DMARDs (Disease modifying antirheumatic drugs)

Question 1

Methotrexate MOA

Answer 1

• Gold standard therapy for RA

- MOA: folic acid antagonist. Also raises extracellular adenosine levels.

Question 2

Methotrexate toxicities

Answer 2

• Microcytic anemia (administer with folic acid)
• Drug induced hepatitis (avoid in patient’s with liver disease or risk of)
• MIAN (methotrexate induced accelerated nodulosis); multiple small nodules over the fingers and pulp spaces
• Pneumonitis
• Tetratogenic and abortifacient (d/c 3 months prior to pregnancy)

monitor LFTs and CBC every 2-3 months

Question 3

Hydroxychloroquine toxicities

Answer 3

-Retinal toxicity (retinal pigment deposition leading to vision loss)

• Baseline and follow up retinal eye exams (q5 yrs)
• Relatively safe in pregnancy and should not be d/c’d
• modest benefit in RA and lupus but good side effect profile

Question 4

Sulfasalazine toxicities

Answer 4

• Gastrointestinal
• Headache
• Agranulocytosis
• Hepatitis
• Reversible oligospermia (low sperm count)

–used in RA. Roughly as effective as methotrexate.

Question 5

Leflunomide toxicities

Answer 5

• Liver toxicity
• Bone marrow toxicity
• Infections
• Interstitial lung disease
• Teratogenic

Question 6

Leflunomide drug elimination protocol

Answer 6

• Long half-life (months) due to enterohepatic circulation
• To remove drug from body give cholestyramine TID x 8 days. After treatment, drug levels must be measured twice to confirmation elimination from the body.

Question 7

Azathioprine indication

Answer 7

Lupus (steroid sparing agent)
Vasculitis
Polymyositis

Question 8

Azathioprine metabolism

Answer 8

requires TPMT (thiopurine methyltransferase) and xanthine oxidase

• Can consider checking TPMT levels prior to administering since patients with low TPMT levels are more prone to toxicities
• Avoid use in patients taking allopurinol or febuxostat

Question 9

Cyclophosphamide toxicities

Answer 9

Leukopenia
Anemia
Increased rate of bacterial and fungal infections
Hemorrhagic cystitis
Bladder cancer
Other long term malignancies
Teratogenic

Question 10

Cyclophosphamide indication

Answer 10

Life threatening lupus

Systemic vasculitis

Question 11

Cyclophosphamide MOA

Answer 11

Acylating agent

Question 12

Mycophenolate Mofetil indication

Answer 12

Lupus, particularly lupus nephritis
Vasculitis
Polymyositis

Question 13

Mycophenolate Mofetil MOA

Answer 13

• inhibits inosine monophosphate dehydrogenase (enzyme in purine synthetic pathway)
• preferentially inhibits T and B lymphocytes

Question 14

Cyclosporine toxicities

Answer 14

• Hypertension
• Nephrotoxicity
• Tremor
• Hirsuitism

3rd line agent in rheumatic conditions