Lecture 9 - Rheum

Question 1

which is more common, osteoarthritis or RA?

Answer 1

Osteoarthritis

Question 2

do DMARDs work immediately or with a delay?

Answer 2

delay (1-6 months)

Question 3

RA:
what HLA is associated with it?
2 environmental exposures that increase risk

Answer 3

HLA-DR4;

smoking, silica

Question 4

RA:

rheumatoid factor is an Ig__ antibody that targets the ___ region of an ____

Answer 4

IgM antibody, targets Fc portion of IgG

Question 5

what is the more specific biomarker for RA?

what is a pannus?

Answer 5

anti-cyclic citrullinated peptide antibody;

proliferative granulation tissue

Question 6

RA cartilage degradation:
_____ releases TNF which causes ____ that causes invasion of synovial fibroblasts and release of _____ and ADAMTS that causes matrix degradation

Answer 6

synovial fibroblasts;
IL 1;
matrix metalloproteinase

Question 7

RA:

____ and _____ causes differentiation of precursors to osteoclasts and is increased in RA

Answer 7

RANKL;

M-CSF

Question 8

RA:
____ cells are activated and activate other cells that contribute to the pathogenesis of RA ie increases cytokine release, attracts B cells

Answer 8

TH17

Question 9

RA:

_____ inhibit gene expression;

Answer 9

glucocorticoids

Question 10

RA treatment:

_____ is a folic acid analog that competiviely inhibits ____ –> decreased dTMP synthesis and decreased DNA synthesis

Answer 10

methotrexate;
dihydrofolate reductase

also inhibits 5-aminoimidazole-4carboxamide ribonucleotide formyltransferase
1st line treatment

Question 11

MTX side effects:
____ suppression, reversible with ____;
____ toxicity, ____ fibrosis, teratogenicity

Answer 11

bone marrow, leucovorin;

hepatic, pulmonary

Question 12

leflunomide:

(reversibly/irreversibly) inhibits _____ _____ –> preventing _____ synthesis

Answer 12

reversibly, dihydroorotate dehydrogenase;
pyrimidine

suppresses T cell proliferation

Question 13

leflunomide:
pro drug or active immediately?
side effects include ____ toxicity and teratogenicity, also diarrhea, _____ blood pressure

Answer 13

pro-drug;
hepatic;
increased (hypertension)

Question 14

hydroxychloroquine:
accumulates in ____ and inhibits _____ secretion;
reversible ____ toxicity

Answer 14

lysosomes, protein;

retinal

Question 15

sulfasalazine:
supresses release of cytokines from ____ and ____;
prodrug cleaved by ____

Answer 15

MQs, monocytes;

colonic bacteria

Question 16

____ is an orally available JAK inhibitor. efficacy shown at ___ months. inhibits ____ signallling

Answer 16

Tofacitinib;

6, cytokine

Question 17

tofacitinib:
increased risk of _____ and ____
_____ suppression

Answer 17

infection, cancer;

bone marrow

Question 18

adalimumab vs infliximab:
both are anti ____ monoclonal ABs.
which is fully human?
which is a mouse chimera?

Answer 18

TNF;
adalimumab;
infliximab

certolizumab and golimumab are also humanized Abs

Question 19

etanercept:
is a fusion protein containing _____ and _____-;
acts a ____ receptor

Answer 19

TNF alpha receptor, IgG1 Fc;

decoy

Question 20

anti-TNF alpha agents have increased risk of ____ reactivation and _____.

Answer 20

Tb, cancer

also demyelination and CHF

Question 21

kineret/anakinra:
recombinant _____ receptor antagonist;
monitor patients for ____

indicated for severe RA (used alone)

Answer 21

IL1;

neutropenia

Question 22

canakinumab is an ____ neutralizing human Ab used for _____

Answer 22

IL 1;

juvenile idiopathic arthritis

Question 23

rilonacept is an _____ binding fusion protein for _____

Answer 23

IL;

juvenile idiopathic arthritis

Question 24

tocilizumb is an ____ receptor antagonist used along with MTX

watch for serious ____, ____ toxicity, thrombocytopenia, and neutropenia

Answer 24

IL 6;
infections, liver

use for moderate/severe refractory RA

Question 25

Rituximab is an humanized MAB against _____. reduces inflammation be reducing activation of ____

Answer 25

CD 20 (b-cell marker);
T cells

Question 26

rituximab: serious ____ is a potential side effect, along with fatal ____ reaction

Answer 26

infection;

infusion

Question 27

_____ is a fusion protein of CTLA-4 and the FC region of human IgG1 that inhibits co-stimulation of ____ by APCs

Answer 27

abatacept;

T-cells

Question 28

Abatacept:
risk of serious _____;
increased risk of ____

Answer 28

infections;

lymphoma

Question 29

should DMARDs be started ASAP as possible or after trying NSAIDs and steroids for awhile?

Answer 29

ASAP as possible