DMARDs Flashcards
What do DMARDs have the ability to do?
Improve inflammatory symptoms and slow progression of joint erosion
What are the non-biological DMARDs?
They are the cornerstone of RA tx; MTX, Sulfasalazine, Leflunomide, Hydroxychloroquine
What is the MOA of MTX?
Immunosuppression by inhibition of AICAR transformylase; this means AICAR doesnt => FAICAR, increased AICAR blocks adenosine deaminase; increased Adenosine inhibits IL-1, TNF-a, IFN-g, lymphocyte proliferation, neutrophil chemotaxis, and histamine release
What is the metabolism/excretion of MTX?
MTX gets polyglutamated, which increases intracellular retention. Hepatic metabolism and enterohepatic recirculation (longer halflife); renal elimination
What are the ADEs of MTX?
Immunosup; blood dyscrasia; infxn; bleeding; contra-HIV and vaccination; pulm fib; CAT-X; malignant lymph; skin rxn; GI fox in pts with ulcerative colitis (esp w/ NSAID)
What do you monitor for in MTX?
CBC, LFT, Creatinine/BUM, Serum Uric Acid, Pregnancy tests
When is sulfasalazine used for?
For when NSAIDs provide inadequate response
What is the MOA of sulfasalazine
Metabolised into sulfapyridine and mesalamine by colonic bacteria = Mesalamine is anti-inf that inhibits PG and LT
What happens to sulfapyridine?
Acetylated in liver therefor slow acetylators can be affected
What is the elimination of sulfasalazine?
Renal
What are the ADEs of sulfasalazine?
Contra-hypersens to salicylates or sulfonamides, Fatal blood dyscrasias
What do you monitor for sulfasalazine?
CBC, LFT, Creatnine/BUM, Urinalysis
What is the MOA of Leflunomide?
Metabolized into A77 1726; this inhibits dihydroorotate dehydrogenase (DHODH) in mitochondria and catalyzes pyrimidine synthesis; This causes T/B cell cycle arrest; no Ig is made; Cytostatic at clinical dosing
What is the met/elim of Leflunomide?
Met into A77 1726 by CYPs and eliminated in feces
What are the ADE’s of Leflunomide?
Hepatitis (CYPs), contra-alcohol, immunodef, bone marrow dysplasia, infxn, CAT-X
What do you monitor with Leflunomide?
CBCs, LFTs, Pregnancy, Serum electrolytes
What is hydroxychlorquine prophylactially given for?
Malaria
What is the MOA of hydrocychloroquine?
Increase intracellular vaculor pH and alters protein degradation by lysosome, macromolecule assemble in endosome, and proetin mod in golgi; MHC not assembled = down regulation in immune response to foreign and self antigens
What is the met/elim of hydroxychloroquine?
Partial hepatic metabolism and then sow and extensive renal elim
What are the ADEs of Hydroxychloroquine?
CNS tox (neuropathy, oto-, seizures), hepatits, blood dyscrasias; Contra-ocular dz
What do you monitor with Hydroxychloroquine?
CBC and Opthalmic exams
What are the biologic agents used for in treatment of RA dz?
Targeted Treatment; Adalimumab, Etanercept, Infliximab, Golimumab, Certolizumab pegol, Abatecept, Rituximab, Anakinra, Tocilizumab
What are the ADEs/worries of ALL of the biologic agents used for the treatment of RA?
All cause immunosuppression, do not give any with an active infection, they increase infxn (especially respiratory in COPD/asthma), worry about Hep B/TB reactivation, NO live vaccines
What is a specific ADE for all of the TNF-a blockers?
increase in malignancies
What is the MOA of adalimumab?
TNF-a mAb, blocks interaction with p55 and p75
What are the specific ADE’s for adalimumab?
CHF or hypotension/angina/dysrhythmia, a lupus like syndrome, and advice patient about save SC injection practice
What is the MOA for etanercept?
TNF-a receptor-Ab fusion protein, p75 bound to IgG1 (inactivates TNF but does not affect production or serum levels)
What are the specific ADE’s for etanercept?
Lupus like syndrome, advise patient about safe SC injection
What is the MOA for Infliximab?
TNF-a Chimeric (mouse) maB (IgG-1k), binds soluble and transmembrane TNF-a and neutralzies
What are the specific ADE’s for infliximab?
CHF/hypotension/angina/dysrhythmia, Lupus like syndrome and perform LFTs
What is the MOA of Golimumab?
Human derived TNF-a antibody that binds soluble and transmembrane TNF-a and neutralizes
What are the specific ADE’s for Golimumab?
CHF/hypotension/angina/dysrhythmia, LFTs, Advise about safe SC injection
What is the MOA of Certolizumab pegol?
Fab fragment of humanized TNF-a that binds soluble and membrane bound TNF-a and neutralizes
What are the specific ADE’s for Certolizumab pegol?
Blood dyscrasias, lupus like syndrome, advise about safe SC injection
What is the MOA of abatacept?
CTLA4/IgG1 fusion protein that binds CD80 and CD86 which blocks CD28 from activating T-cells
What are the specific ADE’s of abatacept?
Contains maltose which can mess with blood glucose test, advise about safe SC injection
What is the MOA of Rituximab?
Chimeric (mouse-human) CD20/IgG1k mAb against B-lymphocyte CD20 receptor which will lyse B-cells, also sensitizes drug resistant human B-cell lymphoma cell lines to cytotoxic chemotherapy
What are the specific ADE’s of Rituximab?
CHF/hypotension/angina/dysrhythmia, Blood dyscrasia, toxic epidermal necrolysis/SJS, Contraindicated in pregnancy
What is the MOA of Anakinra?
IL1 receptor antagonist which inhibits IL1alpha and beta from binding to IL-1R1; decrease inflammatory response
What are the specific ADE’s of Anakinra?
Blood dyscrasia, advise patient about safe SC injection
What is the MOA of Tocilizumab?
IL-6 receptor inhibiting mAb that binds to soluble and membrane bound IL-6 receptors and inhibits signaling which decreases immune response regulator production
What are the specific ADE’s of Tocilizumab?
Blood dyscrasia, LFTs (serum lipids too)
