1、Anticancer DrugsDr.Qamar BarakzaiDepartment of PharmacologyZiauddin Medical UniversityKarachi.Pakistan“CANCER” Refers to a Malignant neoplasm (New growth)Cancer cells can manifest: Uncontrolled Proliferation. Loss of function due to lack of ability to differentiate. Invasiveness. The ability to meta
2、stasize.Cancer arises as a result of a series of genetic changes in the cell, the main genetic lesions being: Inactivation of tumor suppressor genes. The activation of oncogenes.Antineoplastic agents Are cytotoxic not tumoricidal Only kill cells during mitosis, and Not all cancer cells are dividing
3、at the same time. SUCCESS DEPENDS ON: Stage of cancer at time of diagnosis Type of cancer Development of drug resistance Overall health of patient. R Tumor SuppressorGenes -ve (p53) Growth FactorsOncogenes +ve SDNA SynthesisG2PremitoticIntervalMPROPHASEMETAPHASEANAPHASETELOPHASEMITOSISG0G1S PHASESPE
4、CIFICCytosineArbinosideHydroxyureaS PHASESPECIFICSELF LIMITING6-MercaptpurineMethotrexate.M PHASESPECIFICvincristinevinblastinepaclitaxelPHASE NONSPECIFICalkylating agents, cis-platinumnitrosoureas, dacarbazineantibioticsprocarbazineG0DifferentiationCELL GROWTH CYCLE5 DISTINCT PHASES OF MITOSIS 1. G
5、0 - Resting - no mitosis 2. G1 - Postmitotic - first growth 3. S - DNA synthesis phase 4. G2 - Premitotic - second growth 5. M - Mitosis phase GENERATION TIME - one complete cycle different in all tumors, from hours to daysPENTOSTATINInhibits adenosineDeaminasePALAInhibits PyrimidineBiosynthesisPuri
6、nesynthesisPyrimidinesynthesisRibonucleotidesDeoxyribonucleotidesDNAHYDROXYUREAInhibitRibonucleotideReductase6-MERCAPTOPURINE6-THIOGAUNINEInhibit Puring ringbiosynthesisInhibit Neocleotideinterconversions5-FLOUROURACILInhibit TMPSynthesisMETHOTREXATEInhibit dihydrofolatereduction, blocksTMP and Puri
7、nesynthesisDNARNA(Transfer, messenger, ribosomal)CYTARABINEFLUDARABINE2-CHLORODEOXYADENOSINEInhibit DNASynthesisALKYLATING AGENTSMITOMYCETINCISPLATINPROCARBAZINEDACARBAZINEForm adducts w/ DNABLEOMYCINETOPOSIDETENIPOSIDEDamage DNA andPrevent repairDACTINOMYCINEDAUNORUBICINDOXORUBICINMITOXANTRONEInter
8、calate with DNAInhibit RNA synthesisPROTEINSEnzymes MicrotubulesA-ASPARAGINASEDeaminate asparagineInhibits proteinsynthesisPACLITAXELVINCA ALKALOIDSCOLCHICINEInhibit function ofMicrotubulesANTINEOPLASTIC AGENTS DEFINITIONS: ALKYLATION - chemical reaction that cleaves DNA and interferes with mitosis
9、BIFUNCTIONAL ALKYLATING AGENTS - have 2 alkyl groups and alkalate 2 DNA strands DOSE-LIMITED SIDE EFFECTS - adverse effects that preventan agent from being given in higher doses EMETIC POTENTIAL - potential of an agent to cause N & VANTINEOPLASTIC AGENTSADVERSE EFFECTS: Kills all fast growing cells Hair follicles GI tract mucosa Bone marrow suppression (BMS) causing anemiaand leukopenia All are pregnancy category D ! Most are nephro- hepato- and ototoxic Extravasation of IV can result in loss of limb
