pharmacology of alpha adrenergic receptor antagonists 2002

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1、ALPHAandBETAADRENERGICRECEPTORANTAGONISTSFigure10–5Classificationofadrenergicreceptorantagonists.Drugsmarkedbyanasterisk(*)alsoblock1receptors.BottomofFormI.AlphaAdrenergicReceptorAntagonistsA.Introduction1.Alphareceptorsmediatemanyimportantactionsofendo

2、genouscatecholamines.Theseinclude:a.alpha1mediatedvasoconstriction,b.alpha2receptormediatedinhibitionofthereleaseofNEandACh,c.alpha2mediatedinhibitionofinsulinsecretionandinhibitionoflipolysis,d.alpha2mediatedcontractionofbloodvesselsinskinandmucosa(thes

3、ereceptorsarepreferentiallyactivatedbycirculatingcatecholamines,whereasalpha1receptorsareactivatedbyNEreleasedatsympatheticnerveterminals).e.alpha2mediatedcentralinhibitionofsympathetictone.2.Correspondinglythereforeitshouldbeevidentthat"Adetailedknowled

4、geoftheautonomicnervoussystemandthesitesofactionofdrugsthatactonadrenergicreceptorsisessentialforunderstandingthepharmacologyandtherapeuticusesof..."adrenergicreceptorblockingdrugs(G&G,1990,p221).B.Themostimportanteffectsofalpha1&2adrenergicantagonistsar

5、eonthecardiovascularsystem.Thesecardiovasculareffectsaremediatedinlargepartbytheeffectsoftheantagonistsonsympatheticnerveendings,andbyeffectsontheCNS.Theantagonismwhichisobservedinmostcasesiscompetitive.C.CardiovascularEffectsofAlpha1Antagonists1.Alpha1a

6、ntagonistsblockvasoconstrictioninducedbyendogenouscatecholamines.Theresultingfallinperipheralresistanceleadstoafallinmeanbloodpressure.Themagnitudeofthiseffectisdependentuponthedegreeofsympathetictoneatthetimetheantagonistisadministered.Thusthereislesshy

7、potensioninthesupinethaninthestandingpatient.Thedecreaseinbloodpressureleadstoareflextachycardia.Thereflexeffectsareexaggeratedifthedrugalsohasalpha2antagonisteffects,becauseantagonismofalpha2receptorsfacilitatesreleaseofNEpresynapticallytocauseafurthert

8、achycardiceffect.2.Theyblockthevasoconstrictionandhypertensiveeffectsofexogenoussympathomimetics.Forexample,pressorresponsestophenylephrine(apurealpha1agonist)arecompletelyblocked.PressorresponsestoEPIcanbetransformedtodep

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《pharmacology of alpha adrenergic receptor antagonists 2002》由会员上传分享,免费在线阅读,更多相关内容在教育资源-天天文库

1、ALPHAandBETAADRENERGICRECEPTORANTAGONISTSFigure10–5Classificationofadrenergicreceptorantagonists.Drugsmarkedbyanasterisk(*)alsoblock1receptors.BottomofFormI.AlphaAdrenergicReceptorAntagonistsA.Introduction1.Alphareceptorsmediatemanyimportantactionsofendo

2、genouscatecholamines.Theseinclude:a.alpha1mediatedvasoconstriction,b.alpha2receptormediatedinhibitionofthereleaseofNEandACh,c.alpha2mediatedinhibitionofinsulinsecretionandinhibitionoflipolysis,d.alpha2mediatedcontractionofbloodvesselsinskinandmucosa(thes

3、ereceptorsarepreferentiallyactivatedbycirculatingcatecholamines,whereasalpha1receptorsareactivatedbyNEreleasedatsympatheticnerveterminals).e.alpha2mediatedcentralinhibitionofsympathetictone.2.Correspondinglythereforeitshouldbeevidentthat"Adetailedknowled

4、geoftheautonomicnervoussystemandthesitesofactionofdrugsthatactonadrenergicreceptorsisessentialforunderstandingthepharmacologyandtherapeuticusesof..."adrenergicreceptorblockingdrugs(G&G,1990,p221).B.Themostimportanteffectsofalpha1&2adrenergicantagonistsar

5、eonthecardiovascularsystem.Thesecardiovasculareffectsaremediatedinlargepartbytheeffectsoftheantagonistsonsympatheticnerveendings,andbyeffectsontheCNS.Theantagonismwhichisobservedinmostcasesiscompetitive.C.CardiovascularEffectsofAlpha1Antagonists1.Alpha1a

6、ntagonistsblockvasoconstrictioninducedbyendogenouscatecholamines.Theresultingfallinperipheralresistanceleadstoafallinmeanbloodpressure.Themagnitudeofthiseffectisdependentuponthedegreeofsympathetictoneatthetimetheantagonistisadministered.Thusthereislesshy

7、potensioninthesupinethaninthestandingpatient.Thedecreaseinbloodpressureleadstoareflextachycardia.Thereflexeffectsareexaggeratedifthedrugalsohasalpha2antagonisteffects,becauseantagonismofalpha2receptorsfacilitatesreleaseofNEpresynapticallytocauseafurthert

8、achycardiceffect.2.Theyblockthevasoconstrictionandhypertensiveeffectsofexogenoussympathomimetics.Forexample,pressorresponsestophenylephrine(apurealpha1agonist)arecompletelyblocked.PressorresponsestoEPIcanbetransformedtodep

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