Unit 2. Rhematoid arthritis & Gout

Question 1

NSAIDs (in rheum arthritis)

Answer 1

Non-selective (indomethacin, naproxen) or selective (coxibs)
MOA: eliminate pain, reduce inflammation, but do not slow disease process
Uses: RA, acute gouty arthritis
Tox: for non-selective NSAIDs, gastric and duod ulcers; 50% fewer for coxibs
Note: useful for “bridge tx” until DMARD kicks in

Question 2

Gold salts

Answer 2

Class: DMARD
MOA: anti-prutiric, inhibits fxn of macros–> decreased immune response
Use: RA
Tox: serious in 30% pts–>rarely used

Question 3

Anti-malarials in RA

Answer 3

DMARDs (chloroquine, hydroxychloroquine)
MOA: reduce T cell activation & chemotaxis
Uses: RA, SLE (but less efficacious that other DMARDs)
Tox: chloroquine can cause retinal damage

Question 4

Glucocorticoids in RA

Answer 4

Class: DMARD (e.g. prednisone)
MOA: inhibits PLA2, which inhibits release of AA and formation of PGs; it also inhibits cytokine production, which prevents induction of COX2
Uses: RA, acute gouty arthritis
Tox: Cushingoid symptoms
Note: use to induce remission (fast acting); can give oral or intra-articular (esp for acute gout)

Question 5

Sulfasalazine

Answer 5

Class: DMARD
MOA: likely inhibits release of IL-1, TNFa
Use: RA (retards radiographic progression)
Tox: N/V, skin rashes, neutropenia (30% d/c drug)

Question 6

Methotrexate

Answer 6

Class: DMARD, Immunosuppressive
MOA (at lower doses than chemo): inhibition of AICAR transformylase and TS–> adenosine accumulation–>inhibits inflammation; with secondary effects on PMN chemotaxis
Uses: RA
Tox: nausea, stomatitis; hepatotox (rarely)
Note: takes several weeks to start; “gold standard” DMARD

Question 7

Leflunomide

Answer 7

Class: DMARD, Immunosuppressive
MOA: prodrug-> active metabolite inhibits DHODH, inhibiting Tcell response to stimuli
Use: RA
Tox: diarrhea, hepatotox
Note: takes several wks to see effects

Question 8

Etanercept

Answer 8

Class: DMARD, biologic, TNF antagonist
MOA: blocks binding of TNFa to TNF receptors
Use: RA
Tox: incr risk of opportunistic infections
Note: 2/weekly SQ injections; fusion protein made of 2 soluble TNF receptors fused w IgG1 Fc

Question 9

Infliximab

Answer 9

Class: DMARD, biologic; TNF antagonist
MOA: chimeric mAB against TNFa
Use: RA
Tox: antigenic response to murine AB–> production of anti-mouse ABs; increased risk of opp infections

Question 10

Adalimumab

Answer 10

Class: DMARD, biologic; TNF antagonist
MOA: fully human mAB against TNFa
Use: RA
Tox: increased risk of opp infections
Note: as efficacious as etanercept, but better dosing (2/monthly) SQ

Question 11

Golimumab

Answer 11

Class: DMARD, biologic; TNF antagonist
MOA: human mAB that binds membrane-bound and soluble TNFa
Use: RA
Tox: increased risk opp infections

Question 12

Certolizumab

Answer 12

Class: DMARD, biologic, TNF antagonist
MOA: humanized AB Fab fragment conjugated to polyethylene glycol (increases t1/2)
Use: RA
Tox: incr risk of opp infections

Question 13

Anakinra

Answer 13

Class: DMARD, biologic, cytokine antagonist
MOA: recombinant human IL-1 receptor antagonist
Use: RA (monotherapy)
Note: very short t1/2 (6 hrs)–>frequent daily treatments w high doses

Question 14

Tocilizumab

Answer 14

Class: DMARD, biologic, cytokine antagonist
MOA: IL-6 receptor antagonist
Use: RA
Tox: serious opportunistic infections

Question 15

Abatacept

Answer 15

Class: DMARD, biologic, co-stim modulator
MOA: inhibits Tcell activation, induces Tcell apoptosis
Use: RA (refractory to Mtx or TNFa blockers)
Tox: headaches, infections
Note: often used in combo w Mtx

Question 16

Rituximab (in RA)

Answer 16

Class: DMARD, biologic, co-stim modulator
MOA: anti-CD20 mAB that reduces circulating Bcells
Use: RA refractory to TNF inhibitors
Tox: infections, hypersensitivity rxns
Note: often in combo w Mtx

Question 17

Colchicine

Answer 17

MOA: prevents tubulin polymerization–>inhib of leukocyte migrations, phagocytosis, and release of cytokines
Use: acute gouty athritis
Tox: with long term use, peripheral neuropathy and neutropenia (low therapeutic index); short term–> N/V, abdominal pain, diarrhea
Note: works in 12-24 hrs

Question 18

Probenecid

Answer 18

Class: Uricosuric agent
MOA: competes w urate @ anion transporter on renal tubule–>inhibits urate reabsorption
Uses: chronic tophaceous gout
Tox: Acute gouty arthritis due to xstal mobilization
Note: other similar drug = sulfinpyrazone

Question 19

Allopurinol

Answer 19

MOA: competitively inhibits xanthine oxidase; metabolite (via XO), alloxanthine, non-comp inhibits XO–>reduces uric acid synthesis
Use: chronic tophaceous gout; can also prevent massive uricosura following chemo
Tox: acute gouty arthritis (crystal mobilization), maculopapular rash in 2%; rare hypersens syndrome

Question 20

Febuxostat

Answer 20

MOA: non-purine, non-comp antag of XO
Use: chronic tophaceous gout
Tox: nausea, rash, arthralgias

Question 21

Name the classes of DMARDS

Answer 21

gold salts, antimalarials, glucocorticoids, sulfasalazine, immunosuppressives, biologics

Question 22

What are the immunosuppressive DMARDs?

Answer 22

Methotrexate, Leflunomide

Question 23

What are the classes of biologic DMARDS?

Answer 23

TNFa-antags, cytokine antags, co-stimulation modulators

Question 24

Name the TNFa antags. What is their main toxicity?

Answer 24

etanercept, infliximab, adalimumab, golimumab, certolizumab

-increased risk of opportunistic infections

Question 25

Name the non-TNF antag biologic DMARDs

Answer 25

cytokine antags: anakira, tocilizumab

co-stim modulators: abatacept, rituximab

Question 26

Name the drugs used to treat acute gout

Answer 26

colchicine, NSAIDS, corticosteroids

Question 27

Name the drugs used to treat chronic gout

Answer 27

Uricosuric drugs (probenecid)
XO inhibitors (allopurinol, febuxostat)