Pharm - Disease-Modifying Anti-Rheumatic Drugs COPY Flashcards
MOA and effects glucocorticoids - prednisone
binds to glucocorticoid receptor which complexes with NF-kB and AP-1 transcription factors –> indirect mechanism for immunosuppression reduces activity of immune system via suppression of IL-1,2,3,4,5,6,8 and IFN-y suppresses neutrophil migration decreases eosinophils in the blood and tissue
indications for glucocorticoids like prednisone
added to a regimen for RA for a short period to rapidly minimized disease activity while awaiting clinical response to a slower-acting disease-modifying anti-rheumatic drug (DMARD) **effective for up to 6 months
MOA methotrexate
polyglutamation –> MTX-glu –> accumulates in cells over weeks –> blocks thymidylate synthase and 5-aminoimidazole-4-carboxamide ribodnucleotide (AICAR) transformylase –> accumulation of AICAR –> adenosine efflux –> binds to purinergic GPCRs –> ANTI-INFLAMMATORY EFFECTS
indications methotrexate
drug of first choice for RA often used in combo w/ other traditional DMARD
adverse effects methotrexate
bone marrow suppression hepatic fibrosis GI ulceration pneumonitis fetal death
MOA hydroxychloroquine
accumulates in lysosomes and then protonated –> increases pH of lysosome from 4 to 6 –> limits association of peptides with class II MHC –> slows dz progression
indications hydroxychloroquine
antimalarial can be first choice for mild RA with lack of poor prognostic features
often combined with methotrexate ± sulfasalazine in an attempt to control more severe rheumatoid arthritis
can hydroxychloroquine be used during pregnancy?
yep
half life of hydroxychloroquine
23 days so loading doses are needed to speed up onset
adverse effects hydroxychloroquine
retinal damage
MOA sulfasalazine
metabolized to sulfapyridine –> active moiety in RA patients
indications sulfasalazine
RA - used alone or in combo with hydroxychloroquine and/or methotrexate (triple therapy)
side effects sulfasalazine
GI side effects sulfa drug reactions
MOA leflunomide
inhibition of mitochondrial enzyme dihydroorotate dehydrogenase to block the synthesis of the pyrmidine rUMP –> inhibits T cell proliferation
indications leflunomide
second choice drug for RA
used in combination with methotrexate, sufasalazine or hydroxychloroquine
half life leflunomide
16.5 days, so loading doses are needed
adverse effects leflunomide
diarrhea, respiratory infection, reversible alopecia, rash stevens johnson syndrmoe
should biologic DMARDs be combined?
NEVER
what do these suffixes indicate: - cept - mab - ximab - zumab - umab
- cept: fusion of receptor to Fc portion of human IgG1
- mab: monoclonal antibody
- ximab: chimeric monoclonal antibody
- zumab: humanized monoclonal antibody
- umab: human monoclonal antibody
effects of TNF antagonists
highly effective at reducing rheumatoid arthritis symptoms and disease progression
indicated for moderate to severe rheumatoid arthritis, generally after traditional DMARDs have proven to be ineffective
often used in combination with methotrexate
indications for TNF antagonists
moderate to severe RA, generally after traditional DMARDs have been proven to be ineffective often used in combo with methotrexate
adverse effects TNF antagonists
developing serious infections including TB
severe allergic reactions
list the TNF antagonists
etanercept infliximab adalimumab (Humira)
MOA, indications, and administration of etanercept
TNF antagonist a number of forms of inflammatory arthritis including RA, psoriatic arthritis, ankylosing spondylitis 1 or 2 x weekly SC
MOA, indications, and administration of infliximab
TNF antagonist inflammatory arthritis, IBD IV infusion every 6 weeks
MOA, indications, and administration of adalimumab
TNF antagonist RA, psoriatic arthritis, ankylosing spondylitis, crohn’s
subcutaneous infusion every 2 weeks
MOA rituximab
antibody targeting CD20
when taking rituximab, how do immunoglobulin levels stay in the normal range despite targeting CD20
plasma cells have a resistance to rituximab because they do not have CD20 on their surface
overall immunoglobulin levels usually remain within the normal range, despite profound B cell lymphopenia that persists for months following a single course of treatment levels of autoantibodies with the potential for roles in disease pathophysiology are affected by B cell depletion
indications rituximab
non-hodgkin’s lymphoma, chronic lymphocytic leukemia RA pts who have not responded to TNF antagonists
positive testing for RF and CCP antibodies predict greater likelihood of responsiveness
indicated in combination with methotrexate for patients with rheumatoid arthritis
adverse effects rituximab
infusion related hypersensitivity rxns stevens johnson syndrome hep B reactivation
MOA abatacept
compromises CTLA-4 and Fc portion of IgG1
prevents CD28 from binding to CD80/CD86
indications abatacept
moderate to severe RA, generally not used until after failure of TNF antagonists
can be used in combination with nonbiological DMARDs (e.g., methotrexate)
adverse effects abatacept
generally well tolerated
can increase the risk of serious infections, most often pneumonia, cellulitis, bronchitis, diverticulitis, pyelonephritis and urinary tract infections
MOA and effects of tocilizumab
humanized anti-human IL-6 receptor antibody can’t activate JAK kinases and RAS mediated signaling limits hepatic acute phase response and activation of T and B cells
indications tocilizumab
moderate to severe RA if other DMARDs and TNF antagonists have been ineffective
can be used with or without methotrexate
adverse effects tocilizumab
URIs, life threatening infections
MOA tofacitinib
JAK3 antagonist suppresses production of IL-17 and IFN-y and proliferation of CD4 T cells
used with or without methotrexate
indications tofacitinib
moderately to severely active RA who had an inadequate response to methotrexate
considered less efficacious than other biologic DMARDs, so a late choice
administration of tofacitinib
oral (unusual among the DMARDs) ***
adverse effects tofacitinib
serious infections by opportunistic pathogens increased malignancies
MOA anakinra
IL-1 receptor antagonist blocks pro-inflammatory activity of IL-1
indications anakinra
moderate to severe RA that has not responded to DMARDs
adverse effects anakinra
serious infections, hypersensitivity reactions
