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Current Drug Metabolism 2019A folic-acid antagonist, methotrexate, is one of the most commonly prescribed drugs with its expanding use in clinical practice. The drug requires regular monitoring... (Review)
Review
BACKGROUND
A folic-acid antagonist, methotrexate, is one of the most commonly prescribed drugs with its expanding use in clinical practice. The drug requires regular monitoring given its wide range of adverse effects including bone marrow suppression, hepatic or renal dysfunction, gastrointestinal distress, mucocutaneous damage, and neurotoxicity. The toxicity usually occurs rapidly and leads to severe neutropenia, sepsis, and advanced renal failure that are difficult to manage.
METHODS
This review is an update for the clinicians to understand the pharmacology, clinical features, laboratory evaluation, and treatment of patients with methotrexate overdose. High-quality literature of the past six decades was collected and reviewed in this article. Several landmark articles were reviewed using PubMed, EMBASE Ovid, and the Cochrane Library, that have important implications in current clinical practice.
RESULTS
Methotrexate overdose has complex toxicokinetic and produces myriad clinical features mimicking conditions of lesser severity. Organ dysfunction related to bone marrow, kidney or central nervous system is lifethreatening. The management should focus on high-quality supportive care, antidotal therapy (folinic acid and carboxypeptidase- G2) and plasma alkalization.
CONCLUSION
In accordance with the dictum "prevention is better than cure", the author emphasizes on the role of patient education, regular clinical observation, and laboratory monitoring for prompt recognition and diagnosis of methotrexate overdosing at the earliest stage.
Topics: Drug Interactions; Drug Overdose; Drug Prescriptions; Humans; Leucovorin; Methotrexate; Pharmacogenetics
PubMed: 31385765
DOI: 10.2174/1389200220666190806140844 -
Biomedicine & Pharmacotherapy =... Jun 2022Methotrexate (MTX) has been used for the treatment of rheumatoid arthritis (RA) for about forty years and to date MTX remains the part of global standard of treatment... (Review)
Review
Methotrexate (MTX) has been used for the treatment of rheumatoid arthritis (RA) for about forty years and to date MTX remains the part of global standard of treatment for RA. The efficacy of MTX in RA is the result of multiple mechanisms of action. In order to summarize the possible pharmacological mechanisms of MTX in the treatment of RA, this review will elaborate on folate antagonism, promotion of adenosine accumulation, regulation of inflammatory signaling pathways, bone protection and maintenance of immune system function.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Methotrexate
PubMed: 35658215
DOI: 10.1016/j.biopha.2022.113074 -
Actas Dermo-sifiliograficas 2014Although the first study on the efficacy of methotrexate in the treatment of psoriasis was reported in 1958, scientific evidence for this indication has been scant until... (Review)
Review
Although the first study on the efficacy of methotrexate in the treatment of psoriasis was reported in 1958, scientific evidence for this indication has been scant until quite recently. We now have new data on the pharmacokinetics and mechanism of action of methotrexate and new subcutaneous formulations that have improved the bioavailability, efficacy, and ease of administration of the drug. The results of recent clinical trials comparing methotrexate with several biologic agents have shown it to be the first-line therapy among the classic systemic treatments for psoriasis. Moreover, the incremental cost-effectiveness ratio for subcutaneous methotrexate has been shown to be superior to that of ciclosporin, adalimumab, and infliximab.
Topics: Dermatologic Agents; Humans; Methotrexate; Psoriasis
PubMed: 23434058
DOI: 10.1016/j.ad.2012.11.017 -
European Journal of Medicinal Chemistry Oct 2018Methotrexate (MTX) is used as an anchor disease-modifying anti-rheumatic drugs (DMARDs) in treating rheumatoid arthritis (RA) because of its potent efficacy and... (Review)
Review
Methotrexate (MTX) is used as an anchor disease-modifying anti-rheumatic drugs (DMARDs) in treating rheumatoid arthritis (RA) because of its potent efficacy and tolerability. MTX benefits a large number of RA patients but partially suffered from side effects. A variety of side effects can be associated with MTX when treating RA patients, from mild to severe or discontinuation of the treatment. In this report, we reviewed the possible side effects that MTX might cause from the most common gastrointestinal toxicity effects to less frequent malignant diseases. In order to achieve regimen with less side effects, the administration of MTX with appropriate dose and a careful pretreatment inspection is necessary. Further investigations are required when combining MTX with other drugs so as to enhance the efficacy and reduce side effects at the same time. The management of MTX treatment is also discussed to provide strategies for occurred side effects. Thus, this review will provide scholars with a comprehensive understanding the side effects of MTX administration by RA patients.
Topics: Animals; Antirheumatic Agents; Arthritis, Rheumatoid; Gastrointestinal Diseases; Humans; Methotrexate; Neoplasms
PubMed: 30243154
DOI: 10.1016/j.ejmech.2018.09.027 -
Arthritis Care & Research Jul 2018
Topics: Arthritis, Rheumatoid; Humans; Methotrexate
PubMed: 28834302
DOI: 10.1002/acr.23344 -
Clinical Gastroenterology and... Jan 2018
Topics: Hepatitis, Autoimmune; Humans; Methotrexate
PubMed: 28893680
DOI: 10.1016/j.cgh.2017.08.051 -
Clinical Infectious Diseases : An... Jul 2021
Topics: Humans; Methotrexate
PubMed: 33170206
DOI: 10.1093/cid/ciaa1390 -
Current Topics in Medicinal Chemistry 2016Development of new drugs is a time-consuming, hugely expensive and an uncertain endeavor. The pharmaceutical industry is looking for cost-effective alternatives with... (Review)
Review
Development of new drugs is a time-consuming, hugely expensive and an uncertain endeavor. The pharmaceutical industry is looking for cost-effective alternatives with reduced risks of drug failure. Validated target machinery along with established inhibitors indicates usefulness in drug design, discovery and further development. Folate metabolism, found in both prokaryotes and eukaryotes, represents an essential druggable target for chemotherapy. Numerous enzymes in the cell replication cycle use folate either as a cofactor or as a substrate. DHFR, an enzyme of the folate biosynthesis pathway is an established chemotherapeutic target, initially explored for anti-cancer drug discovery. Diaminopteridines e.g. methotrexate and aminopterin, primarily used as anti-cancer agents, are folic acid analogues, first reported in late 1940's, used to produce temporary remission of acute leukaemia in children. However, due to the toxicity of these drugs, they could not be used for other therapeutic implications such as in the treatment of infectious diseases. Development of newer diaminopteridine derivatives has helped in repositioning their therapeutic usefulness. These analogues have now been proven as anti-parasitic, immuno-suppressants, anti-bacterial agents, to enlist a few therapeutic applications. Likewise, diaminopyrimidine, diaminoquinazoline and diaminodihydrotriazines are being explored for structural modifications by which they can be repurposed from their originally developed medicinal applicability and exploited for various other infectious disease conditions. In this review, we encompass the study of DHFR inhibitors potentially to be repurposed for different infectious disease case scenario and also highlight the novel anti-infective drug discovery benefits therein.
Topics: Anti-Infective Agents; Antineoplastic Agents; Drug Repositioning; Folic Acid Antagonists; Humans; Methotrexate; Pteridines; Tetrahydrofolate Dehydrogenase; Trimethoprim
PubMed: 26881719
DOI: 10.2174/1568026616666160216152540 -
The Korean Journal of Internal Medicine Nov 2018
Topics: Arthritis, Rheumatoid; Humans; Methotrexate; Polyethylene Glycols
PubMed: 30396253
DOI: 10.3904/kjim.2018.363 -
ACS Applied Materials & Interfaces Nov 2019Methotrexate (MTX) is one of the first-line treatments for moderate to severe psoriasis, while the side effects caused by injection and oral administration of MTX...
Methotrexate (MTX) is one of the first-line treatments for moderate to severe psoriasis, while the side effects caused by injection and oral administration of MTX greatly restrict its clinical application. Transdermal drug delivery offers a desirable alternative to the conventional approaches, but the performances of the currently available skin penetration enhancement techniques are not so satisfactory. To address these limitations, we developed a dissolving microneedle (MN) patch made of hyaluronic acid (HA) with excellent water solubility, biocompatibility, biodegradability, and mechanical properties. The amount of MTX encapsulated in the needles of the patch could be controlled during the fabrication process for precise dosage. Interestingly, the MTX-loaded MNs successfully penetrated imiquimod (IMQ)-induced thickened epidermis in mice and delivered the drug intralesionally. Meanwhile, fast dissolution of HA endowed the MNs with operability for patients. We found that the MTX-loaded MNs not only showed well-maintained inhibitory effect in vitro but also alleviated the psoriasis-like skin inflammation in mice. Moreover, the MTX-loaded MNs were significantly more efficacious than taking the same dose of drug orally. Consequently, a higher oral dose of MTX was required for a comparable amelioration, which in turn increased its systemic toxicity. Taken together, the proposed MTX-loaded dissolving MN patch strategy provides a new opportunity for efficient and safe treatment of psoriasis.
Topics: Animals; Disease Models, Animal; Drug Delivery Systems; Female; Humans; Hyaluronic Acid; Methotrexate; Mice; Mice, Inbred BALB C; Needles; Psoriasis
PubMed: 31651148
DOI: 10.1021/acsami.9b15668