Arthritis & Gout Flashcards

1
Q

Chronic inflammation of the synovial membrane with infiltration by blood derived cells that produce inflammatory cytokines

A

Rheumatoid Arthritis

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2
Q

Name the general classes of the disease modifying anti-rheumatic drugs (DMARDs)

A

Gold salts, anti-malarials, immunosuppressives

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3
Q

At what point in the progression of RA is joint damage most rapid (early, intermediate, or late)?

A

Early! Once damage is done, it is irreversible

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4
Q

How are indomethacin and naproxen useful for treating RA? What are the drawbacks of using these drugs? What class of NSAID are they getting replaced by?

A

Used to treat the pain and reduce the inflammation but does NOT slow disease progression. Being replaced by COX-2 inhibitors, as there is less GI toxicity.

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5
Q

How do glucocorticoids work to treat RA and in what context are they often used today?

A

Suppress inflammation by inhibiting PLA2 activity and inhibiting the production of cytokines. Used in conjunction with the initiation of a DMARD, because DMARDs are slower acting and take weeks to start having an effect.

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6
Q

Your patient is experiencing an acute gout attack in his thumb that just won’t go away, and it is impairing his ability to perform at his job as a mechanic. He’s in great distress and is begging you for a joint injection. What do you inject?

A

Intraarticular glucocorticoid injection

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7
Q

How does gold work as an immunosuppressant?

A

inhibits the funcational capabilities of the macrophages

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8
Q

What is the likely MOA of sulfasalazine as an immunosuppressant and what is unique about this drug when comparing to other DMARDs?

A

Inhibitions of IL-1 and TNF-a release. Acts more quickly than the other DMARDs

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9
Q

How do the doses of methotrexate when used for RA compare to the doses used for cancer? How does the difference in doses change the mechanism of action of the drug?

A

The RA doses are lower than those used for cancer. Works by inhibition of aminoimidazolecarboxamide (AICAR) transformylase and thymidylate synthetase, causing AMP to accumulate, be converted to adenosine, and inhibit inflammation. Methotrexate is the GOLD STANDARD of RA therapy.

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10
Q

Tell me about Leflunomide.

A

Prodrug DMARD, works by inhibiting DHODH and essentially inhibits T-lymphocyte response to stimuli. Side effects are diarrhea and hepatotoxicity.

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11
Q

How does etanercept work?

A

Blocks binding of TNF to TNF receptors.

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12
Q

What is the major difference between infliximab and adalimumab?

A

Inflixumab is chimeric and adalimumab is fully human, so adalimumab is better tolerated! No antigenic response.

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13
Q

What is a major side effect of golimumab (and of all TNF-a blockers)?

A

Increased risk of serious infections by opportunistic pathogens (TB, fungal, etc)

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14
Q

What is unique about certolizumab when compared to other TNF-a blockers?

A

conjugated to polyethylene glycol, so metabolism and elimination is delayed

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15
Q

How does anakinra work to treat RA?

A

IL-1 receptor antagonist

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16
Q

How does tocilizumab work to treat RA?

A

IL-6 receptor antagonist

17
Q

How does abatacept work to treat RA?

A

inhibits T cell activation and induces T cell apoptosis

18
Q

How does rituximab work to treat RA?

A

anti-CD20 MAB that reduces circulating B cells, often used for RA refractory to TNF-a inhibitors

19
Q
  • recurrent episodes of acute arthritis
  • local infiltration by macrophages and neutrophils
  • lactate production and local decrease in pH
  • presence of urate crystals in joint/cartilage

What is the diagnosis?

A

Gout

20
Q

How is uric acid produced?

A

Hypoxanthine –> xanthine (catalyzed by xanthine oxidase)

Xanthine –> uric acid (catalyzed by xanthine oxidase)

Purine catabolism

21
Q

What are the 4 treatment strategies for approaching gout management?

A
  • decrease synthesis of uric acid
  • increase excretion of uric acid
  • decrease mobility of leukocytes
  • symptomatic relief with NSAIDs or corticosteroids
22
Q

Where is uric acid reabsorbed and secreted?

A

Middle segment of proximal tubule

23
Q

What are some instances that would increase the rate of urate production in a patient?

A
  • disease states associated with rapid production and destruction of cells
  • antineoplastic agents and radiation therapy
  • alcohol use
  • lots of animal muscle, seafood, beer, and high fructose corn syrup in diet
24
Q

What are some instances that would decrease the rate of urate excretion in a patient?

A
  • renal problems
  • low urine volumes
  • drugs, such as thiazide diuretics
25
Q

What is the term for deposits of urate in tissues or joints?

A

Tophi, or tophaceous gout

26
Q

How does colchicine work to treat acute gout?

A

binds to tubulin and prevents polymerization, which leads to the inhibition of leukocyte migration and release of proinflammatory autacoids

27
Q

What are the serious side effects of colchicine?

A

peripheral neuropathy and neutropenia

28
Q

How does probenecid work when treating chronic gout? What is an interesting side effect?

A

Competes with urate at the anionic transport sites of renal tubule to inhibit reabsorption of gout. Sometimes, reduced urate levels may cause urate crystal mobilization and acute gouty arthritis!

29
Q

How does allopurinol work to treat chronic gout?

A

Competitive inhibitor of xanthine oxidase, and is metabolized to alloxanthine which is a non competitive inhibitor of xanthine oxidase

30
Q

How does febuxostat work to treat chronic gout?

A

non-competitive antagonist of xanthine oxidase

31
Q

How does pegloticase work to treat chronic gout?

A

recombinant form of uricase, converts uric acid to allantoin