What Is an Antimetabolite?

Antimetabolites refer to drugs that can specifically bind to metabolites in the body, thereby affecting or antagonizing metabolic functions. Generally, their chemical structures are similar to nucleic acid or protein metabolites in the body.

Antimetabolite

Anti-generation

Antimetabolites: Drugs that affect nucleic acid biosynthesis.

First, the two compete for the same enzyme system, affecting the normal biochemical reaction rate between the enzyme and the metabolite, and reducing or eliminating the production of metabolites;

Second, it participates in biochemical reactions as "pseudo" substances, generating inactive products, and blocking a certain metabolism, resulting in the synthesis pathway being blocked.

Methotrexate is a folate antagonist used to treat children

6-mercaptopurine is a purine antagonist. Its chemical structure is similar to hypoxanthine, and it is an inhibitor of purine nucleotide synthesis.

In the body, catalyzed by hypoxanthine-guanylate enzyme (HGPRT), 6-MP is first converted into thioinosinic acid, which prevents the conversion of inosine to adenylate and guanylate, which interferes with purine metabolism , Hinder DNA synthesis, make

1. Pharmacological action and clinical application

5-Fluorouracil is a pyrimidine antagonist.

5-FU does not work until it is converted into 5-fluorouracil deoxynucleotides in the cell.

Its resistance

Digestive tract reactions are common after intravenous infusion and appear first;

Bone marrow toxicity usually occurs in the second week after administration, and often manifests as leukopenia and thrombocytopenia.

Anti-metabolic drugs act on different aspects of the nucleic acid synthesis process, and can be divided into the following types of drugs according to their effects:

(1) Thymidylate synthase inhibitors: Fluorouracil (5-FU), Furan Fluorouracil (FT-207), Difurafuridine (bisfuridine FD-1), Uflurane (UFT), Fludron ( 5-DFUR).

The antitumor effect is mainly due to its metabolic activator, fluorouracil deoxynucleotide, which interferes with the conversion of deoxyuracil to deoxythymine nucleotides, thus affecting the synthesis of DNA. After forty years of clinical application, it has become commonly used clinically. Antitumor drugs have become the basic drugs for the treatment of lung cancer, breast cancer, and digestive tract cancer.

Adverse reactions were relatively slow. Gastrointestinal mucosal damage occurred 6 to 7 days after administration, such as oral ulcers, loss of appetite, nausea, vomiting, and diarrhea, which caused bone marrow suppression after one week. Mucositis became the main toxic reaction for more than 96 hours. Clinically, if long-term continuous infusion of such drugs, oral care of patients should be done, and patients should be taught how to clean their mouths to prevent severe mucositis.

(2) Dihydrofolate reductase inhibitors: methotrexate (MTX), aminopterin (Baixuening), etc. They have an inhibitory effect on dihydrofolate reductase. After using formyltetrahydrofolate (CF) to rescue the toxicity of MTX, the dose of MTX is greatly increased. It is effective in treating osteosarcoma and head and neck tumors, as well as certain immune disorders. Its adverse reactions can cause severe stomatitis, ulcerative gastritis, hemorrhagic enteritis, and even intestinal perforation and death; bone marrow suppression is related to dosage and administration schedule. Clinically, oral care should be done for patients, and serious adverse reactions such as intestinal perforation should be observed carefully. Report to the doctor in time to prepare for rescue.

(3) DNA polymerase inhibitors: cytarabine (Ara-c), cyclocytidine, and chlorocytidine. They function in the body when they become cytarabine triphosphate (Ara-CTP). This reaction is caused by Deoxycytidine Kinase Catalysis. The content of this kinase is high in leukemia cells and lymphocytes, so it has a selective effect on leukemia, a strong inhibitory effect on DNA polymerase, and affects DNA replication.

General doses can cause adverse effects such as bone marrow suppression, nausea, vomiting, but are mild. At high doses, severe bone marrow suppression such as white blood cells, thrombocytopenia, and anemia, obvious nausea, vomiting, and severe diarrhea. The type of response is to take care of the patient accordingly. Such as do a good job of prevention of infection, bleeding, diarrhea, and reduce complications caused by adverse reactions.

(4) Nucleotide reductase inhibitors: hydroxyurea (HU), inosine dialdehyde, adenosine diialde-hgde, guanazole, including cytidylic acid and guanylic acid , Adenylate and thymidine are reduced to the corresponding deoxynucleotides, ultimately preventing the synthesis of DNA by inhibiting the inhibition of nucleic acid reductase. It is clinically used to treat chronic myelogenous leukemia, malignant melanoma, breast cancer, head and neck cancer, bowel cancer, and is also effective for psoriasis. Adverse reactions were mainly myelosuppression. Clinically, attention should be paid to the monitoring of blood images to prevent infection.

(5) Purine nucleotide synthesis inhibitor: 6-mercaptopurine (6-MP) is a purine derivative. Because 6-GMP has affinity for guanylate kinase, 6-TG can finally replace guanine. Incorporated into the nucleic acid. It can inhibit reactions in purine synthesis. It is used clinically for the treatment of leukemia and can also be used as an immunosuppressant for nephrotic syndrome, organ transplantation, and lupus erythematosus. The main adverse reaction is that bone marrow suppression and gastrointestinal reactions can also cause hyperuricemia. After the medication, the urine should be fully hydrated and alkalized to reduce the incidence of hyperuricemia.