Integrated Cardiopulmonary Pharmacology Third Edition

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1 Integrated Cardiopulmonary Pharmacology Third Edition Chapter 3 Pharmacology of the Autonomic Nervous System

2 Multimedia Directory Slide 19 Slide 37 Slide 38 Slide 39 Slide 40 Slide 41 Slide 42 Slide 43 Muscle Nerve Transmission Animation Parasympathetic Stimulation of the Airway Animation Parasympathetic Stimulation of the Heart Animation Sympathetic Stimulation of the Airway Animation Sympathetic Stimulation of the Heart Animation Parasympathetic and Sympathetic Nervous System Effects Animation #1 Parasympathetic and Sympathetic Nervous System Effects Animation #2 Parasympathetic and Sympathetic Nervous System Effects Animation #3

3 Objectives Upon completion of this chapter, you will be able to Describe the divisions of the central and peripheral nervous systems Define key terms relative to pharmacology of the autonomic nervous system Describe the anatomy, neurotransmitters, and receptors of the autonomic nervous system

4 Objectives State four classifications of autonomic nervous system drugs on the basis of how and where they work Relate the pharmacology of the autonomic nervous system to the relevant specific chapters and drug classifications

5 Nervous System Divisions Central Nervous System Comprised of the brain and spinal cord. Brain Analogous to the CPU, handles information from a variety of sources. Spinal cord The main branch that transmits messages to and from the brain.

6 Nervous System Divisions Peripheral Nervous System Comprised of all the nerves outside the brain and spinal cord. Afferent nerves Carry sensory information from parts of the body to the brain for processing. Efferent nerves Carry impulses away from the brain and spinal cord; also known as motor nerves.

7 Insert Figure 3-1 Figure 3 1: Major Components of the Nervous System

8 Peripheral Nervous System Divided into two main divisions Somatic nervous system Controls skeletal muscles during voluntary movement and is under conscious control. Autonomic nervous system The involuntary or automatic response of the PNS. Regulates the cardiopulmonary and digestive systems. The autonomic system is further divided into the sympathetic and parasympathetic branches.

9 Autonomic System Branches Sympathetic Alert system for stressful situations. Fight-or-flight response. Parasympathetic Concerned with daily body maintenance and maintaining a homeostatic environment.

10 Insert Figure 3-2 Figure 3 2: Organization of the Nervous System

11 Insert figure 3-3 here Figure 3 3: Effects of the Parasympathetic and Sympathetic Nervous Systems Source: Biology: A Guide to the Natural World, 2nd ed. (p.558) by David Krogh, 2002, Upper Saddle River, NJ, Prentice Hall. Reprinted by permission.

12 Insert Table 3-1

13 Steps of Nervous System Conduction A resting nerve receives stimulation. An electrical impulse carries the signal along the nerve fiber or axon. The synapse connects to either another nerve or a muscle or gland. A chemical neurotransmitter substance must now travel across the synapse.

14 Steps of Nervous System Conduction Chemicals are manufactured and stored at the end of the axons and released upon stimulation by the electrical impulse. Two main neurochemical substances stored or manufactured at the ends of the nerve fibers are acetylcholine (ACh) and norepinephrine (NE).

15 Insert Figure 3-4 Figure 3 4: Transmission of a Nerve Impulse

16 The Somatic Nervous System Transmission Controls the skeletal muscles. One junction system where the stimulus travels via a single nerve axon and then travels to a synapse. Neurotransmitter then passes the signal to the brain for sensory input.

17 The Somatic Nervous System Transmission ACh is the neurotransmitter substance found in the somatic system. The synapse is the neuromuscular junction.

18 Insert Figure 3-5 Figure 3 5: Somatic Nervous System Transmission

19 Muscle Nerve Transmission Animation Click the screenshot to view an animation showing muscle nerve transmission. Back to Directory

20 Autonomic Nervous System Transmission There are two junctions to traverse in order for a signal to reach the site. The first neuron is a presynaptic or preganglionic neuron. Ganglion Nerve that lies outside the central nervous system. The ganglion journeys from the brain to the first junction or synapse.

21 Autonomic Nervous System Transmission The second neuron is a postsynaptic or postganglionic neuron, and it travels from the ganglia to the target site.

22 Insert figure 3-6 Figure 3 6: Synapses and Neurotransmitter Substances of the Autonomic Nervous System

23 Ganglionic Neurons Parasympathetic and sympathetic systems have preganglionic and postganglionic neurons. Neurotransmitter substance at both preganglionic sites is ACh (also found at the postganglionic site of the parasympathetic system).

24 Ganglionic Neurons The neurotransmitter that carries the impulse to the involuntary muscle or gland at the postganglionic junction of the sympathetic system is norepinephrine (NE).

25 Insert Figure 3-7 Figure 3 7: Preganglionic Transmission in the ANS. This occurs in both parasympathetic and sympathetic systems, with only the length and location of the nerve fibers being different.

26 Receptors Receptors are where the action is, (the neuroeffector site). Nicotinic receptors Found at the skeletal muscles in the somatic system and at all preganglionic sites in the parasympathetic and sympathetic nervous systems.

27 Receptors Muscarinic receptors Found at the postganglionic site of the parasympathetic nervous system. Cholinergic receptors Receptors that bind with ACh; can be either muscarinic or nicotinic, depending on their location.

28 Sympathetic Receptor Classification Adrenergic receptors Bind with NE found in the sympathetic nervous system; include alpha and beta receptors. Alpha Receptors found in smooth muscle of blood vessels, can be alpha 1 or alpha 2, which cause vasoconstriction.

29 Sympathetic Receptor Classification Beta Two types beta 1 and beta 2 Beta1 are found in the cardiac muscle; stimulation has positive chronotropic, dromotropic, and inotropic effects on the cardiac system. Beta 2 are found within the smooth muscle of the airways and in certain blood vessels. Stimulation results in vasodilation and bronchodilation. Used for the treatment of bronchospasm.

30 Sympathetic Receptor Classification Dopamine receptors Adrenergic receptor found in renal tissue. Stimulation causes relaxation of the renal arteries and increases perfusion to the kidneys.

31 Insert Table 3-2

32 Insert Figure 3-8 Figure 3 8: Synapses, Ganglia, Neurotransmitters, and Receptors of the ANS Note: Adrenergic receptors are classified as alpha (α) or beta (β).

33 Insert Figure 3-9 Figure 3 9: Receptors Found at Nerve Endings

34 Four Categories of Drugs That Affect the Function of the ANS Cholinergics or parasympathomimetics Drugs that stimulate the parasympathetic receptors. Responses cause slow HR and bronchoconstriction. Anticholinergics or parasympatholytics Drugs that block parasympathetic receptors. Responses are to speed the heart and cause bronchodilation.

35 Four Categories of Drugs That Affect the Function of the ANS Adrenergics or sympathomimetics Drugs that stimulate the sympathetic receptors. Can be alpha- or beta-adrenergic drugs, depending on the receptor they stimulate.

36 Four Categories of Drugs That Affect the Function of the ANS Antiadrenergics or sympatholytics Can be referred to as blockers. A beta blocker blocks the expected effects of bronchodilation and increases in HR and therefore causes bronchoconstriction and a decrease in HR.

37 Parasympathetic Stimulation of the Airway Animation Click the screenshot to view an animation showing parasympathetic stimulation of the airway. Back to Directory

38 Parasympathetic Stimulation of the Heart Animation Click the screenshot to view an animation showing parasympathetic stimulation of the heart. Back to Directory

39 Sympathetic Stimulation of the Airway Animation Click the screenshot to view an animation showing sympathetic stimulation of the airway. Back to Directory

40 Sympathetic Stimulation of the Heart Animation Click the screenshot to view an animation showing sympathetic stimulation of the heart. Back to Directory

41 Parasympathetic and Sympathetic Nervous System Effects Animation Click the screenshot to view an animation showing the parasympathetic and sympathetic nervous system effects. Back to Directory

42 Parasympathetic and Sympathetic Nervous System Effects Animation Click the screenshot to view an animation showing the parasympathetic and sympathetic nervous system effects. Back to Directory

43 Parasympathetic and Sympathetic Nervous System Effects Animation Click the screenshot to view an animation showing the parasympathetic and sympathetic nervous system effects. Back to Directory

44 Direct-and Indirect-Acting Agents Drugs can affect different steps in the neurotransmission process. So far, we ve discussed drugs that stimulate the receptors (agonists), which directly affect the levels of neurotransmitter substances.

45 Direct-and Indirect-Acting Agents Indirect agents, such as antagonists, can block the effects of neurotransmitter substances. There are other indirect methods to increase or decrease levels of the neurotransmitter.

46 Parasympathomimetic The main neurotransmitter in all autonomic preganglia sites and at the parasympathetic postganglionic synapses is acetylcholine (ACh). This is synthesized from acetyl CoA and choline by the enzyme choline acetyltransferase. ACh is a simple molecule, yet it has activity at several different receptors.

47 Parasympathomimetic ACh is not a useful drug therapeutically because it is rapidly broken down in the body. Muscarinic agonists are direct-acting parasympathomimetic agents that stimulate the parasympathetic nervous system by increasing ACh production at the effector site.

48 Acetylcholinesterase (AChE) Acetylcholine action is terminated when it is metabolized by AChE. Cholinergic drugs are subdivided based on whether they act directly at the receptor by increasing production of ACh or indirectly through inhibition of AChE, the enzyme that breaks down Ach.

49 Acetylcholinesterase (AChE) The action of ACh is enhanced either by directly increasing production or indirectly by preventing its rapid breakdown, thus allowing ACh to remain active longer.

50 Direct-and Indirect-Acting Agents Direct-Acting Agent Stimulating receptor sites (agonists). Indirect-Acting Agent Blocking the receptor sites (antagonists). Increasing or decreasing transmitter substances by enhancing or inhibiting the enzymes that break them down.

51 Insert Table 3-3

52 Parasympatholytics Anticholinergic drugs of the parasympathetic nervous system. Have cardiovascular effects similar to those of atropine, including tachycardia, bronchodilation, and drying of secretions. Anticholinergic drugs can be broken down into antimuscarinic, where the drug would block the effect at the postganglionic site where muscarinic receptors are found.

53 Parasympatholytics They also block nicotinic receptors found in the ganglion and the skeletal muscles.

54 Insert Table 3-4

55 Sympathomimetic Survival response that enables the body to prepare for dangers. In danger, the lungs bronchodilate to take in more oxygen, and the heart s rate and force increase. Drugs that act on norepinephrine receptors. Mimic sympathetic responses.

56 Sympathomimetic Norepinephrine transmits impulses in the sympathetic postganglionic synapse when released NE crosses the synaptic cleft and binds to postsynaptic adrenergic receptors. NE is recycled back into the synaptic knob to be stored for future use via the process of reuptake.

57 Sympathomimetic Epinephrine is considered the prototype sympathomimetic, with effects on alpha 1, alpha 2, beta 1 and beta 2 receptors and is used to treat anaphylactic shock. Norepinephrine causes vasoconstriction and can be used to treat low blood pressure.

58 Sympathomimetic Alpha-adrenergic agents, when applied locally or taken orally, can relieve symptoms of nasal congestion by constricting swollen vessels in the nasal passageway.

59 Norepinephrine Excess norepinephrine that does not participate in the reuptake process can be metabolized by the enzymes monamine oxidase (MAO) and catechol-o-methyltransferase (COMT).

60 Norepinephrine Direct-acting sympathomimetics increase NE production and bind with adrenergic receptors found at the postsynaptic junction of the sympathetic nervous system. Indirect sympathomimetics inhibit the reuptake and enzyme deactivation of NE, thus preventing its breakdown.

61 Insert figure 3-10 here Figure 3 10: Life cycle of norepinephrine (NE): (1) NE is synthesized from the amino acid tyrosine; (2) NE is released into the synaptic cleft; (3) NE binds to receptors on the postsynaptic membrane; (4) NE is taken back into the presynaptic neuron (reuptake); (5) NE is degraded by MAO; (6) Small amounts of NE enter the postsynaptic cell and are degraded by COMT.

62 Insert Figure 3-11 Figure 3 11: Sympathomimetic Drug Subgroups

63 Insert Table 3-5

64 Sympatholytics Adrenergic blockers. Have cardiovascular indications. Block or slow the effects of the sympathetic system. Drugs are alpha and beta blockers used to treat arrhythmias and hypertension.

65 Insert Table 3-6

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