《利尿药和降血糖药》ppt课件

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1、MedicinalchemistryChapter10DiureticsandSyntheticHypoglycemicDrugsCollegeofPharmacy,SDUShutaoMaEmail:mashutao@sdu.edu.cnChapter10DiureticsandSyntheticHypoglycemicDrugsSection1HypoglycemicDrugsSection2DiureticsSection1HypoglycemicDrugsTheclassictriadofsymptomsi

2、ndiabetesispolyphagia,polydypsia(thirst),andpolyuria(excessurine).Allthreeresultdirectlyfromexcessiveserumglucoselevels.Type1diabetesusuallydevelopsinanacutemanner,althoughthedestructiveautoimmuneprocessmayhavebeenunderwayforsometime.Type2diabeteshasamoreinsidi

3、ous,oftenasymptomaticonsetanditspresenceisusuallydetectedbyroutinemedicalexaminations.DefinitionsTypeIDiabetes.Insulin-dependentdiabetesmellitus(IDDM),thisconditionoccurswhentheβ-cellsofthepancreaticisletsofLangerhansaredestroyed,probablybyanautoimmuneprocess,s

4、uchthatinsulinproductionisdeficient.Type2Diabetes.Noninsulin-dependentdiabetesmellitus(NIDDM)isveryfrequentlyassociatedwithobesityinitsmainlyadultvictims.Seruminsulinlevelsarenormalorelevated,soinessencethisisadiseaseofinsulinresistance.BiochemistryandPathogene

5、sisofDiabetesClassificationsFirstGenerationSulfonylureas:tolbutamide.SecondGenerationSulfonylureas:glibenclamide.ThirdGenerationSulfonylureas:glimepiride,repaglinide.Biguanides:metformin.α-GlucosidaseInhibitors:Acarbose,Miglitol.MechanismofActionSulfonylureasin

6、teractwithreceptorsonpancreaticβ-cellstoblockATP-sensitivepotassiumchannels.Thisinturnleadstoopeningofvoltage-sensitivecalciumchannelswhichproducesaninfluxofcalcium;theinfluxofcalciumresultsinβ-cellsproductionofinsulin.Anadditionaleffectofsulfonylureasissuppres

7、sionofgluconeogenesisintheliver.Physical-ChemicalPropertiesSulfonylureasareweakacidsduetothemarkeddelocalizationofthenitrogenloneelectronpairbythesulfonylgroup.TheirpKa'sclusteraround5.0andtheyarestronglyproteinbound.Structure-activityRelationshipsTheremustbere

8、asonablebulkontheureanitrogen;methylandethylcompoundsarenotactive.Usually,thereisonlyone(normallysubstituentpara)onthesulfonylaromaticring.Manysimplesubstituentsonthesulfony