Rheumatoid Arthritis and DMARDs

Question 1

DMARDs

Answer 1

Disease modifying anti-rheumatic drugs

Not just treating the symptoms, but modifying the course of the disease to slow it down

Question 2

NSAIDs treatment of RA

Answer 2

Milder, safer
Provide initial symptom relief
Need stronger/more toxic - Diclofenac, Indomethacin, etc

Question 3

Glucocorticoids

Answer 3

Anti-inflammatory steroids
Prednisone
Effective but toxicities prevent longterm use
Not usually called a DMARD, but is
Not used alone for RA - used in combo
“Bridge agent” while wait for DMARDs to become effective

Question 4

Methotrexate (Rheumatrex, MTX)

Answer 4

Early stages of RA, but also later
First choice drug of RA for initial tx
Oral, but also IP and IM
1x/week (long duration of action)
Effects may take 4-6 weeks to accumulate enough in tissues
Folic acid analog - enters cell via folate transporter, poly-glutamated inside cell and trapped

Question 5

Mechanisms of MTX

Answer 5

1. Inhibit purine synthesis
2. AICAR
3. Inhibit Pyrimidine synthesis

Question 6

Hydroxychloroquine (Plaquenil)

Answer 6

Antimalarial, anti-inflammatory
Alter cell pH
*The least DMARD
*LONG HALF LIFE 45 days
Combined with other DMARDs

S/E: Retinal damage, decrease BGL, do not use with psoriasis

Question 7

Sulfasalzine (Azulfidine)

Answer 7

Immune suppressive drug - inhibit immune cells and cytokines
Produce salicylate and sulfapyrimidine

SE: Blood disease, folate absorption problem, sulfa allergy

Question 8

Triple drug therapy/Nebraska therapy

Answer 8

1. Methotrexate weekly
2. Add Hydroxycholroquine + Sulfasalzine
3. Try all 3 combination
4. Can add NSAIDs and/or prednisone

Question 9

Lefluonomide (Arava)

Answer 9

Immunosuppressive
Inhibit pyrimidine synthesis, TK
Inhibit T cell formation and auto-antibody formation by B cells
Long half life
*REPEATED ENTEROHEPATIC CIRCULATION
- long half life, need to remove before pregnancy (Cholestryamine)

Question 10

Minocycline

Answer 10

Tetracycline abx
*Inhibit matrix metalloproteinases, collagenase
= decrease collagen degradation

Question 11

Biologics

Answer 11

Newer, peptides, BIG
Immunosuppressive
Early in inflammation cascade
Prevent auto-antibody, Block signaling molecule
*use when DMARDs fail*

Question 12

Risks with Biologics

Answer 12

Increased likelihood of infection
Blood dyscrasias
Increased cancer incidence (non-hodgkins)
GI problems, headache, skin rash
*do not combine multiple biologics*

Question 13

Anti-TNF agents

Answer 13

Anti-tumor necrosis factor
FIRST biologics
Target upstream cytokine (of inflammation and joint destruction)
TNF receptors p55 and p75

Question 14

Etanercept (Enbrel)

Answer 14

Used p75 subunit of HUMAN TNF receptor and attached to antibody heavy chain
TNF antagonist - TNF cannot bind - no downstream effects!

Short duration use with MTX
concern for PML (progressive multifocal leukoencephalopathy)

Question 15

Infliximab

Answer 15

Anti-TNF Monoclonal antibody against TNF
Partial mouse antibody
IV w/ MTX

Question 16

Adalimumab

Answer 16

Anti-TNF antibody
FULLY HUMANIZED
Juvenile idiopathic arthritis
cause demyelination - no MS patients

Question 17

Abatacept

Answer 17

CTLA -4 bind to CD28 Tcell surface protein
No T cell activation - no inflammation
Do NOT combine with anti-TNF

Question 18

Rituximab

Answer 18

anti-CD240 mab= B cell inhibitor
Long duration = 6 months
Combine w/ MTX
New drug