Methotrexate, the most widely used antimetabolite in cancer chemotherapy does not penetrate the central nervous system (CNS). To treat CNS disease this drug must be administered:
A. Intravenously.
B. Subcutaneously.
C. Intrathecally.
D. By inhalation.
Correct Answer: C. Intrathecally.
With intrathecal administration, chemotherapy is injected through the theca of the spinal cord and into the subarachnoid space entering into the cerebrospinal fluid surrounding the brain and spinal cord. The methods in options A, B, and D are ineffective because the medication cannot enter the CNS. Now, methotrexate is one of the major chemotherapeutic choices for various types of cancers. The medication is also safe and effective for patients with psoriasis, systemic lupus erythematosus, inflammatory bowel disease, vasculitis, and many other connective tissue diseases.
Option A: A pre methotrexate evaluation is necessary before initiating medical therapy with methotrexate; this evaluation involves the blood tests which include: complete blood count with differential, renal function tests include the serum creatinine, blood urea nitrogen, and urinalysis, and liver function tests include serum bilirubin, AST, ALT, serum albumin, hepatitis serology. HIV tests are also necessary, and if appropriate, the clinician should obtain a chest radiograph as well.
Option B: Methotrexate has a distinct mechanism of action regarding its use in chemotherapy and immunosuppression in autoimmune diseases. In cancer, methotrexate acts as an antifolate antimetabolite. Methotrexate is taken up into the cell by carriers called the human reduced folate carriers (SLC19A1), and it forms methotrexate-polyglutamate. Both the methotrexate and the methotrexate-polyglutamate inhibit the enzyme dihydrofolate reductase, which catalyzes the conversion of dihydrofolate into tetrahydrofolate, the active form of folic acid.
Option D: In autoimmune diseases, different mechanisms have involvement in choosing methotrexate as a drug of choice. It inhibits enzyme AICAR transformylase, leading to hindrance in Adenosine and Guanine metabolism, Adenosine accumulation; and due to anti-inflammatory action of adenosine, leads to repression of T-cell activation, down-regulation of B-cells, increasing activated CD-95 T cells sensitivity; and repression of methyltransferase activity, inhibition of the binding of beta-1 interleukin to its cell surface receptor.