Anti Cancer Drugs Dr. Prabhakar - PowerPoint Presentation

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Anti Cancer Drugs

Dr.

Prabhakar

Adake

MD

Associate Professor

Department of Pharmacology

Yenepoya

Medical College

MANGALORE

Slide2

Introduction

Also

called

as anti

neoplastic

drugs

or

cytotoxic

agents.

Cancer

Cancer

affects 1 in 3 people and is responsible for 25% of all deaths

Cancer is an unregulated proliferation of cells due to loss of normal controls, resulting in unregulated growth,

local

tissue invasion,

and often

, metastasis.

Cancer can develop in any tissue or organ at any age.

Many cancers are curable if detected at an early stage, and long-term remission is often possible in later stages.

Causes of Cancer

:

1. 30 % is due to

smoking

: lung, mouth, pharynx, larynx, esophagus, urinary bladder, pancreas, and kidney cancers.

2

. Lifestyle

– diet, alcohol consumption

,

exposure to sunlight, etc.

3. At least 15% are related to

viruses

, e.g. cervical cancer caused by human

papillomavirus

.

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Anti Cancer Drugs

Either kill the cancer cells or modify their growth.

Cancer chemotherapy is a recent development.

Combined modality of treatment.

Leukemias

,

Ewings

sarcoma>> Breast cancer >> Ca. Colon

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Classification

Alkylating

agents:

Cyclophosphamide,Chlorambucil

,

Mustine

Antimetabolites

:

Methotrexate

, 6-MP,

Azathioprine, 5-FU

Vinca alkaloids: Vincristine, Vinblastine

Taxanes: Paclitaxel, Docetaxel

Camptothecin: Irinotecan,Topotecan

Antibiotics: Actinomycin-D, Daunorubacin, Doxorubacin

Miscellaneous: Hydroxyurea, L-Asparginase & Hormones

Epipodophyllotoxin

:

Etoposide

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Cell cycle

Gap

0 (G0

):

There are times when a cell will leave the cycle and quit dividing. This may be a temporary resting period or more permanent.

Gap 1 (G1):

Cells increase in size in Gap 1, produce enzymes needed for DNA synthesisS Phase:

DNA

replication occurs during this S (synthesis) phase.

Gap 2 (G2):

It is the gap between DNA synthesis and mitosis, the cell will continue to grow and produce new proteins & RNA.

Mitosis or M Phase: Cell growth and protein production stop at this stage in the cell cycle. All of the cell's energy is focused on the complex and orderly division into two similar daughter cells.

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Cancer chemotherapeutic agents

Cell-cycle

non specific agents(CCNS):

are

cytotoxic

in any phase of the cycle even on G0 phase and so are more effective against large slowly growing tumors.

Ex:

Bleomycin.

Cell-cycle specific (CCS):

are

cytotoxic

on all phases but not on cells out of the cycle(at G0 ) and so are more effective against rapidly growing tumors. Work better in combination than alone

Ex: Mitomycin, doxorubicin,….etc.

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Alkylating Agents

Examples :

Meclorethamine

Cyclophosphamide

Ifosamide

Chlorambucil

Carmustine

Lomustine

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Mechanism of Action

Carbonium

ion

Alkylating

agents

Transfer Alkyl group

Cross linking/ Abnormal base pairing

Scission of DNA strand

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Uses

Leukemias

, Lymphomas,

Bronchogenic

carcinoma, Ca. Breast,

Osteogenic

carcinoma, Testicular cancer & Immunosupressant

Adverse Effects

Haemorrhagic

cystitis, Alopecia, Emesis,

Hyperuricaemia

, Pulmonary fibrosis, Bone marrow depression.

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Antimetabolites

Folate

antagonist



Methotrexate

(

Mtx

)

Purine

antagonist

 Mercaptopurine

6 thioguanine

Azathioprine

Fludarabine

Pyrimidine

antagonist



Flurouracil

Cytarabine

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METHOTREXATE

Dihydrofolic

acid (DHFA)

Tetrahydrofolic

acid(THFA)

One carbon atom transfer

Purine

synthesis

 DNA

Dihydrofolate

Reductase Methotrexate MTX

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Uses

Adverse Effects

Leukemias

,

Choriocarcinoma

, RA, Psoriasis &

Immunosupressant

.

Megaloblastic

anaemia

, Pancytopenia, Rescue

Folinic Acid

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Purine Antagonists

Monoribonucleotides

IMP

Adenine /Guanine Nucleotide

Purine

synthesis

6-MP

6-TG

AZATHIOPRINE

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Uses

Leukemias

,

Choriocarcinoma

& Solid

tumours

Adverse Effects

Hyperuricaemia

, Bone marrow depression, Emesis, Reversible jaundice

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Pyrimidine Antagonists

5-Fluoro-2-deoxy-UMP

Deoxyuridilic

acid

Deoxythymidilic

acid

Pyrimidine

synthesis

Thymidylate

synthase

5-FUCytarabine

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Uses

Leukemias

, Ca. Breast, Colon, Bladder, Liver.

Adverse Effects

Hyperuricaemia

, Bone marrow depression, Emesis, Reversible jaundice

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Vinca Alkaloids

Tubulin

Prevent Polymerization/Assembly of tubules

Disruption of mitotic spindles/Metaphase arrest

Vincristine

Vinblastine

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Uses

Leukemias

, Ca. Lung,

Wilm’s

Tumour

, Ewings Sarcoma, Testicular carcinoma

Adverse Effects

Bone marrow depression, Peripheral Neuropathy, Alopecia

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Taxanes

Tubulin

Enhances Polymerization of tubules

Abnormal arrays/Bundles

Paclitaxel

Docetaxel

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Uses

Metastatic ovarian & breast cancer; Advanced head n neck, small cell cancer of lung, Prostate & esophageal cancer.

Adverse Effects

Bone marrow depression, Peripheral Neuropathy (stocking and glove), chest pain,

artharlgia

,

mucositis

.

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Epipodophyllotoxin

Etoposide

Inhibits

Topoisomerase

-II

Inhibits Resealing of DNA

DNA breaks

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Camptothecin Analogues

Inhibits

Topoisomerase

-I

Topotecan

Irinotecan

DNA breaks

Cell death

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Uses

Metastatic Colorectal cancer; Advanced lung/cervical/ ovarian cancers.

Adverse Effects

Bone marrow depression,

bodyache

, weakness.

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Antibiotics

Actinomycin

-D

Daunorubacin

Doxorubacin

Bleomycin

Free radical Generation

DNA break

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Uses

Choriocarcinoma

,

Wilm’s

Tumour

, Rabdomyosarcoma, Ca. Breast,

Leukemias

.

Adverse Effects

Cardiotoxicity

,

Myelosupression, Pulmonary fibrosis.

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Targeted drugs

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Targeted drugs

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Hormones

Glucocorticoids

CLL, Breast cancer

SERM/

Aromatase

Inhibitors

Breast cancer

Antiandrogen

Prostate cancer

Progestins

Endometrial cancer

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General Toxicity of

Cytotoxic

Drugs

Profound effect on rapidly multiplying cells

Bone marrow

Granulocytopenia

Aplastic

anaemia

thrombocytopenia

Oral cavity

Stomatitis

Xerostomia

Oral infections

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General Toxicity of

Cytotoxic

Drugs

GlT

Diarrhoea

GI bleed

Nausea/Vomiting

SKIN

Alopecia

Dermatitis

GONADS

Amenorrhea

Oligospermia

FETUS

Abortion

Malformation

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