Drugs for Rheumatoid Arthritis and Gout Flashcards
What are some of the drugs used to alleviate joint pain?
- NSAIDs
- Analgesics
- Glucocorticoids
What are the Disease-Modifying Anti-Rheumatic Drugs (DMARDS)?
- Methotrexate
- Hydroxychloroquine
- Sulfasalazine
- Leflunomide
Hydroxychloroquine Indication
Anti-malarial drug that is moderately effective for mild Rheumatoid Arthritis
Hydroxychloroquine MOA
a) inhibition of TLR signaling in dendritic/B cells
b) inhibition of antigen presentation to T cells
Hydroxychloroquine SE
Rare ocular toxicity
Hydroxychloroquine and Pregnancy
Safe during pregnancy and lactation
Sulfasalazine MOA
Thought to interfere with T and B cell immune responses - possibly inhibits activation of NF-B transcription factor
Sulfasalazine and Pregnancy
Safe during pregnancy
Sulfasalazine SE
- Agranulocytosis within 2 weeks - very rare
- Hepatotoxicity
Methotrexate MOA
Indirectly increases the production of adenosine which exhibits known immunosuppressive properties
• decreases the appearance of new bone erosions
• improves the long term clinical outcome.
Methotrexate Indications
Active rheumatoid arthritis that is moderate to severe
Methotrexate SE
- Dose related hepatotoxicity
- Bone marrow suppression
- Increased risk of lymphoma
- Pulmonary toxicity
Methotrxate Contraindications
- Pregnancy
- Renal Disease
- Liver Disease
Leflunomide Indications
- alternative for those unable to take, or non-responsive to MTX
- low cost alternative to TNF inhibitors, or those with a preference for oral medications
Leflunomide MOA
- Inhibits the enzyme dihydroorotate dehydrogenase - uridine synthesis (building block of RNA) - leads to G1 cell cycle arrest
- Inhibits both T cell proliferation and the production of autoantibodies by B cells
Leflunomide SE
- Hypertension - especially with concurrent NSAIDs
- Diarrhea, nausea and rash
- Hepatoxicity - more severe with concurrent methotrexate
Leflunomide Contraindications
- Pregnancy/Breast feeding
- Pre-existing liver disease
What are the TNF-alpha inhibitors?
- Etanercept
- Infliximab
- Adalimumab
Etanercept/Adlimumab/Infliximab MOA
Binds to TNF-alpha and prevents its interaction with its receptor
Etanercept/Adlimumab/Infliximab Indications
Active RA
Etanercept/Adlimumab/Infliximab SE
- Increased risk of infections
- Potential reactivation of latent tuberculosis and latent HBV
- RARE exacerbation of pre-existing congestive heart failure
- RARE development of demyelinating disorders
Etanercept/Adlimumab/Infliximab Contraindications
Treatment should be discontinued if a serious infection or sepsis develops - not for patients with acute or chronic infections
Abatacept Indications
Active RA - used in pts not responsive to TNF-alpha inhibitors
Abatacept MOA
Binds CD80/CD86 Blocks T cell co-stimulation via CD28
Abatacept SE
Increased risk of serious infections - screen for TB and HBV
Abatacept Contraindications
Should not be given in combination with a TNF- blocker or to patients with infection