ANTI-NEOPLASTIC AGENTS.pptx

D. pharm 1st year
Pharmaceutical chemistry

1. ANTI-NEOPLASTIC AGENTS PHARMACEUTICAL CHEMISTRY D. Pharm 1 st year 2022-2023 MISS NIKITA J. BHUTE Assistant professor Nagpur college of Pharmacy, Wanadogari , Higna road, Nagpur 441 110

2. INDEX Cancer Types of cancer Anti-neoplastic agents Classification of anti-neoplastic agents Chemical name, Chemical structure (compounds marked with*) Uses, Stability and storage conditions, different types of formulations and their popular brand names of: 1. Cyclophosphamide * 6. Dactinomycin 2. Busulfan 7. Doxorubicin Hydrochloride 3. Mercaptopurine 8. Vinblastine Sulphate 4. Fluorouracil * 9. Cisplatin * 5. Methotrexate 10. Dromostanolone Propionate

3. CANCER Cancer is a disease characterized by abnormal and uncontrolled cell division attacking the surrounding tissues and organs, and also the distant body parts by circulating with blood and lymph. Cancer is classified into the following categories:

4. ANTI-NEOPLASTIC AGENTS Antineoplastic or anticancer drugs are used for treating malignancies orcancerous growths. Either these drugs are used alone (chemotherapy) or inombination with surgery or radiation therapy. Class Name of Drugs 1) Alkylating agents a) Nitrogen mustards Mechlorethamine( Mustine HCI), Ifosfamide , Cyclophosphamide, Chlorambucil and Melphalan Mechlorethamine ( Mustine HCI), Ifosfamide , Cyclophosphamide, Chlorambucil and Melphalan b) Ethylenimine Thiotepa Thiotepa c) Alkyl sulfonate Busulfan Busulfan, Busulphan d) Nitrosoureas Carmustine (BCNU) and Lomustine (CCNU) Carmustine (BCNU), Lomustine (CCNU) and Semustinee e) Triazine Dacarbazine (DTIC) Dacarbazine (DTIC) 2) Antimetabolites a) Folate antagonist Methotrexate ( Mtx ) Methotrexate ( Mtx ) , Trimetrexate b) Purine antagonist 6-Mercaptopurine (6-MP), 6-Thioguanine(6-TG) and Azathioprine 6-Mercaptopurine (6-MP), 6-Thioguanine(6-TG), Azathioprine and Fludarabine c) Pyrimidine antagonist 5-Fluorouracil (5-FU) and Cytarabine (cytosine arabinoside) 5-Fluorouracil (5-FU) and Cytarabine (cytosine arabinoside) 3) Radioactive Isotopes Sodium phosphate, Sodium iodide, and Radio gold solution 4) Enzymes Asparaginase ( Elspar )

5. Class Name of Drugs 5) Natural Products a) Vinca alkaloids Vincristine (Oncovin) and Vinblastine b) Taxanes Paclitaxel and Docetaxel c) Epipodophyllo toxin Etoposide d) Camptothecin analogues Topotecan and Irinotecan 6) Antibiotics Actinomycin D, Dactinomycin, Doxorubicin, Daunorubicin, Rubidomycin , Mitoxantrone, Bleomycin, Mitomycin C and Mithramycin 7) Hormones a) Glucocorticoids Prednisolone b) Estrogens Fosfestrol and Ethinylestradiol c) Antiestrogen Tamoxifen d) Antiandrogen Flutamide e) 5- α reductase inhibitor Finasteride f) GnRH analogues Nafarein and Goserelin g) Progestins Hydroxyprogesterone Acetate 8) Miscellaneous Hydroxyurea, Procarbazine, L-Asparaginase, Cisplatin and Carboplatin, Imatinib, Procarbazine

6. 1. Cyclophosphamide Structure: Chemical name: 2-[bis(2-chloroethyl)amino]-1,3,2 λ -oxazaphosphinan-2-one Uses: It is used in the treatment of malignant lymphomas, multiple myeloma, leukaemia, mycosis fungoides, neuroblastoma, adenocarcinoma of the ovary, retinoblastoma, and carcinoma of breast. It is also used in biopsy-proven minimal change nephrotic syndrome in paediatrics .

7. Stability and Storage Conditions: These preparations should be refrigerated in glass containers for up to 14 days before using. Cyclophosphamide for Injection, USP is a single-dose injection that contains cyclophosphamide monohydrate. Vials should be kept at or below 25°C (77°F). It is sensitive to light, heat and moisture, hence stored in tightly closed containers and away from light. Formulations: Cyclophosphamide injection I.P., B.P - Initial adult dose of 40-50 mg/kg given IV in divided doses over 2-5 days and for children 2-8 mg/kg daily through IV injection. Powder for solution Cyclophosphamide tablets I.P., B.P. Popular brand names: Procytox 3) Endoxan-Asta Cycloxan 4) Ledoxan

8. 2. Busulfan Chemical name: Butane-1,4-diyl dimethanesulfonate Uses: It is used with cyclophosphamide as a conditioning regimen before allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous (myeloid, myelocytic, and granulocytic) leukemia. It is also a component of pre-transplant conditioning regimen in bone marrow transplantation for acute myeloid leukemia and non-malignant diseases. Stability and Storage Conditions: It is sensitive to light, heat and moisture, hence stored in tightly closed Containers and away from light. Refrigerate intact vials between 2°C and 8°C (36°F and 46°F). Type of Formulation: Busulfan tablets I.P., B.P. - orally 60 µg/kg body weight daily, upto a maximum single daily dose 4 mg and to be continued till the white cell count falls between 15000 and 25000/mm³. Solution Popular Brand Names: Busulfex 2) Myleran

9. 3. Mercaptopurine Chemical name: 3,7-dihydropurine-6-thione Uses: It is used for remission induction and maintenance therapy of acute lymphatic leukaemia. It is used in the treatment of acute monocytic leukaemia, lymphobastomas , myeloblastoma leucosis, and to treat neuroleukemia . Stability and Storage Conditions: It should be kept at room temperature, free from heat and moisture (not in the bathroom). After the opening of the bottle, the mercaptopurine suspension can be kept at room temperature for up to 6 weeks. It is stored at 20 to 25 °C. It is kept in a tightly closed container in a dry and well-ventilated place.

10. Type of Formulation: Tablet Suspension Initial oral dose for children and adult is 2.5 mg/kg body weight daily but dose varies as per individual response and tolerance. Popular Brand Names; Purixan Purinethol

11. 4. Fluorouracil Structure: Chemical Name: 5-Fluoro-1H, 3H-pyrimidine-2,4-dione Uses: It is used in acute lymphocytic leukaemia, Crohn's disease, and ulcerative colitis. It is used for treating the slowly growing solid tumours (e.g., colorectal, breast, ovarian, pancreatic, head, neck, bladder and for actinic, solar creatitis and gastric carcinomas). It is used with levamisole (a veterinary anthelmintic agent) in patients having colon cancer. On topical application, it is effective in superficial basal cell carcinomas.

12. Stability and Storage Conditions: 5-fluorouracil's stability has been evaluated in a variety of liquids and containers at temperatures ranging from 4°C to 35°C. When 5-fluorouracil was synthesized in NS and stored in polyolefin bags at 5°C 3°C for 28 days, it remained stable. It is stored at 25°C (77°F) in tightly closed light resistant containers as it is affected by air and light. Types of Formulations: Fluorouracil injection I.P - 1.2 mg per kg body weight daily to a maximum of1 gm daily for 3 or 4 days. Solutions Fluorouracil cream B.P. Popular Brand Names: Actikerall 5) Fluoroplex Carac 6) Tolak Efudex 7) Fivoflu Flocil 8) Florac

13. 5. Methotrexate Chemical name: (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentane dioic acid Uses: It is effectively used with other drugs in acute lymphocytic leukaemia, choriocarcinoma, Burkitt lymphoma in children, breast cancer, and head and neck carcinomas. It is alone effective in low doses against certain inflammatory diseases (e.g., severe psoriasis). Stability and Storage Conditions : Multidose vials of methotrexate injection USP (with benzyl alcohol as a preservative) should be stored at temperatures between 15°C and 25°C. The vials should be stored between 2°C and 8°C for a maximum of four weeks after being punctured (30 days). It should be protected from light and freezing.

14. Type of Formulation: Methotrexate injection I.P., B.P., Powder for injection Methotrexate tablets I.P., B.P. For the maintenance therapy of acute lymphoblastic leukaemia, the dose is 15-30 mg/m² body surface once or twice weekly either orally or intramuscularly, with other agents such as mercaptopurine. Popular Brand Names; Trexall Xatmep

15. 6. Dactinomycin Chemical name: 2-Amino-N,N′- bis[(6S,9R,10S,13R,18aS)-6,13-diisopropyl-2,5,9- trimethyl-1,4,7,11,14-pentaoxohexadecahydro-1H-pyrrolo [2,1-i][1,4,7,10,13] oxatetraazacyclohexadecin-10-yl]-4,6- dimethyl-3- oxo-3H-phenoxazine-1,9-dicarboxamide Uses: It is used in the treatment or rhabdomyosarcoma in children and methotrexate-resistant choricarcinoma in women. It has also been used to inhibit immunoligical response particularly the rejection of renal transplants. It is used as a part of combination chemotherapy and/or multi-modality treatment regimen for treating Wilms' tumour , childhood rhabdomyosarcoma, Ewing's sarcoma and metastatic, non- seminomatous testicular cancer.

16. Stability and Storage Conditions: Temperatures should be kept between 20° and 25° Celsius (68° and 77 °F) and away from light and humidity. It is caustic to the skin, irritating to the eyes and mucous membranes of the respiratory tract, and highly poisonous when taken orally, according to animal studies. It is kept in tightly closed container under an inert atmosphere, and stored under ambient temperatures. Type of Formulation: Powder for injection- Adults, IV, 0.01 mg (10 mcg) per kg body weight; Children: 0.015 mg/kg body weight for not more than 5 days. Popular Brand Names: Cosmegen Dactinogen Dacmogen

17. 7. Doxorubicin Hydrochloride Chemical name: (7S,9S)-7-[(2R,4S,5S,6S)-4-Amino-5-hydroxy-6-methyloxan-2-yl] oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy -8,10-dihydro-7H-tetracene-5,12-dione Uses: It is used for producing regression in disseminated neoplastic conditions such as acute lymphoblastic leukaemia, acute myeloblastic leukaemia, Wilms' tumour , neuroblastoma, soft tissue and bone sarcomas, breast carcinoma; ovarian carcinoma, transitional cell bladder carcinoma, thyroid carcinoma, gastric carcinoma, Hodgkin's disease, malignant lymphoma and bronchogenic carcinoma in which the small cell histologic type is the most responsive. It is also used as a part of adjuvant therapy in women showing signs of axillary lymph node involvement after the resection of primary breast cancer. It is mainly used in combination with other drugs for treating solid tumors.

18. Stability and Storage Conditions: It is kept in tightly closed container under an inert atmosphere, and stored under ambient temperatures. It should be stored at a temperature of 2° to 8°C. Formulations: Powder for injection: 60 - 75 mg/m² BSA slow I.V. injection every 3 weeks. Doxorubicin HCI injection I.P., Doxorubicin Injection B.P. Doxorubicin HCI tablets IP. Solution Popular brand names: Adriamycin RDF Adriamycin PFS Adriamycin Rubex

19. 8. Vinblastine Sulphate Uses: It is used in the treatment of breast cancer, testicular cancer, lymphomas, neuroblastoma, Hodgkin's and non-Hodgkin's lymphomas, mycosis fungoides. histiocytosis, and Kaposi's sarcoma. It is combined with vincristine in the treatment of lymphocytic and myeloblastic leukemia in children. Stability and Storage Conditions: It is should be refrigerated between 2° and 8 °C. The vial should be kept in the outer carton to ensure safety from light. It is kept in tightly closed container under an inert atmosphere, and stored under ambient temperatures. Formulations: Injection solution Powder Intravenously as a solution containing 1 mg per ml in sodium chloride injection. Popular brand names: Velban 2) Biocristin

20. 9. Cisplatin Structure: Chemical name: (SP-4-2)- diamminedichloroplatinum (II) Uses: It is used for treating metastatic testicular tumours , metastatic ovarian tumours and advanced bladder cancer. It is employed in combination With Vinblastine and Bleomycin for the treatment of metastatic testicular tumors. It is also used for the remission of metastatic ovarian tumors when given either alone or in combination with doxorubicin.

21. It also exhibits activity against a host of other tumors, such as: cervical cancer, neck and head cancer, penile cancer, bladder cancer and small-cell cancer of the lung. It is highly reactive with carcinomas of the testicles, o varies, heat, neck, spleen lungs. Stability and Storage Conditions: It is physically and chemically stable, when stored in glass containers or diluted with 0.9 % sodium chloride in PE bags at a concentration of 10 mg/ml at room temperature (15-25°C) for at least 30 days. It is kept in tightly closed container under an inert atmosphere, and stored under ambient temperatures. Formulations: Cisplatin injection B.P. : for metastatic testicular tumors 20 mg/m² IV daily for five days, followed every 3 weeks for 3 courses., and for metastatic ovarian tumors 50 mg/m² IV once every 3 weeks. Solution Popular brand names: Platinol 3)Cytoxan Lyophilized Cytoxan 4) Neosar

22. 10. Dromostanolone Propionate Uses: It is prescribed for the treatment of breast cancer in women, but it has been withdrawn from the market. It can also be used as to administer injection in the muscle. It is used to treat ovarian cancer, gestational trophoblastic neoplasm, metastatic testicular tumors, gestational trophoblastic neoplasm and locally recurrent or locoregional solid tumors (sarcomas, carcinomas and adenocarcinomas). Stability and Storage Conditions: It should be stored at 0°-4°C for short-term (days to weeks) or at -20°C for long- term (months to years) in dry and dark places. It is kept in tightly closed container under an inert atmosphere, and stored under ambient temperatures. Formulations: Injection Solutions Popular brand names: Drolban Masteril 2) Masteron

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