自主神經(jīng)系統(tǒng)培訓課件

1、Why study autonomic pharmacology?1Why study autonomic pharmacoloAutonomic Pharmacologyis Rewarding!LOGICALCLINICALLYRELEVANT2Autonomic PharmacologyLOGICALC+Anatomical, Physiological &Neurobiological InformationPredict Effects of DrugsMechanism of Drug ActionAutonomic Pharmacology is Logical3+Anatomi

2、cal, PredictMechanismA+Drug A decreases activity oforgan YAutonomic Pharmacology is LogicalDrug A blocks receptors forneurotransmitter XNerves to organ Y release neurotransmitter X, and X increasesthe activity of organ Y4+Drug A decreasesAutonomic PhaAutonomic Pharmacology is Clinically Relevant5Aut

3、onomic Pharmacology 5Autonomic drugs are used for thetreatment of Angina6Autonomic drugs are used for tAutonomic drugs are used for thetreatment of Heart Failure7Autonomic drugs are used for tAutonomic drugs are used for thetreatment of Alzheimers Disease8Autonomic drugs are used for tAutonomic drug

4、s are used for thetreatment of High Blood Pressure9Autonomic drugs are used for tAutonomic drugs are used for thetreatment of Benign Prostatic Hypertrophy 10Autonomic drugs are used for tAutonomic drugs are used for thetreatment of Anaphylactic Shock 11Autonomic drugs are used for tAutonomic drugs a

5、re used for thetreatment of Septic Shock 12Autonomic drugs are used for tAutonomic drugs are used for thetreatment of Asthma 13Autonomic drugs are used for tAutonomic DrugsFirstIntroduction to Autonomic Pharmacology14撰稿、制做：李紅宇Autonomic DrugsFirst14撰稿、制做：李紅 Somatic system :No ganglia present; Largely

6、 non-automatic; Skeletal muscle is innervated by somatic nerves, controlling voluntary actions; 15 Somatic system :No ganglia pAutonomic nervous system(ANS):ANS has ganglia;Largely autonomous (independent) ;Its activities are not under direct conscious control.16Autonomic nervous system(ANS): Both s

7、ystems have important afferent (sensory) inputs that provide sensation and modify motor output through reflex arcs of varying size and complexity.Both systems use chemicals for the transmission of information. 17 Both systems have important aAnatomical features of the autonomic the autonomic nervous

8、 systemClassification of ANSSomaticautonomic sympathetic (thoracolumbar) parasympathetic (craniosacral)Both divisionsoriginate in nuclei within the central nervous system, and give rise to preganglionic efferent fibers that exit from the brain stem or spinal cord ,and terminate in motor ganglia. 18A

9、natomical features of the autThe sympathetic preganglionic fibers leave the central nervous system through the thoracic and lumbar spinal nerves, giving rise to the alternative name thoracolumbar system.“The parasympathetic preganglionic fibers leave the central nervous system through the cranial ne

10、rves(especially the third, seventh, ninth, and tenth) and the third and fourth sacral spinal roots.19The sympathetic preganglionicAnatomy of the Autonomicand Somatic Motor Systems20Anatomy of the Autonomicand S Most of the sympathetic preganglionic fibers terminate in ganglia located in the paravert

11、e- bral chains that lie on either side of the spinal column. From the ganglia, postganglionic sympathetic fibers run to the tissues innervated.21 Most of the sympathetic preThe majority of parasympathetic preganglionic fibers terminate on ganglion cells distributed diffusely or in networks in the wa

12、lls of the innervated organs. Some preganglionic parasympathetic fibers terminate in parasympathetic ganglia located outside the organs innervated. 22The majority of parasympatheti2323乙酰膽堿 Acetylcholine Ach去甲腎上腺素 Noradrenaline NA Norepinephrine NESecondTransmitter 遞質(zhì)Transmitter crosses the cleft by

13、diffusion and activates or inhibits the postsynaptic cell by binding to a specialized receptor molecule.24Second24 The terms sympathetic and parasympathetic are anatomic ones and do not depend on the type of transmitter chemical released from the nerve endings nor on the kind of effect - excitatory

14、or inhibitory-evoked by nerve activity.25 The terms sympathetic and Transmitters at Specific Junctions of the Peripheral Nervous System26Transmitters at Specific JunctAn important traditional classification of autonomic nerves is based on the primary transmitter molecules-acetylcholine or norepineph

15、rine released from their terminal boutons and varicosities. Cholinergic fibers Adrenergic fibers ThreeClassification of autonomic nerves based on the transmitter27An important traditional classA cholinergic fibers A large number of peripheral autonomic nervous system fibers synthesize and release ac

16、etylcholine; they are cholinergic fibers. 28A cholinergic fibers A larA cholinergic fibersThey act by releasing acetylcholine. Almost all efferent fibers leaving the central nervous system (preganglionic efferent autonomic fibers ) are cholinergic. All parasympathetic post-ganglionic and a few sympa

17、thetic postganglionic fibers are cholinergic.the somatic (nonautonomic) motor fibers to skeletal muscle.29撰稿、制做：李紅宇A cholinergic fibersThey act B Adrenergic fibers ie, they act by releasing norepinephrine. Most postganglionic sympathetic fibers release nor-epinephrine (noradrenaline); they are norad

18、renergic (often called simply adrenergic fibers30B Adrenergic fibers ieDopamine is released by some peripheral sympathetic fibers. Adrenal medullary cells, release a mixture of epinephrine and norepinephrine. Most autonomic nerves also release several transmitter substances, or cotransmitters, in ad

19、dition to the primary transmitter.31Dopamine is released by some p3232Five key features of neurotransmitter function represent potential targets of pharmacologic therapy: synthesis, storage, release, activation of receptors, and termination of action. FourNeurotransmitter chemistry of the autonomicn

20、ervous system33Five key features of neurotran1 Cholinergic TransmissionThe terminals of cholinergic neurons contain large numbers of vesicles. The large vesicles contain a high concentration of peptides, while the smaller clear vesicles contain most of the acetylcholine. 341 Cholinergic Transmission

21、The 3535 After release from the presynaptic terminal, acetylcholine molecules may bind to and activate an acetylcholine receptor (cholinoceptor). Eventually (and usually very rapidly), all of the acetylcholine released will diffuse within range of an acetylcholinesterase (ACHE) molecule. Cholinergic

22、: Termination of action of acetylcholine is acetylcholine hydrolysis. 36 After release from the presy AChE very efficiently splits acetylcholine into choline and acetate.Rapid inactivation of acetylcholine is mediated by acetylcholinesterase. Most cholinergic synapses are richly supplied with acetyl

23、cholinesterase; the half-life of acetylcholine in the synapse is therefore very short.37 AChE very efficiently splits AcetylcholinesteraseAcetylcholinesterase is also found in other tissues, eg, red blood cells. (Another cholinesterase with a lower specificity for acetylcholine, butyrylcholinesteras

24、e pseudocholinesterase, is found in blood size the transmitter, and finally store it in plasma, liver, glia, and many other tissues.)38AcetylcholinesteraseAcetylchol39392 Adrenergic Transmission Adrenergic neurons also transport a precursor molecule into the nerve ending, then synthesize the transmi

25、tter, and finally store it in membrane bound vesicles, but the synthesis of the adrenergic transmitters is more complex than that of acetylcholine. 402 Adrenergic Transmission 4141 Termination of noradrenergic transmission results from several processes, including simple diffusion away from the rece

26、ptor site (with eventual metabolism in the plasma or liver) and reuptake into the nerve terminal (uptake 1) or into perisynaptic glia or smooth muscle cells (uptake 2). Two primary degradative enzymes: Monoamine Oxidase (MAO) Catechol-O-Methyl Transferase (COMT) 42 Termination of noradrenergic 43434

27、444Drugs : mimic or block the actions of chemical transmitters Selectively modify many autonomic functions: involve a variety of effector tissues, including cardiac muscle, smooth muscle, vascular endothelium,exocrine glands, and presynaptic nerve terminals. 45Drugs : mimic or block the actFiveAuton

28、omic receptors The definition of different autonomic receptor subtypes, including cholinoceptors; adrenoceptors dopamine receptors46FiveAutonomic receptors The dLocations of Cholinergic and Adrenergic Receptor Subtypes47Locations of Cholinergic and A1 cholinergic receptors acetylcholine receptor sub

29、types :muscarinic and nicotinic receptors. The term cholinoceptor denotes receptors (both muscarinic and nicotinic) that respond to acetylcholine. 481 cholinergic receptors acetycholinergic receptorsMuscarinic receptors M1 Heart,M R M2 (negative feedback) smooth muscles, gland, M3 CNS neuronNicotini

30、c receptors NR N1R(NN) Ganglion N2R(NM) Skeletal muscle (positive feedback) 49cholinergic receptorsMuscarini The term adrenoceptor is widely used to describe receptors that respond to catecholamines such as norepinephrine. The adrenoceptors can be subdivided into (- adrenoceptor and -adrenoceptor ty

31、pes on the basis of both agonist and antagonist selectivity.2 Adrenergic receptor50 The term adrenoceptor is wide Development of more selective blocking drugs has led to the naming of subclasses within these major types; eg, within the (-adrenoceptor class, 1and 2 receptors differ in both agonist an

32、d antagonist selectivity. selective drugs 51 51Adrenergic receptors- adrenoceptor types 1 R: vessels and gut wall smooth muscle 2 R: presynaptic receptors (negative feedback)-adrenoceptor types 1R: myocardium 2R: vessels and bronchi smooth muscle, cardiac muscle (positive feedback)52Adrenergic recep

33、tors- adreno53533 Dopamine receptorsdescribe receptors that respond to dopamine. DA receptors: mesenterium, renal, cardiovascular system, brain 543 Dopamine receptorsdescribe r5555Presynaptic regulation56Presynaptic regulation564 Functional organization of autonomic activity (Function of receptors)

34、A basic understanding of the interactions of autonomic nerves with each other and with their effector organs is essential for an appreciation of the actions of autonomic drugs, especially because of the significant reflex effects that may be evoked by these agents.574 Functional organization of outl

35、ine Function of receptors 58 59 606061616262636364646565outline Function of receptorslocationsreceptorseffectsreceptorseffectsheart1exciteMinhibitSmooth muscle2relaxMcontracteyePupil enlargeMPupil contractCiliary muscle contractBlood vessels2contractrelaxglandMsecrete66outline Function of receptors

36、Central Integration At the highest level-midbrain and medullathe two divisions of the autonomic nervous system and the endocrine system are integrated with each other, with sensory input, and with information from higher central nervous system centers. 67 Central Integration At the These interaction

37、s are such that the parasympathetic system a trophotropic one (ie, leading to growth) and the sympathetic system an ergotropic one (ie, leading to energy expenditure) that was activated for fight or flight. Sympathetic system is most active when the body needs to react to changes in the internal or

38、external environment During rage or fright the sympathetic system can discharge as a unit-affecting multiorgan systems. 68 These interactions are such At a more subtle level of interactions in the brain stem, medulla, and spinal cord, there are important cooperative interactions between the parasymp

39、athetic and sympathetic systems. 69 At a more subtle level of int heart rate increases blood pressure increases blood is shunted to skeletal muscles blood glucose increase bronchioles dilate pupils dilate slows heart rate protects retina from excessive light lowers blood pressure empties the bowel a

40、nd bladder increases gastrointestinal motility promotes absorption of nutrients Sympathetic ResponsesParasympathetic responses70 heart rate increases slows he For some organs, sensory fibers associated with the parasympathetic system exert reflex control over motor outflow in the sympathetic system.

41、 Thus, the sensory carotid sinus baroreceptor fibers in the glossopharyngeal nerve have a major influence on sympathetic outflow from the vasomoter center.71 For some organs, sensory fibe Similarly, parasympathetic sensory fibers in the wall of the urinary bladder significantly influence sympathetic

42、 inhibitory outflow to that organ. Within the enteric nervous system, sensory fibers from the wall of the gut synapse on both preganglionic and postganglionic motor cells that control intestinal smooth muscle and secretory cells.72 Similarly, parasympathetic seIntegration of Cardiovascular FunctionA

43、utonomic reflexes are particularly important in understanding cardiovascular responses to autonomic drugs. Autonomic and hormonal control of cardiovascular function.The sympathetic nervous system directly influences four major variables: peripheral vascular resistance, heart rate, force, and venous

44、tone. It also directly modulates renin production.The parasympathetic nervous system directly influences heart rate. 73Integration of Cardiovascular 74747575Presynaptic regulationPostsynaptic Regulation Up- and down-regulation are known to occur in response to decreased or increased activation, resp

45、ectively, of the receptors. Up- regulation : receptor number incease An extreme form of up-regulation occurs after denervation of some tissues, resulting in dener-vation supersensitivity of the tissue to activators of that receptor typedown-regulation : receptor number decease76Presynaptic regulatio

46、nPostsy77775 Pharmacologic modification of autonomic function Because transmission involves different mechanisms in different segments of the autonomic nervous system, some drugs produce highly specific effects while others are much less selective in their actions. 785 Pharmacologic modification oTh

47、e way on effects of autonomic drugs 1) Direct effect on receptor agonist：receptor activation, similar to transmitter antagonist：receptor blockade 79The way on effects of autonomi Activation or blockade of effector cell receptors offers maximum flexibility and selectivity of effect: adrenoceptors are

48、 easily distinguished from cholinoceptors. Furthermore, individual subgroups can often be selectively activated or blocked within each major type. 80 Activation or blockade of effThe way on effects of autonomic drugs2) To influence transmitter act on the transmitter biochemical synthesis act on the

49、transmitter metabolism (enzymatic inactivation of transmitter) act on the transmitter release act on the transmitter storage 81The way on effects of autonomi Drugs that block action potential propagation (local anesthetics) are very nonselective in their action, since they act on a process that is common to all neurons.On the other hand, drugs that act on the biochemical processes involved in transmitter synthesis and