Drugs in Rheumatoid Arthritis Treatment Flashcards
What drugs are used to reduce acute pain in RA?
Analgesics (Acetaminophen, Capsacin, Opioids)
NSAIDS
Glucocorticoids (dexamethasone)
What drug classes prevent or control joint damage in RA?
DMARDs = Disease Modifying anti-Rheumatic Drugs
BRMs = Biological Response Modifiers
General MOA for DMARDs
Reduce or prevent joint damage
Inhibit the overactive immune system
In general, how long do DMARDs take to work?
Weeks-months
Hydroxychloroquine
Indication and type of drug
DMARD
Anti-malarial drug that is moderately effective for mild RA
Hydroxychloroquine
Rare side effect
Ocular toxicity that may result in permanent visual loss
What DMARDs may be used during pregnancy and lactation?
Hydroxychloroquine
Sulfasalazine
Hydroxychloroquine
How long does it take to work?
3-6 months
Sulfasalazine
Adverse Effect
Agranulocytosis within 2 weeks
Hepatotoxicity
Sulfasalazine
Indication
Decreases signs/symptoms of disease and slows joint destruction
Methotrexate
Indication
DOC for pts with active moderate/severe RA
Decreases appearance of new bone erosions
Improves LT clinical outcome
How long does Methotrexate take to work?
4-6 weeks
Methotrexate
MOA
Indirectly increases adenosine production, which leads to immunosuppression
Methotrexate
AEs (common and rare)
Common:
Dose-related hepatotoxicity (do NOT drink alcohol with methotrexate)
Rare:
- Pulm toxicity
- Bone marrow suppression
- Increased risk lymphoma
Methotrexate
Elimination
Renally excreted
So adverse effects are more common in renal impaired patients
Methotrexate
Contraindications
Pregnancy/Breast Feeding
Pre-existing liver disease
Renal impairment
Leflunomide
Indication
Used in pts with RA who can’t take or are nonresponsive to Methotrexate
Leflunomide
MOA
Inhibits dihyroorotate dehydrogenase, which synthesizes uridine
Causes G1 cell cycle arrest, inhibiting T cell proliferation and production of autoantibodies by B cells
Leflunomide
Contraindications
Pregnancy/Breast feeding
Preexisting liver disease (risk of hepatotoxicity)
Describe how TNF-alpha plays a role in inflammation of RA
Joint inflammation
Cartilage breakdown
Bone erosion
List the anti-TNF-alpha drugs
Etanercept
Infliximab
Adalimumab
Anti-TNF-alpha drugs
MOA
Bind TNF-alpha and prevent it from binding its receptor, thus preventing inflammation
Anti-TNF-alpha drugs
Administration
Clinical Use
Given subQ or IV weekly or biweekly
Used in monotherapy or in combo with methotrexate
Anti-TNF-alpha drugs
AEs
Increased risk of opportunistic infection (fungal/bacterial)
Potential reactivation of latent TB and latent HBV
Before starting Anti-TNF-alpha drugs, you should screen the patient for….
Latent TB infection
Latent HBV infection
Abatacept
What is it?
Clinical Use
Recombinant fusion protein of CTLA4 and human IgG
Used in pts non-responsive to TNF-alpha inhibitors
Abatacept
MOA
It’s CTLA4 domain inhibits T cell activation by blocking delivery of CD28 costimulatory signals
Abatacept
AEs and Contraindications
Increased risk for serious infections
Should NOT be given in combo with a TNF-alpha blocker
Rituximab
MOA
Binds CD20 on B cells and depletes B cells from blood
Rituximab
How long does it last?
Effects not seen for 3 months, though the effects may last 6 months - 2 years after one infusion
Rituximab
AEs
Increased infections
Risk of PML
Anakinra
MOA
IL-1 receptor antagonist
Competitively inhibits pro-inflammatory effects of Il-1
Anakinra
AEs
Neutropenia
Infection risk increases
Never given to patients with an acute/chronic infection
Bad when given with an anti-TNF-alpha drug
Tocilizumab
MOA and Clinical Use
IL-6 receptor antagonist
Used in patients who are non-responsive to TNF inhibitors
May be used in combo with methotrexate
Tocilizumab
AEs
Bone marrow suppression (lymphocytopenia, neutropenia, anemia)
Increased infection risk
Hepatotoxicity
Tofacitinib
MOA
Small molecule inhibitor of JAK tyrosine kinases involved in immune cell cytokine signaling
