Adake MD Associate Professor Department of Pharmacology Yenepoya Medical College MANGALORE Introduction Also called as anti neoplastic drugs or cytotoxic agents ID: 777385
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Slide1
Anti Cancer Drugs
Dr.
Prabhakar
Adake
MD
Associate Professor
Department of Pharmacology
Yenepoya
Medical College
MANGALORE
Slide2Introduction
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
.
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
Slide4Slide5Classification
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
Slide6Slide7Slide8Cell 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.
Slide9Cancer 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.
Slide10Alkylating Agents
Examples :
Meclorethamine
Cyclophosphamide
Ifosamide
Chlorambucil
Carmustine
Lomustine
Slide11Mechanism of Action
Carbonium
ion
Alkylating
agents
Transfer Alkyl group
Cross linking/ Abnormal base pairing
Scission of DNA strand
Slide12Uses
Leukemias
, Lymphomas,
Bronchogenic
carcinoma, Ca. Breast,
Osteogenic
carcinoma, Testicular cancer & Immunosupressant
Adverse Effects
Haemorrhagic
cystitis, Alopecia, Emesis,
Hyperuricaemia
, Pulmonary fibrosis, Bone marrow depression.
Slide13Antimetabolites
Folate
antagonist
Methotrexate
(
Mtx
)
Purine
antagonist
Mercaptopurine
6 thioguanine
Azathioprine
Fludarabine
Pyrimidine
antagonist
Flurouracil
Cytarabine
Slide14METHOTREXATE
Dihydrofolic
acid (DHFA)
Tetrahydrofolic
acid(THFA)
One carbon atom transfer
Purine
synthesis
DNA
Dihydrofolate
Reductase Methotrexate MTX
Slide15Uses
Adverse Effects
Leukemias
,
Choriocarcinoma
, RA, Psoriasis &
Immunosupressant
.
Megaloblastic
anaemia
, Pancytopenia, Rescue
Folinic Acid
Slide16Purine Antagonists
Monoribonucleotides
IMP
Adenine /Guanine Nucleotide
Purine
synthesis
6-MP
6-TG
AZATHIOPRINE
Slide17Uses
Leukemias
,
Choriocarcinoma
& Solid
tumours
Adverse Effects
Hyperuricaemia
, Bone marrow depression, Emesis, Reversible jaundice
Slide18Pyrimidine Antagonists
5-Fluoro-2-deoxy-UMP
Deoxyuridilic
acid
Deoxythymidilic
acid
Pyrimidine
synthesis
Thymidylate
synthase
5-FUCytarabine
Slide19Uses
Leukemias
, Ca. Breast, Colon, Bladder, Liver.
Adverse Effects
Hyperuricaemia
, Bone marrow depression, Emesis, Reversible jaundice
Slide20Vinca Alkaloids
Tubulin
Prevent Polymerization/Assembly of tubules
Disruption of mitotic spindles/Metaphase arrest
Vincristine
Vinblastine
Slide21Uses
Leukemias
, Ca. Lung,
Wilm’s
Tumour
, Ewings Sarcoma, Testicular carcinoma
Adverse Effects
Bone marrow depression, Peripheral Neuropathy, Alopecia
Slide22Taxanes
Tubulin
Enhances Polymerization of tubules
Abnormal arrays/Bundles
Paclitaxel
Docetaxel
Slide23Uses
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
.
Slide24Epipodophyllotoxin
Etoposide
Inhibits
Topoisomerase
-II
Inhibits Resealing of DNA
DNA breaks
Slide25Camptothecin Analogues
Inhibits
Topoisomerase
-I
Topotecan
Irinotecan
DNA breaks
Cell death
Slide26Uses
Metastatic Colorectal cancer; Advanced lung/cervical/ ovarian cancers.
Adverse Effects
Bone marrow depression,
bodyache
, weakness.
Slide27Antibiotics
Actinomycin
-D
Daunorubacin
Doxorubacin
Bleomycin
Free radical Generation
DNA break
Slide28Uses
Choriocarcinoma
,
Wilm’s
Tumour
, Rabdomyosarcoma, Ca. Breast,
Leukemias
.
Adverse Effects
Cardiotoxicity
,
Myelosupression, Pulmonary fibrosis.
Slide29Targeted drugs
Slide30Targeted drugs
Slide31Hormones
Glucocorticoids
CLL, Breast cancer
SERM/
Aromatase
Inhibitors
Breast cancer
Antiandrogen
Prostate cancer
Progestins
Endometrial cancer
Slide32General Toxicity of
Cytotoxic
Drugs
Profound effect on rapidly multiplying cells
Bone marrow
Granulocytopenia
Aplastic
anaemia
thrombocytopenia
Oral cavity
Stomatitis
Xerostomia
Oral infections
Slide33General Toxicity of
Cytotoxic
Drugs
GlT
Diarrhoea
GI bleed
Nausea/Vomiting
SKIN
Alopecia
Dermatitis
GONADS
Amenorrhea
Oligospermia
FETUS
Abortion
Malformation
Slide34Slide35THANK YOU