Cancer Chemotherapy Via Drugs

Cancer Chemotherapy Via Drugs

Cancer Chemotherapy

Cancer chemotherapy remains an intriguing area of pharmacology. On the one hand, use of anti-cancer drugs produces high rates of cure of diseases that, without chemotherapy, result in extreme high mortality rates (eg, acute lymphocytic leukemia in children, testicular cancer, Hodgkin’s and another hand, some types of cancer are barely affected by currently available drug Furthermore, as a group, the anticancer drugs are more toxic than any other pharmaceutics agents, and thus their benefit must be carefully weighed against their risks. Many of the available drugs are cytotoxic agents that act on all dividing cells, cancerous or normal. The ultimate goal in cancer chemotherapy is to use advances in cell biology to develop drugs that selectively target specific cancer cells. A few such agents are in clinical use, and many more are in development.

Cancer Cell Cycle Kinetic

Cancer cell population kinetics and the cancer cell cycle are important determinants of the actions and clinical uses of anticancer drugs. Some anticancer drugs act specifically on tumor cells undergoing cycling (cell cycle-specific [CCS] drugs), and others (cell cycle nonspecific [CCNS] drugs) kill cycling and resting phases of the cell cycle drugs cell cycle are usually most active in a specific phase of the cell cycle. CCS drugs are particularly effective when a large proportion of tumor cells are proliferating.

The Log-Kill Hypothesis

Cytotoxic drugs act with first-order kinetics. That is, a given dose kills a constant propene of a cell rather than a constant number of cells. The log hypothesis proposes that the magnitude of tumor cell kill by anticancer drugs is a logarithmic function. For example, a 3-log-kill dose of an effective drug will reduce a cancer cell population of 1012 cells to 10 (total kill of 999 x cells, the same dose would reduce a starting population of 10 cells to 10 cells (a kill of 999 x 10 cells). In both cases, the dose reduces the numbers of cells by 3 orders of magnitude or 3 log C.

Resistance To Anticancer Drugs

Resistance To Anticancer Drugs
Resistance To Anticancer Drugs

Drug resistance is a major problem in cancer chemotherapy. Mechanisms of resistance include the following:

  • Increased DNA Repair

An increased rate of DNA and repair in tumor cells can be responsible for resistance and is particularly important for alkylating agents and cisplatin.

  • Formation Of Trapping Agents

Increase in the production of some tumor cells thiol trapping agents which interact with anticancer drugs. So that form reactive electrophilic species. This mechanism of resistance is seen with the alkylating agent bleomycin cisplatin and the anthracyclines.

  • Changes In Target Enzymes

When the drug sensitivity of a target enzyme changed then dihydrofolate reeducates increased the synthesis of enzyme are mechanisms of resistance of tumor cells to methotrexate.

  • Decreased Activation Of Pro-Drugs

Resistance to the purine antimetabolites (mercaptopurine), use I nine and the pyrimidine antimetabolites (cytarabine fluorouracil) can result from a decrease in the activity of the tumor cell needed to convert these prodrugs to their cytotoxic metabolites.

  • Decreased Drug Accumulation

The usual form of multidrug resistance also involved the increased expression of the normal gene (the gene) for a cell surface glycoprotein (P.glycoprotein). This transport molecule is drugs in the accelerated efflux of many anticancer resistant cells.

Treatment of chemotherapy

A. CYCLOPHOSPHAMIDE 

  • Pharmacokinetics

Hepatic cytochrome P450. Mediated biotransformation of cyclophosphamide is needed for the antitumor activity. One of the breakdown products is acrolein.

  • Clinical Use

Uses of cyclophosphamide include non-Hodgkin’s lymphoma, breast and ovarian cancers, and neuroblastoma.

  • Toxicity Gastrointestinal distress, myelosuppression, and alopecia are expected adverse effects. Hemorrhagic cystitis resulting from the formation of acrolein may be decreased by vigorous hydration and by use of mercaptoethanesulfonate (mesna). Phosphamide and also cause cardiac dysfunction, pulmonary toxicity, a syndrome of inappropriate antidiuretic hormone (ADH) secretion.

B. MECHLORETHAMINE

Pharmacokinetics Mechlorethamine, Mechanism is spontaneously converted into a reactive cytotoxic product in the body

  • Clinical use Mechlorethamine is best known for use in regimens for Hodgkin’s lymphoma.
  • Toxicity-Gastrointestinal distress, myelosuppression. sterility is common. Mechlorethamine and marked vesicant actions.

C. PROCARBAZINE 

  • Mechanisms

Procarbazine is a reactive agent that forms hydrogen peroxide, which generates free radicals that cause DNA strand scission

  • Pharmacokinetics

Procarbazine is orally active and penetrates into most tissues, including the cerebrospinal fluid. It is eliminated via hepatic metabolism.

  • Clinical Use

The primary use of the drug is as a component of regimens for Hodgkin’s lymphoma

Toxicity-Procarbazine is a myelosuppressant and causes gastrointestinal irritation, CNS dysfunction, peripheral neuropathy, and skin reactions. Procarbazine inhibits many enzymes, including monoamine oxidase (MAO) and those involved in hepatic drug metabolism. Disulfiram-like reactions have occurred with ethanol The drug is leukemogenic.

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