Pharm - Disease-Modifying Anti-Rheumatic Drugs Flashcards
what is the first drug of choice for RA pain relief
what can be added for additional relief
NSAIDs
acetominophen
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
adverse effects glucocorticoids
- cushing’s
- DM
- fluid retention
- menstrual irregularities
many side effects
how is “mild” RA classified
5 or less inflamed joints
normal to increased ESR and CRP
no extra-articular dz
no evidence of erosions or cartilage loss on plain radiographs
most pts lack RF or CCP antibodies
how is “moderate” RA classified
more than 5 inflamed joints
increased ESR and CRP
positive RF and/or CCP antibodies
evidence of inflammation on plain radiographs
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
administration of methotrexate
once per week either orally or injection
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
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
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
reducing RA symptoms and dz progression
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
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
IV 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
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
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
adverse effects abatacept
headache, URI, serious 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
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
indications tofacitinib
moderately to severely active RA who had an inadequate response to methotrexate
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
