Pharmacotherapy For Rheumatoid Arthritis And Gout

Question 1

Methotrexate

Answer 1

Mechanism: folate antagonist, reduced neutrophil adhesion, antiproliferative effect on synovial fibroblasts and endothelial chess, inhibition of leukotriene B4 synthesis by neutrophils, reduction of IL-1, IL-6, and IL-8 levels, suppression of cell-mediated immunity
Side effects: nausea and vomiting, sores in the mouth, headache and fatigue

Question 2

Hydroxylchloroquine

Answer 2

Mechanism: effects on the innate immune system including inhibition of TLR-9 activation by DNA-immune complexes and inhibition of TLR signaling, lysosomotropic acitivity involving increases in intracellular pH, including lysosomal pH, that affect protein processing
Side effects: headache, dizziness, hair loss, nausea, muscle pain, rash

Question 3

Infliximab

Answer 3

Mechanism: anti-TNF-alpha antibody, blocks TNF-alpha action
Side effects: increased incidence of infection, lupus-like syndrome, heart failure, exacerbation of demyelinating disease, headache, nausea, severe infusion reaction

Question 4

Adalimumab

Answer 4

Mechanism: anti-TNF-alpha antibody, blocks TNF-alpha action
Side effects: increased incidence of infection, lupus-like syndrome, heart failure, exacerbation of demyelinating disease, headache, nausea

Question 5

Etanercept

Answer 5

Mechanism: soluble TNF-alpha receptor fusion protein, blocks TNF-alpha action
Side effects: increased incidence of infection, lupus-like syndrome, heart failure, exacerbation of demyelinating disease, headache, nausea

Question 6

Anakinra

Answer 6

Mechanism: inhibits IL-1 function

Side effects: headache, nausea, injection site reaction, increased risk of infection, increased risk of lymphoma

Question 7

Abatacept

Answer 7

Mechanism: extracellular domain of CTLA4, blocks the costimulatory pathway for T cell activation by preventing CD28 from binding to its counterreceptor, CD80/CD86
Side effects: headache, nausea, increased risk of infection

Question 8

Rituximab

Answer 8

Mechanism: mAb againsted the CD20 antigen leads to B cell depletion by Fc receptor gamma-mediated antibody-dependent cytotoxicity and/or antibody-dependent complement-mediated cell lysis and/or growth arrest and/or B-cell apoptosis
Side effects: headache, peripheral edema, fatigue, chills, hematologist disorders

Question 9

Tofacitinib

Answer 9

Mechanism: JAK inhibitor

Side effects: increased risk of infection, nausea

Question 10

Apremilast

Answer 10

Mechanism: PDE-4 inhibitor leading to increased intracellular cAMP, decreases TNF-alpha production
Side effects: diarrhea and nausea in the first year of treatment, then nasopharyngitis and upper respiratory tract infection with continued use

Question 11

Drugs used to treat acute gout

Answer 11

NSAIDs, colchicine, glucocorticoids, (possibly) corticotropin

Question 12

Acute gout treatment

Answer 12

NSAIDs and colchicine as first-line, glucocorticoids or corticotropin when those aren’t working

Question 13

Urate-lowering drugs and acute gout

Answer 13

No benefit, should not be initiated during acute attack, only use if already being treated with urate-lowering agent

Question 14

Aspirin and acute gout

Answer 14

Low doses causes uric acid retention by the kidney, high doses have a uricosuric effect, but doses used for CV protective effects do not need to be discontinued

Question 15

Drugs used to treat chronic gout

Answer 15

Xanthine oxidase inhibitors (febuxostat, allopurinol), uricosuric agents (lesinurad, probenecid), uricase agents (pegloticase)

Question 16

Treatment of chronic gout

Answer 16

Focuses on lowering serum urate levels, but the severity/frequency of flares and coexisting illnesses need to be considered. Patients start ULT therapy 2-4 weeks after flare resolution at a low initial dose and increase as needed, therapy is adjusted to maintain serum urate level and is continued indefinitely, combination therapy is only used when first-line therapy is not sufficient

Question 17

Colchicine

Answer 17

Mechanism: inhibits microtubule assembly, suppresses inflammasome-driven caspase 1 activation, IL-1beta processing and release, and L-selection expression
Side effects: GI symptoms (diarrhea, abdominal pain, nausea, vomiting), reversible peripheral neuropathy, in severe cases blood cytopenias or severe cutaneous eruption

Question 18

Febuxostat

Answer 18

Mechanism: xanthine oxidase inhibitor
Side effects: incidence of liver function test abnormalities, nausea, arthralgia, rash, increased risk of acute gouty attack

Question 19

Lesinurad

Answer 19

Mechanism: uricosuric agent, inhibits activity of URAT1 and OAT4 in vitro
Side effects: headache, influenza, higher levels of blood creatinine, GERD

Question 20

Allopurinol

Answer 20

Mechanism: xanthine oxidase inhibitor, inhibits uric acid synthesis
Side effects: mild rash, leukopenia or thrombocytopenia, diarrhea, can precipitate acute gouty arthritis

Question 21

Probenecid

Answer 21

Mechanism: uricosuric agent, promotes renal clearance of uric acid by inhibiting urate-anion exchangers (including URAT1, GLUT9, ABCG2) in the proximal tubule that mediates urate reabsorption, increases urate excretion
Side effects: rash, precipitation of acute gouty arthritis, GI intolerance, uric acid stone formation

Question 22

Pegloticase

Answer 22

Mechanism: recombinant uricase, converts uric acid to allatoin
Side effects: increased risk of acute gouty attack