DMARDs, Immunomodulators, Immunosuppressors Flashcards
DMARDs - Clinical use
Rheumatoid arthritis – limited use (resistance to drug within 5 years, adverse effects)
Gold salts
Auranofin
Gold sodium thiomalate
Aurothioglucose
Gold salts - MoA
Suggested antimitochondrial activity and cell apoptosis
Gold salts - Adverse effects
Hematologic, dermatologic, GI, renal effects.
Flushing, hypotension, tachycardia
Skin rash & stomatitis
Glucocorticoid
Prednisone
Prednisone - MoA
Induce formation of lipocortin which inhibits phospholipase A2, This inhibits release of arachidonic acid.
Also inhibit production of cytokines (ILs, TNF)
Prednisone - Clinical use
RA to induce remission while waiting for slower-acting DMARD to work.
Short courses during flare-ups.
Continuous low-dose background therapy
Methotrexate - Classification
Antineoplastic and immunomodulating drug
Methotrexate - MoA
Inhibition of human folate reductase which decreases thymidylate and DNA synthesis.
Inhibition of lymphocyte proliferation and production of cytokines and rheumatoid factor.
Interferes with polymorphonuclear leukocyte chemotaxis, which reduces cytotoxins and free radicals
Methotrexate - Clinical use
DMARD of choice in most patients with RA
Methotrexate - Contraindications
Pregnancy and in combination with leflunomide because of hepatotoxicity
Methotrexate - Adverse effects
GI, hematologic, hepatic, pulmonary reactions.
Elevated liver enzymes.
Leflunomide - Classification
Immunosuppressive drug
Leflunomide - MoA
Inhibits leukocyte and T-cell proliferation by inhibiting pyrimidine synthesis (DNA replication, RNA synthesis, protein synthesis) in immune cells
Leflunomide - Clinical use
Alternative to methotrexate for RA
Leflunomide - Contraindications
Pregnancy and in combination with methotrexate because of hepatotoxicity
Leflunomide - Adverse effects
Diarrhea
Reversible alopecia (baldness)
Increased serum hepatic enzymes
Teratogenic
Leflunomide - Interactions
Inhibition of CYP2C9: increases serum levels of many drugs (ibuprofen)
Hydroxychloroquine - Classification
Antimalarial drug
Hydroxychloroquine - MoA
Reduces chemotaxis and phagocytosis of PMNs, reduced superoxides from these cells
Hydroxychloroquine - Adverse effects
GI disturbances
Blurred vision, scotomas, night blindness
Anti TNF-α agents
Etanercept Infliximab Adalimumab Cetrolizumab Golimumab
Anti TNF-α agents - MoA
Binds to and inactivates TNF-α. Newer agents prevents interleukin binding and T-cell activation.
Anti TNF-α agents - Adverse effects
Serious infections and sepsis
Tuberculosis and invasive opportunistic fungal infections
Lymphoma
Etanercept - MoA
Dimer of human TNF receptor fused to IgG constant region
Etanercept - Clinical use
RA resistant to other DMARDs
Etanercept can be combined with
Methotrexate
Etanercept - Adverse effects
Injection site reactions
Infliximab - MoA
MAb binds to TNF-α and prevents it from activating TNF-α receptor
Infliximab - Clinical use
Crohn’s disease and rheumatoid arthritis
ankylosing spondylitis, psoriatic arthritis*
*=Katzung
Infliximab can be combined with
Methotrexate
Infliximab - Adverse effects
Hypersensitivity reactions
Infection
Malignancy
Reactivation of latent TB
Adalimumab - MoA
Human IgG1 MAb similar to daclizumab, specific for human TNF α