M2-C1-L --> Dmards

Front 1

Describe the RA histology vs. normal synovium.

Back 1

Normal synovium has 1-3 cell thcik layer.

RA synovium has:
1. Marked infiltration of inflammatory cells
2. Nodular appearance
3. Thickening of synovial tissue

Front 2

Stages of RA.

Back 2

Early

Intermediate

Late

Front 3

Describe RA progression in terms of:
- Inflammation
- Radiographic changes
- Disability

Back 3

Inflammation is steady or tapers off

Radiograph changes constantly increase

Disability constantly increase

Front 4

Describe the rate of joint erosion in RA

Back 4

Significantly rapid rate of progression in first year, more so than second and third year.

Front 5

Radiographic abnormalities seen in what type of patients?

Back 5

93% have radiographic abnormalities in less than 2 years of RA onset.

Front 6

Joint erosions can be detected by MRI when?

Back 6

Within 4 months of onset.

Front 7

In RA, describe the tissue (steps 1,2) and cell (steps 3,4) pathogenesis of RA in four steps.

Back 7

Synovium thickens

Pannus develops

Neutrophils increase in the synovial fluid

The pannus and synovial membrane contains lots of lymphocytes, macrophage, fibroblasts, and other cells of chronic inflammation.

Front 8

In RA, describe the cytokine signaling pathway involved in RA.

Back 8

In the synovium, T and B lymphocytes to produce lots of cytokines.

T cells produce IFN-gamma to induce macrophages.

Thus macrophages will make TNF-alpha and IL-1.

This will stimulate fibroblast, osteoclasts, and chondrocytes to cause erosion and damage tissue.

Front 9

What is the principle aim of DMARD therapy for RA.

Back 9

Prevent or retard joint erosion/destruction.

Front 10

NSAIDs improve symptoms, but.....

Back 10

it does not reduce progression of joint damage.

Front 11

What is a controversial drug treatment for RA.

Back 11

Prednisone

Front 12

In RA, what do you use NSAIDs for?

Back 12

Base treatment for symptomatic relief --> decrease in swelling and pain.

Front 13

What is prednisone (<10 mg qd) used for?

Back 13

Bridge therapy --> decrease inflammation, thus patient more functional in ADL while waiting for DMARDs to kick in.

Front 14

For what and when do you use intra-articular steroids.

Back 14

Useful for persistent joints, or flairs.

Not feasible for multiple joints.

Front 15

Name the top four DMARDs.

Back 15

1. Methotrexate (Trexall)
2. Leflunomide (Arava)
3. Sulfasalazine (Azulfidine)
4. Hydroxychloroquine (Plaquenil)

Front 16

Methotrexate mechanism of action.

Back 16

Inhibits purine DNA synthesis via DHFR (Dihydrofolate Reductase), thus increasing adenosine (which will down regulate inflammatory process)

Front 17

Methotrexate should be used in concomitant with?

Back 17

Folic acid b/c it alters folic acid related mechanisms.

Front 18

Use for methotrexate.

Back 18

Moderate to severe RA

Front 19

Leflunomide mechanism of action.

Back 19

Inhibits pyrimidine DNA synthesis via dehydrooroate dehydrogenase, thus decreasing radiographic progression.

Front 20

Use for leflunomide.

Back 20

Moderate to severe RA

Front 21

Sulfasalazine mechanism of action.

Back 21

Suppresses leukocyte and lymphocyte function, thus increasing adenosine and decreasing NFkB transcription factor.

Front 22

Sulfasalazine use?

Back 22

Mild to moderate RA

Front 23

Hydroxychloroquine mechanism.

Back 23

Interferes with antigen processing.

Front 24

Hydroxychloroquine use?

Back 24

Mild to early RA.

Front 25

Progression of Joint damage by sharp scores in terms of:

- placebo
- methotrexate
- leflunomide

Back 25

Greatest to least progression of joint damage

Placebo > Methotrexate > Leflunomide

Front 26

What are three ways to inhibit cytokines.

Back 26

1. Receptor blockade
2. Neutralization of cytokines.
3. Activation of anti-inflammatory pathway

Front 27

What to use for Receptor blockade?

Back 27

1. Monoclonal antibodies
(binds to receptor)

2. Receptor Antagonist
(binds to receptor)

Front 28

What to use for Neutralization of cytokines?

Back 28

1. Monoclonal antibodies
(binds to cytokines)

2. Soluble receptor
(binds to cytokines)

Front 29

What to use for Activation of non-inflammatory pathway?

Back 29

Anti-inflammatory cytokines

Front 30

List two monoclonoal antibodies used as Anti-TNF agents.

Back 30

1. Adalimumab
2. Inflixamab

Front 31

List a soluble receptor used as Anti-TNF agent.

Back 31

Etanercept

Front 32

List a receptor antagonist used as an anti-IL-1 agent.

Back 32

Anakinra

Front 33

Biologic DMARDs approved for use in which disorders?

Back 33

Crohn's Disease
RA
Ankylosing Spondylosis
Psoriasis
Psoriatic Arthritis

Front 34

What does Abatacept do?

Back 34

Inhibits the co-stimulatory pathway required for full activation of T-lymphocytes.

Front 35

What does Abatacept bind to? What will this cause?

Back 35

Binds to APC CD80/86.

Prevention of CD80/86 to interact with CD28

Front 36

Rituximab is what?

Back 36

Antibody directed against CD20 antigen on B-lymphocytes.

Front 37

What does Rituximab do?

Back 37

Depletes B-cells lineage

Front 38

What are the targets for Rituximab.

Back 38

Pre-B cell
Immature B cell
Mature B cell
Activated B cell

Front 39

Efficacy of ADA, MTX, and combo for clinical response.

Back 39

Greatest to least.

Combo > MTX > ADA

Front 40

Efficacy of ADA, MTX, and combo for radiographic response.

Back 40

Greatest to least.

Combo > ADA > MTX

Front 41

Safety issues associated with Biologic DMARDSs.

Back 41

1. Serious Infection
2. Opportunistic Infection
3. Malignancies
4. Hematologic abnormalities
5. Administration reactions
6. Demyelination
7. CHF
8. Autoantibodies (and lupus like syndromes)
9. Skin reactions
10. Hepatotoxicity.

Front 42

What infections need to be watched for with Anakinra?

Back 42

Pneumonia

Front 43

TB needs to be monitored for with what biological DMARD?

Back 43

Infliximab and Etanercept

Front 44

Rank the potential for adverse effects for the following:

- Abatacept non-biologic DMARD
- Placebo non-biologic DMARD
- Abatacept biologic DMARD
- Placebo biologic

Back 44

Greatest potential to least.

Abatacept non-biologic DMARD
>
Placebo non-biologic DMARD
>
Abatacept biologic DMARD
>
Placebo biologic