Disease Modifying Anti-rheumatic Drugs Flashcards
What drugs are first choice for RA tx?
NSAIDs- rapid onset and efficacy
- provides anti-inflammation and pain relief but does not alter disease progression
What drug can be given for pain relief in addition to an NSAID for RA treatment?
acetaminophen
What drug complexes with NF-kB and AP-1 transcription factors causing indirect immunosuppression?
glucocorticoids (prednisone)
What can create RA and relieve pain an inflammation while waiting for DMARD effects?
glucocorticoids
- treated RA flares and other autoimmune diseases
- Lymphocytopenia
- Monocytopenia due to redistribution
- neutrophilia
- eosinophila
- PLA2 blockade (decreases eicosanoid synthesis)
Glucocorticoids
What can happen if glucocorticoids are stopped abruptly?
Death
How long should glucocorticoids be used?
less than 6 months
- glucocorticoids should not be used chronically because of adverse side effects
-cept indicates..
fusion of a receptor to the Fc part of human IgG1
-mab indicates…
a monoclonal antibody
-ximab indicates…
indicates a chimeric mAb
zumab indicates..
a humanized mAb
-umab indicates…
indicates a human mAb origin
What DMARD is an inhibitor of dihydrofolate reductase and can cause a thymineless death with loss of TH4 when used as an antiproliferative to treat cancer?
Methotrexate
What DMARD undergoes polyglutamation and accumulates in cells over multiple weeks and thymidylate synthase and AICAR transformylase?
Methotrexate
Methotrexate causes AICAR accumulation leading to adenosine efflux to exert what effects?
anti-inflammatory (reduced B and T cell activity)
What DMARD is effective in 80% of patients and is faster than other DMARDs yielding effects evident in 3-6 weeks?
Methotrexate
What drug is a first choice for RA due to its relative safety, low cost, and extensive use?
Methotrexate
How often is methotrexate administered and how?
RA treatment administered once per week wither oral or injected
Weekly folate supplements should be taken with what drug?
methotrexate - low doses are used for immunosupressin and well-tolerated
What are methotrexate toxicities?
- bone marrow suppression
- hepatic fibrosis
- GI ulceration
- pneumonitis
- fetal death
What DMARD is a lipophilic weak base that can easily go through plasma membranes and accumulate in lysosomes to raise the pH of the lysosomes?
Hydroxychloroquine
What RA drug can safely be used in pregnancies?
Hydroxychloroquine — also used to treat malaria
What DMARD can cause retinal damage?
hydroxychloroquine — low doses carry little risk
What drug can be used to treat ra alone or in combo with hydroxycholorquine and/or methotrexate as a triple therapy?
Sulfasalazine
Can sulfasalazine be used in pregnancy?
seems okay but less studied
What is the most common reason sulfasalazine is discontinued?
GI side effects- N/V, diarrhea, abdominal pain
What drug can cause pruritus, rash and urticaria?
Sulfasalazine- sulfa drug run!
@Lauren
What RA drug inhibits mitochondrial enzyme dihydroorotate dehydrogenase to block the synthesis of rUMP?
Lefunomide
What are the effects of leflunomide?
inhibition of T cell proliferation
- also blocks leukocyte adhesion and NF-kB activation
What drug is a second choice that would be used alternatively to methotrexate?
Leflunomide
- can also be used in combo with methotrexate, sulfasalazine or hydroxyquine
What biologic DMARDs can be combined?
NONE!
When are TNF antagonists indicated?
- moderate to severe rheumatoid arthritis, given after traditional DMARDs have proven to be ineffective
- often used in combination with methotrexate
What RA drug class poses a serious risk of developing serious infections and severe allergic reactions?
TNF antagonists!
- bacterial sepsis, invasive fungal infections, hep B, TB
-
What is Etanercept?
TNF inhibitor that is a fusion protein administered once or twice weekly subQ
What is Infliximab?
chimeric mAB against TNF that is administered intravenously every 6 weeks
What is Adalimumab?
recombinant fully human anti-TNF mAb administer subQ every 2 weeks
What is rituximab?
RA tx that targets CD20 on B lymphocytes
What RA tx causes profound B cell lymphocytopenia but maintains Ig Levels?
Rituximab- targets CD20 that isn’t found on plasma cells so Ig is good
What will indicate a greater likelihood of responsiveness for Rituximab?
positive test for rheumatoid factor or anti-cyclic citrullinated peptide predicts greater responsiveness
How is rituximab administered?
by IV every 6 months
What can cause infusion related hypersensitivity?
Rituximab
- also can cause SJS, Hep B reactivation, and PML
What drug for moderate to severe rheumatoid arthritis prevents CD28 from binding to counter- receptor CD80/CD86?
Abatacept
hey bata bata bata ‘cept you!
fusion protein compromising CTLA-4 and Fc portion of IgG1
-used after TNG antagonist have failed and can be used in combo with non biological DMARDs
What does tocilizumab do?
Humanized anti human IL-6 receptor Ab
- competes for membrane bound and soluble forms of human IL-6 receptor
What drug blocks IL-6 binding to its receptor and prevents JAK3 kinase signaling
and also limits hepatic acute phase response activation of T cells, B cells, macrophages and osteoclasts
Tocilizumab
That ‘cili’ JAK!!!
What RA drug can cause URI, and make the patient susceptible to life threatening reactions?
Tocilizumab?
What is tofacitinib?
JAK 3 antagonist
- directly surpasses the production of IL-17 and IFN-gamma, and proliferation of IL17 cells
How is tofacitinib administered?
orally- unusual for DMARDS
What are warnings of tofacitinib?
Increased risk of malignancies and serious infections
What RA drug is a recombinant non-glycosylated version of human IL-1 receptor antagonist?
Anakinra
What does anakinra do?
Blocks the pro inflammatory activity of naturally occurring IL-1 on many cells including synovitis and cartilage degradation
- use when no good rheumatoid arthritis response to non-biologic DMARS, considered less efficacious
What are toxicities of anakinra?
- increased risk of infection
- Hypersensitivity Rxn
What are the misc. drugs for pain and inflammation in RA?
- NSAIDs
- Acetaminophen
- Glucocorticoids
Treat the NAGging pain
Methotrexate hydroxychoroquine sulfasalazine leflunomide are what type of rheumatoid arthritis drugs?
Traditional non biologic disease modifying anti rheumatoid drugs (DMARDS)
Etanercept
adalimumab
infliximab
are what type of RA drugs?
Biologic DMARDs- TNF alpha blockers
Rituxumab is what type of RA drug?
Biologic DMARD- B cell depletes (CD20 mAb)
Abatacept is what kind of RA drug?
Biological DMARD- T cell activation inhibitor
Tocilizumab is what kind of RA drug?
Biological DMARD IL-6 receptor mAb
What RA drug is Tofacitinib?
Biological DMARD: Jak-3 inhibitor
What kind of drug is anakinra?
Biological DMARD: Recombinant IL-1 antagonist