利尿药和降血糖药ppt课件

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1、MedicinalchemistryChapter10DiureticsandSyntheticHypoglycemicDrugsCollegeofPharmacy,SDUShutaoMaEmail:mashutao@sdu.edu.cnChapter10DiureticsandSyntheticHypoglycemicDrugsSection1HypoglycemicDrugsSection2DiureticsSection1HypoglycemicDrugsTheclassictriadof

2、symptomsindiabetesispolyphagia,polydypsia(thirst),andpolyuria(excessurine).Allthreeresultdirectlyfromexcessiveserumglucoselevels.Type1diabetesusuallydevelopsinanacutemanner,althoughthedestructiveautoimmuneprocessmayhavebeenunderwayforsometime.Type2diab

3、eteshasamoreinsidious,oftenasymptomaticonsetanditspresenceisusuallydetectedbyroutinemedicalexaminations.DefinitionsTypeIDiabetes.Insulin-dependentdiabetesmellitus(IDDM),thisconditionoccurswhentheβ-cellsofthepancreaticisletsofLangerhansaredestroyed,prob

4、ablybyanautoimmuneprocess,suchthatinsulinproductionisdeficient.Type2Diabetes.Noninsulin-dependentdiabetesmellitus(NIDDM)isveryfrequentlyassociatedwithobesityinitsmainlyadultvictims.Seruminsulinlevelsarenormalorelevated,soinessencethisisadiseaseofinsuli

5、nresistance.BiochemistryandPathogenesisofDiabetesClassificationsFirstGenerationSulfonylureas:tolbutamide.SecondGenerationSulfonylureas:glibenclamide.ThirdGenerationSulfonylureas:glimepiride,repaglinide.Biguanides:metformin.α-GlucosidaseInhibitors:Acarb

6、ose,Miglitol.MechanismofActionSulfonylureasinteractwithreceptorsonpancreaticβ-cellstoblockATP-sensitivepotassiumchannels.Thisinturnleadstoopeningofvoltage-sensitivecalciumchannelswhichproducesaninfluxofcalcium;theinfluxofcalciumresultsinβ-cellsproducti

7、onofinsulin.Anadditionaleffectofsulfonylureasissuppressionofgluconeogenesisintheliver.Physical-ChemicalPropertiesSulfonylureasareweakacidsduetothemarkeddelocalizationofthenitrogenloneelectronpairbythesulfonylgroup.TheirpKa'sclusteraround5.0andtheyarest

8、ronglyproteinbound.Structure-activityRelationshipsTheremustbereasonablebulkontheureanitrogen;methylandethylcompoundsarenotactive.Usually,thereisonlyone(normallysubstituentpara)onthesulfonylaromaticring.Manysimplesubstituentsonthesulfony