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Papulosquamous Diseases
Published in Ayşe Serap Karadağ, Lawrence Charles Parish, Jordan V. Wang, Roxburgh's Common Skin Diseases, 2022
Melek Aslan Kayıran, Jordan V. Wang, Ayşe Serap Karadağ
Methotrexate works by inhibiting DNA synthesis through affecting dihydrofolate reductase. It reduces keratinocyte proliferation and has anti-inflammatory and immunomodulatory effects. Generally, 7.5–25 mg/week is sufficient for psoriasis treatment. It is helpful in PV, pustular, erythrodermic, and arthropathic psoriasis and affects nail findings. Patients should be given 1 mg/day of folate supplementation 48–72 hours after taking the medication to reduce gastrointestinal side effects. Before treatment, hepatitis markers, blood count, liver and kidney function tests, chest radiography, and complete urinalysis can be examined. Testing can be performed regularly for monitoring.
Mechanisms of Antibiotic Resistance in Acinetobacter spp. — Genetics of Resistance
Published in E. Bergogne-Bénézin, M.L. Joly-Guillou, K.J. Towner, Acinetobacter, 2020
Trimethoprim acts by competitive inhibition of the bacterial enzyme dihydrofolate reductase (DHFR), which is required for the reduction of dihydrofolate to the essential cofactor tetrahydrofolate. High- level trimethoprim resistance (MIC of >1000 mg/L) in Gram-negative bacteria is mediated generally by the plasmid- or transposon-encoded synthesis of an additional insusceptible DHFR which enables the trimethoprim-sensitive host cell enzyme to be bypassed (Amyes and Towner, 1990). A range of plasmid-encoded DHFRs have been distinguished by their biochemical and molecular characteristics (Amyes et al., 1992), and sequence determination of the respective genes has enabled gene and oligonucleotide probes to be developed (e.g., Amyes and Towner, 1990; Young and Hillyear, 1994). These have been used to determine the prevalence of various trimethoprim resistance genes in clinical isolates (e.g., Heikkila et al., 1990; Towner et al., 1990; Young and Hillyear, 1994).
Other Immunosuppressive Agents in Vitiligo
Published in Vineet Relhan, Vijay Kumar Garg, Sneha Ghunawat, Khushbu Mahajan, Comprehensive Textbook on Vitiligo, 2020
Methotrexate is an antimetabolite, antifolate immunosuppressant drug which acts by inhibiting conversion of dihydrofolate to tetrahydrofolate by binding to dihydrofolate reductase enzyme. Methotrexate possibly suppresses tumor necrosis factor-alpha (TNF-α) production by suppressing T cells. It has been used in autoimmune disorders, cancers, psoriasis, and psoriatic arthritis, in addition to other dermatologic conditions such as vasculitis, mycosis fungoides, and immunobullous and proliferative disorders. There are a few conflicting reports of its use in vitiligo.
IgG antibodies mediated gold nanoparticles conjugated to methotrexate as targeted chemotherapy for lung cancer
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2023
Asad Syed, Abu Baker, Mohamed Mohany, Abdallah M. Elgorban, Mohd Sajid Khan, Salim S. Al-Rejaie
Due to their maximum internalisation, the best-suited NPs against cancer range from 20-50 nm. The as-synthesised anionic MTX-IgGAuNPs were found to internalise via caveolae-mediated endocytosis, followed the trajectory with microtubules, and penetrated the ER. Eventually, they got entry into the cytoplasm, and via the nuclear pore complex, they entered the nucleus without fusing with lysosomes. This trajectory prevents drugs from degrading and allows them to arrive in other organelles. Furthermore, MTX-IgGAuNPs also follow Clathrin-caveolae-independent, Arf6-dependent, Cdc42-dependent, and Rhoa-dependent pathways of endocytosis [35]. Therefore, poorly soluble and bioavailable methotrexate was delivered into the nucleus unaltered, unmodified, and non-degraded, where it inhibited dihydrofolate reductase and halted the propagation of cancer cells. The methotrexate-treated patients also experienced resistance. The MTX-IgGAuNPs internalised through the Clathrin-caveolae independent pathway were found to remain in the cytoplasm and initiate the Cyt-c mediated intrinsic apoptotic pathway by disturbing mitochondrial membrane potential. Though MTX-IgGAuNPs were found to be non-toxic against NRK cells.
Methotrexate concentrations and associated variability factors in high dose therapy of children with acute lymphoblastic leukemia and non-Hodgkin lymphoma
Published in Pediatric Hematology and Oncology, 2023
Biljana Škorić, Miloš Kuzmanović, Marija Jovanović, Branislava Miljković, Dragan Micić, Milena Jović, Ankica Jovanović, Katarina Vučićević
Methotrexate (MTX) is an antifolate derivative used in several indications in pediatric and adult populations.1 It acts as an inhibitor of enzymes involved in the folate pathway, primarily dihydrofolate reductase.2 Depending on the indication and patient population, it is used in low, intermediate and high doses.1,3 High dose of methotrexate (HDMTX) usually represents administration of 1 or more g/m2 intravenous infusion that usually lasts from 6 to 24 h.1 Introduction of HDMTX in pediatric oncology significantly improved the treatment outcomes.3 It is commonly used for the therapy of acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), osteosarcoma and brain tumors in children.4 However, due to significant variability in pharmacokinetic exposure, and the risk of toxicity in high dose treatments, strict monitoring of clinical symptoms, laboratory markers and MTX concentration is required.5,6
Shedding light on key pharmacological knowledge and strategies for pediatric atopic dermatitis
Published in Expert Review of Clinical Pharmacology, 2023
Ariana Moreno, Yael Renert-Yuval, Emma Guttman-Yassky
Methotrexate is a dihydrofolate reductase inhibitor that diminishes cell proliferation. A retrospective study on 31 pediatric AD patients treated with methotrexate reported 75% of patients had reduction in SOCRAD scores, with the first signs of clinical improvement seen by week 12 of treatment [139]. A retrospective chart review of 55 pediatric AD patients treated with methotrexate reported 76% of patients demonstrated disease improvement, measured by improvement in IGA scores [140]. The most common adverse effects associated with methotrexate are GI symptoms including nausea and elevation of liver enzymes, with 14% of patients suffering from both nausea and non-clinically significant increases in liver enzymes [139,140]. Approximately 83% of pediatric patients reported at least one adverse side effect, with the most frequent being abnormal laboratory findings including transient hematologic abnormalities, elevated transaminases, and hyperbilirubinemia [141]. Approximately 17% of patients also reported fatigue, and 29% reported some type of GI side effect [141].