Usage methods of cyclophosphamide, usage methods of methotrexate sodium, new synthesis methods for polymer monomers containing phosphatidylcholine groups

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Pharmacology: Pharmacodynamics It has no antitumor activity in vitro; once it enters the body, it is first converted into aldimide by microsomal oxidase in the liver. Aldimide is unstable and breaks down into chlorambucil and acrolein within tumor cells, with chlorambucil exerting a cytotoxic effect on those tumor cells. Cyclophosphamide is a bifunctional alkylating agent and a cell cycle-nonspecific drug that can interfere with the functions of DNA and RNA, with a greater impact on the former. It forms cross-links with DNA, inhibiting DNA synthesis, and its effect is most pronounced during the S phase. 　　Pharmacokinetics It is completely absorbed after oral administration and rapidly distributed throughout the body; a small amount can pass through the blood-brain barrier. Cyclophosphamide itself does not bind to albumin, while about 50% of its metabolites are bound to proteins. The plasma T1/2 after intravenous injection is 4–6.5 hours, with 50–70% being excreted through the kidneys within 48 hours. 　　Indications: Suitable for malignant lymphoma, multiple myeloma, lymphocytic leukemia, as well as solid tumors such as neuroblastoma, ovarian cancer, breast cancer, various sarcomas, and lung cancer. 　　Dosage and administration: 1. The usual dose for adults is 2–3 mg/kg per day orally; for intravenous injection, it is 4 mg/kg per dose, administered once daily or every other day. Or 600–1200 mg each time, every 7–10 days. 　　2. The usual dosage for children is 2–6 mg/kg per day orally, and 2–6 mg/kg per injection via intravenous route, administered once daily or every other day. Or 10–15 mg/kg per dose, once a week, to be slowly injected after dilution in 20 ml of sodium chloride injection. 　　Cyclophosphamide tablets 50mg Cyclophosphamide for injection: (1) 100mg, (2) 200mg (1) Antitumor: Oral administration, 50mg per dose, 3 times a day ； Administer by intravenous injection at a dose of 400–600 mg per square meter once a week; a total dose of around 8 g constitutes one course of treatment. It can also be administered by intramuscular injection, at the same dose as for intravenous injection. Intr arterial injection: 100–500 mg per dose; intrathecal injection: 50–100 mg per dose. (2) Immunosuppression: 50–150 mg per day, taken in two divided doses as a powder, for 4–6 weeks. Administer by intravenous injection at a dose of 100–200 mg per time, once daily or every other day, for 4–6 weeks. 　　Use with caution/avoid use: (1) Medication use in pregnant women must be considered carefully, especially during the first three months of pregnancy. Since cyclophosphamide has mutagenic and teratogenic effects, it can lead to fetal death or congenital defects. This product is excreted in breast milk; breastfeeding must be discontinued at the start of cyclophosphamide treatment. 　　(2) Use with caution in the following situations: bone marrow suppression; a history of gout, liver function impairment, infection, kidney function impairment, tumor cell infiltration of the bone marrow, a history of urinary tract stones, or prior chemotherapy or radiation therapy. Compiled by Medical Education Network. Use with caution in patients with liver disease. 　　This product has significant teratogenic and mutagenic effects on both humans and animals; it causes embryo resorption and delayed development, as well as deformities such as abnormal limbs and cleft palates, especially during the cell division phase and organ formation phase of pregnancy. However, its toxicity to pregnancy may not be permanent. 　　Administration instructions: (1) In cases of liver or kidney dysfunction, the dose of cyclophosphamide should be reduced to 1/2 to 1/3 of the therapeutic dose. (2) In patients with leukemia or lymphoma who develop uric acid nephropathy, the following methods can be used for prevention: adequate fluid replacement, alkalization of urine, and/or administration of allopurinol. 　　(3) When myelosuppression is caused by tumor cell infiltration or prior chemotherapy or radiotherapy, the dose of cyclophosphamide should be reduced to 1/2 to 1/3 of the therapeutic dose. (4) If there is significant leukopenia (especially granulocytopenia) or thrombocytopenia, cyclophosphamide should be discontinued until the white blood cell and platelet counts return to normal levels. 　　(5) Oral cyclophosphamide is generally administered on an empty stomach. If stomach discomfort occurs, it can be administered in divided doses or with food. 　　(6) Since cyclophosphamide needs to be activated into an active compound in the liver, intraluminal administration has no direct effect. 　　(7) During medication, regular checks should be conducted on the white blood cell count and classification, platelet count, kidney function (blood urea nitrogen, creatinine clearance), liver function (serum bilirubin, alanine aminotransferase), and serum uric acid levels. 　　Adverse reactions: (1) Myelosuppression is the most common toxicity; white blood cell counts usually reach their lowest level 10–14 days after administration, and return to normal by day 21. Thrombocytopenia is less common than with other alkylating agents ； Common side effects also include nausea and vomiting. The severity is related to the dose. 　　(2) The metabolites of cyclophosphamide can cause severe hemorrhagic cystitis, which can be prevented by adequate fluid supplementation. This product can also cause bladder fibrosis. 　　(3) When high doses of cyclophosphamide (50 mg/kg based on body weight) are administered together with large amounts of fluid, water intoxication can occur; furosemide can be given simultaneously to prevent this. 　　(4) Conventional doses of cyclophosphamide do not cause cardiac toxicity, but high doses can lead to myocardial necrosis, with pulmonary fibrosis occurring occasionally. 　　(5) Cyclophosphamide can cause reproductive system toxicity, such as amenorrhea or azoospermia; administration in the early stages of pregnancy can lead to teratogenesis. 　　(6) Prolonged administration of cyclophosphamide can lead to secondary tumors. 　　(7) Cyclophosphamide can cause moderate to severe immunosuppression. 　　(8) When used in the treatment of leukemia or lymphoma, hyperuricemia and uric acid nephropathy are likely to occur. 　　(9) Rare side effects include fever, allergies, pigmentation of the skin and nails, mucosal ulcers, elevated alanine aminotransferase levels in liver function, urticaria, abnormal sensations in the oropharynx, or blurred vision. 　　Loss of appetite, nausea, hair loss, bone marrow suppression, decreased levels of white blood cells and platelets, liver damage; high doses can cause bladder irritation symptoms or cystitis, hematuria, proteinuria, and vomiting. Some experience dizziness, hallucinations, restlessness, etc. 　　Common adverse reactions include gastrointestinal intolerance, bone marrow suppression, hair loss, and aseptic cystitis, but many tissues and organs can also be affected. The use of this drug to treat malignant diseases such as multiple myeloma, chronic lymphocytic leukemia, and ovarian cancer can cause acute leukemia. When it is used to treat non-malignant diseases such as rheumatoid arthritis, bladder cancer can occur. Patients who receive high doses may experience myocardial necrosis, acute myocarditis, which can lead to heart failure and even death. Pulmonary fibrosis is an uncommon side effect of this drug, while liver damage accompanied by temporary increases in liver enzymes is rare. This drug can cause stomatitis ； It can cause **damage and infertility, and is dose-dependent** ； It can also cause ovarian dysfunction, which is related to dosage and age as well. There are reports of allergic reactions occurring when nurses handle this medication. 　　Cardiovascular system: This drug can cause cardiomyopathy, focal transmural myocardial hemorrhage, and coronary arteritis. High doses, 120–240 mg/kg, can cause hemorrhagic myocardial necrosis, and heart failure may occur 2 weeks after the last dose. 　　This drug is toxic to hair follicles, often causing diffuse hair loss. 　　Hepatotoxicity: This product can cause liver damage in a dose-dependent manner, which may be due to the hepatotoxic effects of acrolein, the main metabolite of cyclophosphamide; this leads to hepatocyte necrosis, congestion in the centers of liver lobules, and an increase in amino transferase levels. 　　Digestive system: The most common adverse reactions are nausea and vomiting, with incidence rates of approximately 60% to 90%; these are also the main reasons why patients cannot tolerate the treatment. Although the 5-HT antagonist metoclopramide can alleviate this adverse effect, close attention should be paid to the resulting neurosuppression. 　　Urinary system and nephrotoxicity: This drug can cause renal hemorrhage, bladder fibrosis and hemorrhagic cystitis, hydronephrosis, vesicoureteral reflux, and even secondary renal cancer; however, compared with other alkylating agent anticancer drugs, its nephrotoxicity is relatively low. 　　Skin, mucous membranes: Whether used alone or in combination with other drugs, this product affects the division of hair follicle cells, exhibiting significant toxicity toward hair and hair follicles. The degree of hair loss caused by the medication is dose-dependent, and new hair gradually grows back after discontinuation of the medication. Since this product can inhibit the rapid proliferation of oral mucosa, leading to stomatitis, it can also cause drug-induced dermatitis; when used in combination with other drugs, nail loss and pigmentation have also been observed occasionally. 　　Reproductive toxicity: This substance exhibits significant toxicity toward the reproductive system, causing a decrease in sperm count in men, reducing the function of interstitial cells, and causing damage to the ovaries in women. 　　Interactions: (1) Cyclophosphamide can increase serum uric acid levels; when used in combination with antigout drugs such as allopurinol, colchicine, and probenecid, the doses of these antigout drugs should be adjusted to help control hyperuricemia and gout ； Allopurinol can increase the myelotoxicity of cyclophosphamide; if their combined use is necessary, its toxic effects should be closely monitored. 　　(2) When used together with high doses of barbiturates or corticosteroids, it can increase acute toxicity. 　　(3) When used in combination with doxorubicin, it can increase cardiac toxicity; the total dose of doxorubicin should not exceed 400 mg per square meter based on body surface area. 　　(4) Cyclophosphamide can inhibit cholinesterase, slowing down the metabolism of **, thereby prolonging its effects and increasing its toxicity. 　　(5) Cyclophosphamide can reduce the concentration of pseudocholinesterase in plasma, thereby enhancing the neuromuscular blocking effect of succinylcholine and prolonging apnea. This post was last edited by suiran983527 on 2009-3-18 13:31.]