Drugs used to treat gout and RA

Question 1

Colchicine

Answer 1

Binds tubulin prevents assembly of microtubules. No neutrophil chemotaxis, no phagocytosis. Decreased leukotriene B4 formation. Used in acute attack and prophylaxis.

Question 2

Colchicine side effect

Answer 2

Diarrhea

Question 3

Allopurinol

Answer 3

Inhibits Xanthine Oxidase, used in the management of chronic gout. Can’t use in acute gout because it will increase serum uric acid.

Question 4

Side effect of allopurinol

Answer 4

Interstitial nephritis (80% renal excretion)

Question 5

Febuxostat

Answer 5

Also XO inhibitor. More potent than allopurinol. Less renal excretion so should be safer in renal patients.

Question 6

Probenecid

Answer 6

Decreases reabsorption of uric acid in proximal tubules of the kidney. A uricosuric drug. Used to treat chronic gout.

Question 7

Side effects of probenecid

Answer 7

Increased risk of kidney stones

Question 8

Notable pharmacokinetics of probenecid?

Answer 8

Extensive hepatic metabolism so saturates cyps and can behave zero order.

Question 9

Pegloticase

Answer 9

Recominant mammalian uricase. Turns uric acid into allantoin. Used only in refractory cases.

Question 10

Hydroxychloroquine

Answer 10

Anti-malarial drug that suppresses immune system. Use early in the course of RA (before erosive changes), not very strong. Can also use SLE and Sjogren’s syndrome.

Question 11

Side effects of hydroxychloroquine

Answer 11

Opthalmologic side effects so get eyes checked. Long t1/2 so long time to get to steady state.

Question 12

Sulfasalazine

Answer 12

Unknown mechanism thought to suppress B and T cell function. Used in RA and AS.

Question 13

Methotrexate

Answer 13

Mainstay of DMARDS. Inhibitor of AICAR transformylase, thymidyl synthase, and THF reductase. Major mechanism in RA is through AICAR. Accumulates, inhibits AMP deaminase. This increases AMP and Adenosine, which is a potent anti-inflammatory that interferes with neutrophil mediated attack. Used for RA, psoriatic arthritis, PM/DM, SLE.

Question 14

Side effects of MTX

Answer 14

Nausea, mucosal ulcers. Can co-administer folate to reduce side-effects

Question 15

Leflunomide

Answer 15

Converted to active metabolite A77-1726 which inhibits dihydroorotate dehydrogenase. Arrest cells in G1 phase and decreases Ab production and T cell production.

Question 16

Etanercept

Answer 16

Soluble TNF receptor, binds both TNF a and TNF b. Can also be used in RA, PA, AS. Side effect: Increases ANA and dsDNA ABs.

Question 17

Abatacept

Answer 17

Binds to CD80 (coactivator of T cells) and prevents t-cell activation. Use for refractory RA.