NSAIDs and DMARDs Flashcards
What is the specific name of the enzyme that NSAIDs inhibit?
prostaglandin endoperoxide H synthase (PGHS) or cyclooxygenase (COX – both isoforms)
What are the 5 classes of NSAIDs?
(1) salicylates
(2) arylacetic acids
(3) arylpropionic acids
(4) non-carboxylates
(5) COX-2-selective
general side effects of NSAIDs
(1) GI (dyspepsia, N/V, ulcers)
(2) renal
(3) coagulation issues
(4) Reye’s syndrome (if hypersensitive)
(5) CNS (tinnitus, dizziness, HA)
Reye’s syndrome is the result of hypersensitivity to which group of NSAIDs?
salicylates
What is the role of misoprostol in NSAID therapy?
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.
What class of drugs are often combined with NSAIDs to prevent GI side effects?
PPI (esomeprazole)
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?
anti-coagulants
This is especially a problem with salicylates, which already often prolong bleeding.
Give 3 examples of salicylate NSAIDs.
aspirin, salsalate, diflunisal
What is an advantage that salsalate has over aspirin?
does not cause GI bleeding
Describe the relative anti-pyretic activity, analgesic activity and side effect profile of diflunisal compared to aspirin?
more analgesic, less anti-pyretic, less side effects
What are the 4 arylacetic acid NSAIDs?
(1) indomethacin
(2) sulindac
(3) etodolac
(4) diclofenac
Which of the arylacetic acids has the most extensive side effects, and is therefore not suitable for long term use?
indomethacin
Which arylacetic acid is suitable for long-term treatment of inflammation, and can be used in treatment of gout?
sulindac
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.
diclofenac
Which arylacetic acid is a prodrug?
sulindac (sulfoxide reduced to sulfide)
Which arylacetic acid is as potent as indomethacin, but causes less GI bleeding and is more selective for COX-2?
etodolac
Which arylacetic acid has an amide bond that decreases its stability in solution?
indomethacin
Give 3 examples of arylpropionic acid NSAIDs.
Ibuprofen, Ketorolac, and Naproxen
Which arylpropionic acid is sold as a racemic mixture (though one enantiomer is converted to the other in vivo)?
Ibuprofen (R is converted enzymatically to S)
Which arylpropionic acid is more potent than Ibuprofen and is used in rheumatoid/osteoarthritis?
naproxen
Which arylpropionic acid is indicated only for short term management analgesia and is accepted as an alternative to narcotic pain management?
Ketorolac
What are the 2 non-carboxylate NSAIDs?
nabumetone and meloxicam
Nabumetone is a potent ___________ and a weak ________.
anti-inflammatory, analgesic
What are two advantages of meloxicam compared to some other NSAIDs?
once daily dosing, somewhat selective for COX-2
What are the consequences of COX-1 inhibition?
(1) gastric ulceration
(2) inhibition of prostaglandin mediated renal function
(3) inhibition of platelet aggregation
(4) inhibition of uterine motility
(5) hypersensitivity
What structural difference between COX-1 and COX-2 is exploited by selective COX-2 inhibitors?
Valine present in COX-2 instead of isoleucine in COX-1, creating a bigger binding pocket.
Explain why selective COX-2 inhibition increases the risk of thrombosis.
They do not inhibit TXA2 production by COX-1, so platelet aggregation is heightened.
acetaminophen MOA
diminishes peroxynitrite required for PGHS activity (indirect inhibition of PGHS)
While acetaminophen does not carry the same GI/coagulation side effects, what should we be concerned about in patients using it?
hepatotoxicity at high doses
Give 3 examples of TNF blockers and their frequency of dosing.
Etanercept - once daily SC
Remicade - dosed at 0 ,2, 6, then every 8 weeks
Humira - dosed every other week SC
Which DMARD is an interleukin-1 receptor antagonist? How often is it dosed?
Anakinra - dosed daily
Which non-biologic DMARDs are prodrugs?
leflunomide and sulfasalazine
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?
Rituximab
antibody depletion – higher risk for serious infection…not a first-line agent
Abatacept MOA
inhibition of T-cell costimulation (CTLA-4 and CD80 interaction)
