Drugs antimetabolite

Lu, X., et al. Correlation of nucleoside and nucleobase transporter gene expression with antimetabolite drug cytotoxicity. J. Exp. Ther. Oncol. 2002,... 

Q66 Methotrexate should be avoided in a patient v/ith a creatinine clearance of 12 mL/minute. Methotrexate is an antimetabolite drug that is nephrotoxic. 

Methotrexate is an antimetabolite drug that is excreted primarily by the kidney. It is contraindicated in significant renal impairment and in hepatic impairment. It is nephrotoxic and accumulation may occur in renal impairment. Dose should be reduced in renal impairment that is not severe and drug should be avoided if creatinine clearance is less than 20 mL/minute. 

Mechanism of Action. Although the exact mechanism of azathioprine is unknown, this drug probably interferes with DNA synthesis in cells mediating the immune response. Azathioprine appears to act like the antimetabolite drugs used in cancer chemotherapy (see Chapter 36). The cell normally uses various endogenous substances such as purines as ingredients... 

Explain the meaning of the term antimetabolite. Outline, in general terms, the mode of action of antimetabolite drugs. 

Cell cycle (phase) specific these kill only cells that are actively cycling (often because their site of action is confined to one phase of the cell cycle, e.g. antimetabolite drugs). 

Currently, the compound 217 is the only available antimetabolite drug having antifungal activity. It inhibits fungal protein synthesis by replacing 187 with 177 in fungal RNA. 217 also inhibits thymidylate synthetase via 5-fluorodeoxyuridine monophosphate and thus interferes with fungal DNA synthesis. 

Uracil is used more effectively, in nucleic acid synthesis within a rat hepatoma than in normal liver. This observation appears to have stimulated the synthesis of 5-fluorouracil (1027) as an antimetabolite mainly because the introduction of a fluorine atom involves a minimal increase in size. In the event, 5-fluorouracil did prove to have antineoplastic activity and it is now a valuable drug for treatment of tumors of the breast, colon or rectum, and to a lesser extent, gastric, hepatic, pancreatic, uterine, ovarian and bladder carcinomas. As with other drugs which interfere with DNA synthesis, the therapeutic index is quite low and great care is required during treatment (69MI21301). 

There is evidence the drug acts as an antimetabolite for the i ira-aminobenzoic acid required for bacterial metabolism.) One oT the more recent of the many preparations for this drug involves carboxylation of meta-aminophenol (6) by means of ammonium i.ii bonate under high pressure. ... 

The following sections give selected interactions of die alkylating dragp, antimetabolites, antibiotics, hormones, miotic inhibitors, and miscellaneous antineoplastic dragp. The nurse should consult appropriate sources for a more complete listing of interactions before any antineoplastic drug is administered. 

A thorough discussion of the mechanisms of absorption is provided in Chapter 4. Water-soluble vitamins (B2, B12, and C) and other nutrients (e.g., monosaccharides, amino acids) are absorbed by specialized mechanisms. With the exception of a number of antimetabolites used in cancer chemotherapy, L-dopa, and certain antibiotics (e.g., aminopenicillins, aminoceph-alosporins), virtually all drugs are absorbed in humans by a passive diffusion mechanism. Passive diffusion indicates that the transfer of a compound from an aqueous phase through a membrane may be described by physicochemical laws and by the properties of the membrane. The membrane itself is passive in that it does not partake in the transfer process but acts as a simple barrier to diffusion. The driving force for diffusion across the membrane is the concentration gradient (more correctly, the activity gradient) of the compound across that membrane. This mechanism of... 

Antimetabolites. This class of drugs includes purine, pyrimidine, and folic acid analogs that have been successfully used to treat various carcinomas, autoimmune diseases, and dermatological disorders such as psoriasis. Because of their structural similarities to normal components of DNA and RNA synthesis, they are capable of competing with the normal macromolecules and alkylating biological nucleophiles. 

Nevertheless, drugs effects can compete with BrdU uptake in DNA synthesis machinery in case of antimetabolites treatments [20] or after lacking ability to incorporate following DNA damages accumulation or in case of presence of apoptotic cells. Moreover, when cells are delayed between Gi to S (early S, ES) or S to G2/M (late S, LS), only DNA content analysis make accurate quantifications impossible [25],... 

Anticancer drugs act on cells in active proliferation and may interfere with a specific phase of the cell cycle or act independently from it. Some of these drugs are naturally occurring compounds, identified in plants or microorganisms, some are synthetic chemicals. Among the major classes of chemotherapeutics include antimetabolites, alkylating agents, inhibitors of the... 

Methotrexate is an antimetabolite, which is metabolised by the renal and hepatic systems and may lead to renal and hepatic toxicities. Liver and renal function tests are therefore carried out for patients who are administered the drug. Methotrexate can lead to myelosuppression and therefore full blood counts must be monitored for patients taking it. 

The finding that the administration of 6-mercaptopurine to rabbits following exposure to bovine serum albumin prevented antibody formation [374] formed the basis for a new area of chemotherapy for purine analogues and other antimetabolites and was soon followed by the use of these drugs for the therapy of autoimmune disease and the suppression of homograft rejection. This subject has been reviewed in depth [ 12, 375, 375a], has occasioned a symposium [376], and has received much recent publicity as a result of human heart transplants. 

Antimetabolites are enzyme inhibitors (see p. 96) that selectively block metabolic pathways. The majority of clinically important cytostatic drugs act on nucleotide biosynthesis. Many of these are modified nucleobases or nucleotides that competitively inhibit their target enzymes (see p. 96). Many are also incorporated into the DNA, thereby preventing replication. 

The synthesis of suicide inhibitors and the kinetics of enzyme inactivation have greatly advanced the study of enzyme mechanisms as well as the design of drugs and antimetabolites. 

The pyrimidine 5-fluorouracil (64) is used extensively in the clinic as an antimetabolite antitumor agent. As a consequence of poor absorption by the oral route, the drug is usually administered by the intravenous route. A rather simple latent ated derivative, tegafur (66), has overcome this limitation by providing good oral absorption. Reaction of 5-fluorouracil with trimethylsilyl chloride in the presence of base gives the disilylated derivative (65). Reaction of this with dihydrofuran (obtained by dehydro-... 

Cytarabine is an effective antimetabolite in treating leukemia. Like other pyrimidine antimetabolites, cytarabine must be activated by initially transforming into the corresponding nucleotide. The active form of the drag is cytarabine triphosphate. Cytarabine is used for all types of leukemia. Synonyms of this drug are cytosine, arabinoside, and ara-C. 

The mechanism of action of azathioprine as a cytotoxic drug is not different from the mechanism of action of other antimetabolites. Azathioprine is the primary drug used for transplants, especially for kidney transplants. Today, cyclosporine is used instead of azathioprine in many places. However, azathioprine is useful in combination with cyclosporine, and it is even preferred in certain cases. Synonyms of this drug are azumec, imuran, and others. 

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