Anti-Arthritic Drugs

Question 0

What are the traditional (non-biological) DMARDs?

Answer 0

Methotrexate, Hydroxychloroquine, Leflunomide, Sulfasalazine, Gold, Azathioprine, Cyclosporine

Question 1

Where do traditional DMARDs work?

Answer 1

On T cells - B cell activation by T cells and Macrophage activation by T cells

Question 2

How does arthritis progress?

Answer 2

Either genetic predisposition or An Antigen triggering event –>Dedritic cells costimulate T helper cells –> T helper cells stimulate B cells and Macrophages –> B cells release Rheumatoid factor –> Macrophages secrete cytokines –> Il-1 and TNF and IL-6 –> cause synovial inflammation, destructive changes in the joint and systemic inflammation – Tissue damage & Macrophages can also release prostaglandins causing fever, vasodilation & pain

Question 3

What is the best treatment for RA?

Answer 3

Etanercept (Enbrel) - blocks TNF action!!

Question 4

What does DMARD stand for?

Answer 4

Disease Modifying Anti-rheumatic Drugs

Question 5

What is Methotrexate?

Answer 5

• Non-bio DMARD
• Works as Anti-folate (inhibits purine & pyrimidine synthesis)
• Blocks dihydrofolate reductase (enzyme that converts dihydrofolate to tetrahydrofolate)
• Works on B & T cell

Question 6

Hydroxychloroquine (Plaquenil)

Answer 6

• Prevents acidification of macrophage cytosol

- Suppresses TLR 9 on dendritic (antigen-presenting) cells

Question 7

Leflunomide (Arava)

Answer 7

• Inhibits Pyrimidine synthesis
• Blocks Ororate pathway
• Primarily effects T cells & possibly B cells

Question 8

Sulfasalazine

Answer 8

• Metabolized in colon to active substances
• Not absorbed well from gut but effectively prevents progression of arthritis
• INHIBITS COX & SCAVENGES FREE RADICALS (APC & T CELLS)
• Alternative to methotrexate & hydroxychloroquine
• Tends to be more toxic - rash, neutropenia, myelosuppression

Question 9

Gold

Answer 9

• Suppresses phagocytosis by macrophages
• Suppresses T cell development (affects APCs & T cells)
• Not clear mech.
• Not well tolerated - side effects

Question 10

Azathioprine (Imuran)

Answer 10

• Purine analog used to block DNA synthesis

- Acts on the T cell

Question 11

Cyclosporine

Answer 11

• Immunosuppressaant used to control transplant rejection
• Inhibits calcineurin
• Acts on T cell

Question 12

Inflixumab & Etanercept (Enbrel)

Answer 12

• Tumor Necrosis Factor Inhibitors - bind to TNF and block its action
• Immunosuppressants

Question 13

Anakinra

Answer 13

Interlukin 1 receptor antagonist

-Infrequently used

Question 14

Rituximab

Answer 14

• Binds to CD20 on B cell

- Suppresses B cell activity

Question 15

Abatacept

Answer 15

-Binds to CD80 on T cell preventing its activation

Question 16

What are the biological DMARDs?

Answer 16

Etanercept/Inflixumab - TNF blocker
Anakinra - IL-1 receptor antagonist
Abatarcept - Blocks T cell activation by APC (CD 80)
Ritixumab - Blocks B cell activation (CD 20)