Module 4 Dmards: Flashcards
What is the primary benefit of conventional Disease-Modifying Antirheumatic Drugs (DMARDs) in the management of RA?
The primary benefit of conventional DMARDs in managing RA is immunosuppression, which slows disease progression by suppressing the immune response and associated inflammation.
Why do clinical responses to conventional DMARDs develop slowly in RA patients?
Clinical responses to conventional DMARDs in RA patients develop slowly because these drugs work by suppressing the immune response and inflammation, which takes time to manifest as symptom improvement.
How do the costs of conventional DMARDs compare to biologic and targeted DMARDs?
Conventional DMARDs are generally less expensive than biologic and targeted DMARDs because they are easier to manufacture.
Why do many rheumatologists consider methotrexate the first-choice DMARD for RA?
Methotrexate is considered the first-choice DMARD for RA due to its efficacy, relative safety, low cost, and extensive use. Approximately 80% of patients experience improvement with this drug.
How quickly does methotrexate typically act compared to other DMARDs in RA treatment?
Methotrexate acts faster than all other DMARDs in RA treatment, with therapeutic effects often developing in 3 to 6 weeks.
What is the mechanism of action of methotrexate in RA treatment, and how does it relate to its role in cancer treatment?
Methotrexate is a folate antagonist, inhibiting DNA synthesis and cellular replication by reducing folate levels. While this explains its mechanism of action in cancer treatment, the exact mechanism in RA is not fully understood. It is believed to involve immunosuppression by reducing the activity of B and T lymphocytes.
Besides RA, for what other medical conditions is methotrexate approved?
Methotrexate is approved for the management of severe psoriasis when other treatments have failed. It is also approved under the brand name Xatmep for the treatment of some cases of acute lymphoblastic leukemia and the management of polyarticular juvenile idiopathic arthritis in pediatric patients who do not respond adequately to other therapy.
What are the major toxicities associated with methotrexate use?
The major toxicities of methotrexate include hepatic fibrosis, bone marrow suppression, GI ulceration, and pneumonitis.
How can GI and hepatic toxicity be reduced in methotrexate treatment, and what is the recommended folic acid supplementation dosage?
To reduce GI and hepatic toxicity in methotrexate treatment, supplementing dosing with folic acid is recommended. A minimum of 5 mg per week of folic acid is typically advised. Folic acid supplementation is passive and does not compete with methotrexate.
What medical tests are mandatory for patients taking methotrexate, and why are they necessary?
Patients taking methotrexate should undergo periodic tests of liver and kidney function, as well as complete blood cell and platelet counts. These tests are mandatory to monitor for potential toxicities and ensure patient safety.
Is methotrexate safe to use during pregnancy, and why or why not?
Methotrexate is contraindicated during pregnancy because it can cause fetal death and congenital abnormalities.
What recent data suggest about the long-term use of methotrexate in RA patients?
Recent data suggest that long-term use of methotrexate in RA patients may be associated with a reduced life expectancy due to increased deaths from cardiovascular disease, infection, and certain cancers such as melanoma, lung cancer, and non-Hodgkin lymphoma.
What are the considerations or concerns regarding children and adolescents taking TNF inhibitors as biologic DMARDs?
Children and adolescents taking TNF inhibitors as biologic DMARDs have developed lymphoma and other malignancies, which is a significant concern.
What considerations are there for pregnant women taking conventional DMARDs in terms of teratogenicity and fetal risk?
Azathioprine is teratogenic.
Both leflunomide and methotrexate can cause fetal death and congenital abnormalities.
Hydroxychloroquine, once suspected of causing fetal ocular toxicity, does not appear to do so. Research is ongoing.
In some conditions like maternal lupus or malaria, hydroxychloroquine may decrease fetal risk associated with these conditions.
Sulfasalazine inhibits the absorption and metabolism of folic acid, increasing the risk for neural tube defects.
What concerns are associated with biologic DMARDs and pregnancy, and what do we know about their effects so far?
Research on biologic DMARDs in pregnancy is limited.
Rituximab use may result in B-cell lymphocytopenia lasting up to 6 months.
Agranulocytosis has occurred in neonates born to women taking infliximab.
Animal reproduction studies have shown abnormalities for tocilizumab but not for etanercept or golimumab.
Pregnancy registry data for adalimumab have not identified adverse outcomes, but the number of subjects has been small (74 patients with RA taking adalimumab and 80 patients with RA not taking adalimumab).
Why is breastfeeding not recommended for mothers taking DMARDs?
Breastfeeding is not recommended for mothers taking DMARDs due to potential risks to the infant.
What is the specific concern for older adults taking DMARDs?
Older adults taking DMARDs may be at a greater risk for infection secondary to the immunosuppressive effects of these drugs.
What is the increased risk associated with methotrexate when taken with other drugs that contribute to liver injury, including alcohol?
Methotrexate increases the risk for hepatotoxicity when taken with other drugs that contribute to liver injury, such as alcohol.
What significant risk does methotrexate pose when prescribed for patients taking other drugs that can decrease bone marrow function?
Methotrexate greatly increases the risk for serious myelosuppression (bone marrow suppression) when prescribed for patients taking other drugs that can decrease bone marrow function.
How does methotrexate affect the response to vaccines, and what are the recommendations regarding live and inactivated vaccines for patients taking methotrexate?
Methotrexate reduces the response to vaccines, decreasing their efficacy. Live vaccines are contraindicated for patients taking methotrexate. If inactivated (killed) vaccines are necessary for patients receiving methotrexate, they should be revaccinated within 3 months after therapy is discontinued. Ideally, vaccines needed should be administered before starting methotrexate. The ACR recommends that patients receive vaccines for communicable diseases such as pneumonia, influenza, hepatitis B, HPV, and herpes zoster before beginning DMARD therapy.
What is Leflunomide (Arava)?
Leflunomide is a medication used as an immunosuppressant for adults with active Rheumatoid Arthritis (RA).
What is the primary indication for Leflunomide?
Leflunomide is indicated for adults with active Rheumatoid Arthritis (RA).
What is the impact of Leflunomide in clinical trials for RA?
In clinical trials, Leflunomide has been shown to decrease the signs and symptoms of RA and slow down disease progression.
How does the effectiveness of Leflunomide compare to Methotrexate for RA treatment?
Leflunomide is about equally effective as Methotrexate, but it is potentially more hazardous and expensive.
When is Leflunomide typically reserved for use in RA treatment?
Leflunomide is often reserved for second-line use in RA treatment.
What is the mechanism of action of Leflunomide in the body?
Leflunomide is a prodrug that converts to its active form, metabolite 1 (M1), in the body. M1 inhibits dihydro-orotate dehydrogenase, a mitochondrial enzyme required for de novo synthesis of pyrimidines, which are needed for T-cell proliferation and antibody production.
How does Leflunomide affect T-cell proliferation in vitro?
Leflunomide inhibits T-cell proliferation in vitro.
