Gout and RA drugs Flashcards
What drug is often prescribed for gout? Esp tx for first 24hrs of symptomatic problems?
Indomethacin; NSAIDs for first 24 hours
What is the mechanism of colchicine?
antimitotic, arrests cell division in G1 by interfereing with microtubule and spindle formation; effect is largest in cells with rapid turnover
What is the metabolism of colchicine accomplished by?
50% plasma protein binding, rapid but variable oral absorption.
enterohepatic circulation
Hepatic metabolism via CYP3A4
Who is colchicine contraindicated in?
patients with hepatic or renal impairment requiring concomitant tx with CYP3A4 or PgP inhibitors
What is colchicine used to treat?
acute attacks of gout and is effective for 2/3 of pop if taken wthin 24 hrs of initiaon
What is the mechanism of action of allopurinol?
inhibits xanthine oxidase; active metabolite inhibits reduced form of xanthine oxidase
What is the pharmokinetics of allopurinol?
rapid absorption; metabolized to active metabolite, oxypurinol
half life of oxypurinol is 18-30 hrs
What is the adverse effects of allopurinol?
generally well tolerated
drowsiness, hypersensitivity rxns, increase gout flare at initiation of tx
What is a therapeutic use of allopurinol?
effective tx for primary and secondary gout
goal of tx is to reduce the plasmic uric acid concentration
What is the mechanism of action of febuxostat?
non-purine xanthine oxidase inhibitor; forms a stable complex with both the reduced and oxidized form of zanthine oxidase
What is the pharmokinetics of febuxostat?
oral admin; highly plasma protein; metabolized by CYPs adn non CYP enzymees
What are the adverse effects/contraindications?
liver fxn abnormalites, nausea, joint paina nd rash
liver fxn should be monitored periodically
increased gout flares after initation
increased MIs
What is the mechanism of action of pegloticase?
Pegylated recombinant form of urate-oxidase enzyme. Uricase is normally absent in humans. Pegloticase converts uric acid to allantoin
What is the pharmokinetics of pegloticase?
IV admin
serum half life from 6-14 days
What does pegloticase treat?
refactory gout
What is the mechanism of action of probenecid?
inhibition of organic acid transport in renal tubule
What is adverse effects of probenecid?
well tolerated with mild GI effects; ineffective in those with renal insufficiency
What is probenecid used to treat?
hyperuricemia associated with gout or gouty arthritis
What are some effects of probenecid with diuretics?
enhance adverse/toxic effect of loop diuretics
decrease diuretic effect of loop diuretics
increase serum conc of loop diuretics
What is the mechanism of action of Etanercept?
soluble, recombinant fully human TNF receptor fusion protein bidning ligand portion of TNFalpha receptor
What are the adverse effects of Etanercept?
serious and potentially fatal infections
lymphoma and other malignancies in adolescents and children
What is the mechanism of action of adalimumab?
chimeric IgG monoclonal antibody binds to both forms of TNFalpha
Wat are the adverse effects of adalimumab?
injection site from subQ
infection and upper respiratory tract
What are the therapeutic uses of adalimumab?
moderately to severelya ctive RA
acute juvenitle idiopathic arthritis
often used in conjuction with methotrexate
What is the mechanism of action of infliximab?
a chimeric IgG antibody binds to both forms of TNFalpha
What are hte adverse effects of infliximab?
acute infusion reaction
infection
active TB, invasive pathogens
monitor closely for signs/symptoms of infection
lymphoma and other malignnancies have been reported in children and adolescent pts receiving infliximab
What are the therapeutic uses of infliximab?
moderate to severely active rheumatoid arthiritis
What is the mechanism of action of abatacept?
selective costim modulator; inhibits T-cell activation by binding to CD80 and CD86 on APC thus blocking required CD28 interaction btw T and APCs
What are the adverse effects associated with abatacept?
headache
hypersensitivity
increased risk of infection
should not be used in combo with anakinra or TNF blocking agents
What is the mechanism of action of Rituximab?
monoclonal antibody directed against CD20 on B cells; kills b cells
What are the adverse effects of Rituximab?
severe ocassionally fatal infusion related reactions have been reported usually with the first infusion; fatalities have been reported within 24 hrs of infusion
Tumor lysis syndrome leading to acute renal failure requirng dialysis may occur in the 12-24 hour mark
What is the mechanism of action of Tocilizumab?
humanized antibody; binds to soluble and membrane-bound IL-6 receptor and inhibits the IL6 mediated signaling.
What are the adverse effects of Tocilizumab?
upper resp tracts infections, headache, HTN adn elevated liver enzymes
serious infections including TB, fungal viral and other infections
Neutropenia and reduction in platelet counts and lipids
Gi perforation
What is the mechanism of action of Tofacitinib?
janus kinase inhibitor;
What ar ethe adverse effects of tofacitinib?
pts high risk of infection, tb and lymphoma
GI perforations associate in combo ith other antiinflammatory
increase blood cholesterol levels
What are the therapeutic uses of tofacitinib?
tx of moderately to severe active rheumatorid arthritis
What is the mechanism of action of anakinra?
antagonist of IL1 receptor
What is the adverse effects associated with anakinra?
infection or injections ite reaction
