Autonomic pharmacology General introduction Department of pharmacology Zhu ling ( 朱玲) 20 10.3

1. Autonomic pharmacology General introduction Department of pharmacology Zhu ling (朱玲) 2010.3

2. Why study autonomic pharmacology?

3. Autonomic Pharmacology is Rewarding!! LOGICAL CLINICALLY RELEVANT

4. Autonomic Pharmacology is Logical Anatomical, Physiological & Neurobiological Information Mechanism of Drug Action + Predict Effects of Drugs

5. Autonomic Pharmacology is Logical Nerves to organ Y release neurotransmitter X, and X increases the activity of organ Y Drug A blocks receptors for neurotransmitter X + Drug A decreases activity of organ Y

6. Autonomic Pharmacology is Clinically Relevant

7. Autonomic drugs are used for the treatment of Angina

8. Autonomic drugs are used for the treatment of Heart Failure

9. Autonomic drugs are used for the treatment of Alzheimer’s Disease

10. Autonomic drugs are used for the treatment of High Blood Pressure

11. Autonomic drugs are used for the treatment of Benign Prostatic Hypertrophy

12. Autonomic drugs are used for the treatment of Anaphylactic Shock

13. Autonomic drugs are used for the treatment of Septic Shock

14. Autonomic drugs are used for the treatment of Asthma

15. Autonomic Drugs First Introduction to Autonomic Pharmacology

16. Somatic system :No ganglia present; Largely non-automatic; Skeletal muscle is innervated by somatic nerves, controlling voluntary actions;

17. Autonomic nervous system(ANS):ANS has ganglia;Largely autonomous (independent) ;Its activities are not under direct conscious control.

18. Both systems 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.

19. Anatomical features of the autonomic the autonomic nervous systemClassification of ANS Somatic autonomic sympathetic (thoracolumbar) parasympathetic (craniosacral) Both divisions originate in nuclei within the central nervous system, and give rise topreganglionic efferent fibers that exit from the brain stem or spinal cord , and terminate in motor ganglia.

20. The 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 nerves(especially the third, seventh, ninth, and tenth) and the third and fourth sacral spinal roots.

21. Anatomy of the Autonomicand Somatic Motor Systems

23. Second Transmitter 递质 Transmitter crosses the cleft by diffusion and activates or inhibits the postsynaptic cell by binding to a specialized receptor molecule. 乙酰胆碱 Acetylcholine Ach 去甲肾上腺素 Noradrenaline NA Norepinephrine NE

24. Transmitters at Specific Junctions of the Peripheral Nervous System

25. An important traditional classification of autonomic nerves is based on the primary transmitter molecules--acetylcholine or norepinephrine released from their terminal boutons and varicosities. Cholinergicfibers Adrenergic fibers Three Classification of autonomic nerves based on the transmitter

26. AcholinergicfibersA large number of peripheral autonomic nervous system fibers synthesize and release acetylcholine; they are cholinergic fibers.

27. A cholinergicfibers They 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 sympathetic postganglionic fibers are cholinergic. the somatic (nonautonomic) motor fibers to skeletal muscle.

28. BAdrenergic fibersie, they act by releasing norepinephrine.Most postganglionic sympathetic fibers release nor-epinephrine (noradrenaline); they are noradrenergic (often called simply "adrenergic" fibers

29. Dopamine 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 addition to the primary transmitter.

31. Five key features of neurotransmitter function represent potential targets of pharmacologic therapy: synthesis, storage, release, activation of receptors, and termination of action. Four Neurotransmitter chemistry of the autonomicnervous system

32. 1 Cholinergic Transmission The terminals of cholinergic neurons contain largenumbers of vesicles. The large vesicles contain a high concentration of peptides, while the smaller clear vesicles contain most of the acetylcholine.

34. 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: Termination of action of acetylcholine is acetylcholine hydrolysis.

35. 2 Adrenergic Transmission • Adrenergic neurons also transport a precursor molecule into the nerve ending, then synthesize the transmitter, and finally store it in membrane bound vesicles, but the synthesis of the adrenergic transmitters is more complex than that of acetylcholine.

37. Terminationof noradrenergic transmission results from several processes, including simple diffusion away from the receptor 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)

40. Drugs : 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.

41. FiveAutonomic receptors The definition of different autonomic receptor subtypes, including cholinoceptors; adrenoceptors dopamine receptors

42. Locations of Cholinergic and Adrenergic Receptor Subtypes

43. 1 cholinergic receptorsacetylcholine receptor subtypes :muscarinic and nicotinic receptors. The term cholinoceptor denotes receptors (both muscarinic and nicotinic) that respond to acetylcholine.

44. 2 Adrenergic receptor • The term adrenoceptor is widely used to describe receptors that respond to catecholamines such as norepinephrine. • The adrenoceptors can be subdivided into (α- adrenoceptor and β-adrenoceptor types on the basis of both agonist and antagonist selectivity.

45. Development of more selective blocking drugs has led to the naming of subclasses within these major types; eg, within the (α-adrenoceptor class, α1and α2 receptors differ in both agonist and antagonist selectivity. selective drugs

47. 3 Dopamine receptors • describe receptors that respond to dopamine. DA receptors: mesenterium, renal, cardiovascular system, brain

49. Presynaptic regulation

50. 4 Functional organization of autonomic activity(Function of receptors) 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.