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Ans pharmacology
The autonomic nervous system (ANS) regulates involuntary functions and has two divisions: the parasympathetic nervous system (PNS) and sympathetic nervous system (SNS). Both use two neurons - a preganglionic neuron that synapses in an autonomic ganglion and a postganglionic neuron that innervates the target organ. In the PNS, acetylcholine is released at both synapses to activate nicotinic then muscarinic receptors. In the SNS, acetylcholine is released at the ganglion, while norepinephrine is released at the organ to activate adrenergic receptors. The PNS activates "rest and digest" functions, while the SNS activates "fight
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Ans pharmacology
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- 3. Important Things toRemember about ANS • ANS/Visceral/Vegetative System involuntarily regulates smooth muscles and glands » heart, respiratory system, GI tract, peristalsis (digestion), bladder, and eyes • Has two divisions i.e. PANS & SANS (homeostasis) • Both have relay stations (ganglia) b/w CNS & end organ. • Use the neurotransmitters Ach & NE
- 4. Anatomy of ANS •Pre& Post- ganglionic Neuron •Afferent Neurons •Sympathetic & Parasympathetic Divisions •Enteric Neurons •Innervate •motility, exocri ne and endocrine, micr ocirculation of GI
- 5. Parasympathetic Ganglionic Synapse ActionPotential Na+ ACH Acetylcholinesterase Na+ Preganglionic neuron Nicotinic Receptor
- 6. Parasympathetic Organ Synapse ActionPotential Na+ ACH Acetylcholinesterase K+ G Postganglionic neuron Muscarinic Receptor
- 7. Sympathetic Ganglionic Synapse ActionPotential Na+ ACH Acetylcholinesterase Na+ Preganglionic neuron Nicotinic Receptor
- 8. Sympathetic Organ Synapse ActionPotential Na+ NE Postganglionic neuron Adrenergic Receptor
- 9. Summary Summary of parasympatheticneurons and synapses Preganglionic neurons • Long • Synapse with postganglionic neurons at or near organ • Release acetylcholine (ACH) to activate nicotinic receptors on postganglionic neurons Postganglionic neurons • Short • Synapse on the target organ • Release acetylcholine (ACH) to activate muscarinic receptors on the target organ Summary of sympathetic neurons and synapses Preganglionic neurons • Short • Synapse with postganglionic neurons near spinal cord • Release acetylcholine (ACH) to activate nicotinic receptors on postganglionic neurons Postganglionic neurons • Long • Synapse on the target organ • Release norepinephrine to activate adrenergic receptors on target organs
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- 12. Exceptions in thesympathetic nervous system: • Sweat glands: » Postganglionic neurons involved with stress-related excretion release norepinephrine (“sweaty palms”) » Postganglionic neurons involved with thermoregulation release acetylcholine
- 13. Exceptions in thesympathetic nervous system: • Kidneys: » Postganglionic neurons to the smooth muscle of the renal vascular bed release dopamine • Adrenal gland: » Preganglionic neurons do not synapse in the paraverterbral sympathetic ganglion » Preganglionic neurons synapse directly on the adrenal gland, release acetylcholine, and activate nicotinic receptors on the adrenal gland » Adrenal glands release epinephrine into systemic circulation
- 14. Functions • Sympathetic Stimulation(Fight or Flight) – ↑HR, BP, blood flow – Diffuse distribution (more than one organ innervated) • Parasympathetic Stimulation (Rest & Digest) – Maintaining homeostasis – Discrete distribution/activation • Role of CNS – Reflex Arcs : Afferent input ~ hypothalamus, medulla oblongata, and spinal cord ~ efferent reflex impulse via ANS – Emotions: • Innervation by ANS – Dual – Only sympathetic (adrenal medulla, kidney, pilomotor muscles, and sweat glands)
- 16. Branch Type Location TypicalAgonist Drugs Typical Antagonist Drugs Sympathetic (adrenergic) α1 Most vascular arterioles, Sphincters of bladder & GI tract, Iris dilator Norepinephrine Epinephrine Phenoxybenzamine Phentolamine Prazosin α2 GI tract, presynaptic sympathetic neurons Clonidine Epinephrine Yohimbine β1 Heart muscle, Salivary glands, Fat cells Norepinephrine Isoproteronol Dobutamine Epinephrine "Beta blockers" Propranolol Metoprolol β 2 Bronchioles of lung, Arterioles of skeletal muscles, brain and lungs, Bladder wall, GIT Epinephrine Isoproteronol Albuterol "Beta blockers" Propranolol Butoxamine Parasympathetic (cholinergic) M Heart muscle, Sphincters of bladder & GI tract Bronchioles of lung, Sweat glands Iris constrictor Acetylcholine Muscarine Carbachol Atropine Scopolamine N Neuromuscular junctions, Autonomic ganglia Acetylcholine Nicotine Carbachol Curare
- 17. Dual Innervation ofthe Iris
- 18. Without Dual Innervation •Some effectors receive only sympathetic – adrenal medulla, arrector pili muscles, sweat glands and many blood vessels • Sympathetic tone – a baseline firing frequency – vasomotor tone provides partial constriction • increase in firing frequency = vasoconstriction • decrease in firing frequency = vasodilation • can shift blood flow from one organ to another as needed – sympathetic stimulation increases blood to skeletal and cardiac muscles -- reduced blood to skin
- 20. Classification of drugsaffecting the ANS • Parasympathetic nervous system Mimic acetylcholine = cholinergic = muscarinic agonists = parasympathomimetic Block acetylcholine = anticholinergic = muscarinic antagonist = parasympatholytic • Sympathetic nervous system Mimic norepinephrine = adrenergic = adrenergic agonist = sympathomimetic Block norepinephrine = antiadrenergic = adrenergic antagonist = sympatholytic
Editor's Notes
- #3 Somatic (Skeletal Muscles) & Autonomic NS
- #4 ANSA collection of nuclei, cell bodies, nerves, ganglia and plexus that provides afferent and efferent innervation to smooth muscles and visceral organs of the body. It regulates the functions that are not under conscious control like HR, BP, intestinal motility. The autonomic nervous system—also known as the visceral system—involuntarily regulates smooth muscles and glands including the heart, respiratory system, GI tract, peristalsis (digestion), bladder, and eyes.The autonomic nervous system has two sets of nerves. These are the sensory neurons (afferent) and the motor neurons (efferent). Sensory neurons send impulses to the central nervous system, which are transmitted to the brain where they are interpreted. The brain then sends a response to the motor neuron’s brain through the spinal cord that directs specific organ cells to respond to the sensory neuron’s impulse.Previously in this chapter you learned that the autonomic nervous system has two branches. These are the sympathetic branch and parasympathetic branch. Both branches act on the same organ cells but in an opposite way. The sympathetic branch stimulates a response and the parasympathetic branch depresses a response by the organ cell. Together, they keep the organ in balance (homeostasis).The sympathetic branch stimulates a response using norepinephrine, a neurotransmitter. Medications that mimic the effect of norepinephrine are called adrenergic drugs or sympathomimetics (mimic sympathetic nervous system actions) (see chart). These drugs are also known as adrenergic agonists because they start a response at the adrenergic receptor sites. There are four types of adrenergic receptors. These are alpha1, alpha2, beta1, and beta2. (see chart)The parasympathetic branch depresses a response using adrenergic blockers—also known as sympatholytics. Lytic means to stop effect. Adrenergic blockers prevent the norepinephrine response at the adrenergic receptor sites. The parasympathetic branch is sometimes referred to as the cholinergic system because an acetylcholine neurotransmitter is used to innervate muscle cells at the end of the neuron. Acetylcholine stimulates receptor cells to produce a response. However, the enzyme acetylcholinesterase can inactivate the acetylcholine before it reaches the receptor cell. Drugs that mimic acetylcholine are cholinergic agonists because they initiate a response. These are also known as cholinergic drugs or parasympathomimetics (see chart).Drugs that block the effect of acetylcholine are called anticholinergic, or parasympatholytics. They are also known as cholinergic antagonists because they inhibit the effect of acetylcholine on the organ. There are two types of cholinergic receptors. These are nicotinic or muscarinic. Nicotinic receptors are stimulated by alkaloids nicotine. Muscarinic receptors are stimulated by muscarine.
- #5 Anatomy of the ANS1. Efferent neurons: The ANS carries nerve impulses from the CNS to the effector organs by way of two types of efferent neurons (Figure 3.2). The first nerve cell is called a preganglionic neuron, and its cell body is located within the CNS. 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). These ganglia function as relay stations between a preganglionic neuron and a second nerve cell, the postganglionic neuron. The latter neuron has a cell body originating in the ganglion. It is generally nonmyelinated and terminates on effector organs, such as smooth muscles of the viscera, cardiac muscle, and the exocrine glands.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.3. Sympathetic neurons: The efferent ANS is divided into the sympathetic and the parasympathetic nervous systems as well as theenteric nervous system (see Figure 3.1). 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 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. The preganglionic neurons are short in comparison to the postganglionic ones. Axons of the postganglionic neuron extend from these ganglia to the tissues that they innervate and regulate (see Chapter 6). The sympathetic nervous system is also called the thoracolumbar division because of its origins. In most cases, the preganglionic nerve endings of the sympathetic nervous system are highly branched, enabling one preganglionic neuron to interact withmany postganglionic neurons. This arrangement enables this division to activate numerous effector organs at the same time. [Note: The adrenal medulla, like the sympathetic ganglia, receives preganglionic fibers from the sympathetic system. Lacking axons, the adrenal medulla, in response to stimulation by the ganglionic neurotransmitter acetylcholine, influences other organs by secreting the hormone epinephrine, also known as adrenaline, and lesser amounts of norepinephrine, into the blood.]4. Parasympathetic neurons: The parasympathetic preganglionicfibers 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. [The vagus nerve accounts for 90% of preganglionic parasympathetic fibers in the body. Postganglionic neurons from this nerve innervate most of the organs in the thoracic and abdominal cavity.] Due to the origin of the parasympathetic nervous system, it is also called the craniosacral division. Thus, in contrast to the sympathetic system, the preganglionicfibers 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 the discrete response of this division.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 (, and it constitutes the “brain of the gut.” This system functions independently of the CNS and controls the motility, exocrine and endocrine secretions, and microcirculation of the GI tract. It is modulated by both the sympathetic and parasympathetic nervous systems.
- #13 towards99,Parasympathetic (M3) receptors cause dilation of blood vessels via the NO/endothelium derived relaxing factor ---- no direct innervation though.For example: M3 has receptors on the blood vessels (endothelium cells) but they LACK the innervation. If we were to activate those receptors, we release N.O. (if a drug is capable of activating those receptors, then it can release NO, which can lead to vasidilation)Bottom Line: In order for us to activate those receptors, we release NO. In other words, M3 causes vasodilation via the Nitric oxide pathway. (M3 ---> NO---> those receptors for vasodilation)
- #15 Effects of stimulation of the sympathetic division: The effect of sympathetic output is to increase heart rate and blood pressure, to mobilize energy stores of the body, and to increase 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 the bronchioles (see Figure 3.3). It also affects GI motility and the function of the bladder and sexual organs.2. Fight or flight response: The changes experienced by the body during emergencies have been referred to as the “fight or flight” response (Figure 3.4). These reactions are triggered both by direct sympathetic activation of the 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 (see Figure 6.6). The sympathetic nervous system tends to function as a unit and often discharges asa complete system, for example, during severe exercise or in reactions to fear (see Figure 3.4). 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 nevertheless an important system that prepares the body to handle uncertain situations and unexpected stimuli.D. Functions of the parasympathetic nervous system The parasympathetic division is involved with maintaining homeostasis within the body. To accomplish this, it maintains essential bodily functions, such as digestive processes and elimination of wastes. The parasympathetic division is required for life. It usually acts to oppose or balance the actions of the sympathetic division and is generally dominant over the sympathetic system in “rest and digest” situations. The parasympathetic system is not a functional entity as such and it never discharges as a complete system. If it did, it would produce massive, undesirable, and unpleasant symptoms, such as involuntary urination and defecation. Instead, discrete parasympathetic fibers are activated separately and the system functions to affect specific organs, such as the stomachor eye.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 state of affairs in 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 the stimuli by sending out efferent reflex impulses via the ANS (Figure 3.5).1. Reflex arcs: Most of the afferent impulses are translated into reflex responses without involving consciousness. 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, whichresults in a compensatory rise in blood pressure and tachycardia (see Figure 3.5). [Note: In each case, the reflex arcs of the ANS comprise a sensory (or afferent) arm, and a motor (or efferent, or effector) arm.]Emotions and the ANS: Stimuli that evoke strong feelings, such as rage, fear, and pleasure, can modify the activities of the ANS.F. Innervation by the ANS1. Dual innervation: Most organs in the body are innervated by both divisions of the ANS. Thus, vagal parasympathetic innervation slows the heart rate, and sympathetic innervation increases the heart rate. Despite this dual innervation, one system usually predominates in controlling the activity of a given organ. For example, in the heart,the vagus nerve is the predominant factor for controlling rate. This type of antagonism is considered to be dynamic and is fine-tuned at any given time to control homeostatic organ functions. The activity of a system represents integration of influence of both divisions.2. Organs receiving only 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. The control of blood pressure is also mainly a sympathetic activity, with essentially no participation by the parasympathetic system.G. Somatic nervous systemThe efferent somatic nervous system differs from the autonomic system 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 autonomic system is involuntary. Responses in the somatic divisionare generally faster than those in the ANS.