DMARDs Flashcards
Non-biological DMARDs
methotrexate, hydroxychloroquine, leflunomide, sulfasalazine
Methotrexate
Inhibits AICAR transformylase (catalyzes the last step in synthesis of inosine monophosphate). AICA riboside accumulates → inhibits adenosine deaminase → ↑ circulating adenosine → inhibition of lymphocyte proliferation, ↓ secretion of IL-1, IFN-gamma, TNF, ↑ secretion of IL-4, ↓ release of histamine, ↓ neutrophil chemotaxis
Side effects of methotrexate
Bone marrow suppression (do not use with HIV) & anemia.
Interstitial pneumonitis (can be fatal) & pulmonary fibrosis
Category X.
↑ risk of malignant lymphomas
Fatal derm rxns
GI toxicity, esp with NSAIDS and PUD/UC
↑ LFTs
Monitoring for methotrexate
CBC w/diff
LFTs
serum Cr/BUN
serum uric acid
Sulfasalazine
Metabolized to sulfapyridine & mesalamine by bacteria in colon.
Inhibits PG & LT production → anti-inflammatory
Side effects of sulfasalazine
↑ serum levels in poor acetylators
Contraindicated with hypersensitivity to salicylates or sulfonamide drugs
Rarely, fatal blood dyscrasias
Monitoring for sulfasalazine
CBC w/diff
LFTs
serum Cr/BUN
urinalysis
Leflunomide
Inhibits DHODH → enzyme in mitochondria that is important in pyrimidine synthesis. Arrests cell cycle in T and B cells and ↓ IG production
Side effects of Leflunomide
↑ uric acid excretion
Category X
Contraindications to leflunomide
Severe immunodeficiency, bone marrow dysplasia, uncontrolled infxn, pregnancy
Monitoring for leflunomide
CBC w/diff
LFTs
pregnancy
serum electrolytes
Hydroxychloroquine
↓ presentation of antigenic peptides on MCH class II molecules that stimulate CD4 T-cells
Side effects of hydroxychloroquine
Liver toxicity with hepatic disease or alcoholism
Blood dyscrasias
Contraindicated in ocular disease
CNS toxicity: polyneuritis, ototoxicity, seizures, neuromyopathy
Monitoring for hydroxychloroquine
CBCs
Ophthalmalogic exam
Abatacept
CTLA4/IgG Fc fusion protein
Binds CD80 & CD86 to prevent T-cell co-stimulatory signal from engaging with CD28/B7 on APCs.
Adalimumab
TNF-alpha monoclonal Ab
Prevents TNF-alpha from binding to p55 & p75 cell receptors
Anakinra
IL-1 receptor antagonist
Competitively inhibits IL-1 binding to receptor
Certolizumab pegol
Fab fragment of TNF-alpha Ab → neutralizes membrane-bound & soluble TNF-alpha
Etancercept
Fusion protein of TNF receptor & IgG Fc
Inactivates TNF
Golimumab
TNF-alpha Ab
Neutralizes soluble & membrane-bound TNF-alpha
Infliximab
Mouse-human TNF-alpha MAb
Neutralizes soluble & membrane-bound TNF-alpha
Rituximab
Mouse-human CD20 B-cell receptor MAb
Binds to membrane-bound CD20 receptor & causes immune cells to lyse B-cells
Tocilizumab
IL-6 MAb
Inhibits signaling of IL-6 receptors. ↓ activation of TH17 cells & mø.
Side effects of biological DMARDs
Immunosuppression → no live vaccines, don’t give to pts with active infections, careful with asthmatics & COPD
↑ risk of malignancies → esp the TNF-alpha inhibitors
Biologics causing CHF or hypotension/angina/dysrhythmias
Adalimumab, Golimumab, Infliximab, Rituximab
Biologics causing blood dyscrasias
Anakinra, certolizumab, rituximab, tocilimumab
Do routine CBCs
Biologics causing a lupus-like syndrome
Adalimumab, certolizumab, entanercept, infliximab
Biologics causing SJS or TEN
rituximab
Complication with Abatacept IV
Contains maltose - may affect blood glucose tests
Pregnancy tests recommended for which biologics
rituximab (IgG crosses placenta)
LFTs recommended for which biologics
golimumab, infliximab, tocilimumab (also serum lipids)
