Gout and RA Flashcards
Allopurinol
Used in gout. Prodrug used to inhibit Xanthine oxidase
Inhibits production of urate
AE: increased risk of gouty attack at onset of treatment; skin rash or other allergic reactions; GI disturbances
Drug interactions with other drugs metabolized by xo (azithioprine, mercaptopurin)
Probenecid
Increase uric acid excretion in pct
AE: gastrointestinal irritation, rash
Not used often due to: 1) pt may have reduced kidney function 2) uricosuric agents may cause crystallization following dehydration
3) inhibits secretion of drugs that are weak acids so potential for drug interactions (methotrexate, oral hypogycemic agents, zidovudine)
Uricase enzyme
New drug class that metabolizes uric acid to allantoin. Used following chemotherapy which causes large increase in uric acid
Pt develops ab resulting in decreased efficacy
Febuxostat
Non purine inhibitor of xo. Metabolized by liver
Methotrexate
Dihydrofolate reductase inhibitor. Decreases DNA and protein synthesis (review pathway).
PK:converted to active metabolite in the liver; renal secretion in pct
Clinical use: Rheumatoid arthritis, psoriasis, lupus, chemotherapy,
immunosuppression
AE: mucosal ulcers, nausea, diarrhea
Monitor liver enzymes
Hydroxychloroquine
Base. Accumulates in lysosomal compartment of connective tissue and WBC. Thought to prevent antigen processing by MHC class II
Clinical uses: Second line drug for rheumatoid arthritis, malaria
AE: rashes, leukopenia, GI upset, peripheral neuropathy and ocular effects
Monitor retina function
Clinically used in pt that do not adequately respond to NSAIDs
Sulfasalazine
MOA unknown
PK: sulfapyridine moiety important in RA. Salicylic acid component important with ulcerative colitis
AE: GI or CNS disturbances, neutropenia, skin rash, hepatotoxicity
TNF-a inhibitors (screen for latent TB)
Etanercept- TNF and human Fc: decreases leukocyte migration. Often used in conjunction with methotrexate
Infliximab- monoclonal ab that binds TNF. 2/3 human 1/3 mouse
Adalimumab- fully human anti TNF antibody
Anakinra
Interleukin 1 inhibitor. Interleukin 1 causes cartilage degradation and bone resorption. Used if other DMARDs fail
AE: serious infections
Subcutaneous injection
Not to be used with TNF antagonist
Lymphocyte antagonist
Leflunomide- inhibits dihydrooratate dehydrogenase causing decreased UMP synthesis. Cells arrest in G1. 15 day half life (enterohepatic circulation)
Abatacept- binds CD80/86 preventing co-stimulation of t lymphocytes
Colchicine
MOA: prevents tubulin polymerization, This inhibits leukocyte
migration/phagocytosis, and inhibits leukotriene B4 format ion
Clinical use: Acute treatment of gout, low doses to prevent attack
AE: nausea, vomiting and diarrhea
Tocilizumab
MOA: Antibody against IL-6 receptor
Clinical uses: Rheumatoid arthritis if other drugs fail
AE: Injection site reactions, rash, GI symptoms, headache, respiratory tract infections, nasopharyngitis, activation of latent TB, and elevated liver enzymes
IV infusion
Tofacitinib
Janus kinase (JAK) pathway inhibitor. JAK/STAT play a role in inflammation. Potential for cytochrome P450 interaction
