Chapter 39 Antineoplastic Agents Department of Pharmacology, Yunyang Medical College

1. Chapter 39 Antineoplastic Agents Department of Pharmacology, Yunyang Medical College Lu Juan(卢娟)

2. Teaching outline • To masterthe categories of antineoplastic drugs and the basic mechanisms. • To understand the principles of combination of antineoplastic drugs ,the pharmacologic actions, clinical applications and adverse reactions .

3. Overview • Cancer incidence and treatment measures • The development history of cancer chemotherapy • Novel anticancer drug

4. the adaptation syndrome of antineoplastic drugs: • Systemic tumor • Some solid tumor which have good effect to chemotherapy • the consolidation and adjuvant therapy as post-operation and radiotherapy • the palliative treatment of Late, extensive transfer and recurrent tumors • Neo-adjuvant chemotherapy

7. 眼科检查：双眼瞳孔区可见白色反光，双眼底可见肿瘤眼科检查：双眼瞳孔区可见白色反光，双眼底可见肿瘤

9. Pharmacological Basis

10. GF(growth fraction) composition oftumor cells : Proliferating cell population Whole-cell group GF= 1、Proliferating cell population---Targeting of therapy Rapidly growing tumors, the GF is greater , and sensitive to drugs. 2、Group of non-proliferating cells Including three parts ofquiescent cells, no proliferation cells (already differentiated cells) and dead cells, in which quiescent cells are not sensitive to drugs is a source of tumor recurrence.

11. Cell cycle, including： • Resting (G0 phase) • Proliferating cycle: Presynthesis(G1 phase) DNA synthesis(S phase) Premitotic(G2 phase) Mitosis(M phase)

12. no proliferation cells G2 (19%) S (39%) M(2%) Dead cells G1(40%) (G0) Group of non-proliferating cells Proliferating cell population sensitive to drugs. a source of tumor recurrence.

13. the relationship between Cell proliferation cycle and the anti-cancer drugs

14. Classification of antineoplastic agents According to the role of cycles or phases • cell cycle specific agents, CCSA • cell cycle non-specific agents, CCNSA

16. no proliferation cells G2 (19%) S (39%) M(2%) Dead cells G1(40%) (G0) Group of non-proliferating cells Proliferating cell population sensitive to drugs. a source of tumor recurrence.

17. The relationship between biochemistry and antineoplastic agents

18. Classification of antineoplastic agents According to the biochemical mechanism of action • Drugs that affecting nucleic acid biosynthesis • Drugs that damaging structure and function of DNA directly • Drugs that inhibiting synthesis of RNA by interfering with transcription process • Drugsthat affecting synthesis and functions of proteins • Drugs thataffecting the balance of hormones • Other

20. Classification of antineoplastic agents According to the chemical structure and source • Alkylating agents • Antimetabolites • antitumor antibiotics • plant alkaloids • Hormonal agents

21. Adverse reactions

22. （一）Recent toxicities一common toxicities • bone marrow depression——is the most common serious adverse reactions • Gastrointestinal reactions • Hair follicle damage

23. （二）Recent toxicities一Specific toxicities • Renal toxicity and bladder toxicity • Pulmonary toxicity • Cardiotoxicity • Neurotoxicity • Ototoxicity • Immunosuppression • Hepatotoxicity

24. （三）Long-term toxicity Infertility, mutagenic, teratogenic carcinogenesis：Second primary tumor

25. Commonly used anti-cancer drugs • Alkylating agents（ cell cycle non-specific agents） cyclophosphamide • Antimetabolites （ cell cycle specific agents） methotrexate,MTX

27. antitumor antibiotics （ cell cycle non-specific agents ） ADM • plant alkaloids • vinblastine ,VLB • vincristine,VCR

28. 长 春 花

29. Camptothecine

30. Podophyllotoxin

31. paclitaxel

32. Hormones • other

33. The principles of using drugs

34. 长 春 花 Best Wishes for Your Success in Final Examination