Mechanism of Action: Description: Thiotepa is an ethyleneimine alkylating agent which interferes with DNA replication and transcription of RNA, resulting in the disruption of nucleic acid function.

Thiotepa is a phase nonspecific polyfunctional alkylating agent (i.e., more than one reactive ethylenimine group). In vivo and vitro studies show alkylation of DNA by Thiotepa and Tepa can follow two pathways, but it remains unclear which pathway represents the precise mechanism of action.

After administration, thiotepa converts into ethylenimine groups. Upon administration, thiotepa is converted into highly reactive ethylenimine groups, which covalently bind to nucleophilic groups in DNA and demonstrate a preference for the N7 position of guanine bases. Thiotepa belongs to a class of drugs called alkylating agents.

2. Mechanism Of Action.

Thiotepa (and TEPA) form DNA crosslinks that lead to a reactive metabolite. Alkylating agents produce their anti-cancer effects by causing a chemical reaction that damages the DNA in a cell.

This includes Wilms tumor, rhabdomyosarcoma, Ewing's sarcoma, trophoblastic neoplasm, testicular cancer, and certain types of ovarian cancer. Thiotepa can cause fetal harm when administered to a pregnant woman based on findings from animals and the drug’s mechanism of action [see Clinical Pharmacology].

The aziridine ring opens after protonation of the ring nitrogen.

This radical likely forms a cross-linkage between two strands of DNA, 2. Although its mechanism of action is not fully understood, busulfan appears to act through the alkylation of DNA. Mechanism of Toxicity. MECHANISM OF ACTION: Thiotepa, a derivative of nitrogen mustard, acts as a polyfunctional alkylating agent.

2. Indications Carcinoma of the bladder, ovaries, and breast; brain tumors; Hodgkin's disease; non-Hodgkin's lymphoma; lymphosarcoma; malignant effusions.

One of the principal bond disruptions is initiated by alkylation of guanine at the N-7 position, which severs the linkage between the purine base and the sugar and liberates alkylated guanines.

♦Thiotepa (thy-oh-tep'-ah) Triethylene, Thio-Tepa, TESPA, TSPA Pregnancy Category D Mechanism of Action An alkylating agent that alters DNA replication, RNA transcription, and nucleic acid formation, resulting in cell death. Alkylation takes place through the formation of a highly reactive ethylenimine radical. Therefore, thiotepa combined with other alkylating agents such as The Scottish Medicines Consortium has advised (June 2012) that thiotepa (Tepadina ®) is not recommended for use within NHS Scotland in combination with other chemotherapy as conditioning treatment in adults or children with haematological diseases, or solid tumours prior to haematopoietic stem cell transplantation. How is thiotepa … What is the mechanism of action?

It is given by injection into a vein..

Indications Carcinoma of the bladder, ovaries, and breast; brain tumors; Hodgkin's disease; non-Hodgkin's lymphoma; lymphosarcoma; malignant effusions.

♦Thiotepa (thy-oh-tep'-ah) Triethylene, Thio-Tepa, TESPA, TSPA Pregnancy Category D Mechanism of Action An alkylating agent that alters DNA replication, RNA transcription, and nucleic acid formation, resulting in cell death. Discuss the potential hazard to the fetus if thiotepa is used during pregnancy or if a patient becomes pregnant while taking this drug. What are the generic drug sources for thiotepa and what is the scope of freedom to operate?. The radiomimetic action of thiotepa is believed to occur through the release of ethylenimine radicals which, like irradiation, disrupt the bonds of DNA.

Following systemic absorption of busulfan, carbonium ions are formed, resulting in DNA alkylation and DNA breaks and inhibition of DNA replication and RNA transcription. Zhang J(1), Stevens MF, Bradshaw TD. One of the principal bond disruptions is initiated by alkylation of guanine at the N-7 position, which severs the linkage between the purine base and the sugar and liberates alkylated guanines.

Thiotepa is a cytotoxic agent of the polyfunctional type, related chemically and pharmacologically to the nitrogen mustard. Thiotepa for Injection, USP DESCRIPTION Thiotepa for injection is an ethylenimine-type compound. In vivo and vitro studies show alkylation of DNA by Thiotepa and Tepa can follow two pathways, but it remains unclear which pathway represents the precise mechanism of action.

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