Antirheumatics And Gout

Front 1

NSAIDs for RA
1. effects
2. MOA
3. examples
4. SEs

Back 1

1. moderately reduce pain and inflammation; do not slow disease progression
2. inhibit COX (no arachidonic acid > PGs)
3. aspirin, ibuprofen, naproxen, diclofenac, etodolac, nabumetone, oxaprozin, celecoxib (COX II selective)
4. mostly GI (N/V/D/C, irritation, ulceration), reduced platelet agg, renal dysfunction

Front 2

Corticosteroids for RA
1. effects
2. MOA
3. suggestions for use
4. SEs

Back 2

1. relief in pts not responding to NSAIDs; have many SEs
2. dec monocytes, macrophages, IL-1, PGs, and leukotrienes (anti-inf)
3. add on therapy, usually oral, can directy admin into joint space, safe in pregnant or lactating women
4. HTN, fat redistribution, 2' adrenal insuff, osteoporosis, inc glc, inc lipids, sodium retention, hypokalemia

Front 3

Hydroxychloroquine (DMARD)
1. MOA
2. time to take effect
3. metabolism
4. monitor...

Back 3

1. antimalirial; unknown MOA, probably effect on T cells, lysosomes, and IL-1
2. 3-6mo
3. liver
4. monitor ocular fxn

Front 4

Penicillamine (DMARD)
1. MOA
2. time to take effect
3. dosing, metabolism
4. SEs

Back 4

1. chelator of divalent cations (used for heavy metal toxicity), RA mechanism unkwon
2. 3mo
3. PO, liver metabolism
4. rarely used due to many SEs (GI, leukopenia, TCP, proteinuria, anemia, tiniitus, optic neuritis, skin rxn)

Front 5

Gold (DMARD)
1. MOA
2. time to take effect
3. dosing, metabolism
4. SEs

Back 5

1. unkown, may effect macrophage and PMN function (60-80% of pts have response)
2. 4-6mo
3. IM (most effective) or PO, 70% urine, 30% feces
4. proteinuria (monitor), exofliative dermatitis, mouth ulcers, TCP and granulocytopenia (monitor CBC), N/V (PO only)

Front 6

Methotrexate (DMARD)
1. MOA
2. uses
3. time to take effect
4. dosing, metabolism
5. SEs

Back 6

1. antimetabolite inhibiting DHF reductase > dec THF > inhibits DNA synthesis (impairs function of inflamm cells)
2. gold standard for RA, used for chemo at higher doses
3. 4-6wks
4. PO, SQ, IM, 90% renal
5. GI, myelosuppression (monitor CBC), hepatotoxic (monitor LFT), pulmonary toxicity (is suspect, monitor PFT), skin rash

Front 7

Azathioprine (DMARD)
1. MOA
2. uses
3. metabolism
4. SEs
5. drug interactions

Back 7

1. prodrug metabolized to 6-MP (active metabolite) which inhibits RNA and DNA synthesis (blocks T lymphocytes)
2. pts resistant to all other forms of RA tx, common chemo agent
3. in vivo to 6-MP, then hepatic
4. myelosuppression (dose related), stomatitis, skin rash, hepatotoxic, N/V
5. uses xanthine oxidase pathway, so reduce dosage w/ concomitant allopruinol

Front 8

Sulfasalazine (DMARD)
1. MOA
2. uses
3. time to take effect, metabolism, dosing
4. SEs
5. drug interactions

Back 8

1. conjugate of mesalamine (5-ASA) and sulfapyridine: 5-ASA is anti-inf, sulfa is anti-bacterial
2. mild to moderate disease
3. 1-6mo, urine metabolism, PO
4. GI, HA, leukopenia, fever, rash
5. reduced folate metabolism (may need folate supp)

Front 9

Cyclosporine (DMARD)
1. MOA
2. uses
3. metabolism
4. SEs

Back 9

1. immunosuppressant; blocks T cell activation
2. in RA if methotrexate is ineffective or not tolerated, organ transplants
3. metabolized via CYP3A
4. renal insufficiency (monitor Cr), anemia, HTN, hirsutism, infection risk

Front 10

Leflunomide (new DMARD for RA)
1. MOA
2. uses
3. dosing
4. SEs

Back 10

1. prodrug converted to A77-1776 which inhibits mito enzyme dihydroorotate dehydrogenase > dec pyrimidine rUMP > prevents lymphocyte expansion (immunosupp)
2. RA in pts unresponsive/intolerant to methotrexate
3. PO; need loading dose
4. diarrhea, elevated LFTs (require monitoring), alpecia, rash, teratogenic (cat X)

Front 11

Etanercept (anti-cytokine for RA)
1. MOA
2. dosing
3. SEs
4. use

Back 11

1. human fusion protein that binds 2 TNF receptors with Fc portion of IgG1 (blocks binding of TNFalpha and TNFbeta)
2. SQ
3. black box risk of lymphoma and demyelinating conditions (MS), and TB, injection site pain, potential for infection
4. FDA approved for RA only

Front 12

Infliximab (anti-cytokine for RA)
1. MOA
2. dosing
3. SEs
4. use

Back 12

1. chimeric monoclonal Ab derived partially from murine (mouse cells) that binds TNF-alpha receptor to Fc portion; induces complement; lyses cells
2. IV, long half life (less frequent dosing)
3. loss of efficacy, hypersensitivity rxns, SLE, black box warning for lymphoma, MS, TB (worse risk than other anti-cytokine agents), injection site pain, risk of infection
4. FDA approved for RA (in combo with methotrexate) and chron's disease

Front 13

Adalimumab (anti-cytokine for RA)
1. MOA
2. dosing
3. SEs
4. use

Back 13

1. recombinant human anti-TNFalpha IgG1 antibody (binds TNF-alpha preventing it from binding p55 and p75 on surface of TNF receptors); lyses TNF invitro
2. SQ, long half life (less frequent dosing)
3. black box risk of lymphoma and demyelinating conditions (MS), and TB, injection site pain, potential for infection
4. FDA approved for RA only

Front 14

Anakinra
1. MOA
2. dosing
3. SEs
4. uses

Back 14

1. recombinant, non-glycosylated version of IL-1 receptor antagonist (comp inhibits IL-1 bindings) > dec cytokine production, dec cartilage degradation, dec bone resorption
3. pruritis, rash, neutropenia, black box risk of lymphoma and demyelinating conditions (MS), and TB, injection site pain, potential for infection
4. FDA approved for RA only

Front 15

Other Drugs for RA
1. Abatacept
2. Minocycline
3. Thalidomide
4. chlorambucil, cyclophosphamide

Back 15

1. modulates CD80- or CD86-CD28 costimulatory signal needed for T cell activation, IV dose based on weight, take alone or with other DMARDs) (not TF inhibs or anakinra
2. tetracycline derivative
3. one time sedative (off market due to teratogenicity), being studied for RA
4. chemo agents, not recommended b/c not well tolerated

Front 16

Drugs for Acute Gout
1. NSAIDs
2. Colchicine
3. Corticosteroids

Back 16

1. inhibit COX > dec prostaglandins; also inhibit urate crystal phagocytosis; avoid aspirin and salicylates (inc uric acid levels in low doses); indomethacin used most often in gout
2. anti-inf that inhibits phagocytosis of urate crystals by neutrophils, give pO or IV (not IM or SQ- severe irritation); narrow therapeutic range, SE include GI, BM depression, neuritis, myopathy, alopecia, hepatic/renal impairment, azoospermia, reduce B12 absorption
3. used when NSAIDs or colchicine can't be used (renal dysfunction)

Front 17

Drugs for Chronic Gout
1. Allopurinol (MOA, active metabolites, SEs, dosing)
2. Oxypurinol
3. Febuxostat

Back 17

1. hypoxanthine (purine) anaolg that inhibits xanthine oxidase which convets hypoxanthine > xanthine > uric acid (no anti-inf, no inc in uric acid clearance), forms oxypurinol an active but less potent inhibitor of xanthine oxidase; rash, hypersenstivity, GI, alopecia, BM depression, acute gout attack, dose adjusted for renal fxn
2. alternative for pts who can't tolerate allopurinol
3. new tx, inhibits xanthine oxidase, don't need to adjust for renal fxn, cardiac SEs (angina, arrhythmia, heart block), don't start during acute gout attack

Front 18

Drugs that Increase Uric Acid Excretion
1. Probenecid
2. Sulfinpyrazone

Back 18

1. inhibits tubular reabsorption of urate (uricosuric), also used to prevent secretion of penicillin, exhibits saturation (michaelis mentin), must have adequate renal fxn, avoid in acute gout attack
2. inhibits tubular resorption of urate, antiplatelet effects, inc potentiial for uric acid stones, not well tolerated (rarely used)