Neoplastic disease and Antineoplastic Agents - PowerPoint Presentation

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Neoplastic disease and Antineoplastic Agents

BP 602 T Pharmacology III

Neoplastic disease

Cancer is a disease

characterised

by uncontrolled multiplication and spread of abnormal forms of the body's own cells.

The terms

cancer

,

malignant neoplasm

(neoplasm simply means 'new growth') and

malignant

tumour

are synonymous.

Both

benign

and

malignant

tumours

manifest uncontrolled proliferation, but the latter are distinguished by their capacity for

dedifferentiation

, their

invasiveness

and their ability to

metastasise

(spread to other parts of the body).

Cancer treatment employs six established principal modalities:

Surgery;

Radiotherapy;

Chemotherapy;

Endocrine therapy;

Immunotherapy;

biological therapy.

Chemotherapy of cancer, as compared with that of bacterial disease, presents a difficult problem. In biochemical terms, micro- organisms are both quantitatively and qualitatively different from human cells, but cancer cells and normal cells are so similar in most respects

Rationale for cytotoxic chemotherapy

Modern cancer chemotherapy originated in the 1940s with the demonstration that nitrogen mustard [

with

sulphur

mustards

(oily vesicant liquids) which had been developed and used as chemical weapons in World War I (1914-18). Preparations for World War II (1939-45) included research to increase the potency and toxicity ('efficacy') of these odious substances. Substitution of a nitrogen atom for the

sulphur

atom, i.e. making

nitrogen mustards

The disappearance of lymphocytes and granulocytes from the blood of rabbits was a useful marker of toxicity and gave rise to the idea of possible efficacy in lymphoid cancers.

] possessed antitumor activity against human lymphomas and leukemias.

Other classes of cytotoxic agents, e.g.

antimetabolities

, were subsequently identified and used to treat cancer patients.

General Toxicological Properties of Anticancer Drug

Most of the Anti-cancer drugs

exert toxic effects on both normal and tumor tissues even at optimal dosages. This

lack of selective toxicity

is the major limiting factor in the chemotherapy of cancer. Rapidly proliferating normal tissues are the major sites of acute toxicity of these agents.

Bone Marrow Toxicity:

Maximum toxicity usually is observed 10 to 14 days after initiation of drug treatment, with recovery by 21 to 28 days.

Delayed wound healing

Mucosal Toxicity:

Like d

amage to the normally proliferating mucosa may produce

mouth ulcers/git ulcers,

Oral ulcerations, esophagitis, and proctitis may cause pain and bleeding due

to oral mucosal ulceration and intestinal denudation.

Hair Follicle Toxicity:

So produces partial or complete alopecia. Hair usually re-grows normally within

2-6 months

after completion of chemotherapy.

Germ cells and reproduction:

sterility may

occure

, most cytotoxic drugs are teratogenic and mutagenic.

Nausea and vomiting:

This is common, can be extremely severe and prolonged and cause patients to refuse treatment.

Classes of cytotoxic chemotherapy drugs

/ Classification

The classification can be done on several basis by adding recent agents for example

Cell cycle (phase) specific

Like G1, S, G2 and M specific

OR

Alkylating agents

By incorporating subclasses

Antimetabolites

Including subclasses like folic acid , pyrimidine like

analoges

with examples

Natural and semi-synthetic products

Different agents of natural origin

from plant kingdom and antibiotics

Hormones and antagonists

As were there in previous semester

Miscellaneous agents

Which are not truly falling in above specific classes

Summary of the mechanisms and sites of action of some chemotherapeutic agents useful in neoplastic disease.

PALA =

N

-

phosphonoacetyl

-L-aspartate; TMP = thymidine monophosphate.