Rheumatoid Arthritis Drugs

Question 1

Pathway of autoimmune disease (immunology)

Answer 1

Macrophage/Dendritic Cell takes up self-protein –> presents to Tcell –> Tcell recognizes self protein –> presents to B cells to make autoantibodies –> destroy self cells

Question 2

Types of Drugs for Arthritis

Answer 2

NSAIDs

Nonbiological Disease modifying anti-rheumatic drugs (DMARDs)

Biological DMARDs

Question 3

Nonbiological DMARDs

Answer 3

• Methotrexate
• Hydroxychloroquine
• Leflunomide
• Sulfasalazine
• Gold
• Azathioprine
• Cyclosporine

Question 4

Methotrexate works as _____________

(mechanism)

Answer 4

•Works as an anti-folate

–Blocks dihydrofolate reductase

• Step necessary to activate folic acid (folate) to participate in 1 carbon donor actions
• Results in inhibition of both pyrimidine and purine synthesis
• Most notably prevents conversion of uridine to thymidine

Question 5

Hydroxychloroquine (Plaquenil) mechanism

Answer 5

• Prevents acidification of macrophage cytosol
• Probably major site of action is on Toll-like receptor 9 on the dendritic (antigen presenting) cell (suppressing it)

Antimalarial

Question 6

Leflunomide (Arava)

Answer 6

•Inhibits pyrimidine synthesis

–Blocks ororate pathway

–Primarily affects T cells and potentially B cells

Question 7

Sulfasalazine (azulfidine)

Answer 7

•Metabolized in colon to active substances

–Sulfapyridine, a free radical scavenger

–5 amino-salicylic acid, a cyclooxygenase antagonists

•Not absorbed well from gut but effectively prevents progression of arthritis

Tends to be more toxic

Question 8

Gold

Answer 8

• Suppresses phagocytosis by macrophages
• Also can suppress development of T cells
• Not a clear mechanism
• Least tolerated of all DMARD’s because of side effects

Question 9

Azathioprine (Imuran)

Answer 9

•Purine analog used to block DNA synthesis

–Primary mechanism of action appears to be on T cell

Question 10

Cyclosporine (Sandimmune)

Answer 10

• Immunosuppressant used to control transplant rejection
• Inhibitor of calcineurin
• Major site of action in arthritis is T cell

Question 11

Tumor Necrosis Factor Inhibitors

Answer 11

• Etanercept (enbrel), Inflixumab (remicade) and Adalimumab (humira) (also golimumab & certolizumab)
• These are immunosupressants, so they increase infection risk

Injected

Question 12

Interlukin 1 receptor antagonist

Answer 12

Anakinra (kineret)

Infrequently used

Question 13

CD 20 binder

Answer 13

Rituximab (Rituxan) inds CD20 on B cell

Suppresses B cell activity –> reduce antibodies

Immunosuppressant

Question 14

CD 80 Binding agent

Answer 14

•Abatacept (Orencia) binds to CD80 on T cell preventing its activation

Question 16

folate metabolism inhibitor (T & B cell)

Answer 16

Methotrexate

Question 17

•inhibits macrophages, maybe TLR9 in dendritic cells

Answer 17

Hydroxychloroquine

Question 18

Pyrimidine synthesis inhibitor in T cells

Answer 18

Leflunomide

Question 19

•- Inhibits COX & scavenges free radicals (antigen presenting cells & T cells)

Answer 19

Sulfasalazine

Question 20

•reduces macrophage phagocytosis and affects antigen presenting cells & T cells

Answer 20

Gold

Question 21

•Blocks DNA synthesis, primary site of action T cell

Answer 21

Azathioprine

Question 22

•Calcineurin inhibitor to inhibit T cell activation

Answer 22

Cyclosporine

Question 23

•Block TNF action

Answer 23

Etanercept, Inflixumab

Question 24

•Interleukin 1 receptor antagonist

Answer 24

Anakinra

Question 25

•Blocks T cell activation by antigen presenting cell (CD 80)

Answer 25

Abatacept

Question 26

Blocks B cell activation (CD20)

Answer 26

Rituxumab

Question 27

Where everything works? (Draw picture)

Answer 27