Classification and principles of chemotherapy drugs

  1, alkylating agents / cycle non-specific drugs (acting in all phases of G0 to mitosis) alkylating agents can be further divided into: nitrogen mustard class: all have an active bis-chloroethyl group, the more important ones are nitrogen mustard, nitrogen mustard phenylbutyrate, cyclophosphamide (CTX), isocyclophosphamide (IFO), etc.. Among them, cyclophosphamide is a latent drug that needs activation to work. It is now widely used clinically for the treatment of lymphoma, leukemia, multiple myeloma, and also has certain efficacy for breast cancer and lung cancer.  In addition to myelosuppression, alopecia, and gastrointestinal reactions, this drug can also cause congestive cystitis and patients develop hematuria. Clinics should encourage patients to drink more water when using this drug to achieve hydration and diuresis and reduce the occurrence of congestive cystitis. It can also be combined with the application of the uroprotective agent Mesna.  Nitrosoureas: The earliest structure is N-methylnitrosourea (MNU). Later, a series of compounds added to the chloroethyl group were synthesized, among which the clinically effective ones are ACNU, BCNU, CCNU, methyl CCNU, etc. Streptozotocin have all entered the clinic, but are no longer used. Among them, ACNU, BCNU, CCNU, can pass the blood-brain barrier and are clinically used in the treatment of brain tumors and intracranial metastases. The main adverse reactions are gastrointestinal reactions and delayed myelosuppression, attention should be paid to the observation of blood picture`s and timely detection and treatment.  Ethyleneimine: In the process of studying the effect of nitrogen mustard, it was found that nitrogen mustard is alkylated in the form of ethyleneimine, therefore, 2,4,6-triethylenimine triazine compound (TEM) was synthesized and proved to have anti-tumor effect in the clinic, but only Setipate is currently used in the clinic. This drug is used in the treatment of ovarian cancer, breast cancer and bladder cancer. The main adverse effect is bone marrow suppression, so pay attention to regular monitoring of blood picture.  Methanesulfonate: It is a series of compounds which are compounded according to the cross bond. It is mainly used for chronic granulocytic leukemia. The main adverse reactions are gastrointestinal reactions and myelosuppression, and individual patients can cause fibrosis as a serious adverse reaction. In such cases, the drug should be stopped immediately and replaced by other drugs.  Other: with alkylating effects are dacarbazine (DTIC), methylbenzylhydrazine (PCZ) hexamethonium (HHN), etc. Epoxy compounds, due to serious adverse reactions are now eliminated.  2, cycle-specific antimetabolic drugs thymidylate synthase inhibitors: fluorouracil (5-FU), furan fluorouracil (FT-207), difuridine (difuridine FD-1), ufotaxel (UFT), fluorotiron (5-DFUR).  The antitumor effect is mainly due to the fact that its metabolic activator fluorouracil deoxynucleotide interferes with the transformation of deoxyuridine nucleotide to deoxythymidine nucleotide, thus affecting the synthesis of DNA. After forty years of clinical application, it has become a commonly used antitumor drug in clinical practice and a basic drug for the treatment of lung cancer, breast cancer, and digestive tract cancer.  Adverse reactions are relatively delayed, with mucosal damage in the gastrointestinal tract occurring in 6-7 days of administration, such as: oral ulcers, loss of appetite, nausea, vomiting, diarrhea, etc., and causing bone marrow suppression after one week. In contrast, mucositis becomes its main toxic reaction after 96 hours or more. Clinically, if such drugs are continuously administered for a long time, patients should be given good oral care and taught to learn how to clean their own mouths to prevent the occurrence of severe mucositis.  Dihydrofolate reductase inhibitors: methotrexate (MTX), aminoglutethimide (leucovorin), etc.. They have an inhibitory effect on dihydrofolate reductase, and the application of formyltetrahydrofolate (CF) rescues the toxicity of MTX after a larger increase in the dose of MTX. It is effective in the treatment of osteogenic sarcomas and head and neck tumors, as well as certain immune diseases. Its adverse effects can cause severe stomatitis, ulcerative gastritis, hemorrhagic enteritis, and even death by intestinal perforation; bone marrow suppression is related to the dose and dosing regimen. Clinically, patients should be well taken care of in the oral cavity, carefully observe the occurrence of serious adverse reactions such as intestinal perforation, report to the doctor in time, and be prepared for resuscitation.  DNA polymutase inhibitors: ara-c, cyclic cytidine, and chlorocyclic cytidine, which act in vivo after they become ara-cytidine triphosphate (Ara-CTP), a reaction catalyzed by deoxycytidine kinase. The level of this kinase is high in leukemic cells and lymphocytes, so it has a selective effect on leukemia and has a powerful inhibitory effect on DNA polymorphic enzymes, while affecting the replication of DNA.  The general dose can cause adverse reactions such as bone marrow suppression, nausea, vomiting but light, at high dose there is severe bone marrow suppression such as leukocyte, platelet reduction and anemia, obvious nausea, vomiting, severe diarrhea, nurses should do a good job of patient care accordingly according to the type of adverse reactions that occur in patients. Such as good care to prevent infection, bleeding and diarrhea to reduce the complications brought about by adverse reactions.  Nucleotide reductase inhibitors: hydroxyurea (HU), inosine dialdehyde, adenosinediialde-hgde, guanazole, including cytidylic acid, guanosine, adenosine, thymidylic acid reduction to the corresponding deoxyribonucleotide, and ultimately prevent the synthesis of DNA, by inhibiting nucleic acid reduction enzyme inhibition. It is used clinically for the treatment of chronic granulocytic leukemia, malignant melanoma, breast cancer, head and neck cancer, intestinal cancer, and psoriasis. Adverse effects are mainly myelosuppression. Clinical attention should be paid to monitoring the blood picture and preventing infection.  Purine nucleotide synthesis inhibitor: 6-mercaptopurine (6-MP) is a purine derivative. Because of the affinity of 6-GMP for guanylate kinase, 6-TG can eventually replace guanine and be incorporated into the nucleic acid. It can inhibit the reactions in purine synthesis. It is used clinically for the treatment of leukemia and also as an immunosuppressant for nephrotic syndrome, organ transplantation, and lupus erythematosus. The main adverse effects are bone marrow suppression and gastrointestinal reactions besides can cause hyperuricemia, after using the drug to fully hydrate and alkalize the urine to reduce the occurrence of hyperuricemia.  3, anti-tumor antibiotics Anti-tumor antibiotics are chemical substances with anti-tumor activity produced by microorganisms, which were developed on the basis of anti-infection antibiotic research, and actinomycin D (ACD) was discovered in the search for anti-tuberculosis drugs. ACD is the fifth effective anti-tumor drug discovered, and the first anti-tumor antibiotic discovered.  The mechanism of action uses different mechanisms to affect the biosynthesis of DNA, RNA and proteins, which mutate cells, affect cell division and lead to cell death. They are divided into the following classes of drugs: anthracycline antitumor antibiotics: adriamycin (ADM), erythromycin (DNR), epi-adriamycin (EPI or E-ADM), mitoxantrone (MTT, DHAD), and pyrimethamine (THP). The mechanisms of action are binding to DNA; generation of free radicals; binding to metal ions; and binding to cell membranes.  It is effective in almost 70% of solid tumors, such as breast cancer, malignant lymphoma, lung cancer, acute leukemia, etc.; however, its cardiotoxicity and myelosuppression become the main factors limiting the increase of dose, so clinical application should pay attention to good cardiac monitoring to prevent the occurrence of heart failure. This drug extravasation causes tissue ulcer necrosis, clinical use pay attention to the selection of the vein, add drugs when the nurse should stand by the bedside, to ensure that the drug goes smoothly, found that drug extravasation promptly stop the drug and pull out the needle, give with local closure, Jinhuang San Chinese medicine external application, to reduce the degree of tissue necrosis.  Actinomycin anti-tumor antibiotics: Actinomycin D (ACD). The mechanism of action is Inhibition of RNA synthesis. It can cause phlebitis when injected intravenously, and leakage out of blood vessels may lead to tissue necrosis. Dosage precautions are the same as for Adriamycin.  Bleomycin class anti-tumor antibiotics: Bleomycin (scramblomycin), Pingyangmycin (A5). May cause skin reactions, manifested as hyperpigmentation, dermatitis, increased keratinization, rash, etc. It can also cause fibrosis of the lung tissue, and attention should be paid to checking the lungs during medication, if there is charm νR at the bottom of the lung mitomycin class of antitumor antibiotics: mitomycin A, mitomycin B, mitomycin C (MMC). The mechanism of action is to form inter- or intra-strand cross-links with DNA, thereby inhibiting DNA synthesis. In addition, oxygen radicals caused by MMC had added may also be associated with antitumor activity. Adverse effects of this drug include myelosuppression, mainly manifested by a decrease in platelets, and intensive monitoring of the blood picture when using the drug. Extravasation of the drug may cause tissue ulceration and necrosis, and the precautions for administration are the same as those for adriamycin.  Mitomycin anti-tumor antibiotics: Mitomycin (MTH), olivomycin. The mechanism of action is to bind to DNA and inhibit DNA-dependent RNA polymerase, thus inhibiting the synthesis of RNA. It also blocks the calcium-raising effect of pharmacological doses of vitamin D and inhibits the action of thyroid on osteoclasts. It is mainly used for testicular embryonal carcinoma.  Other anti-tumor antibiotics: streptozotocin (STT). The mechanism of action is to inhibit DNA synthesis and to inhibit certain key enzymes of pyrimidine nucleoside metabolism and glycogen isogenesis. It is mainly used clinically for malignant lymphoma, acute and chronic lymphocytic leukemia and nephroblastoma. The main side effect is myelosuppression, and regular monitoring of the blood picture is important in clinical application.