RA Flashcards
Nonbiological DMARDs (10)
- Methotrexate
- Sulfasalazine
- Lefunomide
- Hydroxychloroquine (Chloroquine)
- Azathioprine
- Gold
- Minocycline
- Cyclosporine
- Penicillamine
- Other antibiotics
Biological DMARDs (9)
- Infliximab
- Etanercept
- Adalimumab
- Anakinra
- Abatacept
- Rituximab
- Tocilizumab
- Golimumab
- Tofacitinib
Methotrexate (MTX)
5 important things
6 ADRs
- Drug of choice (60-70% show response)
- Decreases TNFa and increases IL-10, decreases cytokine production
- Monotherapy or with steroids
- Taken weekly
- Folic acid antagonist (may cause stomatitis)
- ADRs: GI, hepatofibrosis/cirrhosis, myelosuppression, intertitial pneumonitis, stomatitis, alopecia
Leflunamide
4 important things
5 ADRs
- Similar to MTX
- Prevents CD4 proliferation, alters IL-2 and GFs, inhibits leukocyte adhesion
- Has an active metabolite (A77-1726)
- Works well for 2 years
- ADRs: alopecia, rash, diarrhea, increased LFTs, infections
Sulfasalazine
5 important things
4 ADRs
- Sulfapyradine + aspirin
- Anti-inflammatory and immunosuppressive
- Antimicrobial portion is active
- Suppresses TNFa, IL-1, inhibits chemotazis and neutrophil migration, enhances release of adenosine
- Severe ADRs in 25% (discontinue)
- ADRs: GI, rash, hepatitis, blood dyscrasias
Hydroxychloroquine
(Chloroquine)
3 important things
4 ADRs
- Additive therapy
- Suppresses lysosomal enzymes, inhibits B and T cells and IL release
- Caution in those with eye problems (causes irreversible retinopathy)
- ADRs: GI, rash, bone marrow suppression, retinopathy
Azathioprine (AZA)
5 important things
6 ADRs
- Steroid sparing agent (can redoce steroid dose)
- Last resort drug
- Similar to gold and penicillamine but increased toxicity
- Antagonizes purine metabolism and may inhibit DNA, RNA and protein synthesis
- Pro-drug (AZA -> 6 MP -> 6 TG)
- ADRs: hepatic inflammation, lymphoproliferative cancer, N/V/D, bone marrow suppresion
Gold
3 important things
6 ADRs
- Adjunctive treatment
- Alters macrophage function, inhibits mast cell mediator release and lysosomal enzyme activity
- Several metabolites
- ADRs: metallic taste, peripheral neuropathy, dermatitis, proteinuria, bone marrow suppression, stomatitis
Penicillamine
3 important things
5 ADRs
- Comparable to IM gold
- Inhibits T-cells and chemotaxis of phagocytes, decreases RF
- Toxic (impedes absorption of other drugs)
- ADRs: bone marrow suppression, proteinuria, autoimmune (SLE), aplastic anemia, taste disturbance
Minocycline
2 important things
5 ADRs
- Adjunct agent eary in therapy
- Improved inflammatory markers (ESR, CRP, etc)
- ADRs: photosensitivity, vestibular toxicity (dizziness), N/V/D
Cyclosporine
2 important things
8 ADRs
- Retards appearance of new bony erosions
- Very little bone marrow toxicity
- ADRs: nephrotoxicity**, hypertension, hyperglycemia, hyperkalemia, liver dysfunction, seizures, altered mental status, hirsutism
Infliximab
4 important things
8 ADRs
- Binds to TNF
- RA, Crohn’s, UC, PA
- Chimeric, IgG1 monoclonal antibody
- Interacts with anakinra
- ADRs: headache, N/V/D, infusion reactions, respiratory problems (infection, sinusitis), development of antinuclear and DNA antibodies
Entanercept
2 important things
3 ADRs
- Binds TNFa receptor and lymphotoxin alpha
- Recombinant fusion protein
- ADRs: injection site reactions, infections, allergic reactions
Adalimumab
4 important things
- Binds to TNFa
- Fully human recombinant monoclonal antibody
- Inhibits progression of RA and decreases damage
- Interacts with anakinra
Anakinra
3 important things
1 ADR
- Blocks IL-1
- Etanercept increases risk of serious infection
- Don’t give with TNF inhibitors or those allergic to E. coli proteins
- ADRs: injection site reactions
Abatacept
2 important things
- T-Cell lymphocyte (soluble CTLA-4-Ig)
- Infliximab my increase ADRs of abatacept
Rituximab
3 important things
- Depletes B-Cells that have CD-20, induces B-Cell lysis
- Anti-CD20 chimeric monoclonal antibody
- Give with MTX and steroids on days 1 and 15
Tocilizumab
2 important things
3 ADRs
- IL-6 receptor inhibitor
- Refractory patients
- ADRs: latent TB, increased cholesterol, triglycerides, LDL and HDL, shingles
Golimumab
3 important things
- Binds to TNF
- For moderate to severe RA with MTX
- Fully human monoclonal antibody
Tofacitinib
3 important things
1 ADR
- Oral Janis Kinase Inhibitor (JAK)
- Blocks signaling for cytokine proliferation
- For refractory patients
- ADRs: GI
7 Factors that make RA prognosis worse
- Number of affected joints
- Extra-articular involvement
- Nodules
- Early functional decline
- Persistent, active inflammation
- X-Ray evidence of erosive disease
- Genetics
5 Goals of RA therapy
- Control severity
- Alleviate pain
- Maintain ADLs
- Maximize QOL
- Slow progression of joint damage
Non-Pharmacological Management
4 things
- Rest
- Exercise
- Diet/weight control
- Physical/occupational therapy
Duration: less than 6 months
Severity: low
Leflunamide
Methotrexate
Sulfasalazine
Duration: less than 6 months
Severity: moderate to high
Leflunamide
Methotrexate
MTX + Hydroxychloroquine
Duration: 6-24 months
Severity: low
Leflunamide
Methotrexate
Sulfasalazine
Duration: 6-24 months
Severity: moderate to high
Leflunamide
Methotrexate
Sulfasalazine
MTX + non-biologic of choice
Duration: greater than 24 months
Severity: low
Leflunamide
Methotrexate
Sulfasalazine
MTX + Hydroxychloroquine
Duration: greater than 24 months
Severity: moderate to high
Leflunamide
Methotrexate
MTX + non-biologic of choice
3 Advantages of DMARDs
- Reduce signs and symptoms
- Reduce functional disability
- Retard radiographic progression
