《药理学》课程PPT教学课件（讲稿）抗恶性肿瘤药 Antineoplastic Drugs

Chapter 49 Antineoplastic Drugs Department of pharmacology Liu xiaokang(刘小康) 2010.3

Chapter 49 Antineoplastic Drugs Department of pharmacology Liu xiaokang(刘小康） 2010,3

Categories 1) Antimetabolites: a) Folic Acid Analogs (Methotrexate, MTX). b) Pyrimidine analogs (Fluorouracil, 5-FU; Fluorodeoxyuridine; ytarabine). d) Purine analogs (6 Mercaptopurine, 6-MP; 6-Thioguanine, 6-TG). 2) Alkylating agents: Nitrogen mustards Cyclophosphamide; Thiotepa 3) Natural products: Vinca alkaloids (Vincristine; Vinblastine; Vinorelbine); Paclitaxel axo

Categories: • 1) Antimetabolites: a) Folic Acid Analogs (Methotrexate, MTX). b) Pyrimidine analogs (Fluorouracil, 5-FU; Fluorodeoxyuridine; Cytarabine). d) Purine analogs (6- Mercaptopurine, 6-MP; 6-Thioguanine, 6-TG). • 2) Alkylating agents: Nitrogen mustards; Cyclophosphamide; Thiotepa. • 3) Natural products: Vinca alkaloids (Vincristine; Vinblastine; Vinorelbine); Paclitaxel (Taxol® )

4) Antiumor antibiotics: Anthracyclines oxorubicin hydrochloride, Daunorubicin, Bleomycin 5)Miscellaneous agents: Cisplatin; Carboplatin; Asparaginase; Hydroxyurea Corticosteroid

• 4) Antiumor antibiotics: Anthracyclines (Doxorubicin hydrochloride, Daunorubicin, Bleomycin) • 5) Miscellaneous agents: Cisplatin; Carboplatin; Asparaginase; Hydroxyurea; Corticosteroid

Mechanisms Biological mechanism. (1)Cell cycle: a) Gap 1(G phase). b) DNA Synthesis(S phase). c)Gap2(G2 phase). d) Mitosis (M phase). Go is a resting phase in which the cells are not proliferin

Mechanisms: • Biological mechanism: • (1) Cell cycle: • a) Gap 1 (G1 phase). b) DNA synthesis (S phase). c) Gap 2 (G2 phase). d) Mitosis (M phase). G0 is a resting phase in which the cells are not prolifering

THE CELLCTCLE Beginnin Cell divides of cvcle (mitosis) Cell enlai and makes Cell prepares niew fjrutEirIs to dfid Cell rests R Cell replicates Restriction poin its DNA cell decides whethe to commit itself to the complete cycle

(2) Cell cycle nonspecific agents (CCNSA): Kill proliferating cells preferentially, act on cells at all phases. (3) Cell cycle specific agents (CCSA) Act at specific phase of the cell cycle

• (2) Cell cycle nonspecific agents (CCNSA): • Kill proliferating cells preferentially, act on cells at all phases. • (3) Cell cycle specific agents (CCSA): • Act at specific phase of the cell cycle

o Biochemic mechanism 1)Interfere nucleotide synthesis. 2)Impact the structure and function of DNA 3)Interfere transcription and block rNa synthesis 4) Interfere protein synthesis and functions 5) Change hormone lever

• Biochemic mechanism: • 1) Interfere nucleotide synthesis. • 2) Impact the structure and function of DNA • 3) Interfere transcription and block RNA synthesis. • 4) Interfere protein synthesis and functions. • 5) Change hormone lever

Resistance mechanism (1) Defective activation: Cyclophosphamide requires metabolic activation. Methotrexate conversion to more active mtx polyglutamate in cells

Resistance mechanism • (1) Defective activation: Cyclophosphamide requires metabolic activation, Methotrexate conversion to more active MTX￾polyglutamate in cells

(2) Increased inactivation: e.g aldehyde dehydrogenase converse cyclophosphamide to inactive metabolite. (3) Altered nucleotide pools: Can occur with antimetabolites

• (2) Increased inactivation: e.g., aldehyde dehydrogenase converse cyclophosphamide to inactive metabolite. • (3) Altered nucleotide pools: Can occur with antimetabolites

(4) Altered DNA repair: Repair mechanisms increased, i.e., ability to remove cross-links Affect the action of bleomycin and other DNA-directed drugs (5) Altered target: Less affinity for drug, Methotrexate Dihydrofolate reductase changes )

• (4) Altered DNA repair: Repair mechanisms increased, i.e., ability to remove cross-links, Affect the action of bleomycin and other DNA-directed drugs • (5) Altered target: Less affinity for drug, Methotrexate (Dihydrofolate reductase changes )