Pharmacotherapy for RA and Gout Flashcards
What are the five classes of disease-modifying antirheumatic drugs (DMARDs)?
Antineoplastic agents, antimalarial agents, chelating agents (don’t need to know this one), immunosuppressives, mechanism-targeted inhibitors
What antineoplastic agent is most commonly used in the treatment of RA?
Methotrexate
What is the mechanism of anti-inflammatory activity of methotrexate in RA?
Not fully understood; may inhibit T cell activation or suppress expression of adhesion molecules on T cells
What are the most common side effects of methotrexate at doses used to treat RA?
Nausea/vomiting, mouth sores, headache, fatigue, alopecia, rash; rarely life-threatening hepatotoxicity, pulmonary damage, and myelosuppression (usually not at this dose)
What antimalarial agent is used to treat RA?
Hydroxycholorquine
What is the mechanism of action of hydroxychloroquine in treating RA?
Not fully understood; may inhibit TLRs, block antigen processing in macrophages,, and/or block the presentation of antigen-MHC complex to CD4+ T cells
What are the most common side effects of hydroxychloroquine when used to treat MA?
Headache, dizziness, hair loss, nausea, muscle pain, worsening psoriasis; rarely causes leukopenia, thrombocytopenia, anemia, and retinal damage
Why is methotrexate contraindicated in patients with impaired kidney function?
80-90% is eliminated unchanged in the urine; impaired kidney function will increase serum half life and can cause toxicity
Why is hydroxychloroquine most frequently used in combination with other therapies for RA?
Onset of anti-rheumatic activity is relatively slow and has limited efficacy
What are the four most common cytokine blockers used to treat RA?
Infliximab, adalimumab, etanercept, and anakinra
What cytokine do infliximab, adalimumab, and etanercept inhibit?
TNF-α
What cytokine does anakinra inhibit?
IL-1
What is the molecular composition of infliximab?
Chimeric mouse/human anti-TNF-α monoclonal antibody
What is the molecular composition of etanercept?
Human TNF-α receptor linked to the Fc portion of human IgG1; soluble TNF-α receptor binds and inactivates TNF-α, recombinant degrades more slowly than naturally occurring soluble receptor
What is the molecular composition of adalimumab?
Human monoclonal anti-TNF-α antibody
What are the common side effects of anti-TNF-α agents?
Increased risk of infection, lupus-like syndrome, heart failure, exacerbation of demyelinating disease, headache, nausea; infliximab rarely causes a severe, potentally fatal infusion reaction
What is the molecular composition of anakinra?
Recombinant, synthetic form of IL-1 receptor antagonist
What are the common side effects of anakinra?
Headache, nausea, injection site reaction, increased risk of infection, increased risk of lymphoma
What is the molecular composition of abatacept?
Fusion protein of the extracellular domain of the CTLA4 molecule and Fc domain of human IgG1
What is the mechanism of action of abatacept in treating RA?
Abatacept is a soluble protien that binds to CD80/86 and blocks the binding of CD28, the costimulatory signal required for T-cell activation
What are the common side effects of abatacept?
Headache, nausea, increased risk of infection
What is the molecular composition of rituximab?
Mouse/human monoclonal antibody against CD20
What is the mechanism of action of rituximab in treating RA?
Several proposed mechanisms, all involving depletion or inhibition of B cells
What is the mechanism of action of tofacitinib in treating RA?
Blocks JAK1 and JAK3 (and JAK2 to a lesser extent), which blocks transcription of certain cytokines
What are the side effects of tofacitinib?
Inflammation of nasal passages and upper pharynx, upper respiratory infections, increased risk of TB and lymphoma, headache
