Lecture 9 - Rheum Flashcards
which is more common, osteoarthritis or RA?
Osteoarthritis
do DMARDs work immediately or with a delay?
delay (1-6 months)
RA:
what HLA is associated with it?
2 environmental exposures that increase risk
HLA-DR4;
smoking, silica
RA:
rheumatoid factor is an Ig__ antibody that targets the ___ region of an ____
IgM antibody, targets Fc portion of IgG
what is the more specific biomarker for RA?
what is a pannus?
anti-cyclic citrullinated peptide antibody;
proliferative granulation tissue
RA cartilage degradation:
_____ releases TNF which causes ____ that causes invasion of synovial fibroblasts and release of _____ and ADAMTS that causes matrix degradation
synovial fibroblasts;
IL 1;
matrix metalloproteinase
RA:
____ and _____ causes differentiation of precursors to osteoclasts and is increased in RA
RANKL;
M-CSF
RA:
____ cells are activated and activate other cells that contribute to the pathogenesis of RA ie increases cytokine release, attracts B cells
TH17
RA:
_____ inhibit gene expression;
glucocorticoids
RA treatment:
_____ is a folic acid analog that competiviely inhibits ____ –> decreased dTMP synthesis and decreased DNA synthesis
methotrexate;
dihydrofolate reductase
also inhibits 5-aminoimidazole-4carboxamide ribonucleotide formyltransferase
1st line treatment
MTX side effects:
____ suppression, reversible with ____;
____ toxicity, ____ fibrosis, teratogenicity
bone marrow, leucovorin;
hepatic, pulmonary
leflunomide:
(reversibly/irreversibly) inhibits _____ _____ –> preventing _____ synthesis
reversibly, dihydroorotate dehydrogenase;
pyrimidine
suppresses T cell proliferation
leflunomide:
pro drug or active immediately?
side effects include ____ toxicity and teratogenicity, also diarrhea, _____ blood pressure
pro-drug;
hepatic;
increased (hypertension)
hydroxychloroquine:
accumulates in ____ and inhibits _____ secretion;
reversible ____ toxicity
lysosomes, protein;
retinal
sulfasalazine:
supresses release of cytokines from ____ and ____;
prodrug cleaved by ____
MQs, monocytes;
colonic bacteria
____ is an orally available JAK inhibitor. efficacy shown at ___ months. inhibits ____ signallling
Tofacitinib;
6, cytokine
tofacitinib:
increased risk of _____ and ____
_____ suppression
infection, cancer;
bone marrow
adalimumab vs infliximab:
both are anti ____ monoclonal ABs.
which is fully human?
which is a mouse chimera?
TNF;
adalimumab;
infliximab
certolizumab and golimumab are also humanized Abs
etanercept:
is a fusion protein containing _____ and _____-;
acts a ____ receptor
TNF alpha receptor, IgG1 Fc;
decoy
anti-TNF alpha agents have increased risk of ____ reactivation and _____.
Tb, cancer
also demyelination and CHF
kineret/anakinra:
recombinant _____ receptor antagonist;
monitor patients for ____
indicated for severe RA (used alone)
IL1;
neutropenia
canakinumab is an ____ neutralizing human Ab used for _____
IL 1;
juvenile idiopathic arthritis
rilonacept is an _____ binding fusion protein for _____
IL;
juvenile idiopathic arthritis
tocilizumb is an ____ receptor antagonist used along with MTX
watch for serious ____, ____ toxicity, thrombocytopenia, and neutropenia
IL 6;
infections, liver
use for moderate/severe refractory RA
Rituximab is an humanized MAB against _____. reduces inflammation be reducing activation of ____
CD 20 (b-cell marker); T cells
rituximab: serious ____ is a potential side effect, along with fatal ____ reaction
infection;
infusion
_____ is a fusion protein of CTLA-4 and the FC region of human IgG1 that inhibits co-stimulation of ____ by APCs
abatacept;
T-cells
Abatacept:
risk of serious _____;
increased risk of ____
infections;
lymphoma
should DMARDs be started ASAP as possible or after trying NSAIDs and steroids for awhile?
ASAP as possible
