CLASSIFICATION OF ANTI - CANCER DRUGS.pptx

This presentation shows the classification of ANTI-CANCER drugs.
It includes the introduction and classification of anticancer drugs with their mechanism of action and drug of choice in the treatment of various cancer diseases.

1. ANTI-CANCER DRUGS SUBMITTED TO; SUBMITTED BY; Ms. Neelam Painuly Mr. Anupam Associate Professor M. Pharm(PHARMACOLOGY) [email protected] [email protected] SoPR , DBUU, Dehradun SoPR , DBUU, Dehradun

2. CONTENTS INTRODUCTION TYPES OF CANCER CELL CYCLE CLASSIFICATION OF ANTI-CANCER DRUGS DISEASE AND THEIR DRUF OF CHOICE REFERENCES SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 2

3. INTRODUCTION The World Health Organization (WHO) defines the cancer as a wide range of diseases which produces impact on any body part. The term "metastasis" refers to the unchecked proliferation & dissemination of aberrant cells to various parts of body via the lymphatic or circulatory systems. Cancer is a cell disease defined by abnormal, purposeless, progressive, persistent, and uncontrollably growing tissue . Cancer cell produce oncoproteins in the absence of growth factor or external stimuli. SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 3 Fig1: Process of cancer cell development.

4. SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 4

5. Cell Cycle of both Normal as well as Cancer Cells G1 phase (pre-synthetic phase, 40%): Enzyme and other biological components required for DNA synthesis are synthesised . S phase (synthetic phase, 39%): The synthesis of DNA occurs. G2 phase (pre-mitotic phase, 19%): biological components necessary for myosis are synthesised (RNA and protein synthesis). M phase (mitotic phase, 2.1%): Division of mitotic cells occur. G0 phase (resting phase): Stop division of cells. SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 5 Fig2: Cell Cycle

6. CLASSIFICATION SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 6 ANTI- METABOLITES TAXANES CAMPTOTHECINS ENZYME HORMONAL AGENTS ANTIBIOTICS EPIPODOPHYLLOTOXINS VINCA ALKALOIDS ALKYLATING AGENTS ANTI-CANCER DRUGS MISCELLANEOUS AGENTS

7. CLASSIFICATION OF ANTI-CANCER DRUGS SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 7 Alkylating agents Nitrogen Mustered: - Mechlorethamine, Cyclophosphamide, Melphalan, Chlorambucil. Alkyl Sulfonate: - Busulphan. Nitrosoureas: - Carmustine, Lomustine. Platinum-containing compound: - Cisplatin, Carboplatin. Triazene: - Dacarbazine. Antimetabolites Folate antagonists: - Methotrexate. Purine antagonists: - 6-Mercaptopurine, 6-Thioguinine. Pyrimidine antagonists: - 5-Fluorouracil, Cytarabine.

8. Vinca Alkaloid: - Vincristine, Vinblastine. Taxanes : - Paclitaxel, Docetaxel. Epipodophyllotoxins: - Etoposide, Tenoposide. Camptothecins : - Topotecan, Irinotecan. Antibiotics: - Actinomycin, Bleomycin, Mitomycin, Doxorubicin. Enzymes: - L-Asparaginase. Miscellaneous agents: - Hydroxyurea, Imatinib. Hormonal drugs Oestrogen: - Ethnyl estradiol , Fosfestrol . Oestrogen receptor modulator: - Tamoxifen. Aromatase inhibitor: - Anastrozole, Letrozole. Antiandrogen: - Flutamide. Progestin: - Hydroxyprogesterone acetate. Androgen: - Testosterone propionate. GnRH analogue: - Buserelin . Corticosteroids: - Prednisolone. SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 8

9. Anti-Cancer Drugs may be divided into two groups: Cell Cycle Specific (CCS): Act mainly in dividing cell. Cell Cycle Non-Specific (CCNS): Act mainly in dividing cell as well as resting cell. SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 9 Cell Cycle Specific (CCS) Cell Cycle Non-Specific (CCNS) Antimetabolites Alkylating Agents Vinca Alkaloids Antibiotics Taxanes Camptothecins Epipodophyllotoxins  

10. ALKYLATING AGENTS Agents that works by directly damaging the DNA of cancer cell by getting converting to azindinum ion and bond with the nitrogen atom at 7 th position in the guanine of DNA. These drugs come under CCNS (Cell Cycle Non-Specific Drugs). Mechanism of Action: SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 10

11. Nitrogen Mustered: - Mechlorethamine, Cyclophosphamide, Melphalan, Chlorambucil. Cyclophosphamide: It is a prodrug and alkylating agent which activated in liver. It is effective after metabolism and administered orally and IV route. Also have powerful immunosuppressant activity. Drug of choice in Lung Cancer. Mechanism of Action: SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 11

12. Chlorambucil: It is a slow acting alkylating agent. Drug of choice in lymphatic leukaemia. Toxicity of chlorambucil is p ulmonary fibrosis. Melphalan: It is a alkylating agent which is treatment of choice for ovarian and testicular cancer. Alkyl Sulfonate: - Busulphan. Busulphan is a bi-functional methane sulphonic ester that forms transferred cross-linking with DNA results in cell death. Drug of choice in myeloid leukaemia. It depresses bone marrow and have common side effects are hyperuricemia and pigmentation of skin. Nitrosoureas: - Carmustine, Lomustine. These drugs are highly lipid soluble drugs. It reaches in high concentration in Blood Brain Barrier (BBB). Mainly used for Brain Tumours (Drug of choice). SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 12

13. Platinum-containing compound: - Cisplatin, Carboplatin. Heavy metal complex that shows strong neoplastic action. Cisplatin: It causes nephropathy, emesis and nephrotoxicity . Mechanism of Action: Carboplatin: It is a derivative of cisplatin with less Neuro, Nephro and Ototoxicity. Triazene: - Dacarbazine. Dacarbazine inhibit RNA and protein synthesis that results in cell death. Dacarbazine is a drug of choice in malignant myeloma. SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 13

14. ANTIMETABOLITES These drugs inhibit the proliferation and development of cancer cells. These drugs mimic normal cellular metabolites and integrated into DNA and RNA during the cell cycle, disrupting the synthesis of nucleic acids and ultimately leading to cell death. Therse drugs acts in S phase. Folate antagonists: - Methotrexate (inhibit dihydrofolate reductase). Methotrexate drug have anti-neoplastic, immunosuppressant and anti-inflammatory effects. Antidote for methotrexate is Folinic Acid. Methotrexate shows Hepatotoxicity, Obstructive Nephropathy. Mechanism of Action: SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 14

15. Purine antagonists: - 6-Mercaptopurine, 6-Thioguinine. These drugs come under CCS (Cell Cycle Specific Drugs) and acts in S phase. Purine antagonists cause Hepatotoxicity. Mechanism of Action: SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 15

16. Pyrimidine antagonists: - 5-Fluorouracil, Cytarabine. These drugs come under CCS (Cell Cycle Specific Drugs) and acts in S phase. 5-Fluorouracil: It cause Hand and Foot Syndrome and Neurotoxicity. Mechanism of Action: Cytarabine: It cause neurotoxicity. Cytarabine is a drug of choice with combination of Idarubicin in Acute Myeloid Leukaemia. SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 16

17. VINCA ALKALOIDS These drugs are cell cycle specific (CCS) and acts in M phase. Vincristine and Vinblastine are derived from periwinkle plants. Vinca alkaloid cause Peripheral Neuropathy. Vinblastine is used to treat leukaemia in children’s and Vincristine is used to treat breast cancer. Mechanism of Action: SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 17

18. TAXANES It enhanced stability of microtubule preventing the separation of chromosomes during anaphase. It decreases the ability of bone marrow to produce blood cells. e .g., Paclitaxel, Docetaxel. Paclitaxel: It causes peripheral neuropathy and hypersensitivity. Docetaxel: It causes peripheral neuropathy as well as fluid retention. EPIPODOPHYLLOTOXINS Drugs that acts in G2 phase and S phase of cell cycle. e.g., Etoposide, Tenoposide. Etoposide causes Bone marrow depression and GI side effects. Mechanism of Action: SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 18

19. CAMPTOTHECINS Drugs that acts in G2 phase and S phase of cell cycle. e.g., Topotecan, Irinotecan. These are used in Ovarian, Lungs, Colorectal cancer. Mechanism of Action: Camptothecins binds to topoisomerase-I (a nuclear enzyme that replicate DNA and transcription) complex and inhibit the resealing of DNA, thus produce cell death. ANTIBIOTICS All these drugs produce direct action on DNA & they act by blocking the transcription of DNA. e.g., Actinomycin, Bleomycin, Mitomycin, Doxorubicin. Actinomycin: It administered through IV route. Mechanism of Action: Actinomycin also produces direct action of DNA & they act by blocking the transcription of DNA. SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 19

20. Bleomycin: A mixture of glycopeptide antibiotics. It acts on G2 phase and M phase of cell cycle. It also crosses BBB (Blood Brain Barrier), so it is used to treat Brain cancer. Bleomycin is given as a drug of choice with combination of Cisplatin and Etoposide to treat testis cancer. Mitomycin: It causes cross-linking of DNA and generates free radicals which damage DNA. Doxorubicin: It causes Cardiotoxicity. Mechanism of Action: SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 20

21. ENZYME Enzyme is isolated from bacteria specially ecoli . It is a necessary amino acid for the production of proteins. e .g., L-Asparaginase. Cancer cells lack of this enzyme. It causes toxicity of Hypersensitivity, Hyperglycaemia, Haemorrhage. Mechanism of Action: Normal cells can synthesize asparagine because they contain asparagine synthase. SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 21

22. MISCELLANEOUS AGENTS It acts on S phase of cell cycle (CCS drugs) . e.g., Hydroxyurea, Imatinib. Mechanism of Action: Hydroxyurea interferes with the conversion of RBC to DNA by inhibiting ribonucleoside diphosphate reductase, this results in inhibition of DNA synthesis. HORMONAL AGENTS These agents are non-cytotoxic but it modifies the growth of hormones dependent tumour. Oestrogen: - These are physically antagonist of androgen; hence oestrogen is used to antagonise the effect of androgen. Widely used in Prostate cancer. e .g., Ethnyl estradiol , Fosfestrol . SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 22

23. Oestrogen receptor modulator: - It is a compound that can interact with oestrogen receptors in the body and modulate their activities. These can act as either agonist (activating the receptor) or antagonist (blocking the receptor) of oestrogen receptors, depending on the specific tissue type. E.g., Tamoxifen i.e. highly effective in Breast cancer. Aromatase inhibitor: - These are used in the post-monophasic menstrual cycle to treat hormone-dependent breast cancer. e.g., Anastrozole, Letrozole. Antiandrogen: - It antagonizes the androgen action on prostate cancer. E.g., Flutamide. Progestin: - Used to treat endometrium cancer. e.g., Hydroxyprogesterone acetate. SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 23

24. Androgen: - e.g., Testosterone propionate. Testosterone propionate is an injectable medication that is used as hormone replacement therapy in men with less testosterone levels and female breast cancer. GnRH analogue: - These drugs produce arising LH (Luteinizing hormone) and FSH (Follicle stimulating hormone). These are effective in advance prosthetic & breast cancer. e.g., Buserelin . Corticosteroids: - It produces feeling of well-being and it suppress the hypersensitivity reactions. These drugs having anti-inflammatory activity and it decreases Glaucoma. e.g., Prednisolone. Mechanism of Action: Prednisolone interfere with the cell cycle of activated lymphoid cells. SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 24

25. Diseases and their Drug of Choice Diseases Drug of Choice Brain Tumour Nitrosourea Lung Cancer Cyclophosphamide Ovarian and Testicular Cancer Melphalan Acute Myeloid Leukaemia Cytarebine + Idarabicin Testis Cancer Bleomycin + Cisplatin + Etoposide Myeloid Leukaemia Busulfan Breast Cancer Tamoxifen Prostate Cancer Oestrogen Lymphatic Leukaemia Chlorambucil SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 25

26. REFERENCES https://lecture-notes.tiu.edu.iq/wp-content/uploads/2023/06/Anticancer-drugs-26.-4.2023.pptx https://www.intechopen.com/books/potential-of-essential-oils/potential-of-medicinal-use-of-essential-oils-from-aromatic-plants https://1filedownload.com/wp-content/uploads/2020/10/Pharmacology-Dr-Sparsh-Gupta-Book.pdf https://www.slideshare.net/nasertadvi/14cancer-chemotherapy https://tse3.mm.bing.net/th?id=OIP.rDyuhrnIE8uf2FHxzn_EtAHaHa&pid=Api&P=0&h=180 https://tse1.mm.bing.net/th?id=OIP.6HKR8HQQZ_t0EmsbkUx2IwHaGI&pid=Api&P=0&h=180 https://5.imimg.com/data5/SELLER/Default/2021/11/SB/ZW/HY/73501836/ciszest-50-500x500.jpeg https://tse3.mm.bing.net/th?id=OIP.Telrn-utZ6j27mHyOZQyKAHaFj&pid=Api&P=0&h=180 https://tse3.mm.bing.net/th?id=OIP.YxqRigXAdlD4XJ56XhXGpAAAAA&pid=Api&P=0&h=180 https://tse3.mm.bing.net/th?id=OIP.w83pkK9cLq3tdz-2gBHGfAHaHa&pid=Api&P=0&h=180 https://tse4.mm.bing.net/th?id=OIP.WbeCLdryJc48T6K0tnyexAHaHa&pid=Api&P=0&h=180 https://tse1.mm.bing.net/th?id=OIP.tWWEPlzqRZwxBR7uXSrzaAHaHa&pid=Api&P=0&h=180 https://tse1.mm.bing.net/th?id=OIP.Z1n3HiHCk806Fd5KneSqSwHaHa&pid=Api&P=0&h=180 https://www.magicinepharma.com/img/products/blogs/1%20(18).jpg https://tse1.mm.bing.net/th?id=OIP.AtNHmXd2AUpJ4ygD8Yi7AwHaGE&pid=Api&P=0&h=180 https://cpimg.tistatic.com/05475036/b/4/extra-05475036.jpg SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 26

27. THANK YOU SOPR, DEV BHOOMI UTTARAKHAND UNIVERSITY 27