What are the side effects of alkylating agents on bone marrow?
Most alkylating agents cause gastrointestinal side effects and dose-limiting toxicity to bone marrow. Most of the alkylating agents produce an acute suppression of the bone marrow, with the major effect being a decreased granulocyte count. Busulfan depresses all blood elements, particularly stem cells.
What is an example of an alkylating agent?
Triazines (for example, temozolomide and dacarbazine). Alkylating agents may cause critical vomiting and nausea and decreases the number of white blood cells and red blood cells as well. The decrease in the white blood cell count results in susceptibility to the infection.
Why are alkylating agents toxic to normal cells?
Because alkylating agents affect all cells that are dividing frequently, they are also toxic to normal cells, particularly those of the gastrointestinal tract, bone marrow, testicles, and ovaries.
What organ systems are affected by alkylating agents?
In addition to the effect on the bone marrow, alkylating agents are highly toxic to mucosal cells resulting in oral mucosal ulceration and effects on the intestinal mucosa. Other organ systems affected by some alkylating agents include the lungs (pulmonary fibrosis) and the liver.
What is the major toxicity of alkylating agents?
The major clinical toxicities of most of the alkylating agents are similar to those of mechloramine, primarily bone marrow depression (including anemia, leukopenia, and thrombocytopenia) and nausea and vomiting. As noted above, alkylating agents generally have low TIs, because they target all dividing cells.
What is one of the most common side effects of antimetabolites?
Side Effects of Antimetabolites If you're going to take a particular antimetabolite to treat cancer, you should talk to your doctor about the common side effects of that drug. In general, side effects found in many antimetabolites include: Nausea, vomiting, or loss of appetite. Tiredness, weakness, or sore muscles.
What are alkylating agents?
Alkylating agents (ATC code L01A) are highly reactive compounds that easily attach to DNA and cellular proteins. The primary mode of action for most alkylating drugs is via cross-linking of DNA strands.
Which of the following is a commonly reported adverse effect associated with the use of alkylating agents Mcq?
Nausea and vomiting are frequent side effects of alkylating agents.
Which one of the following drug is alkylating agent?
Some examples of alkylating agents are nitrogen mustards (chlorambucil and cyclophosphamide), cisplatin, nitrosoureas (carmustine, lomustine, and semustine), alkylsulfonates (busulfan), ethyleneimines (thiotepa), and triazines (dacarbazine).
What do alkylating agents do to DNA?
Alkylating agents work by destroying the DNA in cancer cells. This is done by replacing alkyl groups with hydrogen atoms in the DNA so the cells can't repair themselves. As a result, the lack of functioning DNA prevents cancer cell division and replication.
How does alkylating agents cause mutations?
Mutagenicity is related to the ability of alkylating agents to form crosslinks and/or transfer an alkyl group to form monoadducts in DNA. The most frequent location of adducts in the DNA is at guanines. Expressed mutations involve different base substitutions, including all types of transitions and transversions.
What chemical reaction do alkylating agents participate in?
The alkylating agents are a group of strong disinfecting chemicals that act by replacing a hydrogen atom within a molecule with an alkyl group (CnH2n+1), thereby inactivating enzymes and nucleic acids (Figure 13.3. 11).
What is an alkylating agent in chemotherapy?
Alkylating agents were among the first anti-cancer drugs and are the most commonly used agents in chemotherapy today. Alkylating agents act directly on DNA, causing cross-linking of DNA strands, abnormal base pairing, or DNA strand breaks, thus preventing the cell from dividing.
What side effects does chemotherapy have?
Here's a list of many of the common side effects, but it's unlikely you'll have all of these.Tiredness. Tiredness (fatigue) is one of the most common side effects of chemotherapy. ... Feeling and being sick. ... Hair loss. ... Infections. ... Anaemia. ... Bruising and bleeding. ... Sore mouth. ... Loss of appetite.More items...
Which of the following is alkylating agent Mcq with answers?
1. Which of the following alkylating agents is employed for carbon-carbon alkylations? Explanation: The alkylating agents employed most extensively for carbon-carbon alkylations are ethylene, propylene, butylenes, and amylenes.
Which of these are examples of alkylating agents quizlet?
Nitrogen mustard.Alkylsulfonates.Nitrosoureas.Triazines.Ethylenimines.Methylhyderazine.
What is antimetabolite drug?
Listen to pronunciation. (AN-tee-meh-TA-boh-lite) A drug that is very similar to natural chemicals in a normal biochemical reaction in cells but different enough to interfere with the normal division and functions of cells.
What are antimetabolites and examples?
Antimetabolites. Antimetabolites are group of anticancer agents that exert their cytotoxic effects by interfering with the DNA synthesis. Some of the important drugs from this class are 5-fluorouracil (5-FU), capecitabine, floxuridine, cytarabine, gemcitabine, decitabine, and vidaza.
What are the adverse effects of methotrexate?
Methotrexate may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:dizziness.drowsiness.headache.swollen, tender gums.decreased appetite.reddened eyes.hair loss.
What is the mechanism of action of antimetabolites?
Their first mechanism of action is, therefore, to induce depletion in nucleotides inducing in turn an inhibition of DNA replication. However, some of them are able to get inserted fraudulently into nucleic acids, inducing structural abnormalities leading to cell death by other mechanisms, including DNA breaks.
What is an alkylating agent?
Alkylating agents are a class of antineoplastic or anticancer drugs which act by inhibiting the transcription of DNA into RNA and thereby stopping the protein synthesis. Alkylating agents substitute alkyl groups for hydrogen atoms on DNA, resulting in the formation of cross links within the DNA chain and thereby resulting in cytotoxic, mutagenic, ...
Which cell is most affected by alkylating agents?
Cancer cells are among the most affected because they are among the most rapidly dividing cells. However, hematopoetic, reproductive, and endothelial cells also divide rapidly which accounts for the common side effects of the alkylating agents: anemia, pancytopenia, amenorrhea, impaired spermatogenesis, intestinal mucosal damage, alopecia, ...
What are the side effects of alkylating agents?
Most alkylating agents cause gastrointestinal side effects and dose-limiting toxicity to bone marrow. Most of the alkylating agents produce an acute suppression of the bone marrow, with the major effect being a decreased granulocyte count. Busulfan depresses all blood elements, particularly stem cells. Because both cellular and humoral immunity are suppressed by alkylating agents some are used for the treatment of autoimmune disease. In addition to the effect on the bone marrow, alkylating agents are highly toxic to mucosal cells resulting in oral mucosal ulceration and effects on the intestinal mucosa. Other organ systems affected by some alkylating agents include the lungs (pulmonary fibrosis) and the liver. Cyclophosphamide and ifosfamide cause a severe hemorrhagic cystitis due to their release of acrolein, a metabolite. This condition is manageable with thiol flushing agents. Because the more unstable alkylating agents, such as nitrogen mustard and the nitrosoureas, have strong vesicant properties they damage veins with repeated use and produce ulceration if extravasated. Alkylating agents cause alopecia and have immunosuppressive effects Chabner et al (2001), Pratt et al (1994), Tew et al (2001), Fraiser et al (1991).
What alkylating agents are used in chemo?
Cisplatin, oxaliplatin, carboplatin, chlorambucil, cyclophosphamide, mechlorethamine, and melphalan are some of the most important alkylating agents used for chemotherapy. The exposure of cells to alkylating agents causes a specific reduction in DNA synthesis, chromosomal aberrations, and genetic mutations [15].
What is the role of alkylating agents in cancer?
Alkylating agents play a significant role in the treatment of lymphoma, Hodgkin's disease, breast cancer, multiple myeloma, and other malignancies. In addition to conventional chemotherapy, the linear dose–response curve of alkylating agents expands their role for incorporation into transplant regimens. Table 2.
Why are alkylating agents toxic?
Because both cellular and humoral immunity are suppressed by alkylating agents some are used for the treatment of autoimmune disease. In addition to the effect on the bone marrow, alkylating agents are highly toxic to mucosal cells resulting in oral mucosal ulceration and effects on the intestinal mucosa.
What is the primary mode of action for most alkylating drugs?
The primary mode of action for most alkylating drugs is via cross-linking of DNA strands. They can be classified as either monofunctional alkylating agents, implying reactions with only one strand of DNA, or bifunctional alkylating agents, which cross-link two strands of DNA.
How do alkylating agents react with DNA?
Alkylating agents react with electron-rich atoms to form covalent bonds. The common alkane transferred by classical alkylating agents is a single-carbon methyl group that also includes longer hydrocarbons. The most important reactions with regard to the agents' antitumor activities are reactions with DNA bases. Some alkylating agents are monofunctional and react with only one strand of DNA. Others are bifunctional and react with an atom on both strands of DNA, producing a cross-link that covalently links the two strands of the DNA double helix. Unless repaired, this lesion will prevent the cell from replicating effectively. The lethality of the monofunctional alkylating agents results from the recognition of the DNA lesion by the cell and by the response of the cell to that lesion.
How do alkylating agents prevent cell division?
Alkylating agents prevent cell division primarily by cross-linking strands of DNA. Because of continued synthesis of other cell constituents, such as RNA and protein, growth is unbalanced, and the cell dies. Activity of alkylating agents does not depend on DNA synthesis in the target cells.
What is the mechanism of action of busulfan?
Answer: Busulfan (alkylating agents mechanism of action) is a bifunctional alkylating agent that can be used to bind two labile methanesulfonate groups to opposite ends of a four-carbon alkyl chain. Busulfan hydrolyzes in aqueous media, releasing methanesulfonate groups.
How does Melphalan affect DNA?
Answer: Melphalan chemically changes the DNA nucleotide guanine via the alkylation process and causes the linkages between DNA strands. This chemical alteration inhibits the RNA synthesis and DNA synthesis, functions required for cells to survive. These particular changes cause cytotoxicity in the dividing and non-dividing tumour cells.
What happens if the MGMT promoter region gets methylated?
If the MGMT promoter region gets methylated, the cells will no longer produce the MGMT, and they are thus more responsive to the alkylating agents. In gliomas, methylation of the MGMT promoter is a valuable indicator of tumour responsiveness to alkylating agents.
What is nitrogen mustard?
Nitrogen mustards are the cytotoxic organic compounds having the functional group - chloroethylamine (Cl (CH2)2NR2). Although originally it is produced as chemical warfare agents, they were the first chemotherapeutic agents for cancer treatment. Nitrogen mustards are said to be the nonspecific DNA alkylating agents.
What is the name of the drug group that is used to treat brain cancer?
Answer: A cancer drug group, which is called alkylating agents due for the reason they act by the process of alkylation to inhibit the DNA repair. The nitrosoureas may cross the blood-brain barrier and can be used in the treatment of brain tumours. The nitrosoureas include lomustine (CCNU), carmustine (BCNU), and semustine.
How do alkylating agents stop cancer?
They stop the tumour growth by cross-linking guanine nucleobases in the double-helix strands of DNA, directly attacking DNA. This process makes the strands unable to separate and uncoil. As this is quite necessary for DNA replication, the cells may no longer divide. These particular drugs act nonspecifically.
What are the types of molecular changes that are induced by the alkylating agents?
The types of molecular changes that are induced by the alkylating agents can be given as cross-linking between the DNA strands and the loss of a basic component (which is purine) from or the nucleic acid breaking. The result is, nucleic acid will not be replicated.
What are Alkylating agents?
Alkylating agents are compounds that work by adding an alkyl group to the guanine base of the DNA molecule, preventing the strands of the double helix from linking as they should. This causes breakage of the DNA strands, affecting the ability of the cancer cell to multiply. Eventually, the cancer cell dies.
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