RA and Gout Flashcards
What cytokines play a primary role in arthritic inflammation?
IL-1 and TNF-alpha
What are the three hallmark signs of rheumatoid arthritis?
Pain, Stiffness, and Swelling of joints
What are the three categories of drug therapies for rheumatoid arthritis?
NSAIDs, DMARDs, and biological response modifiers
What NSAIDs are used for RA?
Indomethacin, naproxen, celecoxib(better because COX2 specific)
What are the DMARD categories?
Corticosteroids, Gold salts, Anti-malarials, Sulfasalazine, Immunosuppressive drugs
What is the mechanism if the glucocorticoids’ anti-inflammatory effects? Wha tare the long-term side effects? What is the current usage regimen?
Inhibit prostaglandin synthesis and cytokine/COX2 induction; immunosuppressive/lymphoma risk; Bridge therapy till other drugs are effective
What is the MOA for gold salts? Why are they rarely used for RA today?
slow down immune responsiveness, especially macrophages; high levels of side effects and less efficacy than DMARDs
What is the major side effects of antimalarials?
Retinal damage
What is the MOA for anti-malarials in RA treatment?
Reduce T cell activation and chemotaxis
What is the MOA for sulfasalazine in RA? Where is it primarily used? What are the major side effects?
TNF-alpha and IL-1 release inhibition; Europe primarily; nausea, vomiting, headaches, skin rashes, and neutropenia (30% discontinue)
What are the two major immunosuppressive drugs in RA? What is the major consideration in their treatment?
Methotrexate and Leflunomide; Take several weeks/months to show full effect
What is the difference between dosages of methotrexate in cancer and RA chemotherapy? Why?
RA doses are much lower; thought to inhibit AICAR transformylase and some effect on thymidylate synthase with PMN inhibition
What are the side effects of methotrexate?
Nausea, stomatitis, and hepatotoxicity (rare)
What is the MOA of Leflunomide?
Immunosuppressive due to
What are the major cytokine targets for RA therapy?
TNF-alpha, IL-1, and IL-6
What are three routes of cytokine inhibition in RA?
Antibody binding (to cytokine or receptor), small-molecule binding to chytokine, and small-molecule binding to receptor
What is the MOA for Infliximab?
anti-TNF Mab (chimeric) with long term effect
What is the structure of Etanercept and its MOA?
TNF-RII-Fc to bind TNF in serum
What is the MOA of Adalimumab?
anti-TNF Mab with effect similar to infliximab - used in combo
What is the action of Golimumab?
anti-TNF
What is the action of Certolizumab?
anti-TNF
What is the MOA and use for Anakinra?
IL-1 Receptor antagonist used mono or combo with methotrexate for RA
What is the action of Abatacept? What are its side effects?
T-cell activation inhibitor; headaches and infections as side effects
What is the action of Tocilizumab?
IL-6R antagonist
What is the MOA for Rituxumab? What are its side effects?
antiCD20 Mab preventing B cell activation; headaches, hypersensitivity reactions, and infections as side effects
What would be the indication for a monotherapy in RA? For combination or anti-TNF therapy?
Low disease or high without complications=monotherapy; high level disease with complications is a target of combo or anti-TNF therapy
What enzyme and end product are at high levels in gout?
Xanthine oxidase and uric acid
What are the 4 strategies used in pharmacological treatment of gout?
decrease uric acid synthesis, increase uric acid excretion, decrease levels of leukacytes, combat inflammation
What are the 4 reasons for high urate production?
diseases with rapid cell destruction, metabolism i.e. lactic acidosis, drug induced, high purine diet
What three issues can cause low urate excretion?
renal function loss, suboptimal urine volumes, drug (i.e. thiazide diuretics)
What are the two forms of gout presentation?
Acute gouty arthritis and chronic gout with intradermal tophi
What are the therapies for acute gouty arthritis?
Colchizine, NSAIDs, and Corticosteroids
What is the MOA for colchizine? Side effects? What is a major concern in dosing?
alkaloid prevent tubulin polymerization and inhibits leukocytes; adverse: NVD, hair loss, and bone marrow depression; LOW THERAPEUTIC INDEX
How are corticosteroids used in acute gouty artheritis?
Intraarticular injection for local effects
What Uricosuric organic acid is used to inhibit urate reabsoprtion in the proximal tubules?
Probenecid (sulfinpyrazone overseas)
What are the side effects of probenecid?
GI effects, acute gout due to uric acid mobilization, lower penicillin secretion
What is the MOA of allopurinol that makes it useful in gout? What are its indications?
It is a competitive inhibitor of xanthine oxidase as it is a good substrate. Used for overproducers and also as prophylactic in chemotherapy (esp leukemia) or kidney disease patients
What are the three common treatments in chronic gout?
Allopurinol, probenecid, and Febuxostat
