RA and Gout

Question 1

What cytokines play a primary role in arthritic inflammation?

Answer 1

IL-1 and TNF-alpha

Question 2

What are the three hallmark signs of rheumatoid arthritis?

Answer 2

Pain, Stiffness, and Swelling of joints

Question 3

What are the three categories of drug therapies for rheumatoid arthritis?

Answer 3

NSAIDs, DMARDs, and biological response modifiers

Question 4

What NSAIDs are used for RA?

Answer 4

Indomethacin, naproxen, celecoxib(better because COX2 specific)

Question 5

What are the DMARD categories?

Answer 5

Corticosteroids, Gold salts, Anti-malarials, Sulfasalazine, Immunosuppressive drugs

Question 6

What is the mechanism if the glucocorticoids’ anti-inflammatory effects? Wha tare the long-term side effects? What is the current usage regimen?

Answer 6

Inhibit prostaglandin synthesis and cytokine/COX2 induction; immunosuppressive/lymphoma risk; Bridge therapy till other drugs are effective

Question 7

What is the MOA for gold salts? Why are they rarely used for RA today?

Answer 7

slow down immune responsiveness, especially macrophages; high levels of side effects and less efficacy than DMARDs

Question 8

What is the major side effects of antimalarials?

Answer 8

Retinal damage

Question 9

What is the MOA for anti-malarials in RA treatment?

Answer 9

Reduce T cell activation and chemotaxis

Question 10

What is the MOA for sulfasalazine in RA? Where is it primarily used? What are the major side effects?

Answer 10

TNF-alpha and IL-1 release inhibition; Europe primarily; nausea, vomiting, headaches, skin rashes, and neutropenia (30% discontinue)

Question 11

What are the two major immunosuppressive drugs in RA? What is the major consideration in their treatment?

Answer 11

Methotrexate and Leflunomide; Take several weeks/months to show full effect

Question 12

What is the difference between dosages of methotrexate in cancer and RA chemotherapy? Why?

Answer 12

RA doses are much lower; thought to inhibit AICAR transformylase and some effect on thymidylate synthase with PMN inhibition

Question 13

What are the side effects of methotrexate?

Answer 13

Nausea, stomatitis, and hepatotoxicity (rare)

Question 14

What is the MOA of Leflunomide?

Answer 14

Immunosuppressive due to

Question 15

What are the major cytokine targets for RA therapy?

Answer 15

TNF-alpha, IL-1, and IL-6

Question 16

What are three routes of cytokine inhibition in RA?

Answer 16

Antibody binding (to cytokine or receptor), small-molecule binding to chytokine, and small-molecule binding to receptor

Question 17

What is the MOA for Infliximab?

Answer 17

anti-TNF Mab (chimeric) with long term effect

Question 18

What is the structure of Etanercept and its MOA?

Answer 18

TNF-RII-Fc to bind TNF in serum

Question 19

What is the MOA of Adalimumab?

Answer 19

anti-TNF Mab with effect similar to infliximab - used in combo

Question 20

What is the action of Golimumab?

Answer 20

anti-TNF

Question 21

What is the action of Certolizumab?

Answer 21

anti-TNF

Question 22

What is the MOA and use for Anakinra?

Answer 22

IL-1 Receptor antagonist used mono or combo with methotrexate for RA

Question 23

What is the action of Abatacept? What are its side effects?

Answer 23

T-cell activation inhibitor; headaches and infections as side effects

Question 24

What is the action of Tocilizumab?

Answer 24

IL-6R antagonist

Question 25

What is the MOA for Rituxumab? What are its side effects?

Answer 25

antiCD20 Mab preventing B cell activation; headaches, hypersensitivity reactions, and infections as side effects

Question 26

What would be the indication for a monotherapy in RA? For combination or anti-TNF therapy?

Answer 26

Low disease or high without complications=monotherapy; high level disease with complications is a target of combo or anti-TNF therapy

Question 27

What enzyme and end product are at high levels in gout?

Answer 27

Xanthine oxidase and uric acid

Question 28

What are the 4 strategies used in pharmacological treatment of gout?

Answer 28

decrease uric acid synthesis, increase uric acid excretion, decrease levels of leukacytes, combat inflammation

Question 29

What are the 4 reasons for high urate production?

Answer 29

diseases with rapid cell destruction, metabolism i.e. lactic acidosis, drug induced, high purine diet

Question 30

What three issues can cause low urate excretion?

Answer 30

renal function loss, suboptimal urine volumes, drug (i.e. thiazide diuretics)

Question 31

What are the two forms of gout presentation?

Answer 31

Acute gouty arthritis and chronic gout with intradermal tophi

Question 32

What are the therapies for acute gouty arthritis?

Answer 32

Colchizine, NSAIDs, and Corticosteroids

Question 33

What is the MOA for colchizine? Side effects? What is a major concern in dosing?

Answer 33

alkaloid prevent tubulin polymerization and inhibits leukocytes; adverse: NVD, hair loss, and bone marrow depression; LOW THERAPEUTIC INDEX

Question 34

How are corticosteroids used in acute gouty artheritis?

Answer 34

Intraarticular injection for local effects

Question 35

What Uricosuric organic acid is used to inhibit urate reabsoprtion in the proximal tubules?

Answer 35

Probenecid (sulfinpyrazone overseas)

Question 36

What are the side effects of probenecid?

Answer 36

GI effects, acute gout due to uric acid mobilization, lower penicillin secretion

Question 37

What is the MOA of allopurinol that makes it useful in gout? What are its indications?

Answer 37

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

Question 38

What are the three common treatments in chronic gout?

Answer 38

Allopurinol, probenecid, and Febuxostat