Rheumatoid Arthritis (exam 1) Flashcards
rheumatoid arthritis
chronic inflammation of the synovial tissue
pannus
invades the cartilage and bone surface
produces erosion of bone and cartilage
who is more likely to have arthritis?
women
RA symtoms can be associated with many diseases including
fibromyalgia
SLE
gouty arthritis
psoriatic arthritis
osteoarthritis pathology
thinned cartilage leads to bone ends rubbing together
rheumatoid arthritis pathology
bone erosion and swollen inflamed synovial membrane
in 75% of cases, T cell antigen motif ______________ signaling pathway involved in T cell ______________
Q(K/R)RA IL2
activation and proliferation
inflammation of RA leads to
severe pain
palpable synovial swelling
morning stiffness
loss of function in joints
RA occurs in a _________________ and typically involves the ______________
symmetrical pattern
wrists, MCP and PIP joints
MCP
metacarpophalangeal joints
PIP
proximal interphalangeal joints
what can cause RA?
infectious agents
environmental triggers
genetic risk factors
rheumatoid factor
autoantibody associated with RA
antibody against the Fc portion of IgG
RF and IgG form ____________ that contribute to the disease process
immune complexes
rheumatoid factors are antibodies with
various isotopes and affinities
most commonly mentioned RF
is an IgM
loss of tolerance to the proteins that have a citrulline residue likely produce autoantibodies like
anti-cyclic citrullinated protein/peptide antibody (ACPA) and RF
synovitis stage of RA
synovial membrane inflamed and thickened
bones and cartilage gradually eroded
pannus stage of RA
extensive cartilage loss
exposed and pitted bones
fibrous anklosis stage of RA
joint invaded by fibrous connective tissue
bony anklosis stage of RA
bones fused
RF is ____________ in the first 6 months and ____________ with established disease
45% positive
85% positive
PIP swelling in RA
swelling is confined to the area of the joint capsule
synovial thickening feels like a firm sponge
Rheumatoid arthritis is not
restricted to the joints in the wrists
can be anywhere in the body!
genetic factors that can cause RA
HLA-DRB1
STAT4
PADI4
DR1
production of inflammatory cytokines leads to
decreased production of hyaluronan
inflammation increases MMP production, increases cartilage damage
plasma cell antibodies form immune complexes
joint damage recruits _____________________ which causes _____________ of the synovial membrane. This leads to ______________
neutrophils, T cells and B cells
hyperplasia and angiogenesis
palpable lumps in the joints (boggy joints)
pannus invades and _______________ which leads to __________ and continued usage on the joints can ______________
enzymatically destroys joint tissue
decreased joint mobility
Mal-align, sublux or collapse joints
diagnostic factor of RA
RF
anti-cyclic citrullinated peptide
treatment for RA
NSAIDS
TNF-a inhibitors
steroids/corticosteroids
DMARDs
immunosuppressants
within the first three months, treatment is
MTX (or other DMARD), NSAID and prednisone
when there is poor response for initial treatment of RA,
try other combination
triple drug (DMARD and biologic), low dose prednisone long term and consider second line DMARD
NSAIDs effects for RA
relieve pain
reduce inflammation
types of NSAIDs for RA
ibuprofen (Advil, Motrin)
naproxen (aleve)
side effects of NSAIDs
tinnitus
stomach irritation
heart problems
liver/kidney damage
TNF-a inhibitors effects for RA
reduce pain, morning stiffness and tender or swollen joints
examples of TNF-a inhibitors for RA
Etanercept (Enbrel)
infliximab (Remicade)
adalimumab (HUMIRA)
Golimumab (simponi)
certolizumab (cimzia)
side effects of TNF-a inhibitors
risk of serious infections
congestive heart failure
cancer
steroids/corticosteroids effects for RA
reduce inflammation and pain
slow joint damage
side effects of steroids/corticosteroids
thinning of bones, cataracts, weight gain, and diabetes
DMARDs effects for RA
slow the progression of RA
save joints/tissues from permanent damage
side effects of DMARDs
liver damage
bone marrow suppression
severe lung infections
DMARDs examples for RA
methotrexate (Trexall)
leflunomide (Arava)
hydroxychloroquine (Plaquenil)
sulfasalazine (Azulfidine)
minocycline (Dynacin, Minocin)
immunosuppressants effects of RA
side effects?
tackle immune system
increase susceptibility to infection
examples of immunosuppressants for RA
azathioprine (Imuran, Azasan)
cyclosporine (Neoral, sandimmune, Gengraf)
cyclophosphamide (cytoxan)
which TNF-a inhibitors are human monoclonal antibodies?
adalimumab
certolizumab
which TNF-a inhibitors are chimeric monoclonal antibodies?
infliximab
methotrexate MOA
interferes with DNA synthesis, repair and cellular replication
inhibits dihydrofolate reductase
MTX inhibits _____________ uptake which shows
DNA precursor
spleen cell hypo responsiveness and suppresses IL-2 production
what happens when dihydrofolate reductase is inhibited?
dihydrofolates cannot be converted to tetrahydrofolates which are needed for synthesis of purine nucleotides and thymidylate
what type of metabolism does MTX go through?
hepatic and intracellular metabolism to polyglutamated forms
polyglutamates act as
inhibitors to dihydrofolate reductase and thymidylate synthetase
how is MTX excreted?
renally
80-90% unchanged in urine
what is given to reduce toxicity of high dose regimens/delayed excretion of MTX?
leucovorin calcium (leucovorin rescue)
what is the half life of MTX?
at high doses?
3-10 hours
8-15 hours
ADRs of MTX
bone marrow suppression
aplastic anemia
GI toxicity
after prolonged use, MTX can cause
hepatotoxicity, fibrosis, cirrhosis and pulmonary toxicity
MTX can be detected in _________ which can be an issue with babies
human breast milk
