Rheumatoid Arthritis

Question 1

Methotrexate

Answer 1

• DMARD (1st choice, slows disease progression); Anti-metabolite ; Immunosuppressant
• Binds dihydrofolate reductase, decr reduced form of folate and interferes with de novo thymidine synth: DNA, RNA and protein synthesis; Enhances adenosine release; decr lymphocytes
• Low dose PO weekly (RA, psoriasis); high dose for chemotherapy (Choriocarcinoma, Breast cancer (CMF))
• Common: Nausea & mucosal ulcers. (bone marrow suppression, pneumonitis, hepatotoxicity long-term) & teratogen
• AKA Rheumatrex

Question 2

Leflunomide

Answer 2

• DMARD [RA]
• Pyrimidine synthesis inhib, Reduces rUMP levels in lymphocytesàblocks cell cycle
• AEs: Rash, hepatotoxicity, bone marrow suppression

AKA Arava

Question 3

Azathioprine

Answer 3

• DMARD, Immunosuppressant
• Converted to 6-mercaptopurine, thio analog of purine (hypoxanthine) inhibits purine synthesis and interconversion (salvage); phosphorylated analog incorporated into DNA and RNA
• Prototype: mercaptopurine
• PO; metabolism bimodal
• RA (severe) , autoimmune hepatitis, organ transplant
• AEs: Bone marrow suppression, incr risk infections and malignancy (Drug rxn: allopurinol)
• AKA Imuram

Question 4

Prednisone

Answer 4

• Prototype: cortisol (3-4x more potent)
• Anti-inflammatory ; Glucocorticoid (bind receptor); Anti-neoplastic hormone agonist ; Immunosuppressant
• Reduces expression and action of pro-inflammatory cytokines (AP-1); Induces expression of anti-inflammatory genes (IkappaB); (Lympholytic)
• PO, hepatic conversion to active (prednisolone)
• RA (acute attacks only, tapers), Asthma, Leukemia, Hodgkin’s lymphoma, gout, transplant rejection prophylaxis
• AEs (common): Adrenal insufficiency after acute withdrawal, incr risk infections, ulcers, hyperglycemia, osteoporosis, myopathy, behavioral disturbances, cataracts, growth retardation, fat redist, hirsutism, acne

Question 5

Hydroxycloroquine

Answer 5

• DMARD [RA] & [anti-malaria]
• UNK anti-inflammatory, not slow progression
• Take 12-24 wks to work, no bone marrow supp
• AEs: Retinopathy (rarer than with chloroquine)
• AKA Plaquenil

Question 6

Sulfasalazine

Answer 6

• DMARD [RA] & [IBD]
• UNK anti-inflammatory, reduce symptoms & slows disease
• AEs: hypersensitivity to sulfa allergy
• AKA Azulfidine

Question 7

Anakinra

Answer 7

• Il-1-1b receptor antagonist [prototype]
• SC
• RA
• AEs: same as ant-TNF (lymphoma, bad infection)
• AKA Kineret

Question 8

Rilonacept

Answer 8

• Soluble IL-1-1b receptor
• Prototype: Anakinra
• AKA Arcalyst, Regeneron

Question 9

Infliximab

Answer 9

• DMARD, Immunosuppressant, Anti-TNF
• Humanized monclonal Ab to TNF (decr TNF)
• Single dose IV infusion >2 hrs (1-3 mo); t1/2 10 d; metab & excret unk
• RA & Chrohn’s
• AEs: Infusion rxns: chest pain, nausea, fever, facial flushing, headache, urticaria, dyspnea, hypotension. Incr risk serious infections (lymphoma)
• AKA Remicade

Question 10

Adalimumab

Answer 10

• DMARD, Anti-TNF
• Humanized anti-TNF monoclonal Ab
• SC
• RA, Crohn’s, Ankylosing spondylitis, Psoriatic arthritis
• AKA Humira

Question 11

Etanercept

Answer 11

• DMARD (refractory), Immunosuppressant, Anti-TNF
• Fusion protein: TNF receptor ligand binding domain with IgG Fc
• SC (2x per week), $$$$
• RA, reactive arthritis, Ankylosing spondylitis

AKA Enbrel

Question 12

Abatacept

Answer 12

• DMARD [RA]
• Prototype: Etanercept
• CTLA4-Ig (recombinant fusion protein) – inhibit T-cell co-stimulatory signal (CD28-CD80/CD86)
• IV
• AKA Orencia

Question 13

Rituximab

Answer 13

• Anti-neoplastic
• Anti-CD20 monoclonal Ab block B-cell co-stim pathway
• IV
• RA & B-cell Lymphoma
• (AEs: Infusion rxns,hypersensitivity, Rituximab tumor lysis syndrome)
• AKA Rituxan