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60 Cards in this Set
- Front
- Back
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What is RA?
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Progressive, systemic, inflammatory disorder Characterized by: symmetric synovitis, joint erosions, and multisystem extra-articular manifests (pulm vasc, keratoconjunctivitis, sensory peripheral neuropathy)
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What's the prognosis of RA?
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40% to 60% with advanced RA will: Survive 5 years or less following diagnosis or Die 10-15 years earlier than expected
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Prevalence of RA?
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Approximately 1% of the total adult population is affected by RA (2.5 x in women)
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What alleles are assoc with severe RA? Concordance rate of RA?
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HLA-DR4+ alleles
30% to 50% concordance rate for monozygotic twins |
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What percent of RA patients are RF+?
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70-80% (humoral immunity plays a role along with cellular)
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What's the main joint differences in RA vs OA?
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RA's inflammatory and so has a swollen, inflammed membrane whereas OA isn't and has thinned cartilage and bones rub together.
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Why is early diagnosis of RA important?
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Structural damage/disability occurs within first 2 to 3 years of disease - Slower progression linked to early tx
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What should you ask the patient during baseline RA eval?
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Degree of joint pain
Duration of morning stiffness Presence/absence of fatigue Functional limitation(s) |
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What acute phase reactants are elevated in RA?
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C-reactive protein
ESR cyclic citrullinated polypeptide |
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What are the different classes of RA?
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I is able to preform usual activities, II has limited avocational activities, III has limited vocational, IV has limited self-care.
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What social factors increase morb and mort for RA? (4)
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Low socioeconomic status
Lack of formal education Psychosocial stress Low HAQ scores |
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What physical factors increase morb and mort for RA? (5)
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Extra-articular manifestations
Elevated CRP and ESR High titers of RF/CC-P Erosions on x-ray Duration of disease |
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What are the goals of RA therapy? (5)
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Control disease activity
Alleviate pain Maintain function for essential daily activities Maximize quality of life Slow progression/rate of joint damage |
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What's the difference in COX2 inhibs versus COX1? (4)
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Somewhat improved GI tolerability
Reduced effects on renal blood flow (?) No effect on platelet function Increase in CV events |
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What are the pros for NSAID therapy in RA?
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Effective control of inflamm and pain = improves mobility, flexibility, range of motion, quality of life
Low-cost |
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What are the cons for NSAID therapy in RA?
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Doesn't affect disease progres.
GI toxicity common Renal complications (eg, irreversible renal insufficiency, papillary necrosis may occur) Hepatic dysfunction CNS toxicity with high dose (salicylates) |
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What are the pros for Corticosteroid therapy in RA?
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Anti-inflammatory and immunosuppressive effects
Can be used to bridge gap between initiation of DMARD therapy and onset of action Intra-articluar injections can be used for individual joint flares |
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What are the cons for Corticosteroid therapy in RA?
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Does not conclusively affect disease progression
Tapering and discontinuation of use often unsuccessful Low doses = skin thinning, ecchymoses, and Cushingoid appearance Significant cause of steroid-induced osteopenia |
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Name the DMARDs (8)
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Azathioprine
Cyclosporin Gold Hydroxychloroquine Leflunomide Methotrexate D-Penicillamine Sulfasalazine |
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What are the advantages of DMARDs in RA tx?
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Slow disease progression
Improve functional disability Decrease pain Interfere with inflam processes Retard develop of joint erosions |
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What's the time needed for Azathioprine to benefit RA? What are it's toxicities?
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2-3 months
Moderate risk: myelosuppression, hepatotoxicity, lymphoproliferative |
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What's the time needed for Gold, oral to benefit RA? What are it's toxicities?
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4-6 months
Low risk of: Myelosuppression, rash, proteinuria, gastrointestinal |
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What's the time needed for Gold, parenteral to benefit RA? What are it's toxicities?
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3-6 months
Moderate risk of Myelosuppression, rash, proteinuria |
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What's the time needed for Hydroxychloroquine to benefit RA? What are it's toxicities?
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2-4 months
low/high risk of macular damage |
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What's the time needed for Leflunomide to benefit RA? What are it's toxicities?
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4-8 weeks
Low risk of hepatotox, gi |
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What's the time needed for Methotrexate to benefit RA? What are it's toxicities?
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1-3 months
Moderate risk of hepatotox, pulmonary, myelosuppression |
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What's the time needed for D-Penicillamine to benefit RA? What are it's toxicities?
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3-6 months
High risk of myelosuppression and proteinuria |
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What's the time needed for Sulfasalazine to benefit RA? What are it's toxicities?
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1-3 months
Low risk of myelosuppression and GI |
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What are the pros of Methotrexate as a primary RA drug?
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Long-term clinical experience
Favorable rate of continuation of therapy (50% - 3 yrs) Proven efficacy in moderate to severe RA |
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What are the cons of Methotrexate as a primary RA drug?
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Laboratory monitoring every 4-8 weeks
Toxicities: hepatotoxicity, myelosuppression, pulmonary (pneumonitis) |
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What are the pros of Sulfasalazine as a primary RA drug?
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Clinical effectiveness demonstrated in short-term use
Mild level of toxicity COX and Lipoxygenase inhibitor |
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What are the cons of Sulfasalazine as a primary RA drug?
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Contraindicated in patients with sulfa intolerance or G6PD deficiency
Rate of AEs dose-dependent CBC every 2-4 weeks for 3 months, then every 12 weeks |
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What's methotrexate's mechanism of action?
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Blocks dihydrofolate reductase thus inhibiting many carbon transfer reactions. Blocks thymidylate synthase. May be selective at lower doses
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What are the pros of Azathioprine as a primary RA drug?
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Effective in refractory RA
Metabolized to 6-mercaptopurine |
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What are the cons of Azathioprine as a primary RA drug?
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High risk for severe leukopenia and/or thrombocytopenia
Other toxicities: hepatotoxicity, may increase cancer risk, high risk for opportunistic infections, macrocytic anemia, severe bone marrow depression, GI Requires monitoring every 1-2 weeks with dosage change, every 1-3 months thereafter; myelosupression increased with ACE -I or Allopurinol |
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What are the pros of Gold Auranofin as a primary RA drug?
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Effective in refractory RA
Only gold preparation for oral use Accumulates in synovium Blocks phagocytosis |
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What are the cons of Gold Auranofin as a primary RA drug?
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Requires long course to determine effectiveness (6 mo.)
Toxicities: skin lesions, stomatitis, oral ulcerations, glomerulonephritis, nephrosis, thrombocytopenia, agranulocytosis Requires close monitoring for side effects, contraindicated in hepatic or renal disease, should not be combined with other immunosuppressants; caution with X-rays. |
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Mechanism of action for Azathioprine?
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Immunosuppressant; purine synthesis inhibitor. Prevents leukocyte proliferation.
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What are the pros of Leflunomide as a primary RA drug?
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Early onset (~ 4 weeks)
Stabilized benefit for long-term use Selectively targets autoimmune lymphocytes to reduce untoward AEs |
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What are the cons of Leflunomide as a primary RA drug?
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Lack of clinical experience
Toxicities: hepatotoxicity, GI A new agent that we know less about Expensive |
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Leflunomide mechanism of action?
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Leflunomide inhibits de novo pyrimidine biosynthesis through the inhibition of the enzyme dihydroorotate dehydrogenase. It also has effects on stimulated T cells
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Name 3 TNFalpha blockers
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Etanercept (Enbrel)
Infliximab (Remicade) Adalimumab (Humira) |
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Name a IL1 blocker
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anakinra (Kineret)
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Name a CD20 antibody.
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rituximab (Rituxan)
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What's Etanercept (structurally)?
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A dimeric fusion protein of the extracellular ligand-binding portion of the TNFR linked to the Fc portion of human IgG1
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Etanercept mechanism of action?
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Binds to TNF and prevents its interaction with the TNF receptor
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Etanercept clinical uses?
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RA: inhibs structural damage and improves physical function for mod-severe RA. Can be combo'd with methotrexate.
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Etanercept side effects?
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Serious and sometimes fatal infections due opportunistic pathogens
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Etanercept contraindications?
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Avoid in diabetics and anyone prone to infection
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Etanercept adverse reactions?
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Most common is injection site reactions (erythema/itching) and infection. May increase malignancies.
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What's Infliximab?
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Chimeric, mouse/human IgG1 monoclonal antibody that binds to TNFα with high affinity and specificity
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Infliximab mechanism of action?
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neutralizes the biological activity of TNFα by binding with high affinity to the soluble and transmembrane forms of TNFα
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Infliximab clinical use?
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in combo with methotrexate for RA.
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Issues with the use of Infliximab?
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Can't be used long-term due to antichimeric antibody development
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What's Adalimumab?
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recombinant human IgG1 monoclonal antibody specific for human TNF
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Adalimumab mechanism of action?
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binds specifically to TNFα and blocks its interaction with the p55 and p75 cell surface receptors
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Adalimumab use?
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RA combo'd with methotrexate
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What's cool about combination regimens of DMARD in RA tx?
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Doesn't increase toxicities
More favorable longterm outcome Superior efficiency to single tx |
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Name 4 possible DMARD combos used to tx RA?
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1. Methotrexate/sulfasalazine/
hydroxychloroquine 2. Cyclosporine/methotrexate 3. Leflunomide/methotrexate 4. Anti-TNF agent/methotrexate |
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When are biologics indicated in the tx of RA?
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when DMARDs are not successful
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