Antineoplastic Agents

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Chapter: Medicinal Chemistry : Antineoplastic Agents

Antineoplastic agents are drugs used for the treatment of cancer, malignancy, tumour, carcinoma, sarcoma, leukaemia, or neoplasm (Greek neo = new, Plasm = formation).


Antineoplastic Agents

INTRODUCTION

Antineoplastic agents are drugs used for the treatment of cancer, malignancy, tumour, carcinoma, sarcoma, leukaemia, or neoplasm (Greek neo = new, Plasm = formation). Neoplasm refers to a group of diseases caused by several agents, namely, chemical compounds and radiant energy. Cancer is characterized by an abnormal and uncontrolled, division of cells, which produces tumours and invades adjacent normal tissues. Often, cancer cells separate themselves from the primary tumour, and are carried by the lymphatic system to reach distant sites of the organs, where they divide and form secondary tumours (metastasis).

 

Cell Cycle Kinetics

Two key aspects of cellular life are the following:

1.           DNA synthesis and mitosis to produce new cells.

2.           Cell differentiation that produces specialized cells.

 

Limitations of Therapy

·Cancer cells very rapidly develop resistance to antineoplastic drugs.

·Differences between normal and neoplastic human cells are merely quantitative.

·Biochemical and morphological differences between normal and neoplastic cells are slight; therefore, antineoplastic agents are devoid of selective toxicity to tumour cells.

·Antineoplastic agents kill cells by first-order kinetics, that is, they kill a constant fraction of cells.

However, some of the cancer cells elude killing and one of these cells may restablize the tumour. It is extremely difficult to kill all the malignant cells.

·Most antineoplastic drugs are highly toxic to the patients.

 

Adverse Effects

The prominent adverse effects of antineoplastic drugs are exerted on rapidly proliferating normal tissues, in addition, to their chronic and cumulative toxicities.

·Bone marrow toxicity: Bleomycin, L-asparaginase.

·Hair follicle toxicity: Methotrexate, Vincristine, Cyclophosphamide, and Doxoroubicin.

·Hepatotoxicity: Azathiopurine, Mercaptopurine, and L-asparaginase.

·Skin rashes: Vinca alkaloids, Nitrosourea, Anthracyclins, and Mitomycin C.

·Pulmonary toxicity: Bleomycin, Methotrexate, and Busulfan.

·Cardiac toxicity: Doxorubicin, Daunorubicin, and Anthracyclins.

·Other toxicities: Intestinal epithelium, central nervous system (CNS) toxicity, nephrotoxicity, immunosuppression, fever, anaphylaxis, cataracts, haemolytic anaemia, pancreatitis, pituitary insufficiency, adrenal insufficiency, coagulation problems, suppression of growth, and carcinogenicity.

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