds, producing a zwitterionic form of the drug.

Front 36

What is diphenoxylate co-administered with and why?

Back 36

Atropine sulfate; taking too much atropine causes a lot of discomfort and thus limits abuse potential

Front 37

Which of the antidiarrheal agents is NOT on the controlled substances list? Why not?

Back 37

Loperamide HCl or Imodium; substrate for efflux transporter P-gp