第八章腎上腺素受體激動藥Adrenoceptor-activating-drugs課件

1、Chapter 8Adrenoceptor-Activating & Other Sympathomimetic drugs南開大學醫(yī)學院張京玲 陳彤云Chapter 8Adrenoceptor-ActivatChapter 8目的 按照及受體的相對選擇作用，掌握腎上腺素，去甲腎上腺素，異丙腎上腺素的作用與應(yīng)用。了解多巴胺，麻黃堿，間羥胺（阿拉明），去氧腎上腺素（苯腎上腺素，新福林）等的作用與應(yīng)用。Chapter 8目的Chapter 8內(nèi)容 擬腎上腺素藥的基本化學結(jié)構(gòu)和構(gòu)效關(guān)系。去甲腎上腺素：不同給藥途徑的吸收情況。消除的主要方式是再攝取，MAO及COMT在兒茶酚胺代謝中的作用。去甲腎上腺素

2、主要興奮及1受體。對比心血管系統(tǒng)的作用，加強心肌收縮力，收縮血管，血壓上升，反射性減慢心率，用途，不良反應(yīng)及防治。腎上腺素：興奮及受體，對心臟的作用，對不同部位血管的作用，對血壓的影響，對支氣管平滑肌，糖代謝的影響，用途，不良反應(yīng)和禁忌癥。Chapter 8內(nèi)容Chapter 8內(nèi)容 異丙腎上腺素：興奮1及2受體，對心臟，血管，支氣管平滑肌的作用，臨床應(yīng)用，不良反應(yīng)及禁忌癥。多巴胺：對，多巴胺受體的興奮作用，加強心肌收縮力，對心率的影響少，增加腎及腸系膜血流量，利尿。對腎臟的作用劑量與效應(yīng)的關(guān)系。用途。其它擬腎上腺素藥：間羥胺（阿拉明），甲氧胺的作用特點，用途。麻黃堿對心血管，支氣管平滑肌及中

3、樞神經(jīng)系統(tǒng)的作用，快速耐受性，與腎上腺素作用和體內(nèi)過程的不同點。用途。Chapter 8內(nèi)容Adrenoceptor agonistsDefinitionThe mode & spectrum of action of sympathomimetic drugsThe molecular mechanismsStructure-activity relationshipAdrenoceptor agonistsDefinitioAdrenoceptor agonistsClassification -adrenoceptor agonists , -adrenoceptor agonists-

4、adrenoceptor agonists Adrenoceptor agonistsClassificAdrenoceptor agonistsDefinition Also called adrenomimetic drugs or sympathomimetic amines. Adrenoceptor agonistsDefinitioAdrenoceptor agonistsThe mode & spectrum of action of sympathomimetic drugsAct by a direct modeAct by a indirect modeBoth 1 and

5、 2Adrenoceptor agonistsThe mode Adrenoceptor agonistsAct by a indirect mode Displacement of stored catecholamines from the adrenergic nerve endingInhibition of reuptake of catecholamines already releasedAdrenoceptor agonistsAct by a Adrenoceptor agonistsThe molecular mechanisms of sympathomimetic ac

6、tionAlpha receptorsBeta receptorsDopamine receptorsAdrenoceptor agonistsThe molec第八章腎上腺素受體激動藥Adrenoceptor-activating-drugs課件第八章腎上腺素受體激動藥Adrenoceptor-activating-drugs課件Adrenoceptor agonistsStructure-activity relationshipBasic structureAdrenoceptor agonistsStructureAdrenoceptor agonistsSubstitution ma

7、y be made:On the amino group;On the benzene ring;On the - carbon;On the - carbon;Adrenoceptor agonistsSubstitut第八章腎上腺素受體激動藥Adrenoceptor-activating-drugs課件Adrenoceptor agonistsClassification-adrenoceptor agonists; (NA) , -adrenoceptor agonists; (Adrenaline)-adrenoceptor agonists; (isoprenaline)Adreno

8、ceptor agonistsClassificAdrenoceptor agonists-adrenoceptor agonistsNoradrenaline NA, or norepinephrine NEMetaraminol, also called araminePhenylephrine, also called neosynephrineMethoxamineAdrenoceptor agonists-adrenocAdrenoceptor agonistsNoradrenaline, norepinephrineChemistry: unstablePharmacokineti

9、cs: given by intravenous infusion, cant across BBB, short duration of action, metabolite by MAO and COMT, excretion by urine.Adrenoceptor agonistsNoradrenaAdrenoceptor agonistsPharmacodynamics Activate -R strongly &1-R weaklyAdrenoceptor agonistsPharmacodAdrenoceptor agonistsHeartWeak positive chron

10、otropic effect on pacemaker activity, in the intact heart, HR Positive inotropic effect on intrinsic contractilityAdrenoceptor agonistsHeartAdrenoceptor agonistsBlood vesselsStrong activate 1-R on the smooth muscles of blood vessels, especially splanchnic and skin vesselsPeripheral vascular resistan

11、ceAdrenoceptor agonistsBlood vesAdrenoceptor agonistsBlood pressure Low dose lightly increase blood pressure Large dose marked increase blood pressureOther Large dose increase glucoseAdrenoceptor agonistsBlood preAdrenoceptor agonistsClinical usesEarly phase of shockHypotension caused by drug toxica

12、tionUpper digestive tract bleedingAdrenoceptor agonistsClinical Adrenoceptor agonistsAdverse effectsLocal tissue marked ischemia and necrosis, procaine or phentolamine can be used to relieve themAcute renal dysfunction Adrenoceptor agonistsAdverse eAdrenoceptor agonistsContraindications and precauti

13、ons hypertension, atherosclerosis, coronary heart disease, oliguria, and anuriaAdrenoceptor agonistsContraindAdrenoceptor agonistsMetaraminol or aramineChemistry: stable, cant be destroyed by MAO, long duration of action The mode of actionDirect actionIndirect actionAdrenoceptor agonistsMetaraminAdr

14、enoceptor agonistsProduce tachyphylaxisLess side reaction than NABoth intravenous infusion and imUsed to treat hypotensive statesAdrenoceptor agonistsProduce tAdrenoceptor agonistsPhenylephrine, or neosynephrine & methoxamineChemistry: stable, cant destroyed by MAOAction: similar to above one, activ

15、ate 1-R, less or no action on -RAdrenoceptor agonistsPhenylephAdrenoceptor agonistsPhenylephrine, or neosynephrine & methoxamineChemistry: stable, cant destroyed by MAOAction: similar to above one, activate 1-R, less or no action on -RAdrenoceptor agonistsPhenylephAdrenoceptor agonistsIntravenous in

16、fusion or im to treat shock, hypotension states & relieve attacks of supraventricular tachycardiaPhenylephrine is an effective mydriatic agent used to examination of the retina, (+) -R on iris dilatorsAdrenoceptor agonistsIntravenoAdrenoceptor agonists, -adrenoceptor agonistsAdrenaline or epinepheri

17、neDopamine, DAEphedrineAdrenoceptor agonists, -adreAdrenoceptor agonistsAdrenaline or epinepherineChemistry: unstable, similar to NAPharmacokinetics: im or sc, metabolite by MAO and COMT in human bodyAdrenoceptor agonistsAdrenalinAdrenoceptor agonistsPharmacodynamics activate both - and -receptors s

18、tronglyAdrenoceptor agonistsPharmacodAdrenoceptor agonistsHeartMarked positive chronotropic effect on both normal and abnormal pacemaker activityStrong positive inotropic effect on intrinsic contractilityAdrenoceptor agonistsHeartAdrenoceptor agonistsPromote conduction of heartCardiac output Relaxat

19、e coronary arteriesAdrenoceptor agonistsPromote Adrenoceptor agonistsBlood vesselsLow dose can activate 2-R on the smooth muscles and cause relaxationLarge dose can strong activate 1-R on the smooth muscles, peripheral vascular resistance Adrenoceptor agonistsBlood vesAdrenoceptor agonistsBlood pres

20、sureLow dose systolic pressure and diastolic pressure normal or (heart 1-R and peripheral 2-R)Large dose marked increase blood pressure (peripheral 1-R and 1-R of juxtaglomerular cells, excretion renin)Adrenoceptor agonistsBlood preAdrenoceptor agonistsSmooth muscles (SM)Bronchial SM relaxation, 2-R

21、(+), stronglyGastrointestinal tract tone , 1-R(+)Adrenoceptor agonistsSmooth muAdrenoceptor agonistsMetabolismLipolysis , 3-R(+); glycogenolysis in liver , - &2-R (+), blood sugar markedly, plasma K+ when stress or exercise, 2-R (+)Adrenoceptor agonistsMetabolisAdrenoceptor agonistsClinical usesCard

22、iac arrest Anaphylactic shock: sc or imBronchial asthma: sc or imLocal application: local anaesthesia (1250000), stop bleedingAdrenoceptor agonistsClinical Adrenoceptor agonistsAdverse effectsBP marked elevation, cerebral hemorrhage or pulmonary edemaSevere angina or myocardial infarctionSinus tachy

23、cardia or serious ventricular arrhythmiasAdrenoceptor agonistsAdverse eAdrenoceptor agonistsContraindications Hypertension, sclerosis of cerebral artery, ischemic heart disease, congestive heart failure, hyperthyroidism, and diabetes. Use with care for old patients.Adrenoceptor agonistsContraindAdre

24、noceptor agonistsDopamine, DAPharmacokineticsDopamine is the precursor of NA and Adr. intravenous infusion, destroyed by MAO & COMT rapidly, t1/2=1-2 min. cant across BBB,Adrenoceptor agonistsDopamine,Adrenoceptor agonistsPharmacodynamicsLow concentration of dopamine activates DA1-R in renal, corona

25、ry artery and mesentery vascular beds, leads to vasodilationAdrenoceptor agonistsPharmacodAdrenoceptor agonistsLarge dose activate 1-R and -R leading to vasoconstriction, including renal blood vessels, BP ,It also causes the release of NA from nerve endings.Adrenoceptor agonistsLarge dosAdrenoceptor

26、 agonistsInfusion of low dose of dopamine causes an increase in glomerulus filtration rate, renal blood flow and Na+ excretion. Adrenoceptor agonistsInfusion Adrenoceptor agonistsClinical usesTreatment of various shockAcute renal dysfunction and heart failure, combination of dopamine and diuretics,A

27、drenoceptor agonistsClinical Adrenoceptor agonistsAdverse effects If infused very fast, it may induce tachycardia, arrhythmia, headache and hypertension. Adrenoceptor agonistsAdverse eAdrenoceptor agonistsEphedrineactivate both and receptorsDirect act on themIndirect act on them: enhances the releas

28、e of NA from adrenergic nerve endings Adrenoceptor agonistsEphedrineAdrenoceptor agonistsStable chemistry property, has effect after oral administrationSympathomimetic action less than adr. But longer duration than that of adr.Markedly excitement effects of CNS, because it can cross BBBAdrenoceptor

29、agonistsStable cAdrenoceptor agonistsProduce tachyphylaxis rapidly Clinical usesBronchial asthma, light symptomsNasal decongestant; Adrenoceptor agonistsProduce tAdrenoceptor agonistsPrevent hypotension induced by epidermal anesthesia or subarachnoid anesthesia; Relieve symptoms of allergic reaction

30、 on the skin and mucous membrane Adrenoceptor agonistsPrevent hAdrenoceptor agonistsAdverse effects Anxiety, insomnia, tachyphylaxis;Intraindications Hypertension, atherosclerosis, hyperthyroidism, and coronary heart disease. Adrenoceptor agonistsAdverse eAdrenoceptor agonists-adrenoceptor agonists

31、- adrenoceptor agonist isoprenaline1-selective agonist dobutamine2-selective agonist salbutamolAdrenoceptor agonists-adrenocAdrenoceptor agonistsIsoprenalineChemistry: synthesis productPharmacokinetics: administration by inhalation as aerosol or sublingual, absorbed fast, most are destroyed by COMT,

32、 few by MAO, duration longer than adr.Adrenoceptor agonistsIsoprenalAdrenoceptor agonistsPharmacodynamics Extremely potent -R agonist, having little effect on -R.Adrenoceptor agonistsPharmacodAdrenoceptor agonistsHeart Positive chronotropic and inotropic action, promote conduction, cardiac output, c

33、onsume oxygen ,Blood vessels a potent vasodilatorAdrenoceptor agonistsHeartAdrenoceptor agonistsBlood pressure A fall in diastolic and mean arterial pressure, and a lesser decrease or a slight increase in systolic pressure. the blood flow of coronary artery increaseAdrenoceptor agonistsBlood preAdre

34、noceptor agonistsSmooth muscles Bronchial SM dilate, long time administration cause tolerance of body, oxygen consume, metabolism , difficult to cross BBB, (+) CNS weak.Adrenoceptor agonistsSmooth muAdrenoceptor agonistsClinical usesBronchial asthma: control acute attack, sublingual or inhalation Serious atria-ventricular conduction blocking: sublingual or intravenous infusionAdrenoceptor agonistsClinical