DMARDS Flashcards
Q: What are DMARDs, and what are the two main types?
A: Disease-modifying anti-rheumatic drugs (DMARDs) are medications used to modify or slow down the progression of rheumatoid arthritis. They come in two types: biologic DMARDs, developed from microorganisms, animals, or humans, and non-biologic DMARDs, chemically synthesized in laboratories.
Q: Briefly describe the physiology related to DNA synthesis during the S phase of the cell cycle.
A: DNA replication involves deoxyribonucleotides, composed of a phosphate group, a five-carbon sugar like deoxyribose, and a nucleobase (pyrimidine like cytosine or thymidine, or purine like adenine or guanine). Pyrimidine synthesis begins with folic acid converted to dihydrofolate (DHF), then DHFR turns DHF into tetrahydrofolate (THF). THF accepts a methyl group from serine, becoming 5,10-methyl-THF, transferred by thymidylate synthetase to dUMP, forming dTMP (deoxythymidine monophosphate), eventually leading to thymine for DNA synthesis. Purine synthesis starts with glutamine, aspartate, glycine, bicarbonate, and formate, resulting in inosine monophosphate (IMP), a precursor to adenine and guanine for DNA synthesis.
This explanation provides insights into DNA synthesis during the cell cycle’s S phase, demonstrating the intricate pathways involved in producing nucleotides crucial for DNA formation.
Q: What are DMARDs, and what are the two main types?
A: Disease-modifying anti-rheumatic drugs (DMARDs) are medications used to modify or slow down the progression of rheumatoid arthritis. They come in two types: biologic DMARDs, developed from microorganisms, animals, or humans, and non-biologic DMARDs, chemically synthesized in laboratories.
Q: Briefly describe the physiology related to DNA synthesis during the S phase of the cell cycle.
A: DNA replication involves deoxyribonucleotides, composed of a phosphate group, a five-carbon sugar like deoxyribose, and a nucleobase (pyrimidine like cytosine or thymidine, or purine like adenine or guanine). Pyrimidine synthesis begins with folic acid converted to dihydrofolate (DHF), then DHFR turns DHF into tetrahydrofolate (THF). THF accepts a methyl group from serine, becoming 5,10-methyl-THF, transferred by thymidylate synthetase to dUMP, forming dTMP (deoxythymidine monophosphate), eventually leading to thymine for DNA synthesis. Purine synthesis starts with glutamine, aspartate, glycine, bicarbonate, and formate, resulting in inosine monophosphate (IMP), a precursor to adenine and guanine for DNA synthesis.
This explanation provides insights into DNA synthesis during the cell cycle’s S phase, demonstrating the intricate pathways involved in producing nucleotides crucial for DNA formation.
Q: What is rheumatoid arthritis (RA) and what does it primarily affect?
A: Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory disorder primarily affecting synovial joints. It can also impact other body parts like the skin and lungs. While considered an autoimmune reaction, the exact cause remains unknown. It’s associated with environmental risk factors such as infections and smoking, along with a genetic predisposition, including alleles HLA-DR1 and HLA–DR4.
Q: Describe the immune system’s involvement and the role of cytokines in rheumatoid arthritis.
A: In RA, immune cells like T-cells and macrophages infiltrate the joint space, releasing inflammatory cytokines such as tumor necrosis factor (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). These cytokines stimulate synovial cell proliferation, forming a thickened synovial membrane called a pannus. The pannus, comprising fibroblasts, myofibroblasts, and inflammatory cells, releases more cytokines that eventually degrade articular cartilage, leading to bone erosion over time.
This overview provides insights into the pathophysiology of RA, highlighting its autoimmune nature, the involvement of immune cells, and the role of cytokines in joint inflammation and damage.
Q: What is rheumatoid arthritis (RA) and what does it primarily affect?
A: Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory disorder primarily affecting synovial joints. It can also impact other body parts like the skin and lungs. While considered an autoimmune reaction, the exact cause remains unknown. It’s associated with environmental risk factors such as infections and smoking, along with a genetic predisposition, including alleles HLA-DR1 and HLA–DR4.
Q: Describe the immune system’s involvement and the role of cytokines in rheumatoid arthritis.
A: In RA, immune cells like T-cells and macrophages infiltrate the joint space, releasing inflammatory cytokines such as tumor necrosis factor (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). These cytokines stimulate synovial cell proliferation, forming a thickened synovial membrane called a pannus. The pannus, comprising fibroblasts, myofibroblasts, and inflammatory cells, releases more cytokines that eventually degrade articular cartilage, leading to bone erosion over time.
This overview provides insights into the pathophysiology of RA, highlighting its autoimmune nature, the involvement of immune cells, and the role of cytokines in joint inflammation and damage.
Q: How can the progression of joint damage in rheumatoid arthritis be slowed down, and what are some non-biologic DMARDs used for this purpose?
A: Non-biologic DMARDs like methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine are employed to slow down the progression of joint damage in rheumatoid arthritis. These medications can also be used for other conditions such as inflammatory bowel disease (IBD) and certain cancers like leukemia.
Q: Explain the mechanism of action of methotrexate in treating rheumatoid arthritis.
A: Methotrexate, a folic acid analog, inhibits nucleotide synthesis. It exhibits higher affinity for DHFR (dihydrofolate reductase) than DHF (dihydrofolate), irreversibly inhibiting the enzyme, leading to decreased levels of THF (tetrahydrofolate). Reduced THF limits thymidylate production and inhibits an enzyme involved in purine synthesis, consequently decreasing DNA synthesis. This impedes cell cycle progression to the S phase, affecting rapidly dividing cells, including immune cells, thereby reducing joint inflammation and injury in rheumatoid arthritis.
This explanation delves into the specific actions of methotrexate, elucidating how it targets nucleotide synthesis to alleviate joint inflammation in rheumatoid arthritis.
Q: How can the progression of joint damage in rheumatoid arthritis be slowed down, and what are some non-biologic DMARDs used for this purpose?
A: Non-biologic DMARDs like methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine are employed to slow down the progression of joint damage in rheumatoid arthritis. These medications can also be used for other conditions such as inflammatory bowel disease (IBD) and certain cancers like leukemia.
Q: Explain the mechanism of action of methotrexate in treating rheumatoid arthritis.
A: Methotrexate, a folic acid analog, inhibits nucleotide synthesis. It exhibits higher affinity for DHFR (dihydrofolate reductase) than DHF (dihydrofolate), irreversibly inhibiting the enzyme, leading to decreased levels of THF (tetrahydrofolate). Reduced THF limits thymidylate production and inhibits an enzyme involved in purine synthesis, consequently decreasing DNA synthesis. This impedes cell cycle progression to the S phase, affecting rapidly dividing cells, including immune cells, thereby reducing joint inflammation and injury in rheumatoid arthritis.
This explanation delves into the specific actions of methotrexate, elucidating how it targets nucleotide synthesis to alleviate joint inflammation in rheumatoid arthritis.
Q: What major side effects are associated with methotrexate usage?
A: Methotrexate’s major side effects include bone marrow suppression, leading to low white blood cell (leukopenia), red blood cell (anemia), and platelet (thrombocytopenia) counts. It causes megaloblastic anemia, producing large, immature red blood cells due to impaired DNA synthesis. Rapidly dividing cells, including those in the gastrointestinal tract, are affected, resulting in oral ulcers, gum bleeding, peptic ulcers, and hemorrhagic enteritis. It also leads to alopecia due to the impact on hair cells. Additionally, methotrexate induces liver toxicity (hepatotoxicity) with manifestations of macrovesicular fatty change and pulmonary toxicity seen as pulmonary fibrosis.
Q: What is the teratogenic effect of methotrexate, and why is it contraindicated during pregnancy?
A: Methotrexate is teratogenic, meaning its use during pregnancy can result in neural tube defects and congenital heart defects, categorizing it as category X for pregnancy contraindication. It’s used to terminate unruptured ectopic pregnancies where continuation poses a hazard to the mother, leveraging its teratogenic properties.
This overview illustrates the spectrum of side effects associated with methotrexate usage, highlighting its impact on various body systems and its contraindication during pregnancy due to teratogenicity.
Q: What major side effects are associated with methotrexate usage?
A: Methotrexate’s major side effects include bone marrow suppression, leading to low white blood cell (leukopenia), red blood cell (anemia), and platelet (thrombocytopenia) counts. It causes megaloblastic anemia, producing large, immature red blood cells due to impaired DNA synthesis. Rapidly dividing cells, including those in the gastrointestinal tract, are affected, resulting in oral ulcers, gum bleeding, peptic ulcers, and hemorrhagic enteritis. It also leads to alopecia due to the impact on hair cells. Additionally, methotrexate induces liver toxicity (hepatotoxicity) with manifestations of macrovesicular fatty change and pulmonary toxicity seen as pulmonary fibrosis.
Q: What is the teratogenic effect of methotrexate, and why is it contraindicated during pregnancy?
A: Methotrexate is teratogenic, meaning its use during pregnancy can result in neural tube defects and congenital heart defects, categorizing it as category X for pregnancy contraindication. It’s used to terminate unruptured ectopic pregnancies where continuation poses a hazard to the mother, leveraging its teratogenic properties.
This overview illustrates the spectrum of side effects associated with methotrexate usage, highlighting its impact on various body systems and its contraindication during pregnancy due to teratogenicity.
Q: How can the incidence of methotrexate’s side effects be reduced, and what role does folic acid supplementation play?
A: Folic acid supplementation can decrease the occurrence of methotrexate’s side effects without compromising its efficacy. High concentrations of folic acid can displace methotrexate from the active site of DHFR, restoring nucleotide synthesis. Folinic acid or leucovorin, an antidote, can be used for immediate action in “leucovorin rescue” to reverse bone marrow suppression caused by methotrexate. Leucovorin, as a reduced form of folic acid, doesn’t require DHFR activation; it readily converts into 5,10-methyl-THF within the cell, aiding nucleotide synthesis.
Q: Explain the concept of “leucovorin rescue” and its role in mitigating the effects of methotrexate.
A: “Leucovorin rescue” involves using folinic acid or leucovorin as an antidote to counteract bone marrow suppression caused by methotrexate. Leucovorin, being a reduced form of folic acid, bypasses the need for DHFR activation. It directly converts into 5,10-methyl-THF inside the cell, facilitating nucleotide synthesis, thereby counteracting methotrexate’s effects more rapidly than folic acid supplementation.
These insights shed light on the role of folic acid supplementation and leucovorin rescue as strategies to minimize the side effects associated with methotrexate therapy, offering potential solutions to mitigate its impact on the body.
Q: How can the incidence of methotrexate’s side effects be reduced, and what role does folic acid supplementation play?
A: Folic acid supplementation can decrease the occurrence of methotrexate’s side effects without compromising its efficacy. High concentrations of folic acid can displace methotrexate from the active site of DHFR, restoring nucleotide synthesis. Folinic acid or leucovorin, an antidote, can be used for immediate action in “leucovorin rescue” to reverse bone marrow suppression caused by methotrexate. Leucovorin, as a reduced form of folic acid, doesn’t require DHFR activation; it readily converts into 5,10-methyl-THF within the cell, aiding nucleotide synthesis.
Q: Explain the concept of “leucovorin rescue” and its role in mitigating the effects of methotrexate.
A: “Leucovorin rescue” involves using folinic acid or leucovorin as an antidote to counteract bone marrow suppression caused by methotrexate. Leucovorin, being a reduced form of folic acid, bypasses the need for DHFR activation. It directly converts into 5,10-methyl-THF inside the cell, facilitating nucleotide synthesis, thereby counteracting methotrexate’s effects more rapidly than folic acid supplementation.
These insights shed light on the role of folic acid supplementation and leucovorin rescue as strategies to minimize the side effects associated with methotrexate therapy, offering potential solutions to mitigate its impact on the body.
Q: What is the mechanism of action of leflunomide in treating rheumatoid arthritis, and how does it impact T-cell proliferation?
A: Leflunomide, a prodrug metabolized to teriflunomide, inhibits the mitochondrial enzyme DHODH (dihydroorotate dehydrogenase) reversibly. DHODH inhibition in activated T-cells, crucial for pyrimidine synthesis necessary for DNA production, suppresses T-cell proliferation, thereby reducing joint damage in rheumatoid arthritis.
Q: What are the major side effects associated with leflunomide usage?
A: Leflunomide’s major side effects encompass bone marrow suppression and hepatotoxicity. Additionally, it may cause gastrointestinal disturbances (nausea, vomiting, diarrhea), peripheral neuropathy, and alopecia. Similar to methotrexate, leflunomide is teratogenic, necessitating avoidance during pregnancy. If pregnancy occurs during leflunomide use, immediate cessation is recommended, with cholestyramine used to eliminate residual leflunomide from the body.
These flashcards highlight leflunomide’s mechanism of action in inhibiting T-cell proliferation and outline its notable side effects and the precautions necessary, especially concerning pregnancy, emphasizing its teratogenic potential.
Q: What is the mechanism of action of leflunomide in treating rheumatoid arthritis, and how does it impact T-cell proliferation?
A: Leflunomide, a prodrug metabolized to teriflunomide, inhibits the mitochondrial enzyme DHODH (dihydroorotate dehydrogenase) reversibly. DHODH inhibition in activated T-cells, crucial for pyrimidine synthesis necessary for DNA production, suppresses T-cell proliferation, thereby reducing joint damage in rheumatoid arthritis.
Q: What are the major side effects associated with leflunomide usage?
A: Leflunomide’s major side effects encompass bone marrow suppression and hepatotoxicity. Additionally, it may cause gastrointestinal disturbances (nausea, vomiting, diarrhea), peripheral neuropathy, and alopecia. Similar to methotrexate, leflunomide is teratogenic, necessitating avoidance during pregnancy. If pregnancy occurs during leflunomide use, immediate cessation is recommended, with cholestyramine used to eliminate residual leflunomide from the body.
These flashcards highlight leflunomide’s mechanism of action in inhibiting T-cell proliferation and outline its notable side effects and the precautions necessary, especially concerning pregnancy, emphasizing its teratogenic potential.
Q: How does hydroxychloroquine impact the progression of rheumatoid arthritis, and what is believed to be its mechanism of action?
A: Hydroxychloroquine (HCQ) is believed to inhibit the release of inflammatory cytokines like TNF-α and IL-1 by macrophages. This inhibition potentially prevents synovial cell proliferation and pannus formation, thereby slowing down joint destruction in individuals with rheumatoid arthritis.
Q: What are the major side effects associated with long-term use of hydroxychloroquine?
A: Long-term use of hydroxychloroquine can lead to the accumulation of the medication in melanin-rich tissues like the skin and retina. This accumulation may result in skin hyperpigmentation and retinal damage (retinopathy). Other side effects include myopathy leading to muscle weakness, premature greying of hair, and gastrointestinal disturbances. Notably, hydroxychloroquine is considered safe to use during pregnancy.
These flashcards highlight the potential mechanism of hydroxychloroquine in managing rheumatoid arthritis while outlining its major side effects, especially the risks associated with long-term usage regarding skin, retina, and other bodily systems.
Q: How does hydroxychloroquine impact the progression of rheumatoid arthritis, and what is believed to be its mechanism of action?
A: Hydroxychloroquine (HCQ) is believed to inhibit the release of inflammatory cytokines like TNF-α and IL-1 by macrophages. This inhibition potentially prevents synovial cell proliferation and pannus formation, thereby slowing down joint destruction in individuals with rheumatoid arthritis.
Q: What are the major side effects associated with long-term use of hydroxychloroquine?
A: Long-term use of hydroxychloroquine can lead to the accumulation of the medication in melanin-rich tissues like the skin and retina. This accumulation may result in skin hyperpigmentation and retinal damage (retinopathy). Other side effects include myopathy leading to muscle weakness, premature greying of hair, and gastrointestinal disturbances. Notably, hydroxychloroquine is considered safe to use during pregnancy.
These flashcards highlight the potential mechanism of hydroxychloroquine in managing rheumatoid arthritis while outlining its major side effects, especially the risks associated with long-term usage regarding skin, retina, and other bodily systems.
Q: How does sulfasalazine impact the progression of rheumatoid arthritis, and what is its mechanism of action?
A: Sulfasalazine consists of sulfapyridine and 5-aminosalicylic acid linked through an azo bond. Once in the colon, gut flora break down the azo bond, releasing sulfapyridine into the bloodstream. Similar to hydroxychloroquine, sulfapyridine inhibits macrophages from releasing TNF-α, IL-1, and IL-6. This inhibition suppresses synovial cell proliferation and pannus formation in the joints of individuals with rheumatoid arthritis.
Q: What are the main side effects associated with sulfasalazine usage?
A: Side effects of sulfasalazine primarily include malaise, nausea, headache, skin rash, and gastrointestinal disturbances. Notably, oligospermia (low sperm count) can occur, but it typically reverses upon cessation of sulfasalazine use.
These flashcards highlight the mechanism of action of sulfasalazine in managing rheumatoid arthritis and outline its primary side effects, emphasizing its impact on inflammation and potential reproductive effects.
Q: How does sulfasalazine impact the progression of rheumatoid arthritis, and what is its mechanism of action?
A: Sulfasalazine consists of sulfapyridine and 5-aminosalicylic acid linked through an azo bond. Once in the colon, gut flora break down the azo bond, releasing sulfapyridine into the bloodstream. Similar to hydroxychloroquine, sulfapyridine inhibits macrophages from releasing TNF-α, IL-1, and IL-6. This inhibition suppresses synovial cell proliferation and pannus formation in the joints of individuals with rheumatoid arthritis.
Q: What are the main side effects associated with sulfasalazine usage?
A: Side effects of sulfasalazine primarily include malaise, nausea, headache, skin rash, and gastrointestinal disturbances. Notably, oligospermia (low sperm count) can occur, but it typically reverses upon cessation of sulfasalazine use.
These flashcards highlight the mechanism of action of sulfasalazine in managing rheumatoid arthritis and outline its primary side effects, emphasizing its impact on inflammation and potential reproductive effects.
Q: What are non-biologic DMARDs, and how do they function in managing rheumatoid arthritis?
A: Non-biologic DMARDs (Disease-Modifying Anti-Rheumatic Drugs) like methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine work by suppressing the immune response. This suppression helps reduce joint destruction in individuals with rheumatoid arthritis.
Q: What are some common side effects associated with non-biologic DMARDs?
A: Common side effects of non-biologic DMARDs include bone marrow suppression, gastrointestinal disturbances, and hepatotoxicity. Additionally, methotrexate, leflunomide, and sulfasalazine are contraindicated during pregnancy due to their teratogenic effects.
Q: What are non-biologic DMARDs, and how do they function in managing rheumatoid arthritis?
A: Non-biologic DMARDs (Disease-Modifying Anti-Rheumatic Drugs) like methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine work by suppressing the immune response. This suppression helps reduce joint destruction in individuals with rheumatoid arthritis.
Q: What are some common side effects associated with non-biologic DMARDs?
A: Common side effects of non-biologic DMARDs include bone marrow suppression, gastrointestinal disturbances, and hepatotoxicity. Additionally, methotrexate, leflunomide, and sulfasalazine are contraindicated during pregnancy due to their teratogenic effects.
