肾上腺能受体激动剂-山东大学药理学英文课件

Chapter8Adrenoceptoragonists

(adrenomimeticdrugs,Sympathomimeticamines)α,β-Ragonistsα-Ragonists,β-Ragonists

Section1Structure-activityrelationshipandclassification

Chemistry

structure-activityrelationship(1)Catecholamine

(CA,儿茶酚胺)(2)

-C：blockMAO

(3)N-：

or

selective

classificationsα,β-Ragonists:

AD,ephedrine（麻黄碱）α-Ragonists

α1、α2-Ragonists

：NA

α1-Ragonists:phenylephrine(去氧肾上腺素)

α2-Ragonists：oxymetazoline(羟甲唑啉）apraclonidine(阿可乐定)β-Ragonists,

β1、β2-Ragonists:Isoprenaline

β1-Ragonists：dobutamine(多巴酚丁胺)

β2-Ragonists:

salbutamol（沙丁胺醇）section2α、β

-RagonistsAdrenaline(AD,肾上腺素)Ephedrine（麻黄碱）Dopamine(DA，多巴胺)Adrenaline(epinephrine,AD,肾上腺素)

SourceandChemistry1.adrenalmedulla:pheochromocyte(嗜铬细胞)2.PNMT(苯乙胺-N-甲基转移酶)

THDDCDβHPNMTTyr→→→dopa→→→→DA→→→→NA→→→→→AD

ADPharmacokinetics1.

Absorption2.Termination

Uptakemetabolism:MAO/COMT3.Excretion:VMA(3甲氧4羟扁桃酸)Normal:2-6.8mg/24hPheochromocytoma:10-250mg/24h（嗜铬细胞瘤）pharmacologicalactions:

activateα,β-R1.heart:stronglyexcited(β1-R)positiveinotropiceffectpositivechronotropiceffectpositivedromotropiceffect

Coronary:dilation(1)Agonistβ2-R(2)Prolongdiastolicphase(3)Increasemyocardialoxygenconsumptionadenosine↑Advantageanddisadvantage2.vessels:

(1)contraction(α-R)

Skin,mucosa:strongKidney:strongjuxtaglomerularcells(β1-R):Reninrelease↑

Cerebral:

(2)dilation:

SkeletalMuscle(β2-R)

Coronary:directeffect:β2-Rindirecteffect:timeofperfusion

↑

adenosine↑

pharmacologicalactions3.BP:

smalldose:SBP↑,DBP↓largedose:SBP↑,DBP↑

Doublephasedresponse

pharmacologicalactions4.smoothmuscle:

bronchialsmoothmuscle:

2,

1Gastrointestinaltract:(negativefeedback)

Uterus,bladder:

2Pupillarydilatormuscle:

1

pharmacologicalactions5.metabolism:↑20%-30%(1)Carbohydrate:bloodGlu↑

,

2:glycogenolysis↑(糖原分解）glyconeogenesis↑(糖原异生)

2:insulin↓

:glucagon↑(2)Lipolysis:bloodfattyacid↑

3:triglyceridelipase(三酰甘油酶)↑

6.skeletalmuscle7.CNSclinicaluses

1.cardiacarrest2.allergicshock:firstchoicecautions3.bronchialasthma4.prolongationoflocalanestheticduration5.topicalhemorrhage:0.1%6.glaucoma

adversereactionsArhythmiaHypertensionCNSreactionscontraindicationsEphedrine(麻黄碱)陈克恢（１８９８—１９８８）药理学家。长期致力于中药药理研究，是２０世纪国际药理学的一代宗师，也是现代中药药理学研究的创始人。他的突出贡献是，首先发现麻黄素的药理作用，为推动交感胺类化合物的化学合成奠定了基础，并为从天然产物中寻找开发新药起了典范作用。他还发现解救急性氰化合物中毒的方法，并被沿用至今。EphedrineMechanisms:1.directactions：

1,

1,

2

,

2-R2.indirectactions

Characteristics:1.stable,orally.2.action:slower,weakerandlongerVSAD3.centralexcitation4.tachyphylaxisActions:1.CNSeffects2.CVS3.Smoothmuscle4.Increaseskeletalmuscletension

ephedrineclinicaluses1.bronchialasthma2.nasalcongestion3.hypotensivestates4.Allergy(urticaria,angioneuroedema)adversereactionsCardiacandCNSexcitation

dopamine(DA,多巴胺)

Pharmacokinetics:

ivd,shortt1/2,notacrossBBB

pharmacologicalactionsactivateα,β1,DA

-R,↑NAreleasepharmacologicalactions

1.Cardiovascularsystem:

vessel:dilation(D1A-R),contraction(α-R)Smalldose:DBP↓(D1A-R)SBP→Midddledose:SBP↑(β1-R)DBP↑→Largedose:DBP↑(α-R)SBP↑2.renalvessels:smalldosedilation(D1A-R)largedosecontraction(α-R)clinicaluses

1.shock2.chronicheartfailure(CHF)3.acuterenalfailure(ARF)Mephentermine

(美芬丁胺,wyamine,恢压敏)Similartoephedrine(direct,indirect)centralexcitationUsedtopreventhypotensionstateUsedtotreatnasalcongestionsection3α-Ragonistsα-Ragonists

α1、α2-Ragonistsα1-Ragonistsα2-Ragonists

1,

2Agonists

noradrenaline(去甲肾上腺素，norepinephrine，NA，NE)[sourceandchemistry]

NA

pharmacokineticspharmacologicalactionsstronglyactivateα1,α2-Rslightlyactivateβ1-R.pharmacologicalactions1.vessels:contraction(α-R)

coronaryvessels:dilation(similartoAD)presynapticadrenergicterminals(α2-R):NE↓negativefeedback2.heart:excitation(β1-R)3.BP:smalldose:SBP↑DBP→largedose:SBP↑DBP↑4.others:weakerthanADclinicaluses

1.shock：early2.hypotensioncausedbydrugs’intoxication3.upperdigestivetracthemorrhageadversereactions1.localischemiaandnecrosis2.acuterenalfailure

metaraminol

(间羟胺,aramine,阿拉明)[Mechanisms]1.directactions2.indirectactions[Characteristics]1.weakerandlongerthanNA2.littleadversereactions:renalfailure,arrhythmias3.tachyphylaxis[Uses]

substituteforNAintreatmentofshock

1-RAgonistsPhenylephrine(去氧肾上腺素)Methoxamine(甲氧明)Phenylephrineandmethoxamine

1.selectiveα1-Ragonists:shock,hypotension2.renalvasoconstriction:significant3.paroxysmalsupraventricular

tachycardia4.phenylephrine→mydriasis(rapid,weak,short)

2-RAgonistsPeripheral

2-RAgonists:

oxymetazoline(羟甲唑啉)：nasalcongestionapraclonidine(阿可乐定):

GlaucomaCentral

2-RAgonists：HBP

clonidine(可乐定)，methyldopa（甲基多巴）Section4β-Ragonistsβ1、β2-Ragonistβ1-Ragonistsβ2-Ragonistsβ1、β2-RagonistIsoprenaline(Isop,异丙肾上腺素)pharmacologicalactions:

stronglyactivateβ1、β2-Rpharmacologicalactions1.heart:excitation(β1-R)positiveinotropiceffectpositivechronotropiceffectpositivedrom