I.classificationbasedontheselectivityforthemainadrenoceptorsubtypes.

α-adrenoceptoragonists

--Noradrenaline（去甲腎上腺素）、Metaraminol（間羥胺）、Phenylephrine（去氧腎上腺素）α,β-adrenoceptoragonists

--Adrenaline（腎上腺素）、Dopamine（多巴胺）、ephedrine（麻黃堿）β-adrenoceptoragonists--Isoprenaline（異丙甲腎上腺素）、Dobutamine（多巴酚丁胺）、Salbutamol（沙丁胺醇）etc.

第一節(jié)腎上腺素受體激動藥第一頁，共36頁。1)兒茶酚胺(catecholamines)類腎上腺素、去甲上腺素、多巴胺、異丙腎上腺素；作用強，維持時間短，易被COMT滅活。2)非兒茶酚胺類間羥胺、麻黃堿、甲氧明、苯腎上腺素(新福林）；作用弱，維持時間長（碳原子上的氫被-CH3取代），不易被MAO、COMT滅活。構效關系H第二頁，共36頁。第三頁，共36頁。Noradrenaline（去甲腎上腺素）actsmainlyonαreceptors,feweffectsonβ1;shouldbegivenbyiv.

A.Pharmacologicaleffects

1.Bloodvessels

①verystrongbloodvesselsconstrictioneffect

②dilation（擴張）ofcoronarybloodvessels（冠狀血管）2.HeartsomeeffectasAdr.--weak,lesslikelytocausetachy-cardia（心動過速）第四頁，共36頁。3.Bloodpressureincreasesystolic（心臟收縮的）anddiastolic（心臟舒張的）pressure--increasesBPB.Uses①Hypotension（低血壓）

②earlyphaseofneurogenicshock（神經源性休克）③uppergastrointestinaltractbleeding（上消化道出血）

C.Sideeffects①anxiety,respiratorydifficulty,forcefulheartbeatandtransientheadache,hypertension（高血壓）

②necrosis（壞疽）ofthesiteofintravenousinjection（靜脈注射）

③reducedbloodsupplytokidneyandperipheries第五頁，共36頁。D.contraindicationsandprecautionsHypertension,atherosclerosis（動脈硬化癥）,coronaryheartdisease（冠心?。?oliguria（少尿）andanuria（無尿）Metaraminol（間羥胺，又稱阿拉明，Aramine）actsonα1receptor;causesNAreleaseactions:increasesBPandcardiacoutput;reflexly（反射性）decreasesheartrateUses:hypotensivestates;attacksofsupraventriculartachycardia（陣發(fā)性室上性心動過速）第六頁，共36頁。Methoxamine（甲氧明）actsonα1receptoractions:inreceasesBP;reflexdecreasesinheartrate;goodforhypotensionwithtachycardia.uses:treathypotensivestates&paroxysmal（發(fā)作性的）atria（心房）tachycardia.Phenylephrine（去氧腎上腺素）actsonα1receptoruses:mydriasis（瞳孔散大）forexaminationofretina（視網膜）第七頁，共36頁。Adrenaline（epinephrine,腎上腺素）actsonα1,α2andβ1,β2receptorsPharmacologicalEffects1.Cardiovascularsystem

a.bloodvessels①skin,mucousmembranes--constriction②smallarteriole（細動脈）--constriction③splanchnic（內臟的）vessels

-renalandmesenteric（腸系膜的）--constriction

-cerebral（腦的）andpulmonary（肺部的）--weak第八頁，共36頁。④skeletalmuscle(α,β2)lowdoses—dilatationlargerdoses—constrictionlowdosesAdr.activateβ2

largerdosesAdr.activateα⑤coronaryartery（冠狀動脈）vessels--dilatation-increasecardiaccontraction-stimulationofβ2-receptor,dilatationofcoronaryartery-increasemyocardial（心肌的）metabolites第九頁，共36頁。b.Heart(β1)①increasecontractility--正性肌力②increaseheartrate--正性心率③increasestrokevolume（每搏輸出量）④increasecardiacoutput⑤increasemyocardium（心?。﹐xygenconsumption第十頁，共36頁。c.Bloodpressure

①Cardiacoutput—SP(systolicbloodpressure)②peripheralvascularresistance—DP(diastolicbloodpressure)③meanarterialbloodpressure--berelatedwithdosesmalldose-SP-DP(relaxvesselsinskeletalmuscle—β2)-BPmaybedecreasedorremainunchangedlargerdose-SP-DP-BP（雙相反應）

④pretreatment（預處理）withαblocker--reverseoftheAdr.effect→decreaseBP第十一頁，共36頁。2.Smoothmuscle

①relaxationofbronchialsmoothmuscle(β2)②mydriasis(α)3.metaboliceffects

①bloodsugar(α,β2)②freefattyacid(β1,β3)③oxygenconsumption④renin(β1)第十二頁，共36頁。B.ClinicalUses

1.Cardiacarrest（心臟驟停）--drowning,intoxicationofCNSinhibitors,acuteinfectiousdisease,etc.--intraventricular（心室內的）injection

（過敏性疾?。?-anaphylacticshock--TypeIallergicreactions

第十三頁，共36頁。3.Bronchialasthma（支氣管哮喘）--relaxationmuscle--inhibitionthesecretionofhistamineandleukotaxine（白細胞誘素）4.Localapplication

--usewithlocalanesthetics--epistaxis（鼻衄）--gingival（齒齦的）bleeding第十四頁，共36頁。C.SideEffects

cardiovascularandCNS-restlessness（煩躁）,anxiety,insomnia（失眠）,headache-elevationofBP,thedangerofcerebralhemorrhage（出血）,arrhythmia（心律不齊）,etc.D.Contraindicationhypertension,sclerosis（硬化）ofcerebralartery,ischemic（局部缺血的）heartdisease,CHF(congestiveheartfailure)第十五頁，共36頁。Dopamine（多巴胺）precursor（前體）ofNAandAdr,actsonDA,β1,β2,α1receptors,metabolizedbyCOMTandMAO,t1/2=1~2min,noeffectonCNS--notpenetrateBBB.A.PharmecologicalEffects

(dosedependent)a.lowdose(1)increasecardiaccontractility--β1+NArelease(2)increasesystolicbloodpressure(3)diastolicpressurenochangeordecrease(4)increaseinglomerularfiltration（腎小球濾過）rate,renalbloodflowandNa+excretion(DA)第十六頁，共36頁。b.largedoseactsonα1–vasoconstriction--decreasesrenalbloodflow.B.Uses

(1)sometypesofshock--cardiogenic（心源性的）andseptic（膿毒性的）shock--hemorrhagicshockespeciallywithcardiacdysfunction,oliguria（少尿）oranuria（無尿）(2)acuterenalinsufficiency--withdiuretics（利尿劑）C.SideEffects

(1)tachycardia,arrhythmia,headacheandhypertension–infused（滴注）veryfast(2)actsonα1receptor:inreceasesBP;reflexdecreasesinheartrate;goodforhypotensionwithtachycardia第十七頁，共36頁。Ephedrine（麻黃堿）αandβagonist;enhancesthereleaseofNA–indirectsympathomimetic（擬交感神經的）A.Pharmacologicaleffect①similartoadrenaline②actiondurationlonger③lowerpotency④bronchialmusclerelaxationlessprominentbutmoresustainedB.Uses①preventhypotension②asthma③nasal（鼻的）decongestant（消除充血藥）第十八頁，共36頁。C.Sideeffectstachyphylaxis（快速耐受性）,hypertension,anxiety,insomnia,etc.Isoprenaline（異丙腎上腺素）syntheticderivative（衍生物）ofnoradrenalineA.Pharmacologicaleffects

Cardiovascularsystem①β1,β2receptorsagonist②intravenous--lowerperipheralvascularresistance③increaseheartrate,increasecontractility→increasecardiacoutput第十九頁，共36頁。④cardiaceffectsmayleadtopalpitations（心悸）,sinus（竇性）tachycardiaandmoreseriousarrhyth-mias2.Bronchialsmoothmuscle①relaxationofbronchialmuscle(β2)②inhibitreleaseofhistamineandothermediatorsofinflammation--strongerthanAdr.3.Metabolismincreaseoxygenconsumption,fattyacid,bloodsugar.第二十頁，共36頁。B.Uses1.asthma(treatacuteasthma)2.cardiacarrest3.shock---nowseldomusedC.Sideeffects①palpitation,tachycardia,headacheandflushedskinarecommon.②cardiacischemia（局部缺血）andarrhythmiasmayoccur.D.ContraindicationCoronaryheartdisease,myocarditis（心肌炎）,hyperthyroidism（甲狀腺功能亢進）第二十一頁，共36頁。討論：比較幾種擬交感胺類藥的作用，分析其作用機制。第二十二頁，共36頁。I.classificationα-AdrenoceptorBlockingDrugs

--NonselectiveαReceptorBlocker—Phentolamine（酚妥拉明）etc.--α1-Rblocker—Prazosin（哌唑嗪）--α2-Rblocker—Yohimbine（育亨賓）β-ReceptorBlockingDrugs--Nonselectiveβ-Rblocker–propranolol（普萘洛爾）--Selectiveβ-Rblocker–atenolol（阿替洛爾）αandβ-ReceptorBlockingDrugs--labetalol（拉貝洛爾）

第二節(jié)腎上腺素受體阻斷藥第二十三頁，共36頁。Phentolamine（酚妥拉明）A.Pharmacologicaleffects

1.Reducesperipheralresistance--blockα1

2.Cardiacstimulation

--reflexeffect--blockspresynaptic（突觸前的）α2→

enhancedNArelease

3.Inhibits5-HT1,H2agonist1.Peripheralvasculardiseases2.Excesslocalvasoconstrictor3.Shockα-ReceptorBlockingDrugs第二十四頁，共36頁。（心肌的）infarction（梗死形成）andstubborn（頑固的）congestiveheartfailure5.Pheochromocytoma（嗜鉻細胞瘤）Tolazoline（妥拉唑啉）

1.Effectssimilartophentolaminebutlesspotent.（擬膽堿樣作用）effectandhistaminelikeeffectsarestronger.A.Sideeffects

posturalhypotension（體位性低血壓）,tachycardia(reflex),arrhythmiaandangina（絞痛）第二十五頁，共36頁。1.Peripheralvasospastic（血管痙攣的）disease（溢出）ofiv.NAPhenoxybenzamine（酚芐明，又名苯芐胺dibenzyline）1.Bindstoαreceptorsproducingirreversible（不可逆的）blockade(14-48h).2.Inhibitsreuptake（再攝?。﹐fNA3.BlocksH1and5-HTreceptors.第二十六頁，共36頁。A.Pharmacologicalactions（對抗）αreceptor2.Blocksvasoconstrictionbutlittlefallinbloodpressure3.Cardiacoutputincreased--reflexeffect--blockadeofpresynapticα21.Peripheralvasculardiseases（嗜鉻細胞瘤）第二十七頁，共36頁。C.Sideeffects1.Nasalstuffiness（鼻塞）（疲乏）,sedation（嗜睡）,nausea（惡心）4.PosturalhypotensionPrazosin（哌唑嗪）1.Highlyselectiveforα1,lowaffinityforα2

2.Relaxationofbotharterialandvenoussmoothmuscle--fallinbloodpressure第二十八頁，共36頁。3.Decreasespreloadandafterloadofheart4.EffectiveinthemanagementofhypertensionYohimbine（育亨賓）--usedasatoolinlab.第二十九頁，共36頁。β-ReceptorBlockingDrugs第三十頁，共36頁。A.PharmacologicalEffects1.β-blockingeffectsa.Heart(1)Decreasesheartrate,cardiaccontractility,andcardiacoutput(2)Decreasesmyocardialoxygenconsumptionb.BloodvesselandBP--decreasesbloodpressureinhypertensionpatients(1)heartβ1-Rblockade(2)smoothmuscleofbloodvesselsβ2-Rblockade(3)inhibitsrenin（腎素）-angiotensin（血管緊張素）system(RAS)第三十一頁，共36頁。c.RespiratorytractIncreasesairwayresistance-β2-Rblockade--patientswithasthmad.MetaboliceffectsInhibitslipolysis（脂解）andglycogenolysis（肝糖原分解）e.OthereffectsBlockspresynapticβ2-R--decreasesNAsecretion2.Intrinsicsympathomimeticactivity(ISA)partialagonisticaction--Pindolol（吲哚洛爾）第三十二頁，共36頁。3.Membranestabilizingaction①Localanaestheticeffect--decreasesmembraneionchannelpermeability(Na+channels)②Needshighconcentrations--50-10