Structure and Toxicity of Methotrexate - Research Paper Example

Its crystal structure contains two strontium ions in a coordinate bond with glutamate carboxyl groups of two independent Methotrexate molecules. Its chemical formula is determined to be n-[4[[(2,4-diamino-6-pyridinyl)methyl]methyl-amino]benzoyl]-glutamic acid (RxList). Route of Exposure Methotrexate is administered orally in the form of a tablet. It can also be administered by an injection in liquid form intramuscularly, intravenously, or subcutaneously. Also since it’s an insect chemosterilant that is sprayed, humans may unwantedly come into contact with it in the environment (Pohanish 1733).

Pharmacokinetics Oral adsorption of Methotrexate is dose-dependent and is well adsorbed at the dosage of 30mg/m2 or less. Food intake during its half-life period delays the adsorption rate and the peak concentration that can be achieved. After the intake, it competes with natural foliates in the process of active transport across cell membranes. In serum, it is approximately 50% protein bound. After Methotrexate is adsorbed, the hepatic and intracellular mechanisms change it to polyglutamated forms which inhibit dihydrofolate reductase and thymidylates synthase.

These polyglutamate forms may remain in trace amounts in tissues for extended periods. It has a half-life period of 3-10 hours in patients receiving treatment for arthritis or psoriasis. It is eliminated as a waste from the body as renal excretion, which is independent of dosage and route of administration (DrugLib). Methotrexate Toxicity Methotrexate (MTX) is a powerful medication. Patient susceptibility during treatment, therapeutic errors by patients, or oral overdoses lead to Methotrexate toxicity.

Its toxicity can be explained as follows. Methotrexate binds to an enzyme dihydrofolate reductase (DHFR), which converts dihydrofolate to the enzyme tetrahydrofolate. Because of this binding, this conversion mechanism is hindered and higher amounts of dihydrofolate begin to accumulate. Folate is essential in FNA synthesis, which is being inhibited and this reflects in hindered production of DNA, RNA, thymidylates, and proteins. Severe vomiting, diarrhea, low white blood cell count, nausea, anemia, renal failure, and hypotension are some of the symptoms that manifest in a patient exposed to toxic amounts of Methotrexate.

These effects begin to appear typically from days to weeks after administering an overdose of Methotrexate. It also decreases the activity of the human immune system making the body more susceptible to infection by bacteria and other microbes (Wells and Schwinghammer 172). Treatment Methotrexate toxicity can be treated in various methods which mainly include treating with antidotes like leucovorin, thymidine, and glucarpidase. Leucovorin rescues normal cells by terminating the process of inhibition of the production of reduced folates.

Thymidine functions to protect the cells from the cytotoxic effects of MTX. Glucarpidase converts MTX into inactive form thereby lowering the MTX blood levels. Hemoperfusion and hemodialysis can be used to treat MTX toxicity. Methotrexate inhibits the growth of rapidly growing cells such as embryonic, fetal, and early placenta cells. So Methotrexate can be used for the treatment of ectopic pregnancy. Methotrexate is given until the pregnancy hormone (hCG) blood tests confirm that the pregnancy has ended.