Arthritis & Gout Flashcards
Indomethacin, naproxen
Relieve symptoms in the long-term tx of RA
COX-2 Inhibitors
Decrease incidence gastric/duo ulcers by 50% in tx of RA, replacing the conventionals of the NSAIDS; “bridge” therapy
List the small molecule DMARDS in clinical use
Sulfasalazine, antimalarials, glucocorticoids, methotrexate, cyclosporine A, leflunomide
Glucocorticoids: Have what effect, inhibit which enzyme and the production of what.
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
Antimalarials: Name the two and the process they act upon.
Chloroquine and hydroxychloroquine. Inhibit CHEMOTAXIS. S.E. of chloro is it can cause irreversible retinal dmg
Sulfasalazine: What does it do
Retards radiographic progression of RA by possibly inhibiting IL-1 and TNF-a release. S.E. n/v/HA/neutropenia/rashes
Immunosuppressives: What do they reduce
Reduce pain AND swelling in affected joints, slow the progression of destruction. Best given early.
Methotrexate: Class of med, what does it inhibit, in RA what enzymes does it inhibit, and what accumulates because of this that inhibits inflammation?
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.
Methotrexate S.E.
Nausea and stomatitis, HEPATOTOXICITY.
Leflunomide: Name the class. What enzyme does it inhibit and in doing so what is blocked? What other response is affected?
Immunosupp. Prodrug, oral. Inhibits DHODH (blocks de novo syn of UMP (pyrimidine). T-cell response to stimuli is inhibited. S.E. alopecia, diarrhea, hepatotox
TNF-a antagonists: Name the class of drug. Name the 5 and describe them
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.
Other cytokine antagonists: Name the class. Name the 2 and describe what receptors each antagonizes
Biological response modifiers. Anakinra is a human IL-1 receptor antagonist. Tocilizumab is a IL-6 receptor antagonist; S.E. Tb, viral, fungal, opportunistics.
Co-stimulation modifiers: Name the class. Name the 2 and describe what cells they inhibit and what they’re used for
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.
Approach to RA therapy
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.
Recurrent episodes of acute arthritis due to the presence of monosodium urate crystals in joints and cartilage
Gout
The inflammatory response in gout involves local infiltration by what two things that phagocytize the urate crystals?
Macrophages and neutrophils
Causes of high rate of urate production causing hyperuricemia
Disease states (rapid t/o of cells), metabolism (ketosis, LA), drug-induced, diet (high purine intake)
Causes of low rate of urate excretion causing hyperuricemia
Renal problems, suboptimal urine volumes, drugs (thiazide diuretics)
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?
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.
Colchicine S.E.
N/V/D/Abd pain. Low thx index. Peripheral neuropathy or neutropenia in long term use.
NSAIDS for acute gouty arthritis do what?
Inhibit eicosanoid-mediated pain and inflamm.
Corticosteroids for acute gouty arthritis are given how and for what?
Intraarticular injection for those with acute monoarticular gout. Good pain relief, good for those in whom NSAIDS and colchicine are ineffective or contra’d.
Uricosuric agents: What are they, how do they work, and what are they used for?
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.
Probenecid: What type of agent, list S.E.s
Uricosuric agent. S.E. GI irritation, nausea, paradoxical acute gouty arthritis, reduced secretion of PCN.
Allopurinol: Reduces what by inhibiting which enzyme? What two groups of people would warrant prescription of this drug?
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.
Febuxostat: What type of antagonist, and what enzyme does it antagonize?
Non-competitive antagonist of XO. S.E. n/rash/arthralgias/expensive.
