DMARDS

Question 1

What are DMARDs?

Answer 1

• disease-modifying antirheumatic drugs (DMARDs)

Question 2

What is the role of NSAIDs in rheumatic disease?

Answer 2

• to reduce ACUTE inflammation, thereby decreasing pain and improving function.

Question 3

Are NSAIDs ALONE typically sufficient to change the course of rheumatic disease or RA or prevent joint destruction?

Answer 3

• NO

* use when starting therapy though.

Question 4

When are CORTICOSTEROIDS used for rheumatic diseases?

Answer 4

• EARLY disease as temporary ADJUNCTIVE therapy, while waiting for DMARDs to exert their anti-inflammatory effects.
• CHRONIC ADJUNCTIVE therapy in pts with severe disease that is not well controlled.

Question 5

What corticosteroids are commonly used for rheumatic diseases?

Answer 5

• prednisone
• methylprednisolone
• both have anti-inflammatory and immunoregulatory activity.

Question 6

What are the specific remission-inducing agents for rheumatic diseases?

Answer 6

• gold preparations
• antimalarials
• penicillamine
• cytotoxic drugs
• immunologic agents

Question 7

*** What are the 2 GOLD PREPARATIONS?

Answer 7

1. gold sodium thiomalate= suppresses arthritis and synovitis (IM)
2. auroanofin= oral
   - takes 4-6 months
   * old drugs

Question 8

How do the gold preparations work?

Answer 8

• inhibit maturation of mononuclear phagocytes, thereby suppressing immune responsiveness.
• decreases concentrations of rheumatoid factor and immunoglobulin in pts.

Question 9

How are the gold preparations excreted?

Answer 9

• via the kidney

Question 10

What ADRs will you see with the gold preparations?

Answer 10

• erythema to severe exfoliative dermatitis

- thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia…

Question 11

Can you use the gold preparations during pregnancy or breast feeding?

Answer 11

• NO

Question 12

** What are the 2 ANTIMALARIALS?

Answer 12

1. HYDROXYCHLOROQUINE
2. CHLOROQUINE
   * takes 2-4 months

Question 13

Are antimalarials safe in pregnancy?

Answer 13

• YES

Question 14

How do the antimalarials work?

Answer 14

• possibly by stabilizing leukocyte lysosomal membranes

Question 15

How are the antimalarials excreted?

Answer 15

• kidney

Question 16

What are some ADRs of the antimalarials?

Answer 16

• retinal damage (irreversible).

- GI (anorexia, nausea, vomiting…)

Question 17

What is D-penicillamine?

Answer 17

• older immunosuppressive drug, with unknown MOA.

Question 18

What are some ADRs of D-penicillamine?

Answer 18

• GI
• Leukopenia, aplastic anemia…
• dermatologic
• renal

Question 19

** What are the 3 CYTOTOXIC drugs used for rheumatoid diseases?

Answer 19

1. METHOTREXATE
2. LEFLUNOMIDE
3. AZATHIOPRINE

Question 20

How does methotrexate work?

Answer 20

• inhibits dihydrofolate reductase, thereby stopping production of dTMP (thymidine), which is necessary for DNA, RNA, and protein synthesis.
• will see negative regulation via build up of AMP.
• first-line therapy for moderate to severe active RA.

Question 21

Can you use methotrexate in combination with other agents?

Answer 21

• YES, but try as monotherapy first.

Question 22

What should you do before using methotrexate?

Answer 22

• labs for CBC, serum creatinine, AST, and ALT

Question 23

** What are the ADRs of methotrexate?

Answer 23

• pulmonary fibrosis
• macrocytic anemia
• hepatitis
• mucositis

Question 24

Can methotrexate be used in pregnancy?

Answer 24

• NOOOO!!!! It is also used for abortions.

Question 25

**** What is leflunomide?

Answer 25

- dihydroorotate dehydrogenase inhibitor leading to anti-inflammatory activity.

Question 26

Can you combine leflunomide with NSAIDs or low dose corticosteroids?

Answer 26

- YES | * but not with other DMARDs

Question 27

What are the ADRs of leflunomide?

Answer 27

- hepatotoxicity

Question 28

Can you give leflunomide in pregnancy?

Answer 28

- NO!!

Question 29

**** What is azathioprine? (PICMONIC)

Answer 29

- immunosuppressive agent used in severe refractory RA.

Question 30

What are the ADRs of azathioprine?

Answer 30

- leukopenia, thrombocytopenia | - nausea and vomiting

Question 31

**** What is sulfasalazine?

Answer 31

- suppresses T cell responses and indirectly B cell responses. - used for RA, IBD, ankylosing spondylitis, and juvenile chronic arthritis.

Question 32

What are the ADRs of sulfasalazine?

Answer 32

- toxicity in 30% of pts.

Question 33

**** What is the biologic agent ETANERCEPT? (PICMONIC; anti-TNF inhibitors)

Answer 33

- TNF decoy receptor, which binds to TNF and blunts the immune response. - used for severe RA and ankylosing spondylitis.

Question 34

Can you use etancercept with methotrexate?

Answer 34

- YES

Question 35

Can you use etanercept with other biologics?

Answer 35

- NO

Question 36

What are the side effects of etanercept?

Answer 36

- infection - headache - injection site reaction - rhinitis - dizziness - potential for autoimmune antibodies developing.

Question 37

**** What is INFLIXIMAB? (PICMONIC)

Answer 37

- monoclonal antibody that binds to and inactivates TNF-alpha. - used for severe RA and Crohn's disease.

Question 38

**** What is ADALIMUMAB (humira)?

Answer 38

- monoclonal antibody that binds to and inactivates TNF-alpha.

Question 39

**** What is ANAKINRA?

Answer 39

- nonglycosylated competitive antagonist of the IL-1 receptor. - used for severe RA

Question 40

Can you use anakinra with methotrexate?

Answer 40

- YES | * but do not use with other biologics.

Question 41

What is the main ADRS of anakinra?

Answer 41

- serious infections | * DO NOT give live vaccines to these pts.

Question 42

**** What is TOFACITINIB?

Answer 42

- JAK inhibitor, thus affecting type I and II cytokine receptors. - used for moderate to severe RA * can use with methotrexate.

Question 43

What are the side effects of tofacitinib?

Answer 43

- upper resp. infections - headache - diarrhea - serious infections - malignancies (lymphoma)

Question 44

**** What is TOCILIZUMAB?

Answer 44

- IL- 6 inhibitor used when TNF-alpha inhibitors don't work.