藥理學(xué)英文版教學(xué)課件：Chapter 47-1 Histamine receptor agonist-antagonist

DrugsactonHistaminereceptors(p331)§1HistamineAnautocoid(自分泌物質(zhì))Histamineisabiogenicamine（生物胺）involvedinlocalimmuneresponsesaswellasregulatingphysiologicalfunctioninthegut（腸道）andactingasaneurotransmitter.Histaminetriggerstheinflammatoryresponse.producedbybasophils（嗜堿性粒細(xì)胞）andbymastcells（肥大細(xì)胞）foundinnearbyconnectivetissues.Histamineincreasesthepermeabilityofthecapillariestowhitebloodcellsandotherproteins,inordertoallowthemtofightforeigninvadersintheaffectedtissues.HistaminereceptorsandfunctionsH1,H2,H3

receptorsbelongingtothefamilyofG-protein-coupledreceptors.H1

isexpressedthroughoutthebody,specificallyinsmoothmuscles,onvascularendothelialcells,intheheart,andintheCNS.Causesvasodilation,bronchoconstriction,separationofendothelialcells(responsibleforhives蕁麻疹),andpainanditchingduetoinsectstings;involvedinallergicrhinitis（過(guò)敏性鼻炎）symptomsandmotionsickness.H2locatedonparietalcells.PrimarilystimulategastricacidsecretionH3receptoriscoupledtotheGi,soitleadstoinhibitionoftheformationofcAMP,interactwithN-typevoltagegatedcalciumchannels,toreduceactionpotentialmediatedinfluxofcalciumandhencereduceneurotransmitterglutamaterelease.Leprosy（麻風(fēng)）diagnosisThehistaminetest:usedforthestudyofthephysiologyofthecirculationandperipheralinnervationdifferentialdiagnosisfortruegastricaciddificiency§2AntihistaminedrugsI.H1receptorantagonistCompetitiveantagonist1stgeneration:diphenhydramine（苯海拉明，苯那君）、promethazine（異丙嗪，非那根）、pyribenzamine（曲吡那敏，撲敏寧）、chlorpheniramine（氯苯那敏，撲爾敏）、doxepin（多塞平)CNSeffect---sedation&hypnosis;Mreceptorblockeffect2ndgeneration:cetirizine(西替利嗪，仙特敏)、mequitazine(美喹他嗪，甲喹酚嗪)、astemizole（阿司咪唑，息斯敏）、acrivastine（阿伐斯汀，新敏樂）、levocabastin(左卡巴斯汀，立復(fù)汀)andmizolastine(咪唑斯汀)FewCNSeffects,stillhaveMblockeffectClinicaluses:AllergicdiseasesofskinormucosaMotionsicknessSleepdisorder:1stgenerationII.H2receptorAntagonistCimetidine(西咪替丁)、ranitidine(雷尼替丁)、famotidine(法莫替丁)andnizatidine(尼扎替丁)InhibitgastricacidsecretionModulatingimmunologicfunction:reducetheproductionofhistamineinducedsuppresserfactorfromTcellsUsedingastriculcerIII.H3receptorantagonistUnderR&DH3receptorwidelydistributedinCNS&PNS,mainlypresynaptic(突觸前膜)located.RelatedwithsomecerebraldiseasessuchasAlzheimer’sandParkinson’sdiseasespracticesTheH1receptorantagonistsuchas()canbeusedtotreat(),()and().thesideeffectof1stgenerationofH1blockerinclude(),(