What is the mechanism of action of methotrexate?
Methotrexate inhibits enzymes responsible for nucleotide synthesis which prevents cell division and leads to anti-inflammatory actions. It has a long duration of action and is generally given to patients once weekly. Methotrexate has a narrow therapeutic index.
What are the pharmacokinetics of methotrexate?
Methotrexate is mainly excreted by the kidney as intact drug regardless of the route of administration. The drug is filtered by the glomeruli, and then undergoes both secretion and reabsorption processes within the tubule.
What is methotrexate toxicity?
MTX toxicity is characterized by nausea, vomiting, diarrhea, myelosuppression, pancytopenia, liver dysfunction, acute renal failure (ARF), pulmonary symptoms, mucositis, stomatitis, ulceration/erosion of the gastrointestinal system and cutaneous ulcerations (9-11).
What is the mechanism of action of methotrexate in rheumatoid arthritis?
Currently, adenosine signaling is probably the most widely accepted explanation for the methotrexate mechanism in RA given that methotrexate increases adenosine levels and on engagement of adenosine with its extracellular receptors an intracellular cascade is activated promoting an overall anti-inflammatory state.
Which biochemical pathway does methotrexate inhibit?
The primary action of methotrexate is inhibition of the enzyme dihydrofolate reductase (DHFR), which converts dihydrofolate to tetrahydrofolate (THF)[112].
How does methotrexate toxicity occur?
Methotrexate toxicity develops due to increased patient susceptibility during treatment, excessive parenteral or intrathecal administration, therapeutic errors by patients (e.g. taking MTX orally daily instead of weekly), self-administration to induce abortion, or intentional oral overdoses.
What biochemical pathway does methotrexate inhibit?
How do you monitor methotrexate toxicity?
The American College of Rheumatology (ACR) recommends monitoring with blood tests to check the liver enzymes alanine transaminase and aspartate transaminase and levels of serum albumin, a protein made by the liver (every two to four weeks when you start MTX, every eight to 12 weeks in the third to six month of …
Why is methotrexate toxic?
It is generally considered to be safe and therefore, it is not unusual to prescribe doses as high as 25 to 30 mg per week in modern rheumatology [6, 7]. Methotrexate toxicity is mainly due to its effects on folate metabolism.