Drugs for RA Flashcards
What are the therapeutic goals for treating RA?
- Relieve pain
- Reduce inflammation
- Slow down or stop joint damage
- Improve a person’s sense of well being and ability to function
Have minimal effect on progression of joint deformity
Used in large doses for long duration of treatment
Relieve symptom pain
NSAIDs
What does DMARDs stand for?
Disease-Modifying Anti-Rheumatics
Inhibits the ability of TNF-a to bind to its receptor
Recombinant fusion protein
Etanercept
Pharmacokinetics of Etanercept.
IV or subcut administration
Onset of action 1-2 weeks
Elimination half life > 3 days
Adverse effects of Etanercept
Injection site reactions
Increase risk of infections (screen for latent TB before beginning treatment and closely monitored during and after drug therapy)
Lymphomas in children/adolescent patients
What is etanercept therapeutically used for?
Moderate to severe RA
Juvenile RA
Early stage
IgG monoclonal antibody (human)
Binds to soluble AND transmembrane forms of TNF-a
Prevents TNF-a binding to its receptor
Adalimumab
How and how often is Adalimumab administered?
Subq
Every other week
Adverse effects of Adalimumab
Injection site reactions
Increased risk of infections
Lymphomas in children/adolescent patients
What are the therapeutic uses of Adalimumab?
Active RA (moderate to severe); may be used alone or in combination with methotrexate or other DMARDs
Active juvenile idiopathic arthritis (moderate to severe); may be used alone or in combo with methotrexate
How does Infliximab and Adalimumab differ from Etanercept in regards to binding TNF-a?
Infliximab and Adalimumab can bind to both m-TNF and s-TNF, neutralizing their biologic activity – may also induce apoptosis of the expressing cells
Etanercept also neutralizes s-TNF but does not bind to m-TNF or induce apoptosis of expressing cells
Humanized antibody, binds to soluble and membrane bound IL-6 receptors
Inhibits IL-6 mediated signaling via these receptors
Tocilizumab
How often is Tocilizumab administered?
IV every 4 weeks
SubQ every other week
Adverse effects to Tocilizumab
Injection site reactions
Increased risk of infections
Alterations in lipid profile – increases in total cholesterol, triglycerides, LDL, and/or HDL
What is Tocilizumab therapeutically used for?
Indicated for adult patients with moderatly to severely active RA who have had an inadequate reponse to one or more TNF antagonists
Janus kinase (JAK) inhibitor
Tofacitinib
How is Tofacitinib metabolized?
Administered orally
Metabolism mediated by CYP3A4 with minor contribution from CYP2C19
Adverse effects of Tofacitinib
Increase risk of infections
Increase in cholesterol
How is Tofacitinib therapeutically used?
For treatment of moderately to severely active RA in patients who are unable to take methotrexate
May be used as monotherapy or in combo with methotrexate or other DMARDs
Sites of action of drugs:
- Abatacept
- Methotrexate and Leflunomide
- Etanercept, Infliximab, Adalimumab
- Anakinra and Tocilizumab
- Glucocorticoids
- Abatacept blocks co-stim of T cells
- Methotrexate and Leflunomide inhibits the proliferation and activity of T and B cells
- Etanercept, Infliximab and Adalimumab inactivate TNF-a
- Anakinra blocks the action of IL-1 and Tocilizumab inactivates IL-6
Blocks IL-1 Receptor
Anakinra
Inhibits T-cell activation
Abatacept
Antibody directed against CD20 antigen on B-lymphocytes
Rituximab
