RA Flashcards
Non-pharmacologic tx for RA
patient education, psychosocial intervention, rest, exercise, therapy, nutrition/dietary counseling, risk reduction intervention (CV disorders, smoking, osteoporosis), immunizations
pretreatment evaluation of RA
baseline labs, serologic testing for hepatitis (B/C), opthamalogic screening, latent TB
baseline labs for RA
CBC, serum creatinine, LFT, ESR, CRP
treatment option choices for RA based on what
level of disease, stage of therapy, outside decision maker (insurance), patient preference (cost, frequency, ROA)
NSAID use for RA
pain and inflammatino
corticosteroid use and administratino in RA
antiinflammation - intraarticular, systemic
non-biologic DMARDS
methotrexate, leflunomide, hydroxychloroquine, sulfasalazine
biologic DMARDS
infliximab, etanercept
DMARD
disease modifying anti-rheumatic drugs
how to treat mild active RA
antiinflammatory with NSAID, DMARD (methotrexate)
how to treat moderate to severe RA
antiinflammatory (NSAID or corticosteroid), DMARD (methotrexate at first then add hydroxychloroquine + sulfasazine)
monitoring of RA
see pt on a regular basis: clinical evaluation (sxs improvement, better QOL), lab test reevaluation, drug toxicity detection
how long does it take drugs for RA to work?
wekks-months
true or false: early treatment of RA is best
true - 90 day window, start with DMARDs
uses for hydroxychloroquine
RA, SLE, malaria preventino/treatment
RA drug that it ototoxic
hydroxychloroquine
how fast is the response to hydroxychloroquine?
slow-acting, 4-6 weeks for response time, 3-6 months to see response
kinetics of hydroxychloroquine
rapid, 50% plasma protein binding, extended half life
ototoxic effects of hydroxychloroquine
depigmentation around the fovea (dose related retinopathy) from any dose that can be temproary or permanent
ADR of hydroxychloroquine
GI (n/v, abd pain, dyspepsia), CNS (HA, irritability, psychosis, nightmares, seizures), hemolytic anemia (G6PD deficiency (AA, mediterranean, middle eastern))
uses for sulfasalazine
RA, ulcerative colitis, crohn’s disease
ADR of sulfasalazine
GI (nausea/dyspepsia), skin rash, Headache, hematologic (leukopenia, throbocytopenia, neutropenia)
True or false: 30% of pts stop sulfasalazine d/t ADR
true
max dose of sulfasalazine
3g/day
what should be given along with methotrexate to ensure it doesn’t get depleted?
folic acid - look very similar
MOA of methotrexate
increases AMP with increases adenosine (anti-inflammatory)
true or false: methotrexate is a prodrug
true - takes up to 28 weeks to change
uses of methotrexate
RA, psoriasis, juvenile idiopathic arthritis, oncology indications (NHL, lymphoma, osteolymphomas)
ADR of methotrexate
minor GI side effects, stomatitis, minor transaminase elevations, leukopenia, thrombocytopenia, hepatotoxicity, interstitial pneumonitis
how often is methotrexate given?
once a week
uses for leflunomide
RA (unlabeled for CMV disease)
do you need to dose adjust leflunomide for renal/hepatic disease?
no but check labs anyway
if a pt had previous problems with hematoglogic disorders, is leflunomide a risk?
slight risk for this
ADR of leflunomide
hepatotoxicity, infections, pulmonary (rare ILD), peripheral neuropathy, cancer (lymphoma?)
good combo therapy for leflunamide
MTX, TNF blockers
risks of taking immune modulators
risk of infection, malignancy (similar rate seen with DMARDs or RA)
ADR of immune modulators
local injectino site reaction, CNS (fever, fatigue, chills, HA), GI (nausea, diarrhea, abd pain), hematologic (neurtopenia, thrombocytopenia, positive ANA titer)
administration of immune modulators
subQ/IV
goals of therapy for RA
control pain and swelling, minimize disability, improved QOL, educate on disease management
important inflammatory cytokines in RA
TNF, IL, PGE, IGF
what type of joints does RA affect?
synovial membranes of multiple joints - can also affect many other body systems
how often should you get BW for RA?
every 2-3 weeks for 3 months then every 2-3 months for 6 months, then every 3 months once stabilized
SAARDs
slow acting anti-rheumatic drugs (same as DMARDs)
hydroxychloroquine is a derivative of?
quinine (used for malaria)
MOA of hydroxychloroquine
decreases T lymphocyte response, blockade of toll-like receptors, trap free radicals
MOA of sulfasalazine
enters the GI system, leaves the GI system and comes back then is worked on by azoreductase and turned into sulfapyridine (goes to CV, hepatic, and renal systems) and 5-aminosalicylic acid
Onset of action for sulfasalazine
slightly faster than hydroxychloroquine, variable between 1-4 months
pts with G6P insufficiency are at risk for developing
hemolytic anemia (sulfasalazine)
with methotrexate, as oral dose rises?
bioavailability decfreases
best ROA for methotrexate
subQ, IV
what does MTX bind to in the blood?
plasma proteins - this is good! If displaced by NSAIDs or other drugs, could be too much MTX!
does MTX need dosed differently for renal impairment?
yes, NSAIDs also reduce renal clearance so if using both need to dose adjust!
max dose of MTX
20mg/week
is it OK to use ASA with MTX?
no!
lower doses of MTX are required in?
DM, renal failure, obese pts
is it ok to drink EtOH with MTX?
no
when should folic acid be administered with MTX use?
every day except the day you give the first dose of MTX
MOA of leflunomide
pro-drug, RUMP inhibitor
Selective T cell costimulation blocker
abatacept
TNF blocker
humira, enbrel, remicade
IL3 receptor agonist
anakira
IL6 receptor agonist
Actemra
JAK inhibitor
Xeljanz
B cell depletion
rituxan
what are cytokines
mediators that influence activation and migration of leukocytes
primary cytokines
IL1 and TNFalpha
how to cytokines signal leukocytes?
NF-B, Jak/STAT signlaing pathway
what exactly is RA caused by?
abnormal response of cytokines to increase migration of macrophages
MOA of immune modulators
inhibit the second signal required for T cell activation, deplete B cells
what are the Th1 cytokines?
TNF, IL-1beta
how do Th cells contribute to RA?
stimulate synovial cells to proliferate and synthesize collagenase (breaks down bone, stimulates bone resorption, decreased proteoglycans which lubricates joints)
cept immune modulators
fusion of receptor to the Fc part of human IgG1
mab immune modulators
monoclonal antibodies
ximab immune modulators
chimeric monoclonal antibodies
umab immune modulators
humanized monoclonal antibody
how do soluble receptor antagonists work?
bind the target cytokine thus inhibiting interaction with cell surface receptors
how do monoclonal antibodies work?
higher affinity for certain sytokines than soluble receptor antagonists, bind target cytokine not only when in serum but also when bound to cell surface
how do cell surface receptor antagonists work?
biologically inactive protein that complexes with the cytokine at the cell surface receptor
how does costimulation blockade work?
activation of T cells needs binding of T cell receptor to peptide and peptide to MHC complex II, binding of CD28 and/or CTLA-4 or CD40. This regulates t-cell activation and T-cell dependent B-cell function
indications of etanercept
RA. Psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, polyarticular juvenile idiopathic arthritis
indications for adalimumab and infliximab
same as etanercept plus crohns and ulcerative colitis
indications for tofacitinib
RA
why is tofacitinib called two faced?
head and tail look the same
MOA of tofacitinib
works intracellularly as an immune modulator
