Arthritis & Gout

Question 1

Indomethacin, naproxen

Answer 1

Relieve symptoms in the long-term tx of RA

Question 2

COX-2 Inhibitors

Answer 2

Decrease incidence gastric/duo ulcers by 50% in tx of RA, replacing the conventionals of the NSAIDS; “bridge” therapy

Question 3

List the small molecule DMARDS in clinical use

Answer 3

Sulfasalazine, antimalarials, glucocorticoids, methotrexate, cyclosporine A, leflunomide

Question 4

Glucocorticoids: Have what effect, inhibit which enzyme and the production of what.

Answer 4

Produce a rapid decrease in pain AND swelling of joints, induce remission before DMARDs kick in. Inhibit phospholipase A2 activity (and thus eventual prostaglandin formation) and inhibit prod of many CYTOKINES (preventing induction of COX-2).
S.E. hyperglycemia, OP, poor wound healing

Question 5

Antimalarials: Name the two and the process they act upon.

Answer 5

Chloroquine and hydroxychloroquine. Inhibit CHEMOTAXIS. S.E. of chloro is it can cause irreversible retinal dmg

Question 6

Sulfasalazine: What does it do

Answer 6

Retards radiographic progression of RA by possibly inhibiting IL-1 and TNF-a release. S.E. n/v/HA/neutropenia/rashes

Question 7

Immunosuppressives: What do they reduce

Answer 7

Reduce pain AND swelling in affected joints, slow the progression of destruction. Best given early.

Question 8

Methotrexate: Class of med, what does it inhibit, in RA what enzymes does it inhibit, and what accumulates because of this that inhibits inflammation?

Answer 8

Immunosupp. Folate analog, inhibits DHFR. In RA, inhibits AICAR transformylase and TS, and 2ndry fx on poly’s chemotaxis. AMP accumulates and is converted to adenosine which inhibits inflammation.

Question 9

Methotrexate S.E.

Answer 9

Nausea and stomatitis, HEPATOTOXICITY.

Question 10

Leflunomide: Name the class. What enzyme does it inhibit and in doing so what is blocked? What other response is affected?

Answer 10

Immunosupp. Prodrug, oral. Inhibits DHODH (blocks de novo syn of UMP (pyrimidine). T-cell response to stimuli is inhibited. S.E. alopecia, diarrhea, hepatotox

Question 11

TNF-a antagonists: Name the class of drug. Name the 5 and describe them

Answer 11

Biological response modifiers. Etanercept is a TNF-a receptor soluble fusion protein that binds to TNF, prevents its binding to receptors. Infliximab is a chimeric monoclonal IgG1 vs TNF-a. Adalimumab is a hmAb anti-TNF-a as effective as Etanercept but better dosing. Golimumab is a hmAb that binds to memb and soluble TNF-a; S.E. Tb, fungi, opportunistics. Certolizumab is a humanized Fab fragment conj to PEG.

Question 12

Other cytokine antagonists: Name the class. Name the 2 and describe what receptors each antagonizes

Answer 12

Biological response modifiers. Anakinra is a human IL-1 receptor antagonist. Tocilizumab is a IL-6 receptor antagonist; S.E. Tb, viral, fungal, opportunistics.

Question 13

Co-stimulation modifiers: Name the class. Name the 2 and describe what cells they inhibit and what they’re used for

Answer 13

Biological response modifiers. Abatacept inhibits T-cell activation and induces T-cell apoptosis; S.E. HA, infections. Rituximab anti-CD20 mAb that reduces circ B-cells, for RA refractory to TNF-a inhibitors; S.E. infections, hypersens rxns.

Question 14

Approach to RA therapy

Answer 14

Early RA w/ low disease activity = nonbiologic DMARD monotherapy. Mod or high w/o poor prognostic features = DMARD mono or combo of Mtx and hydroxychloroquine. Mod or high w/ poor prognostic features = combo Mtx/hydroxychlrqne, Mtx/sulfasalazine, or Mtx/sulfasal/hydxychlrqne. Altn, start on anti-TNF therapy w/ or w/o Mtx.

Question 15

Recurrent episodes of acute arthritis due to the presence of monosodium urate crystals in joints and cartilage

Answer 15

Gout

Question 16

The inflammatory response in gout involves local infiltration by what two things that phagocytize the urate crystals?

Answer 16

Macrophages and neutrophils

Question 17

Causes of high rate of urate production causing hyperuricemia

Answer 17

Disease states (rapid t/o of cells), metabolism (ketosis, LA), drug-induced, diet (high purine intake)

Question 18

Causes of low rate of urate excretion causing hyperuricemia

Answer 18

Renal problems, suboptimal urine volumes, drugs (thiazide diuretics)

Question 19

Colchicine: Attacks of what does it tx? What does it relieve? What does it bind and prevent the polymerization of, and what does that lead to?

Answer 19

Drug therapy for acute gouty arthritis. Dramatically relieves pain AND inflamm. Binds to the tubulin, prevents its polymerization and leads to the inhibition of leukocyte migration, phagocytosis, metabolic activity & the release of proinflammatory autocoids.

Question 20

Colchicine S.E.

Answer 20

N/V/D/Abd pain. Low thx index. Peripheral neuropathy or neutropenia in long term use.

Question 21

NSAIDS for acute gouty arthritis do what?

Answer 21

Inhibit eicosanoid-mediated pain and inflamm.

Question 22

Corticosteroids for acute gouty arthritis are given how and for what?

Answer 22

Intraarticular injection for those with acute monoarticular gout. Good pain relief, good for those in whom NSAIDS and colchicine are ineffective or contra’d.

Question 23

Uricosuric agents: What are they, how do they work, and what are they used for?

Answer 23

Drugs that increase the rate of excretion of uric acid. Used for chronic tophaceous gout. They compete with urate at the anionic transport sites of the renal tubule and inhibit reabsorption. Can reabsorb tophaceous deposits, relieving arthritis and remineralizing the bone.

Question 24

Probenecid: What type of agent, list S.E.s

Answer 24

Uricosuric agent. S.E. GI irritation, nausea, paradoxical acute gouty arthritis, reduced secretion of PCN.

Question 25

Allopurinol: Reduces what by inhibiting which enzyme? What two groups of people would warrant prescription of this drug?

Answer 25

Reduces uric acid synthesis by competitively inhibiting XO. Its metabolite thru XO is alloxanthine, which non-competitively inhibits XO. Useful in ppl who produce a lot of uric acid and to prevent massive uricosuria following chemo of leukemias and lymphomas. S.E. macpap rash, hypersens syndrome, acute gouty arthritis.

Question 26

Febuxostat: What type of antagonist, and what enzyme does it antagonize?

Answer 26

Non-competitive antagonist of XO. S.E. n/rash/arthralgias/expensive.