Antineplastic+Drugs

The role of antineoplastic drugs are to are to fight cancer. Goals of these drugs are to destroy cancer tumor cells without significantly damaging healthy cells. All neoplastic drugs are extremely cytotoxic and have a low margin of safety. The tumor must be receptive to the drug selection to be successful and not all tumors are responsive to the same drugs. Early detection of cancer tumors are key. Smaller tumors have a higher success of being eradicated. These are several drugs that control or kill neoplastic cells; used in chemotherapy to kill cancer cells; all have unpleasant side effects that may include nausea and vomiting and hair loss and suppression of bone marrow function The very nature of antineoplastic agents makes them harmful to healthy [|constantly dividing cells] and tissues, as well as the cancerous cells. For cancer patients with a life-threatening disease, there is a great benefit to treatment with these agents. However, for the health care workers that are exposed to antineoplastic agents as part of their work practice, precautions should be taken to eliminate or reduce exposure as much as possible. There are many classes of antineoplastics:
 * [|Alkylating agents]




 * [|Antimetabolites]
 * [|Antimitotics]: bind to [|tubulin] and inhibit spindle dynamics and thus block cell division
 * [|topoisomerase II inhibitors], stopping DNA from being unwound, which is required for both DNA replication and RNA/protein synthesis.
 * Generating [|free radicals].[//[|citation]//

Examples

 * [|actinomycin]
 * The most important [|immunosuppressant] from this group is [|Actinomycin D], which is used in [|kidney transplantations].

Mechanism of Action: 1. Alkylating agents: 1.) Inhibits the incorporation of radioactive thymidine and uridine in to DNA and RNA; thus, inhibiting DNA and RNA synthesis. 2.) Reactive intermediates covalently bind to microsomal proteins and DNA

2. Antimetabolites: Inhibits protein synthesis and interferes with the DNA synthesisna d to a lesser degree, RNA synthesis.

3. Antimitotics: Inhibits the depolymerization of tubulin which stabilizes microtubules in the cell; thus, resulting in the inhibition of DNA, RNA, and protein synthesis. Most activity occurs during the M phase of the cell cycle.

=The Principles of Cancer Chemotherapy= ====The goal of chemotherapy is to eradicate every viable tumor cell without significantly damaging normal host tissue. Unfortunately chemotherapy agents are not tumor cell-specific and will kill all cells actively undergoing cell division. They work by killing or impairing susceptible tumor cells by blocking a drug-sensitive biochemical metabolic pathway, such as the cell cycle phase-specific antimetabolites to inhibit DNA synthesis. __**All**__ are extremely cytotoxic and have low margins of safety. The principles that govern the useful application of cancer chemotherapy include the following:====


 * 1) The tumor must be susceptible to the drugs selected for treatment. Not all tumors are responsive to the same agents.
 * 2) The drugs or methods of administration must not have intolerable local or systemic toxicity that would prevent the completion of an adequate course of treatment.
 * 3) The dosages and schedules for the drugs must be calculated to maximize the contact with the tumor cells, ant eh drugs must be present in sufficient concentration during the crucial periods of the cell's metabolic cycle.
 * 4) Cancer chemotherapy is more effective when the tumor mass is small than when the tumor cell burden is high. A larger fraction of the tumor cell population is undergoing active division in a small tumor mass, and the blood supply is more plentiful, allowing for increased sensitivity and delivery of the drugs. Debulking by surgery or irradiation reduces tumor cell burden and can induce resting cell populations into active cell division, increasing the growth fraction of the tumor.
 * 5) Anticancer drugs kill cells according to first-order kinetics. Even a drug that destroys 99.99% of the tumor cells will leave a substantial number of tumor cells intact if the initial quantity was large. Because survival of a few or perhaps even a single malignant cell may lead to tumor regrowth, chemotherapy is generally given in cycles to maximize tumor cell reduction. The optimal interval between cycles is determined by the time required to allow for sufficient bone marrow recovery without allowing significant tumor regrowth.
 * 6) The administration of combinations of antineoplastic drugs takes advantage of the different mechanisms of action By using agents that act at different phases of the cell cycle, synergistic effects may be obtained as well as an increase in the collective antitumor effect without a concomitant increase in undesirable side effects. Combination chemotherapy may prevent or slow the development of resistant strains.
 * 7) Cancer cells may build up resistance to a previously effective drug, which then becomes ineffective. Such resistance has been ascribed to a variety of causes, including decreased drug penetration resulting from a reduction in tumor blood supply, drug-provoked mutations, enzyme alterations, and acquired resistance through natural selection of tumor cells insensitive to the drug. The therapeutic potential of the antineoplastic drugs may be enhanced by active antitumor defense mechanisms in the host. Immunotherapy given with chemotherapy, either concurrently or sequentially, may boosy the tumoricidal effect of the drugs.


 * Yagiela p. 698-699


 * ==**HOW DOES CHEMOTHERAPY WORK??**==

To understand how chemotherapy works, it is helpful to understand the normal life cycle of a cell, or the cell cycle. All living tissue is made up of cells. Cells grow and reproduce to replace cells lost during injury or normal "wear and tear." The cell cycle is a series of steps that both normal cells and cancer cells go through in order to form new cells. This discussion is somewhat technical, but it can help you understand how doctors predict which drugs are likely to work well together and how doctors decide how often doses of each drug should be given. There are 5 phases in the cell cycle, which are labeled below using letters and numbers. Since cell reproduction happens over and over, the cell cycle is shown below as a circle. All the steps lead back to the resting phase (G0), which is the starting point. After a cell reproduces, the 2 new cells are identical. Each of the 2 cells made from the first cell can go through this cell cycle again when new cells are needed. The Cell Cycle ==This cell cycle is important to cancer doctors (oncologists) because many chemotherapy drugs work only on cells that are actively reproducing (not on cells in the resting phase, G0). Some drugs specifically attack cells in a particular phase of the cell cycle (the M or S phases, for example). Understanding how these drugs work helps oncologists predict which drugs are likely to work well together. Doctors can also plan how often doses of each drug should be given based on the timing of the cell phases.== When chemotherapy drugs attack reproducing cells, they cannot tell the difference between reproducing cells of normal tissues (those that are replacing worn-out normal cells) and cancer cells. The damage to normal cells can cause side effects. Each time chemotherapy is given, it involves trying to find a balance between destroying the cancer cells (in order to cure or control the disease) and sparing the normal cells (to lessen unwanted side effects).
 * **G0 phase (resting stage):** The cell has not yet started to divide. Cells spend much of their lives in this phase. Depending on the type of cell, G0 can last for a few hours to a few years. When the cell gets a signal to reproduce, it moves into the G1 phase.
 * **G1 phase:** During this phase, the cell starts making more proteins and growing larger, so the new cells will be of normal size. This phase lasts about 18 to 30 hours.
 * **S phase:** In the S phase, the chromosomes containing the genetic code (DNA) are copied so that both of the new cells formed will have matching strands of DNA. S phase lasts about 18 to 20 hours.
 * **G2 phase:** In the G2 phase, the cell checks the DNA and gets ready to start splitting into 2 cells. This phase lasts from 2 to 10 hours.
 * **M phase (mitosis):** In this phase, which lasts only 30 to 60 minutes, the cell actually splits into 2 new cells.

Cyclophosphamide
Chemocare.com uses generic names in all descriptions of drugs. Cytoxan is the trade name for cyclophosphamide. Neosar is another name for cyclophosphamide. In some cases, health care professionals may use the trade name cytoxan or other names neosar when referring to the generic drug name cyclophosphamide. Important things to remember about the side effects of cyclophosphamide:
 * Trade names:** Cytoxan®, Neosar®
 * Drug type:** Cyclophosphamide is an anti-cancer (“antineoplastic” or “cytotoxic”) chemotherapy drug. This medication is classified as an “alkylating agent.” (For more detail, see “How this drug works” section below).
 * What this drug is used for:**
 * Cancers treated with cyclophosphamide include: Hodgkin’s and non-Hodgkin's lymphoma, Burkitt’s lymphoma, chronic lymphocytic leukemia (CLL), chronic myelocytic leukemia (CML), acute myelocytic leukemia (AML), acute lymphocytic leukemia (ALL), t-cell lymphoma (mycosis fungoides), multiple myeloma, neuroblastoma, retinoblastoma, rhabdomyosarcoma, Ewing's sarcoma; breast, testicular, endometrial, ovarian, and lung cancers, and in conditioning regimens for bone marrow transplantation.
 * Cyclophosphamide is also used to treat many disorders that are not cancer.
 * Note:** If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful.
 * How this drug is given:**
 * Cyclophosphamide can be given can be given by a number of different routes. The route that it is given depends on the dosage, the condition being treated, as well as the purpose it is being used for.
 * It is usually given through a vein by injection or infusion (intravenous, IV) or by mouth in tablet form, depending upon the diagnosis.
 * Cyclophosphamide is also approved to be given by a shot into a muscle (IM), into the abdominal lining (intraperitoneal, IP), or into the lining of the lung (intrapleural).
 * Tablets should be given with food or after meals. Tablets should not be cut or crushed.
 * The amount of cyclophosphamide that you will receive depends on many factors, including your height and weight, your general health or other health problems, and the type of cancer or condition you have. Your doctor will determine your exact dosage and schedule.
 * Side effects:**
 * The side effects of cyclophosphamide and their severity depend on how much of the drug is given. In other word, high doses may produce more severe side effects.
 * You will not get all of the side effects mentioned below.
 * Side effects are often predictable in terms of their onset, duration, and severity.
 * Side effects are almost always reversible and will go away after therapy is complete.
 * Side effects are quite manageable. There are many options to minimize or prevent them.

Chlorambucil
(klor-AM-byoo-sil) Chemocare.com uses generic drug names in all descriptions of drugs. Leukeran is the trade name for chlorambucil. In some cases, health care professionals may use the trade name leukeran when referring to the generic drug name chlorambucil. Used to treat chronic lymphocytic leukemia (CLL), Hodgkin's disease, non-Hodgkin's lymphoma, breast, ovarian and testicular cancer, Waldenstrom's macroglobulinemia, thrombocythemia, choriocarcinoma. Important things to remember about the side effects of chlorambucil: Most people do not experience all of the side effects listed.
 * Chlorambucil**
 * Trade name:** Leukeran
 * Drug Type:** Chlorambucil is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. This medication is classified as an "alkylating agent." (For more detail, see "How this drug works" section below).
 * What this drug is used for:**
 * Note:** If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful.
 * How this drug is given:**
 * Chlorambucil is given by mouth as a coated tablet.
 * Take 1 hour before or 2 hours after meals.
 * The amount of chlorambucil you receive and how often it is administered, depends on many factors, including your height and weight, your general health, any other health problems you may have, and the type of cancer or condition being treated. Your doctor will determine your dose and schedule.
 * Side effects:**
 * Side effects are often predictable in terms of their onset and duration.
 * Side effects are almost always reversible and will go away after treatment is complete.
 * There are many options to help minimize or prevent side effects.
 * There is no relationship between the presence or severity of side effects and the effectiveness of the medication.


 * Direct toxicocites || Indirect ||
 * Oral mucositis || Myelosuppression ||
 * Mucosal inflammation || Neutropenia ||
 * Cytotoxicity || Immunosuppression ||
 * Bacterial infection || Anemia ||
 * Salivary gland dysfunction || Thrombocytopenia ||

Drugs that damage the oral mucosa: methotrexate, doxorubicin,fluorouracil, platinum, and aldesleukin. Management: Palliative treatment
 * 1) bland rinses (saline or sodium bicarbonate)
 * 2) mucosal coating (antacid solutions, kaolin solutions)
 * 3) water-soluable like artificial saliva
 * 4) topical anesthetic like benzocaine
 * 5) film-forming agents like hydroxypropyl cellulose.
 * 6) Suggest to eat soft, bland, non-spicy foods.
 * 7) Fluoride rinses or flouride trays made. Use fluoride everynight.