ANTINEOPLASTIC AGENTS

PHARMACOLOGY

LECTURE 9 B

OBJECTIVE

• To cause a lethal lesion that can arrest tumor’s progression.

• The attack is generally against the metabolic sites that are essential for cell replication.

• Ideally, only malignant cells should be targeted.• However, currently no such drugs are available

that specifically recognize neoplastic cells, resulting in the appearance of adverse drug reactions (ADRs).

CLASSIFICATION

• Antimetabolites• Antibiotics• Alkylating agents• Microtubule inhibtors• Steroids• Others

ANTIMETABOLITES

• Methotrexate, mercaptpurine• Act at S phase of the cell cycle• They inhibit the synthesis of nucleotides by

altering various genetic mechanisms• Used in leukemia, lymphoma, inflammatory

diseases.• ADRs: Neurological, renal, hepatic, pulmonary,

resistance.

METHOTREXATE MOA

Mercaptopurine MOA

ANTIBIOTICS

• Dactinomycin , Bleomycin, Daunorubicin, Doxorubicin

• Interaction with DNA, leading to disruption of DNA function

• Usually in combination with other anticancer agents• Choriocarcinoma, Breast, lung, leukemia, lymphoma• ADRs: Same as for antimetabolites plus skin

reactions and immunosuppression

ALKYLATING AGENTS

• Cyclophophamide, nitrosoureas (carmustine)• Covalently binding to nucleophilic groups on

the DNA. Resulting in the disruption of cell growth

• Used in lymphomas, leukemias and solid tumors

• Same as above plus nausea, latent viral infections (why?), alopecia, neutropenia.

MICROTUBULE INHIBITORS

• Vincristine, vinblastine, paclitaxel• Act on the spindle fibers to halt cell division• The most commonly used anticancer agents. • Lekemia, lymphoma, soft and hard tissue

tumors.• ADRs: Same as above plus neuropathy (ataxia,

foot drop)

STEROIDS

• Prednisone, tamoxifen, estrogens• Only good for hormone responsive tumors• Breast, ovarian, prostatic (plus sometimes in

addition to other agents for decreasing inflammation)

• ADRs: Same as above

OTHERS

• Cisplatin – similar to alkylating agents• Carbaplatin - similar to alkylating agents• Etoposide – irreversible DSBs (double stranded

breaks)• Interferons – active against tumor cells by

initiating immune response against them.

THANK YOU