1._Autonomic_Nervous_System_(1)[1]-1 (1).pdf

Pharmacology Drugs Affecting the Autonomic Nervous System Autonomic Nervous System Autonomic Nervous System Content: Introduction to the Nervous System …………………………………………………….. 5 Chemical Signaling Between Cells …………………………………………………….. 52 Signal Transduction in the Effector Cell ………………………………………………….......

Pharmacology Drugs Affecting the Autonomic Nervous System Autonomic Nervous System Autonomic Nervous System Content: Introduction to the Nervous System …………………………………………………….. 5 Chemical Signaling Between Cells …………………………………………………….. 52 Signal Transduction in the Effector Cell …………………………………………………..... 64 Autonomic Nervous System Overview: The autonomic nervous system (ANS), along with the endocrine system, coordinates the regulation and integration of bodily functions. The endocrine system sends signals to target tissues by varying the levels of bloodborne hormones. By contrast, the nervous system exerts effects by the rapid transmission of electrical impulses over nerve fibers that terminate at effector cells, which specifically respond to the release of neuromediator substances. Drugs that produce their primary therapeutic effect by mimicking or altering the functions of the ANS are called autonomic drugs. Autonomic Nervous System Overview: The autonomic agents act either by stimulating portions of the ANS or by blocking the action of the autonomic nerves. This chapter outlines the fundamental physiology of the ANS and describes the role of neurotransmitters in the communication between extracellular events and chemical changes within the cell. Introduction to the Nervous System Introduction to the Nervous System The Nervous System is Divided into two Anatomical Divisions: Central nervous system (CNS), which is composed of the brain and spinal cord. Peripheral nervous system, which includes neurons located outside the brain and spinal cord, that is, any nerves that enter or leave the CNS. Introduction to the Nervous System Introduction to the Nervous System The peripheral nervous system is subdivided into the efferent and afferent divisions. Efferent neurons: carry signals away from the brain and spinal cord to the peripheral tissues, and the afferent neurons bring information from the periphery to the CNS. Afferent neurons: provide sensory input to modulate the function of the efferent division through reflex arcs or neural pathways that mediate a reflex action. Introduction to the Nervous System Introduction to the Nervous System A. Functional Divisions within the Nervous System: The efferent portion of the peripheral nervous system is further divided into two major functional subdivisions: Somatic nervous system and the ANS. Somatic efferent neurons: are involved in the voluntary control of functions such as contraction of the skeletal muscles essential for locomotion. ANS, conversely, regulates the everyday requirements of vital bodily functions without the conscious participation of the mind. Introduction to the Nervous System Introduction to the Nervous System A. Functional Divisions within the Nervous System: Because of the involuntary nature of the ANS as well as its functions, it is also known as the visceral, vegetative, or involuntary nervous system. It is composed of efferent neurons that innervate visceral smooth muscle, cardiac muscle, vasculature, and the exocrine glands, thereby controlling digestion, cardiac output, blood flow, and glandular secretions. Introduction to the Nervous System B. Anatomy of the ANS: 1. Efferent Neurons: The ANS carries nerve impulses from the CNS to the effector organs through two types of efferent neurons: the preganglionic neurons and the postganglionic neurons. The cell body of the first nerve cell, the preganglionic neuron, is located within the CNS. The preganglionic neurons emerge from the brainstem or spinal cord and make a synaptic connection in ganglia (an aggregation of nerve cell bodies located in the peripheral nervous system). Introduction to the Nervous System B. Anatomy of the ANS: 1. Efferent Neurons: Introduction to the Nervous System B. Anatomy of the ANS: 1. Efferent Neurons: The ganglia function as relay stations between the preganglionic neuron and the second nerve cell, the postganglionic neuron. The cell body of the postganglionic neuron originates in the ganglion. It is generally nonmyelinated and terminates on effector organs, such as visceral smooth muscle, cardiac muscle, and the exocrine glands. Introduction to the Nervous System Introduction to the Nervous System B. Anatomy of the ANS: 2. Afferent Neurons: The afferent neurons (fibers) of the ANS are important in the reflex regulation of this system (for example, by sensing pressure in the carotid sinus and aortic arch) and in signaling the CNS to influence the efferent branch of the system to respond. Introduction to the Nervous System B. Anatomy of the ANS: 3. Sympathetic Neurons: The efferent ANS is divided into the sympathetic and the parasympathetic nervous systems, as well as the enteric nervous system. Anatomically, the sympathetic and the parasympathetic neurons originate in the CNS and emerge from two different spinal cord regions. The preganglionic neurons of the sympathetic system come from the thoracic and lumbar regions (T1 to L2) of the spinal cord, and they synapse in two cordlike chains of ganglia that run close to and in parallel on each side of the spinal cord. Introduction to the Nervous System Introduction to the Nervous System B. Anatomy of the ANS: 3. Sympathetic Neurons: The preganglionic neurons are short in comparison to the postganglionic ones. Axons of the postganglionic neuron extend from the ganglia to tissues they innervate and regulate. In most cases, the preganglionic nerve endings of the sympathetic nervous system are highly branched, enabling one preganglionic neuron to interact with many postganglionic neurons. This arrangement enables activation of numerous effector organs at the same time. Introduction to the Nervous System B. Anatomy of the ANS: 3. Sympathetic Neurons: Note: The adrenal medulla, like the sympathetic ganglia, receives preganglionic fibers from the sympathetic system. The adrenal medulla, in response to stimulation by the ganglionic neurotransmitter acetylcholine, secretes epinephrine (adrenaline), and lesser amounts of norepinephrine, directly into the blood. Introduction to the Nervous System Introduction to the Nervous System Introduction to the Nervous System B. Anatomy of the ANS: 4. Parasympathetic Neurons The parasympathetic preganglionic fibers arise from cranial nerves III (oculomotor), VII (facial), IX (glossopharyngeal), and X (vagus), as well as from the sacral region (S2 to S4) of the spinal cord and synapse in ganglia near or on the effector organs. Note: The vagus nerve accounts for 90% of preganglionic parasympathetic fibers. Postganglionic neurons from this nerve innervate most organs in the thoracic and abdominal cavity. Introduction to the Nervous System Introduction to the Nervous System B. Anatomy of the ANS: 4. Parasympathetic Neurons Thus, in contrast to the sympathetic system, the preganglionic fibers are long, and the postganglionic ones are short, with the ganglia close to or within the organ innervated. In most instances, there is a one-to-one connection between the preganglionic and postganglionic neurons, enabling discrete response of this system. Introduction to the Nervous System B. Anatomy of the ANS: 5. Enteric Neurons: The enteric nervous system is the third division of the ANS. It is a collection of nerve fibers that innervate the gastrointestinal (GI) tract, pancreas, and gallbladder, and it constitutes the “brain of the gut.” This system functions independently of the CNS and controls motility, exocrine and endocrine secretions, and microcirculation of the GI tract. It is modulated by both the sympathetic and parasympathetic nervous systems. Introduction to the Nervous System C. Functions of the Sympathetic Nervous System: Although continually active to some degree (for example, in maintaining tone of vascular beds), the sympathetic division is responsible for adjusting in response to stressful situations, such as trauma, fear, hypoglycemia, cold, and exercise Introduction to the Nervous System Introduction to the Nervous System C. Functions of the Sympathetic Nervous System: 1. Effects of Stimulation of the Sympathetic Division: The effect of sympathetic stimulation is an increase in heart rate and blood pressure, mobilization of energy stores, and increase in blood flow to skeletal muscles and the heart while diverting flow from the skin and internal organs. Sympathetic stimulation results in dilation of the pupils and bronchioles. It also reduces GI motility and affects function of the bladder and sexual organs. Introduction to the Nervous System C. Functions of the Sympathetic Nervous System: 2. Fight or Flight Response: The changes experienced by the body during emergencies are referred to as the “fight or flight” response. These reactions are triggered both by direct sympathetic activation of effector organs and by stimulation of the adrenal medulla to release epinephrine and lesser amounts of norepinephrine. Hormones released by the adrenal medulla directly enter the bloodstream and promote responses in effector organs that contain adrenergic receptors. Introduction to the Nervous System Introduction to the Nervous System C. Functions of the Sympathetic Nervous System: 2. Fight or Flight Response: The sympathetic nervous system tends to function as a unit and often discharges as a complete system, for example, during severe exercise or in reactions to fear. This system, with its diffuse distribution of postganglionic fibers, is involved in a wide array of physiologic activities. Although it is not essential for survival, it is essential in preparing the body to handle uncertain situations and unexpected stimuli. Introduction to the Nervous System Introduction to the Nervous System D. Functions of the Parasympathetic Nervous System: The parasympathetic division is involved with maintaining homeostasis within the body. It is required for life, since it maintains essential bodily functions, such as digestion and elimination. The parasympathetic division usually acts to oppose or balance the actions of the sympathetic division and generally predominates the sympathetic system in “rest-and-digest” situations. Introduction to the Nervous System D. Functions of the Parasympathetic Nervous System: If it did, it would produce massive, undesirable, and unpleasant symptoms, such as involuntary urination and defecation. Instead, parasympathetic fibers innervating specific organs such as the gut, heart, or eye are activated separately, and the system affects these organs individually. Introduction to the Nervous System E. Role of the CNS in the Control of Autonomic Functions: Although the ANS is a motor system, it does require sensory input from peripheral structures to provide information on the current state of the body. This feedback is provided by streams of afferent impulses, originating in the viscera and other autonomically innervated structures that travel to integrating centers in the CNS, such as the hypothalamus, medulla oblongata, and spinal cord. These centers respond to stimuli by sending out efferent reflex impulses via the ANS. Introduction to the Nervous System E. Role of the CNS in the Control of Autonomic Functions: Introduction to the Nervous System E. Role of the CNS in the Control of Autonomic Functions: 1. Reflex Arcs: Most of the afferent impulses are involuntarily translated into reflex responses. For example, a fall in blood pressure causes pressure-sensitive neurons (baroreceptors in the heart, vena cava, aortic arch, and carotid sinuses) to send fewer impulses to cardiovascular centers in the brain. This prompts a reflex response of increased sympathetic output to the heart and vasculature and decreased parasympathetic output to the heart, which results in a compensatory rise in blood pressure and heart rate. Introduction to the Nervous System Introduction to the Nervous System E. Role of the CNS in the Control of Autonomic Functions: 1. Reflex Arcs: Note: In each case, the reflex arcs of the ANS comprise a sensory (afferent) arm and a motor (efferent or effector) arm. Introduction to the Nervous System Introduction to the Nervous System E. Role of the CNS in the Control of Autonomic Functions: 1. Emotions and the ANS: Stimuli that evoke strong feelings, such as rage, fear, and pleasure, can modify activities of the ANS. Introduction to the Nervous System F. Innervation by the ANS: 1. Dual Innervation: Most organs are innervated by both divisions of the ANS. Thus, vagal parasympathetic innervation slows the heart rate, and sympathetic innervation increases heart rate. Despite this dual innervation, one system usually predominates in controlling the activity of a given organ. For example, the vagus nerve is the predominant factor for controlling heart rate. The dual innervation of organs is dynamic, and fine-tuned continually to maintain homeostasis. Introduction to the Nervous System Introduction to the Nervous System F. Innervation by the ANS: 2. Sympathetic Innervation: Although most tissues receive dual innervation, some effector organs, such as the adrenal medulla, kidney, pilomotor muscles, and sweat glands, receive innervation only from the sympathetic system. Introduction to the Nervous System G. Somatic Nervous System: The efferent somatic nervous system differs from the ANS in that a single myelinated motor neuron, originating in the CNS, travels directly to skeletal muscle without the mediation of ganglia. As noted earlier, the somatic nervous system is under voluntary control, whereas the ANS is involuntary. Responses in the somatic division are generally faster than those in the ANS. Introduction to the Nervous System H. Summary of Differences Between Sympathetic, Parasympathetic, and Motor Nerves: Major differences in the anatomical arrangement of neurons lead to variations of the functions in each division. The sympathetic nervous system is widely distributed, innervating practically all effector systems in the body. By contrast, the distribution of the parasympathetic division is more limited. The sympathetic preganglionic fibers have a much broader influence than the parasympathetic fibers and synapse with a larger number of postganglionic fibers. This type of organization permits a diffuse discharge of the sympathetic nervous system. Introduction to the Nervous System H. Summary of Differences Between Sympathetic, Parasympathetic, and Motor Nerves: The parasympathetic division is more circumscribed, with mostly one-to-one interactions, and the ganglia are also close to, or within, organs they innervate. This limits the amount of branching that can be done by this division. [A notable exception is found in the myenteric plexus (major nerve supply to the GI tract), where one preganglionic neuron has been shown to interact with 8000 or more postganglionic fibers.] The anatomical arrangement of the parasympathetic system results in the distinct functions of this division. Introduction to the Nervous System H. Summary of Differences Between Sympathetic, Parasympathetic, and Motor Nerves: The somatic nervous system innervates skeletal muscles. One somatic motor neuron axon is highly branched, and each branch innervates a single muscle fiber. Thus, one somatic motor neuron may innervate 100 muscle fibers. This arrangement leads to the formation of a motor unit. The lack of ganglia and the myelination of the motor nerves enable a fast response by the somatic nervous system. Introduction to the Nervous System H. Summary of Differences Between Sympathetic, Parasympathetic, and Motor Nerves: Figure – Characteristics of the sympathetic and parasympathetic nervous systems Chemical Signaling Between Cells Chemical Signaling Between Cells Neurotransmission in the ANS is an example of chemical signaling between cells. In addition to neurotransmission, other types of chemical signaling include the secretion of hormones and the release of local mediators. Figure – Some commonly used mechanisms for transmission of regulatory signals between cells. Chemical Signaling Between Cells A. Hormones: Specialized endocrine cells secrete hormones into the bloodstream, where they travel throughout the body, exerting effects on broadly distributed target cells. B. Local Mediators: Most cells secrete chemicals that act locally on cells in the immediate environment. Because these chemical signals are rapidly destroyed or removed, they do not enter the blood and are not distributed throughout the body. Histamine and prostaglandins are examples of local mediators. Chemical Signaling Between Cells C. Neurotransmitters: Communication between nerve cells, and between nerve cells and effector organs, occurs through the release of specific chemical signals (neurotransmitters) from the nerve terminals. The release is triggered by arrival of the action potential at the nerve ending, leading to depolarization. An increase in intracellular 𝐶𝑎+2 initiates fusion of synaptic vesicles with the presynaptic membrane and release of their contents. The neurotransmitters rapidly diffuse across the synaptic cleft, or space (synapse), between neurons and combine with specific receptors on the postsynaptic (target) cell. Chemical Signaling Between Cells Chemical Signaling Between Cells C. Neurotransmitters: 1. Membrane Receptors: All neurotransmitters, and most hormones and local mediators, are too hydrophilic to penetrate the lipid bilayers of target cell plasma membranes. Instead, their signal is mediated by binding to specific receptors on the cell surface of target organs. Chemical Signaling Between Cells C. Neurotransmitters: 1. Membrane Receptors: Note: A receptor is defined as a recognition site for a substance. It has a binding specificity and is coupled to processes that eventually evoke a response. Most receptors are proteins. Chemical Signaling Between Cells C. Neurotransmitters: 2. Types of Neurotransmitters: Although over 50 signal molecules in the nervous system have been identified, norepinephrine (and the closely related epinephrine), acetylcholine, dopamine, serotonin, histamine, glutamate, and γ-aminobutyric acid are most commonly involved in the actions of therapeutically useful drugs. Each of these chemical signals binds to a specific family of receptors. Acetylcholine and norepinephrine are the primary chemical signals in the ANS, whereas a wide variety of neurotransmitters function in the CNS. Chemical Signaling Between Cells C. Neurotransmitters: a. Acetylcholine: The autonomic nerve fibers can be divided into two groups based on the type of neurotransmitter released. If transmission is mediated by acetylcholine, the neuron is termed cholinergic. Acetylcholine mediates the transmission of nerve impulses across autonomic ganglia in both the sympathetic and parasympathetic nervous systems. It is the neurotransmitter at the adrenal medulla. Chemical Signaling Between Cells C. Neurotransmitters: a. Acetylcholine: Transmission from the autonomic postganglionic nerves to the effector organs in the parasympathetic system, and a few sympathetic system organs, also involves the release of acetylcholine. In the somatic nervous system, transmission at the neuromuscular junction (the junction of nerve fibers and voluntary muscles) is also cholinergic. Chemical Signaling Between Cells Chemical Signaling Between Cells C. Neurotransmitters: b. Norepinephrine and Epinephrine: When norepinephrine is the neurotransmitter, the fiber is termed adrenergic. In the sympathetic system, norepinephrine mediates the transmission of nerve impulses from autonomic postganglionic nerves to effector organs. Epinephrine secreted by the adrenal medulla (not sympathetic neurons) also acts as a chemical messenger in the effector organs. Note: A few sympathetic fibers, such as those involved in sweating, are cholinergic. Signal Transduction in the Effector Cell Signal Transduction in the Effector Cell The binding of chemical signals to receptors activates enzymatic processes within the cell membrane that ultimately results in a cellular response, such as the phosphorylation of intracellular proteins or changes in the conductivity of ion channels. A neurotransmitter can be thought of as a signal and a receptor as a signal detector and transducer. The receptors in the ANS effector cells are classified as adrenergic or cholinergic based on the neurotransmitters or hormones that bind to them. Epinephrine and norepinephrine bind to adrenergic receptors, and acetylcholine binds to cholinergic receptors. Cholinergic receptors are further classified as nicotinic or muscarinic. Signal Transduction in the Effector Cell Some receptors, such as the postsynaptic cholinergic nicotinic receptors in skeletal muscle cells, are directly linked to membrane ion channels and are known as ionotropic receptors. Binding of neurotransmitter to ionotropic receptors directly affects ion permeability. All adrenergic receptors and cholinergic muscarinic receptors are G protein–coupled receptors (metabotropic receptors). Metabotropic receptors mediate the effects of ligands by activating a second messenger system inside the cell. The two most widely recognized second messengers are the adenylyl cyclase system and the calcium/phosphatidylinositol system. Signal Transduction in the Effector Cell Figure – Three mechanisms whereby binding of a neurotransmitter leads to a cellular effect. Signal Transduction in the Effector Cell A. Membrane Receptors Affecting Ion Permeability (Ionotropic Receptors): Neurotransmitter receptors are membrane proteins that provide a binding site that recognizes and responds to neurotransmitter molecules. Some receptors, such as the postsynaptic nicotinic receptors in the skeletal muscle cells, are directly linked to membrane ion channels. Therefore, binding of the neurotransmitter occurs rapidly (within fractions of a millisecond) and directly affects ion permeability. These types of receptors are known as ionotropic receptors. Signal Transduction in the Effector Cell Signal Transduction in the Effector Cell B. Membrane Receptors Coupled to Second Messengers (Metabotropic Receptors): Many receptors are not directly coupled to ion channels. Rather, the receptor signals its recognition of a bound neurotransmitter by initiating a series of reactions that ultimately result in a specific intracellular response. Second messenger molecules, so named because they intervene between the original message (the neurotransmitter or hormone) and the ultimate effect on the cell, are part of the cascade of events that translate neurotransmitter binding into a cellular response, usually through the intervention of a G protein. Signal Transduction in the Effector Cell B. Membrane Receptors Coupled to Second Messengers (Metabotropic Receptors): The two most widely recognized second messengers are the adenylyl cyclase system and the calcium/phosphatidylinositol system. The receptors coupled to the second messenger system are known as metabotropic receptors. Muscarinic and adrenergic receptors are examples of metabotropic receptors.