Autonomic Drugs Chapter 3.pptx

Autonomic Drugs UNIT 2- DRUGS AFFECTING THE AUTONOMIC NERVOUS SYSTEM CHAPTERS 3, 4, 5, 6, & 7 © 2022-2024, Dr. Susan Wrenn, All rights reserved Whalen, K., Lerchenfeldt, S., Giordano, C. (2023). Lippincott illustrated reviews: Pharmacology (8th ed.). Philadelphia, PA: Wolter...

Autonomic Drugs UNIT 2- DRUGS AFFECTING THE AUTONOMIC NERVOUS SYSTEM CHAPTERS 3, 4, 5, 6, & 7 © 2022-2024, Dr. Susan Wrenn, All rights reserved Whalen, K., Lerchenfeldt, S., Giordano, C. (2023). Lippincott illustrated reviews: Pharmacology (8th ed.). Philadelphia, PA: Wolters Kluwer.​  Chapter 3 THE AUTONOMIC NERVOUS SYSTEM Overview Introduction to the Nervous System Central Nervous System (CNS): Brain and spinal cord (Semester 3, Module 2) Peripheral Nervous System: Neurons located outside the brain and spinal cord- includes nerves that connect the CNS with peripheral structures Efferent neurons: carry signals away from the CNS to the peripheral tissues Afferent neurons: bring information from the periphery to the CNS ◦ Modulate the function of the efferent division through reflex arcs or neural pathways that mediate a reflex action Introduction to the Nervous System Somatic system: efferent neurons involved in the voluntary control of functions such as contraction of the skeletal muscles essential for locomotion Autonomic nervous system (ANS): regulates the everyday requirements of vital bodily functions without the conscious participation of the mind. 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. ◦ Involuntary ◦ Also known as the visceral, vegetative, or involuntary nervous system Introduction to the Nervous System Anatomy of the ANS ◦ The ANS carries nerve impulses from the CNS to the effector organs through a two-neuron pathway consisting of preganglionic neurons and postganglionic neurons ◦ Preganglionic neurons: the cell body is within the CNS- emerge from the brainstem or spinal cord and make a synaptic connection in ganglia. Axon is lightly myelinated. ◦ Postganglionic neurons: the cell body originates in the ganglion and terminates on effector organs. Axon is unmyelinated. ◦ Ganglia- an aggregation of neuron cell bodies located in the peripheral nervous system. The ganglia function as relay stations between the preganglionic neuron and the second nerve cell, the postganglionic neuron. Introduction to the Nervous System Anatomy of the ANS Sympathetic neurons: (Sympathetic nervous system- SNS) ◦ Short preganglionic neurons come from the thoracic and lumbar regions (T1 to L2) ◦ Synapse in two cord-like chains of ganglia that run close to and parallel to the spinal cord. ◦ Preganglionic neurons are shorter than postganglionic neurons ◦ Preganglionic neurons are highly branched, allowing one preganglionic neuron to interact with many postganglionic neurons- activates several effector organs at the same time ◦ Adrenal medulla is innervated by preganglionic neurons from the sympathetic system- releases epinephrine (adrenaline) and norepinephrine Introduction to the Nervous System Anatomy of the ANS Parasympathetic neurons: (Parasympathetic nervous system- PSNS) ◦ Long preganglionic neurons come from cranial nerves III (oculomotor), VII (facial), IX (glossopharyngeal) to synapse with cranial ganglia and innervate effectors of the head. ◦ The majority of preganglionic fibers leave the CNS within cranial nerve X (vagus) for distribution to ganglia associated with organs of the thoracic cavity and abdominal viscera. ◦ Sacral preganglionic fibers (S2 to S4) exit through pelvis splanchnic nerves and are distributed to ganglia associated with the bladder, reproductive organs, and distal portions of the GI tract. ◦ Postganglionic neurons innervate most organs in the thoracic and abdominal cavity. ◦ Preganglionic neurons are longer than postganglionic neurons- synapse in ganglia near or on the effector organs. ◦ Preganglionic neurons generally interact with one postganglionic neuron- enables discrete response of this system Introduction to the Nervous System Anatomy of the ANS Enteric neurons: (Enteric nervous system) ◦ A collection of nerve fibers that innervate the gastrointestinal (GI) tract, pancreas, and gallbladder. ◦ “brain of the gut” ◦ Functions independently of the CNS ◦ Controls motility, exocrine and endocrine secretions, and microcirculation of the GI tract. ◦ Modulated by both the sympathetic and parasympathetic nervous systems Comparison of Sympathetic and Parasympathetic Anatomy Sympathetic neurons: Parasympathetic neurons: ◦ Preganglionic neurons come from the ◦ Preganglionic neurons come from cranial thoracic and lumbar regions (T1 to L2) nerves III (oculomotor), VII (facial), IX ◦ Synapse in two cord-like chains of ganglia (glossopharyngeal) and X (vagus)* and that run close to and parallel to the spinal the sacral region (S2 to S4) cord. ◦ Synapse in ganglia near or on the ◦ Preganglionic neurons are shorter than effector organs. postganglionic neurons ◦ Postganglionic neurons innervate most ◦ Preganglionic neurons are highly organs in the thoracic and abdominal branched, allowing one preganglionic cavity. neuron to interact with many ◦ Preganglionic neurons are longer than postganglionic neurons- activates several postganglionic neurons effector organs at the same time ◦ Preganglionic neurons generally interact ◦ Adrenal medulla receives preganglionic with one postganglionic neurons- enables neurons from the sympathetic system- discrete response of this system releases epinephrine (adrenaline) and norepinephrine Introduction to the Nervous System Functions of the sympathetic nervous system The sympathetic division is responsible for adjusting in response to stressful situations, such as trauma, fear, hypoglycemia, cold, and exercise. Effects of sympathetic stimulation: ◦ Increase in cardiac output and blood pressure ◦ Mobilization of energy stores ◦ Increased blood flow to skeletal muscles and the heart / decreased blood flow from the skin and internal organs ◦ Dilation of pupils and bronchioles *The sympathetic ◦ Reduced GI motility nervous system Fight or flight response tends to function ◦ Triggered by both direct sympathetic activation of effector organs and as a unit and by stimulation of the adrenal medulla to release epinephrine (and often discharges norepinephrine) as a complete system* Introduction to the Nervous System Functions of the parasympathetic nervous system The parasympathetic division is involved in maintaining homeostasis within the body. ◦ It is required for life- maintains essential bodily functions, such as digestion and excretion ◦ Usually acts to oppose or balance the actions of the sympathetic division ◦ Predominates in rest-and-digest situations ◦ Never discharges as a complete system Introduction to the Nervous System Role of the CNS in the control of autonomic functions ◦ ANS requires sensory input from peripheral structures to provide information on the current state of the body. ◦ Feedback is provided by streams of afferent impulses that travel to the CNS. ◦ The CNS then responds to stimuli by sending out efferent reflex impulses via the ANS. ◦ Reflex arcs: ◦ Afferent impulses are involuntarily translated into reflex responses. ◦ Example: drop in BP causes pressure-sensitive neurons to send fewer impulses to cardiovascular centers in the brain. This prompts a reflex response of increased sympathetic output to the heart and vasculature. ◦ Emotions and the ANS: ◦ Stimuli that evoke strong feelings can modify the activities of the ANS Introduction to the Nervous System Innervation by the ANS ◦ Most organs are innervated by both the divisions of the ANS. ◦ Example: parasympathetic innervation slows the heart rate and sympathetic innervation increases the heart rate ◦ Despite dual innervation, one system usually predominates in controlling the activity of a given organ. ◦ There is constant input to make fine-tuned adjustments to maintain homeostasis. ◦ There are a few effector organs, such as the adrenal medulla, kidney, pilomotor muscles, and sweat glands that receive innervation only form the sympathetic system. Introduction to the Nervous System Somatic nervous system ◦ A single myelinated motor neuron, originating in the CNS, travels directly to skeletal muscle without the mediation of ganglia. ◦ The somatic system is under voluntary control. ◦ Responses in the somatic division are generally faster than those in the ANS Introduction to the Nervous System Chemical Signaling Between Cells Hormones Endocrine cells secrete hormones into the bloodstream, where they travel throughout the body and exert effects on broadly distributed target cells Local mediators Cells secrete chemicals that act locally on cells in the immediate environment. These chemicals are rapidly destroyed or removed and do not enter the blood and are not distributed through the body. Neurotransmitters Specific chemical signals (neurotransmitters) are released from nerve terminals to allow communication between nerve cells and between nerve cells and effector organs. Chemical Signaling Between Cells Neurotransmitters ◦ Release of neurotransmitters is triggered by the arrival of an action potential at the nerve ending, leading to depolarization. ◦ An increase in intracellular Ca2+ initiates fusion of synaptic vesicles with the presynaptic membrane and causes release of their contents (neurotransmitters). ◦ 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 Neurotransmitters ◦ Membrane receptors ◦ Neurotransmitters bind to specific receptors on the cell surface of target organs ◦ Types of neurotransmitters ◦ Norepinephrine*- primary chemical signal in ANS ◦ Epinephrine ◦ Acetylcholine*- primary chemical signal in ANS ◦ Dopamine ◦ Serotonin ◦ Histamine ◦ Glutamate ◦ Gamma-aminobutyric acid (GABA) Chemical Signaling Between Cells Neurotransmitters ◦ Acetylcholine (ACh) ◦ Acts on cholinergic receptors ◦ Present in both sympathetic and parasympathetic nervous systems ◦ Neurotransmitter at the adrenal medulla ◦ Released at the neuromuscular junction in the somatic nervous system ◦ Norepinephrine and Epinephrine ◦ Acts on adrenergic receptors ◦ Predominately found in the sympathetic nervous system Signal Transduction in the Effector Cell Neurotransmitter= signal Receptor= signal detector and transducer Receptors in the ANS are either adrenergic or cholinergic. Cholinergic receptors are further classified as nicotinic or muscarinic. Cholinergic nicotinic receptors are ionotropic receptors. These receptors are linked directly to membrane ion channels. An example is a postsynaptic cholinergic nicotinic receptor in skeletal muscle. Adrenergic and cholinergic muscarinic receptors are G protein- coupled receptors (metabotropic receptors). These receptors mediate the effects of ligands by activating a second messenger system. The two most widely recognized second messengers are the adenylyl cyclase system and the calcium/phosphatidylinositol system.