What are the indications and doses of methotrexate?
Methotrexate is a metabolic inhibitor of folic acid analogues. Dihydrofolate reductase will be inhibited by it and interfere with DNA synthesis, cell repair and replication. It is generally more sensitive to actively proliferating tissues such as malignant cells, bone marrow, fetal cells, oral cavity cells, intestinal mucosal cells, and bladder cells. It is mainly suitable for the treatment of hematological malignancies, solid tumors, psoriasis and various arthritis.
Treatment of adult hematological malignancies:
- Various acute leukemias (especially acute lymphoblastic leukemia), non-Hodgkin lymphoma, malignant lymphoma and mycosis fungoides, multiple myelopathy.
- Intrathecal methotrexate can be used to prevent and treat neural invasion of meningeal leukemias and malignant lymphomas.
- Methotrexate is used in combination with other chemotherapy drugs for the palliative treatment of acute leukemias, especially acute lymphoblastic leukemia. It is also used to treat Burkitt's lymphoma, coronal lymphosarcoma and mycosis fungoides.
- High-dose methotrexate is used to treat non-Hodgkin's disease subtypes but must be combined with rescue therapy with leucovorin.
- Oral administration: Adults take 1 to 2 days a week, once a day, 5 to 10 mg each time. The safe dosage for a course of treatment is 50 to 100 mg. Its maintenance dose for acute lymphoblastic leukemia is 15 to 20 mg/m2 once a week.
Treatment of various solid tumors in adults including head and neck cancer, lung cancer, various soft tissue sarcomas, breast cancer, ovarian cancer, cervical cancer, malignant mole, chorioepithelial cancer, and testicular cancer. Commonly used oral tablet dosages are as follows:
- Adults take it orally 1 to 2 days a week, once a day, 5 to 10 mg each time. The safe dose for a course of treatment is 50 to 100 mg.
For the treatment of rheumatoid arthritis in adults. Common dosages are as follows:
- Rheumatoid Arthritis: 7.5 to 15 mg orally once weekly, with the highest dose being 25 mg once weekly. The dose of methotrexate should be reduced when used in combination with other immunosuppressants.
- Psoriatic Arthritis: 15 to 20 mg orally once weekly.
- Peripheral arthritis in ankylosing spondylitis: 7.5 to 10 mg orally once weekly.
Methotrexate is also used to treat severe, refractory and disabling psoriasis in adults who are unresponsive to conventional treatments. Commonly used injectable dosage forms.
What is the pharmacological mechanism of methotrexate?
Its main mechanism of action is to competitively inhibit folate reductase. Folic acid is reduced to tetrahydrofolate by folate reductase during DNA synthesis and cell replication. Folate reductase is inhibited by methotrexate, which interferes with cell replication. Methotrexate is a cell cycle-specific drug and acts primarily on cells during the DNA synthesis phase.
Tissues and cells with active proliferation such as bladder cells, bone marrow, embryonic cells, intestinal mucosal cells, malignant tumor cells, oral cells, and skin epithelial cells are generally more sensitive to the effects of methotrexate. In addition, most normal tissues proliferate more slowly than malignant tumor tissues, so methotrexate will preferentially weaken the growth of malignant tumors. The skin epithelial cells of patients with psoriasis also have a greater ability to proliferate than normal skin cells, so methotrexate can also be used to control the progression of psoriasis.
One of the important coenzymes in the synthesis of pyrimidine deoxynucleotides and purine nucleotides in the human body is tetrahydrofolate. Methotrexate is a folate reductase inhibitor. It inhibits dihydrofolate reductase and prevents dihydrofolate from being reduced to active tetrahydrofolate. This blocks the transfer of carbon groups during the biosynthesis of pyrimidine deoxynucleotides and purine nucleotides. DNA biosynthesis will be inhibited. In addition, although methotrexate also inhibits thymus nucleotide synthase, its inhibitory effect on protein and RNA synthesis is weak. It mainly acts in the S phase of the cell cycle. It is a cell cycle specific drug. It also delays cells in the G1/S phase, but the effect is weaker.
What are the common side effects of methotrexate?
Blood and Lymphatic System: Myelosuppression, pancytopenia, agranulocytosis, granulocytopenia, anemia, leukopenia, aplastic anemia, neutropenia, thrombocytopenia, lymphopenia.
Cardiovascular system: palpitations, tachycardia, increased blood pressure.
Gastrointestinal system: nausea, vomiting, oral ulcers, abdominal pain, diarrhea, oral mucositis, oropharyngeal pain, abdominal distension, acid reflux, gastrointestinal bleeding, lip ulcers, indigestion, blood in the stool, flatulence, dry mouth, oral bleeding, Belching, tongue ulcers, dysphagia, bleeding gums, peptic ulcers, melena, anal ulcers, and tongue pain.
Hepatobiliary system: abnormal liver function, liver cell damage, liver damage, hepatitis, jaundice, liver failure.
Immune system: Hypersensitivity reactions, anaphylactoid reactions, graft-versus-host disease.
Infections: infectious pneumonia, cytomegalovirus infection, fungal infection, herpes virus infection, sepsis, herpes zoster, Epstein-Barr virus infection.
Kidney and urinary system: renal damage, hematuria, hemorrhagic cystitis.
Nervous system: dizziness, headache, hypoesthesia, tremor.
Respiratory system: cough, dyspnea, pneumonia, pharyngitis, interstitial lung disease, pulmonary fibrosis, respiratory failure.
Skin and subcutaneous tissue: rash, pruritus, alopecia, erythema, skin ulcers, ecchymosis, erythema multiforme, maculopapular rash, vesicular rash, papules, erythematous eruption, urticaria, peeling, dermatitis, pruritic rash, purpura, Petechiae, exfoliative dermatitis, skin erosions.
Systemic reactions: fatigue, fever, mucosal ulcers, chest tightness, pain, chills, mucosal erosion, chills, facial edema, high fever, peripheral edema.
Others: loss of appetite, appetite disorder, joint pain, irregular menstruation, blurred vision, visual impairment, flushing, tinnitus.
Adverse effects of methotrexate can be prevented by using low-dose folic acid, but it should be used 24 hours after the patient takes the drug. It is recommended that patients supplement 5mg of folic acid every week to reduce gastrointestinal adverse reactions and liver function damage. Leucovorin and levofolinic acid are antidotes for methotrexate overdose. Patients with methotrexate overdose should be given an antidote as soon as possible and should undergo hydration and alkalinization of the urine.
