Methotrexate

src: i.ytimg.com

Methotrexate ( MTX ), formerly known as amethopterin , is a chemotherapy and immune system suppressant agent. It is used to treat cancer, autoimmune disease, ectopic pregnancy, and for medical abortion. The types of cancers used to include breast cancer, leukemia, lung cancer, lymphoma, and osteosarcoma. This type of autoimmune disease is used to include psoriasis, rheumatoid arthritis, and Crohn's disease. Can be given by mouth or by injection.

Common side effects include nausea, fatigue, fever, increased risk of infection, low white blood cell count, and skin damage in the mouth. Other side effects may include liver disease, lung disease, lymphoma, and severe skin rashes. People who undergo long-term treatment should be regularly checked for side effects. Not safe during breastfeeding. In those with kidney problems, a lower dose may be required. It acts by blocking the use of folic acid by the body.

Methotrexate was made in 1947 and was originally used for the treatment of cancer, because it was less toxic than the current treatment. In 1956 it gave the first drug of metastatic cancer. It's in the List of Essential Medicines of the World Health Organization, the most effective and safe drugs needed in the health system. Methotrexate is available as a generic drug. Wholesale costs in 2014 in developing countries are between US $ 0.06 and 0.36 per day for forms taken by mouth. In the United States, the typical maintenance month is $ 25 to $ 50.

Video Methotrexate

Medical use

Chemotherapy

Methotrexate was originally developed and continuously used for chemotherapy, either alone or in combination with other agents. It is effective for the treatment of a number of cancers, including: breast, head and neck, leukemia, lymphoma, lung, osteosarcoma, bladder, and trophoblast neoplasm.

Autoimmune disorders

It is used as a disease-modifying treatment for some autoimmune diseases, including rheumatoid arthritis, juvenile dermatomyositis, psoriasis, psoriatic arthritis, lupus, sarcoidosis, Crohn's disease, eczema and various forms of vasculitis. Although initially designed as a chemotherapy drug (using high doses), in low doses, methotrexate is a drug that is generally safe and well tolerated in the treatment of certain autoimmune diseases. Because of its effectiveness, low-dose methotrexate is now the first-line therapy for the treatment of rheumatoid arthritis. Weekly doses are useful for therapy duration 12 to 52 weeks, although the discontinuation rate as high as 16% due to side effects. Although methotrexate for autoimmune diseases is taken in lower doses than for cancer, side effects such as hair loss, nausea, headache, and skin pigmentation are still common. The use of low-dose methotrexate along with NSAIDS such as aspirin or analgesics such as paracetamol is relatively safe in people treated for rheumatoid arthritis, if adequate monitoring is performed.

Not all people with rheumatoid arthritis respond well to treatment with methotrexate, but some studies and reviews suggest that the majority of people who receive methotrexate for up to a year have less pain, better functioning, have fewer swollen and tender joints, and have disease activity which is less overall. as reported by themselves and their doctors. X-rays also show that the progression of the disease slows down or stops in many people who receive methotrexate, with development completely stopped at about 30% of those receiving the drug. People with rheumatoid arthritis treated with methotrexate have been found to have a lower risk of cardiovascular events such as myocardial infarction (heart attack) and stroke.

More recently, the use of methotrexate in combination with anti-TNF agents has been shown to be effective for the treatment of ulcerative colitis.

Methotrexate has also been used for multiple sclerosis.

It is not commonly used for lupus, and there is only temporary evidence to support the exercise.

During pregnancy

Methotrexate is abortifacient and is commonly used to terminate pregnancy during the early stages, generally in combination with misoprostol. It is also used to treat ectopic pregnancy, provided the fallopian tube is not broken. Methotrexate with dilatation and curettage is used to treat molar pregnancies.

Administration

Methotrexate may be given by mouth or by injection (intramuscular, intravenous, subcutaneous, or intrathecal). Doses are usually taken every week, not every day, to limit toxicity. Routine monitoring of complete blood count, liver function tests, and creatinine is recommended. Creatinine measurement is recommended at least every 2 months.

Maps Methotrexate

Adverse effects

The most common side effects include: hepatotoxicity (liver damage), ulcerative stomatitis, leukopenia and thus a tendency to infection, nausea, abdominal pain, fatigue, fever, dizziness, acute pneumonitis, rare pulmonary fibrosis, and renal failure. Methotrexate is teratogenic and hence it is not advisable either the expectant father to take it before or for the mother to take it before or during pregnancy (category of pregnancy X) and for the period after birth.

Central nervous system reactions to methotrexate have been reported, especially when administered via the intrathecal route (directly into the cerebrospinal fluid), which includes myelopathy and leukleensial. It has various skin side effects, especially when given in high doses.

The little-known but serious side effects of methotrexate are neurological damage and memory loss. Neurotoxicity can occur as a result of a drug crossing the blood-brain barrier and destroying the neurons in the cerebral cortex. People with cancer who receive drugs often label these effects "chemo brain" or "chemo fog".

Drug interactions

Penicillin may reduce methotrexate elimination, thus increasing the risk of toxicity. Although they can be used together, improved monitoring is recommended. Aminoglycosides, neomycin and paromomycin, have been found to reduce the absorption of gastrointestinal (GI) methotrexate. Probenecid inhibits methotrexate excretion, which increases the risk of methotrexate toxicity. Likewise, retinoids and trimethoprim have been known to interact with methotrexate to produce additive hepatotoxicity and hematoxicity, respectively. Other immunosuppressants such as ciclosporin may potentiate the hematologic effects of methotrexate, potentially leading to toxicity. NSAIDs have also been found to interact fatal with methotrexate in various case reports. Nitrous oxide that potentiates the hematologic toxicity of methotrexate has also been documented. Proton pump inhibitors such as omeprazole and anticonvulsant valproate have been found to increase plasma methotrexate concentrations, as do nephrotoxic agents such as cisplatin, GI drug colestyramine, and dantrolene.

College Joints: So you've been put on methotrexate, eh?

src: 4.bp.blogspot.com

Action mechanism

Methotrexate is an antimetabolite of the antifolate type. It is thought to affect cancer and rheumatoid arthritis by two different pathways. For cancer, methotrexate competitively inhibits dihydrofolate reductase (DHFR), an enzyme that participates in the synthesis of tetrahydrofolate. The affinity of methotrexate for DHFR is about 1000 times that of folate. DHFR catalyzes the conversion of dihydrofolate to active tetrahydrofolate. Folic acid is required for the synthesis of deÃƒ,novo from the nucleoside timid, which is necessary for DNA synthesis. Also, folate is essential for the biosynthesis of the purine and pyrimidine bases, so that synthesis will be inhibited. Methotrexate, therefore, inhibits DNA synthesis, RNA, thymidylate, and protein.

For the treatment of rheumatoid arthritis, DHFR inhibition is not considered a primary mechanism, but some mechanisms seem to be involved, including inhibition of enzymes involved in purine metabolism, leading to the accumulation of adenosine; inhibition of T cell activation and suppression of expression of adhesion molecules between cells by T cells; selective B cell settings; increase the sensitivity of CD95 T cells activated; and inhibition of methyltransferase activity, leading to the deactivation of enzyme activity relevant to the functioning of the immune system. Another mechanism of MTX is the inhibition of the binding of interleukin 1-beta to its cell surface receptor.

Boxes of pre-filled methotrexate auto injectors Stock Photo ...

src: c8.alamy.com

History

In 1947, a team led by Sidney Farber showed aminopterin, a chemical analog of folic acid developed by Yellapragada Subbarao from Lederle, can cause remission in children with acute lymphoblastic leukemia. The development of folic acid analogs has been driven by the discovery that the administration of folic acid worsens leukemia, and that dietary deficiencies in folic acid can, in turn, lead to improvement; the mechanism of action behind this effect is still unknown at the time. Another analogy of folic acid is under development, and in 1950, methotrexate (later known as amethopterin) was being proposed as a treatment for leukemia. Animal studies published in 1956 showed a better therapeutic methotrexate index than aminopterin, and clinical use of aminopterin was thus abandoned for methotrexate.

In 1951, Jane C. Wright demonstrated the use of methotrexate in solid tumors, showing remission in breast cancer. Wright's group is the first to demonstrate the use of drugs in solid tumors, compared with leukemia, which is a bone marrow cancer. Min Chiu Li and his collaborators then showed complete remission in women with choriocarcinoma and chorioadenoma in 1956, and in 1960 Wright et al. produce remission in mycosis fungoides.