RA & Gout

Question 1

Indomethacin (Indocin)

Answer 1

Class: Non-selective NSAID
MOA: Eliminate pain; reduce inflammation (but does not slow disease progression)
Uses: Rheumatoid arthritis; acute gouty arthritis
SE: Gastric and duodenal ulcers

Question 2

Naproxen (Aleve)

Answer 2

Class: Non-selective NSAID
MOA: Eliminate pain; reduce inflammation (but does not slow disease progression)
Uses: Rheumatoid arthritis; acute gouty arthritis
SE: Gastric and duodenal ulcers

Question 3

COX-2 inhibitors

Answer 3

Class: Selective NSAID
MOA: Eliminate pain; reduce inflammation (but does not slow disease progression)
Uses: Superseding conventional NSAIDs for rheumatoid arthritis
SE: 50% fewer gastric and duodenal ulcers than traditional NSAIDs

Question 4

Gold Salts

Answer 4

Class: DMARD
MOA: Antipruritic; represses immune responsiveness (inhibits functional capabilities of macrophages)
Uses: Rheumatoid arthritis
SE: Serious side effects in 30% of pts
Misc: Rarely used today

Question 5

Quinolones

Answer 5

Class: DMARD (antimalarial)
MOA: Reduces T-cell activation & chemotaxis
Uses: Rheumatoid arthritis, SLE
SE: Retinal damage (chloroquine)

Question 6

Glucocorticoids (Corticosteroids)

Answer 6

Class: DMARD
MOA: 1. Inhibits phospholipase A2 (inhibiting release of arachidonic acid and, thus, formation of prostaglandins) 2. Inhibits cytokine production (which prevents induction of COX-2)
Uses: Rheumatoid arthritis; acute gouty arthritis (intraarticular injection for relief of acute monoarticular gout)
SE: Cushingoid symptoms

Question 7

Sulfasalazine (Azulfidine)

Answer 7

Class: DMARD
MOA: Likely inhibition of IL-1 & TNF-alpha release
Uses: Rheumatoid arthritis
SE: N/V, skin rashes, neutropenia (30% of patient discontinue drug); headaches
Misc: Acts more quickly than other drugs

Question 8

Methotrexate (Trexall)

Answer 8

Class: DMARD (Immunosuppressive)
MOA: 1. Inhibition of aminoimidazolecarboxamide (AICAR) transformylase and
thymidylate synthetase, with secondary effects on PMN chemotaxis 2. Causes adenosine accumulation, which inhibits inflammation
Uses: Rheumatoid arthritis
SE: Nausea, stomatitis, hepatotoxicity (rare)
Misc: Takes several weeks to start working; “gold standard” of therapy

Question 9

Leflunomide (Arava)

Answer 9

Class: DMARD (Immunosuppressive)
MOA: Inhibits dihydroorotate dehydrogenase (DHODH), which inhibits T-lymphocyte response to stimuli
Uses: Rheumatoid arthritis
SE: Diarrhea, hepatotoxity
Misc: Takes several weeks to start working; oral prodrug

Question 10

Etanercept (Enbrel)

Answer 10

Class: Biologic Response Modifiers
MOA: Blocks binding of TNF to TNF receptors
Uses: Rheumatoid arthritis

Misc: Twice weekly subcutaneous injections

Question 11

Infliximab (Remicade)

Answer 11

Class: Biologic Response Modifiers
MOA: Blocks binding of TNF to TNF receptors
Uses: Rheumatoid arthritis
SE: Antigenic response to murine monoclonal Ab

Question 12

Adalimumab (Humira)

Answer 12

Class: Biologic Response Modifiers
MOA: Blocks binding of TNF to TNF receptors
Uses: Rheumatoid arthritis

Misc:Fully human, so no antigenic response; twice monthly injections

Question 13

Golimumab

Answer 13

Class: Biologic Response Modifiers
MOA: Blocks binding of TNF to TNF receptors
Uses: Rheumatoid arthritis
SE: Risk of serious infections

Question 14

Certolizumab

Answer 14

Class: Biologic Response Modifiers
MOA: Blocks binding of TNF to TNF receptors
Uses: Rheumatoid arthritis
SE: Risk of serious infections
Misc:Conjugated to PEG for stabilization

Question 15

Anakinra (Kineret)

Answer 15

Class: Biologic Response Modifiers
MOA: IL-1 Receptor Antagonist
Uses: Rheumatoid arthritis

Misc:Short (6 hr) plasma half-life; daily treatment with high doses

Question 16

Tocilizumab (Actemra)

Answer 16

Class: Biologic Response Modifiers
MOA: IL-6 Receptor Antagonist
Uses: Rheumatoid arthritis

Question 17

Rituximab (Rituxan)

Answer 17

Class: Biologic Response Modifiers
MOA: Anti-CD20 mAb, reduces circulating B cells
Uses: Rheumatoid arthritis
SE: Infections; hypersensitivity reactions
Misc: Used for RA refractory to TNF-alpha inhibitors

Question 18

Abatacept (Orencia)

Answer 18

Class: Biologic Response Modifiers
MOA: Inhibits T-cell activation and induces T-cell apoptosis
Uses: Rheumatoid arthritis
SE: Headaches; infections
Misc: Used in patients for RA refractory to MTX or TNF-alpha inhibitors

Question 19

Colchicine (Colcrys)

Answer 19

MOA: Prevents tubulin polymerization & leads to inibition of leukocyte migration, phagocytosis, and release of cytokines
Uses: Acute gouty arthritis
SE: Long-term use causes peripheral neuropathy & neutropenia; GI issues
Misc: Works in 12-24 hours!

Question 20

Probenecid (Benemid)

Answer 20

Class: Uricosuric Agent
MOA: Compete with urate at the anionic transport site of the renal tubule and inhibit urate reabsorption
Uses: Chronic tophaceous gout
SE: Urate crystal mobilization and acute gouty arthritis; GI irritation
Misc: Secretion of some weak acids (e.g., penicillin) is reduced

Question 21

Allopurinol (Zyloprim)

Answer 21

MOA: 1. Reduces uric acid synthesis by inhibiting xanthine oxidase (competitive inhibition) –> alloxanthine 2. Alloxanthine is a non-competitive inhibitor of xanthine oxidase
Uses: Chronic tophaceous gout
SE: Acute attacks of gouty arthritis early in treatment due to mobilization of urate crystals

Question 22

Febuxostat (Uloric)

Answer 22

MOA: Non-purine, non-competitive antagonist of xanthine oxidase
Uses: Chronic tophaceous gout
SE: Nausea, rash, arthralgias
Misc: Expensive

Question 23

Pegloticase (Krystexxa)

Answer 23

Class: Recombinant, stabilized uricase
MOA: Converts uric acid to allantoin
Uses: Chronic tophaceous gout