Rheumatoid Arthritis Drugs (DMARDS) Flashcards
What is the general pathway for autoimmune arthritis?
Antigen presenting cells take in a foreign or self antigent (protein) and present it in their MHC.
A CD4 Helper T-Cell then forms an MHC/Antigen Complex with the APC, resulting in release of cytokines to B-Cells and CD8 (Cytotoxic T-cell).
- B-Cells are stimulated to create and release antibodies that are specific for pathogens or accidentally target your own cells (self)!
- CD8 T-Cells attack the cells labeled by specific antibodies (even if they are safe!).
Name the Non-biological Disease Modifying Drugs (DMARDs)
Methotrexate Hydroxychloroquine Leflunomide Sulfasalazine Gold Azathioprine Cyclosporine
How does Methotrexate work?
- Methotrexate acts as a folate synthesis inhibitor by blocking dihydrofolate reductase.
- This stops production of purines preventing synthesis of B and T -Cells
How does Hydroxychloroquine work?
- Major site of action is on “Toll-like Receptor 9” of the APC/Dendritic cell
- Also prevents acidification of macrophage cytosol.
How does Leflunomide work?
I. Inhibits pyrimidine synthesis by blocking the orotate pathway
II. Affects mainly B and T cells
How does Sulfasalazine work?
What side effects accompany it?
I. It acts in the same way as methotrexate and hydroxychloroquine.
II. It is more toxic than Methotrexate and hydroxychloroquine
a. Creates a rash
b. Causes neutropenia and myelosuppresion
How does Azathioprine work?
What type of cell in the auto-immune pathway does this drug target?
I. It is a purine analog that blocks DNA synthesis affecting primarily T-Cells
What does Cyclosporine do?
What cell does it mainly target in the auto-immune pathway?
I. This inhibits calcineurin which usually will stimulate IL-2 –> stimulation of T-Cells in the immune pathway.
II. This drug mainly targets T-Cells because it prevents their activation via calcineurin.
III. This drug is most commonly used as an immunosuppressant in transplant patients to control transplant rejection.
I. Name the Tumor Necrosis Factor inhibitors
II. How do they work?
III. What extra precautions should be considered when using them?
I. Etanercept, Inflixumab, and Adalimumab
II. These block receptors on CD4 helper T-Cells that normally bind TNF released from APCs
III. These drugs are immunosupressants, so consider a patient’s risk of infection or disease before using them.
I. What is the name of an IL-1 receptor antagonist?
II. How does it work?
I. Anakinra
II. It binds to an IL-1 receptor and blocks a normal IL-1 molecule from signaling for tissue damage
*This drug is infrequently used
I.) How does Rituxumab work?
II.) What cell does it target in the auto-immune pathway?
I. Rituxumab binds to CD20 receptors, preventing the actions of B-cells
II. It targets B-Cells
I.) How does Abatacept work?
I.) Abatacept binds to CD80 receptors on APCs to prevent stimulation of T-Cells.
Describe how you would reduce inflammation and reduce uric acid in gout patients
I. You can use NSAIDs to reduce the inflammation
* Do not use salicylates (Aspirin!)
II.Reduce uric acid levels with:
- Allopurinol (inhibits Xanthine oxidase)
- Probenicid or Sulfinpyrazone (these both inhibit a transporter in the kidneys, reducing reuptake of Uric acid and speeding its excretion)
-Limit diet that will lead to uric acid production
For a gout patient, what will Colchicine do? Should Colchicine or Allopurinol be used first?
I. Colchicine is a microtubule inhibitor that has antiinflammatory properties.
II. Use colchicine first. If you use Allopurinol first you run the risk of making the inflammation worse.
What does Gold do?
Gold - reduces macrophages and phagocytosis as well as affects APCs & T-Cells.
