Arthritis Flashcards
Gout/Hyperuricemia
Drug Options
Allopurinol (Zyloprim) Colchicine (Colcrys) Febuxostat (Uloric) Probenecid (Benemid) Rasburicase (Elitek) Pegloticase (Krystexxa)
Tx for Chronic Gout
Xanthine Oxidase Inhibitors: decrease of urimic acids
Allopurinol (Zyloprim)
MOA: Xanthine Oxidase inhibitor; Purine analog;
Reduces production of uric acids
Indications: primary or secondary gout (chronic Tx); chemo pts @ risk of tumor lysis syndrome (hematologic malignancies); recurrent calcium oxalate stones
NOT for asym hyperuricemia
-aids in dissolution of tophi, prevents dev or prog of chronic gout, decrease risk of perm renal damage
DI: Azathioprine, 6-mercaptopurine (inh enxymatic inactivation, reduce dose); Warfarin; theophylline
ADRs: rash (D/C imm), SJS, D/N, inc LFTs, acute gout attack (give colchicine or NSAID to settle flare)
Probenecid (Benemid)
MOA: blocks renal tubular reabsorption of urate (inc uric acid excrete, lowers serum urate levels); inhib PCN secretion (boost PCN levels)
Ind: hyperuricemia w/ gout (Chronic Tx) [alt med]
adj to PCN and ampicillin
ADRs: HA, N, worse gout flare, dizzy, uric acid kid stones, blood dyscrasias
Febuxostat (Uloric)
MOA: xantine oxidase inhibitor
Ind: chronic Tx
Caution: higher rate of CV events, hepatic failure (monitor LFTs)
Lensinurad (Zurampic)
MOA: blocks uric acid reabsorption
Ind: adj therapy with an XOI (not on guidelines yet)
Met: p450 2C9, induce 3A4
DI: p450 reduce efficacy of amlopdipine, sildenafil
ADRs: increase sCr, renal failure, kidney stones, HA, flu, GERD
Uric Acid Lowering Agents
Med Names
Colchicine (Colcrys)
Pegloticase (Krystexxa)
Rasburicase (Elitek)
Colchicine (Colcrys)
MOA: not well known, inhibits microtubule formation in bone cells and prevents neutrophil activation
Ind: prophylaxis and Tx of acute gout flares; familial Mediterranean Fever
ADRs: DIARRHEA!!!; throat pain
Met: PGP and CYP3A4 sub
CI: strong 3A4 inhibitors
Caution: narrow therapeutic window; blood dyscrasias, neuromusc toxicity, rhabdomyolysis,
Renal adjust
Pegloticase (Krystexxa)
MOA: catalyzes oxidation of uric acid to allantoin (inert H20 soluble molecule that’s renally excreted)
Ind: refractory chronic gout
Given IV due to risk of anaphylaxis and infusion rxn + premed with antihistamines and corticosteroids
ADRs: gout flare, infusion reaction, nausea, ecchymosis, nasopharyngitis, constipation, chest pain, vomiting, CHF exacerbation
Rasburicase (Elitek)
-just recog. and know what it’s for
Ind: hyperuricemia due to tumor lysis
ADRs: anaphylaxis, hemolysis, methemoglobinemia
Hyperuricemia/Chronic Gout
- -The first-line pharmacological ULT in gout is XOI therapy with either allopurinol or febuxostat.
- Patient education regarding diet, lifestyle, treatment objectives, and management of comorbid conditions is a core therapeutic measure for gout and for hyperuricemia.
- -Target serum urate level should be lower than 6 mg/dL, and often lower than 5 mg/dL, to maintain improvements in gout signs and symptoms.
- -The starting dosage of allopurinol should not exceed 100 mg/day (or less in moderate to severe CKD). This should be gradually titrated upward.
- -Even in patients with CKD, the maintenance dose of allopurinol can exceed 300 mg daily.
Hyperuricenmia/Gout
–prior to starting allopurinol
Due to risk of severe allergic rxn:
test for HLA-B*5801 in
high risk groups: asians of Han Chinese and Thai descent
Rheumatologic agents
Systemic corticosteroids
Systemic corticosteroids
Meds: Prednisone (Deltasone); Methylprednisolone (Medrol); Prednisolone MOA: Inhibit cytokine production, adhesion, protein activation, inflammatory cell migration and activation; Anti-inflammatory agents
Ind:
Asthma (short term to gain control; long term Sx prevention in severe persistent) [lowest effective dose for shortest duration];
life-long/low-dose for RA
ADRs:
short term: Hyperglycemia, increased appetite, fluid retention, wt gain, mood alteration, hypertension, peptic ulcer
Long term: Adrenal axis suppression; Growth suppression; Thinning of skin; Osteoporosis, HTN,
Diabetes, Cushing’s syndrome, Impaired immune function
MUST taper to take them off (to help with adrenals) and some will never come off it
**bone density tests MUST be done; age independent
DMARDs for Rheumatoid Arthritis
DMARDs: Methotrexate Leflunomide Hydroxychloroquine Sulfasalazine Minocycline
Biologics:
Anti-TNF
Adalimumab, certolizumab pegol, etanercept, infliximab, golimumab
Non-TNF biologics:
Abatacept, rituximab, tocilizumab
Methotrexate (Rheumatrex, Trexall)
MOA: folate analog, inhibits dihydrofolate reductase (DHFR); interferes w/ DNA synthesis, repair, and replication;
Use: 1st line RA; relieves inflammation, swelling and pain; revents dz progression and joint destruction; psoriasis, cancers
ADRs: N/V, hair loss, skin rash, abn liver enzymes*, fatigue, mouth sores, diarrhea, low blood counts (inc infxn risk)
CI: pregnancy [teratogenic both male and female (wait 3 months for male, women one month] and lactation; liver dz/alcoholism; blood dyscrasias
Renal elim.
Leflunomide (Arava)
MOA: pyrimidine synthesis inhibitor (enz block); anti-inflam; prodrug
Ind: reduce S/Sx, inhibit structural damage as evidenced by x-ray erosions and joint space narrowing and improve phys fxn in RA pts
ADRs: Diarrhea (20%); N/ stomach pain, indigestion, rash, hair loss;
Hydroxychloroquine (Planquenil)
MOA: Antimalarial
Ind: Malaria treatment and prophylaxis; Rheumatoid arthritis; Discoid and systemic lupus
ADRs: N/D/ skin and hair changes, rash; major rare: vision changes; Bull’s eye maculopathy (need eye exams);
CI: Retinal or visual field changes; Long-term use in kids
Sulfasalazine (Azulfidine)
MOA: Sulfa + salicylate; Anti-inflammatory and immunomod properties
Ind: Ulcerative colitis
Uses: Treats pain, swelling and stiffness in RA
Juvenile RA, ankylosing spondilitis, psoriatic arthritis
ADRs:
Nausea, abd discomfort
(Take w/ food and full glass of water);
photosensitivity (skin)
Minocycline (Minocin)
MOA: Tetracycline antibiotic
Anti-inflammatory properties; decreases prostaglandin, metalloproteinases and leukotrienes; Increases IL-10 (ant-inflammatory)
Use: mild RA
ADRs: GI, dizziness, rash, photosensitivity
S-L-O-O-O-O-W onset
2-3 months to start working, one year for maximum benefits
ADRs: GI, dizziness, rash, photosensitivity
Biologics
Will accept brand names!
Anti-TNF: Adalimumab (Humira) Etanercept (Enbrel) Infliximab (Remicade) Certolizumab pegol (Cimzia) Golimumab (Simponi)
Non-TNF Abatacept (Orencia) Rituximab (Rituxan) Tocilizumab (Actemra) Ustekinumab (Stelara) Psoriasis Psoriatic arthritis
Anti-TNF drugs
MOA: Genetically engineered proteins;
Block proinflammatory cytokines: TNF-a, IL-1, IL-6
Use: when DMARDs fail
Ind: RA, psoriatic arthritis, juvenile arthritis, Crohn’s colitis, ankylosing spondylitis and psoriasis
(can be in combo w/ DMARDs)
ADRs: Infection:
URI, sinusitis, and pharyngitis; Injection-site reactions: local rash, itching, burning; infusion-related reactions, headache, and abdominal pain
30% pts D/C due to not working or bad ADRs
Caution: increased risk of infxn and reactivate latent TB (need a TB test 1st); increase HF; worsen MS; increase risk of lymphoproliferative cancer
Infliximab dosed via IV infusion; Infliximab and golimumab given with MTX;
Golimumab has longest half-life
Non-TNF Drug Names
Abatacept (Orencia)
Rituximab (Rituxan)
Tocilizumab (Actemra)
Ustekinumab (Stelara)
Abatacept (Orencia)
MOA: selective T-cell costimulation modulator; binds antigenic CD80/86 receptors, blocks interaction with T cell CD28; prevents stim w/ second signal (caps it off)
Ind: 2nd-line RA; juvenile arthritis after MTX and biologics (Tx swelling, pain, and prolonged joint stiffness)
CI: concomitant use with biologics (worsens infxns)
ADRs: COPD flares; HA; URI; naopharyngitis; N
Rituximab (Rituxan)
MOA: chemo drug; CD20-directed cytolytic antibody; targets abn B cells, decreasing AI response
Ind: NHL, CLL; 2nd line RA; Wegener’s Granulomatosis; Micro Polyangitis
ADRs: Infusion Rxns (premed w/ prednisone, benadryl); hypotension
Warnings: Tumor lysis syndrome; SJS; TEN; Hep B reactivation; cardiac arrhythmias; renal texicity; bowl obs/perf
Tocilizumab (Actemra)
MOA: IL-6 receptor antagonists; mediates T cell activation, immunoglob secretion, hematopoietic cell proliferation and diff.
Ind: RA; juvenile arthritis
ADRs: inc cholesterol; URI, nasopharyngitis, HA, HTN, inc ALT
Warnings: serious infxn, GI perf, neutropenia, live vaccines
Ustekinumab (Stelara)
MOA: selectively targets IL-12 and IL-23
Ind: Psoriasis, psoriatic arthritis
ADRs: nasopharyngitis, URI, HA, fatigue, arthralgia, N
Caution: malignancies
Guidelines
Look at slide 66
Low: MTX or DMARD monotherapy
Mod-High Active: DMARD monotherapy
