NSAIDs and DMARDs

Question 1

What is the specific name of the enzyme that NSAIDs inhibit?

Answer 1

prostaglandin endoperoxide H synthase (PGHS) or cyclooxygenase (COX – both isoforms)

Question 2

What are the 5 classes of NSAIDs?

Answer 2

(1) salicylates
(2) arylacetic acids
(3) arylpropionic acids
(4) non-carboxylates
(5) COX-2-selective

Question 3

general side effects of NSAIDs

Answer 3

(1) GI (dyspepsia, N/V, ulcers)
(2) renal
(3) coagulation issues
(4) Reye’s syndrome (if hypersensitive)
(5) CNS (tinnitus, dizziness, HA)

Question 4

Reye’s syndrome is the result of hypersensitivity to which group of NSAIDs?

Answer 4

salicylates

Question 5

What is the role of misoprostol in NSAID therapy?

Answer 5

Misoprostol can prevent the GI-related side effects of NSAIDs. It is a synthetic PGE analog used in patients at high risk for ulcers using NSAIDs.

Question 6

What class of drugs are often combined with NSAIDs to prevent GI side effects?

Answer 6

PPI (esomeprazole)

Question 7

Because NSAIDs are highly bound to albumin, they often compete with other drugs for protein binding. What class of drugs mentioned in lecture will interact with NSAIDs by competing for albumin binding?

Answer 7

anti-coagulants

This is especially a problem with salicylates, which already often prolong bleeding.

Question 8

Give 3 examples of salicylate NSAIDs.

Answer 8

aspirin, salsalate, diflunisal

Question 9

What is an advantage that salsalate has over aspirin?

Answer 9

does not cause GI bleeding

Question 10

Describe the relative anti-pyretic activity, analgesic activity and side effect profile of diflunisal compared to aspirin?

Answer 10

more analgesic, less anti-pyretic, less side effects

Question 11

What are the 4 arylacetic acid NSAIDs?

Answer 11

(1) indomethacin
(2) sulindac
(3) etodolac
(4) diclofenac

Question 12

Which of the arylacetic acids has the most extensive side effects, and is therefore not suitable for long term use?

Answer 12

indomethacin

Question 13

Which arylacetic acid is suitable for long-term treatment of inflammation, and can be used in treatment of gout?

Answer 13

sulindac

Question 14

This NSAID is the most widely used in the world. It is somewhat selective for COX-2 and inhibits both the COX and lipoxygenase pathways.

Answer 14

diclofenac

Question 15

Which arylacetic acid is a prodrug?

Answer 15

sulindac (sulfoxide reduced to sulfide)

Question 16

Which arylacetic acid is as potent as indomethacin, but causes less GI bleeding and is more selective for COX-2?

Answer 16

etodolac

Question 17

Which arylacetic acid has an amide bond that decreases its stability in solution?

Answer 17

indomethacin

Question 18

Give 3 examples of arylpropionic acid NSAIDs.

Answer 18

Ibuprofen, Ketorolac, and Naproxen

Question 19

Which arylpropionic acid is sold as a racemic mixture (though one enantiomer is converted to the other in vivo)?

Answer 19

Ibuprofen (R is converted enzymatically to S)

Question 20

Which arylpropionic acid is more potent than Ibuprofen and is used in rheumatoid/osteoarthritis?

Answer 20

naproxen

Question 21

Which arylpropionic acid is indicated only for short term management analgesia and is accepted as an alternative to narcotic pain management?

Answer 21

Ketorolac

Question 22

What are the 2 non-carboxylate NSAIDs?

Answer 22

nabumetone and meloxicam

Question 23

Nabumetone is a potent ___________ and a weak ________.

Answer 23

anti-inflammatory, analgesic

Question 24

What are two advantages of meloxicam compared to some other NSAIDs?

Answer 24

once daily dosing, somewhat selective for COX-2

Question 25

What are the consequences of COX-1 inhibition?

Answer 25

(1) gastric ulceration (2) inhibition of prostaglandin mediated renal function (3) inhibition of platelet aggregation (4) inhibition of uterine motility (5) hypersensitivity

Question 26

What structural difference between COX-1 and COX-2 is exploited by selective COX-2 inhibitors?

Answer 26

Valine present in COX-2 instead of isoleucine in COX-1, creating a bigger binding pocket.

Question 27

Explain why selective COX-2 inhibition increases the risk of thrombosis.

Answer 27

They do not inhibit TXA2 production by COX-1, so platelet aggregation is heightened.

Question 28

acetaminophen MOA

Answer 28

diminishes peroxynitrite required for PGHS activity (indirect inhibition of PGHS)

Question 29

While acetaminophen does not carry the same GI/coagulation side effects, what should we be concerned about in patients using it?

Answer 29

hepatotoxicity at high doses

Question 30

Give 3 examples of TNF blockers and their frequency of dosing.

Answer 30

Etanercept - once daily SC Remicade - dosed at 0 ,2, 6, then every 8 weeks Humira - dosed every other week SC

Question 31

Which DMARD is an interleukin-1 receptor antagonist? How often is it dosed?

Answer 31

Anakinra - dosed daily

Question 32

Which non-biologic DMARDs are prodrugs?

Answer 32

leflunomide and sulfasalazine

Question 33

Which DMARD is used more as a last ditch effort (patients with inadequate response to more than 1 DMARD), and blocks CD20 stimulation of B cells?

Answer 33

Rituximab antibody depletion -- higher risk for serious infection...not a first-line agent

Question 34

Abatacept MOA

Answer 34

inhibition of T-cell costimulation (CTLA-4 and CD80 interaction)