CoverModule 1.0. Homeostasis, Membranes, Electrophysiology and ANS1.1. Homeostasis1.1.1. Homeostasis Defined1.1.2. Homeostatic Control Systems1.1.3. Feedback Response Loop1.2. Cell Transport; Water & Solutes1.2.1. Fluid Compartments1.2.2. Osmosis1.2.3. Diffusion of Solutes1.2.4. Active Transport1.2.5. Bulk Transport1.3. Electrophysiology1.3.1. Ions and Cell Membranes1.3.2. Membrane Potentials1.3.3. Graded Potential1.3.4. Action Potentials1.3.5. Refractory Periods1.3.6. Propagation of an Action Potential1.4. The Synapse1.5. The Autonomic Nervous System1.5.1. Organization of the Nervous System1.5.2. Structural Organization of the ANS1.5.3. The SNS and the PNS1.5.4. The Enteric Nervous System1.5.5. Physiology of the ANS1.5.6. Neurotransmitters of the ANS1.5.7. Receptors of the ANS1.5.8. Actions of the Autonomic Nervous System1.5.9. Table of Actions for the SNS and PNS and Some Common DrugsModule 2.0. Skeletal Muscle and Special Senses2.1. Structural Organization of Skeletal Muscle2.2.1. Neuromuscular Junction, Excitation-Contraction Coupling2.2.2. Muscle Contractures and Cramps2.3. Whole Muscle Contraction, Fiber Type, Fatigue and Muscle Pharmacology2.3.1. Motor Units2.3.2. Factors that Influence the Force of Contraction2.3.2. Factors that Influence the Force of Muscle Contraction2.3.3. Energy Source for Muscle Contraction2.3.4. Skeletal Muscle Fiber Types2.3.5. Fatigue2.3.6. Muscle Pharmacology2.4. Smooth Muscle2.4.1. Smooth Muscle Contraction2.5. Control of Body Movement2.5.1. Voluntary Control of Muscle2.5.2. Reflexes2.6. Taste and Smell2.6.1. Taste2.6.2. The Sense of Smell2.7. Vision2.7.1. Structure of the Eye2.7.2. Focusing Light on the Retina2.7.3. Converting Light to Action Potentials2.7.4. The Retina2.7.5. Phototransduction2.7.6. Receptive Fields2.8. Hearing and Equilibrium2.8.1. The Nature of Sound2.8.2. The Hearing Apparatus2.8.3. Sound Vibrations to Action Potentials2.8.4. The Sense of Balance and EquilibriumModule 3.0. Cardiovascular System3.1. Structure of the Heart3.1.1. Chambers and Circulation3.2. Cardiac Cell Action Potentials3.2.1. Action Potentials in Cardiac Muscle Cells3.2.2. Action Potentials in Cardiac Autorhythmic cells3.2.3. Cellular Mechanisms of Inotropy and Chronotropy3.3. Electrophysiology of Heart Muscle3.3.1. Heart Conduction System3.3.2. Electrocardiogram (ECG)3.3.3. Abnormal ECG - Current of Injury3.4. The Cardiac Cycle3.4.1. Cardiac cycle3.4.2. Cardiac Measurements and Pressure Volume Loops3.5. Blood vessels and Blood Pressure3.5.1. Arteries and Veins3.5.2. Capillaries3.5.3. Blood Pressure Regulation and Shock3.5.4. Capillary Exchange3.5.5. Myogenic and Paracrine Regulation of Vasoconstriction and Vasodilation3.6. Blood3.6.1. Composition of Blood3.6.2. Hematopoeisis3.6.3. Breaking Down Red Blood Cells3.6.4. HemostasisModule 4.0. Urinary and Respiratory Systems4.1. Function and Structure of the Kidney4.1.1. Urinary System Function4.1.2. Functional Anatomy of the Urinary System4.1.3. The Nephron: Functional Unit of the Kidney4.1.4. The Renal Corpuscle: Bowman's Capsule4.2. Physiology of Urine Production4.2.1. Filtration4.2.2. Renal Clearance4.2.3. Tubular Reabsorption4.2.4. Urine Concentration and Dilution4.2.5. Hormonal Regulation of Urine Production4.3. Acid/Base Balance4.3.1. Buffers4.3.2. Acid/Base Disturbances4.4. The Respiratory System4.4.1. Respiratory System Structure and Function4.4.2. Respiratory Membrane4.4.3. Respiratory pressures and Inspriation/Expiration4.4.4. Alveoli and Surfactant4.4.5. Pneumothorax4.4.6. Pressure-Volume Loops and the Work of Breathing4.5. Gas Exchange and Transport4.5.1. Gas Laws4.5.2. Partial Pressure Gradients in the Lung4.5.3. Alveolar Gas Equation4.5.4. Oxygen and Carbon Dioxide Transport in the Blood4.5.5. Alveolar Ventilation4.5.6. Ventilation/Perfusion Ratio4.6. Chronic Bronchitis and Emphysema4.6.1. Respiratory Control by the Medulla Oblongata4.6.2. Chemicals that Regulate VentilationModule 5.0. Digestive, Endocrine and Reproductive Systems5.1. Functional Anatomy of the Digestive System5.1.1. Layers of the Digestive Tract5.1.2. Enteric Nervous System5.1.3. Organs of the Digestive System5.2. Digestion5.2.1. Carbohydrates5.2.2. Proteins5.2.3. Lipids5.2.4. Lipoproteins5.3. Regulation of Digestive Secretions5.4. Endocrine System5.4.1. Overview of the Endocrine System5.4.2. Hormone Receptors5.4.3. Hormones of the Body5.4.4. Other Hormones: Melatonin and Pheromones5.5. The Hypothalamus and Pituitary Gland5.5.1. Structure and Function of the Hypothalamus and Pituitary Gland5.5.2. The Posterior Pituitary5.5.3. The Anterior Pituitary5.5.4. Growth Hormone5.5.5. Prolactin5.5.6. Thyroid Hormones5.5.7. Adrenal Hormones5.6. Pancreas5.6.1. Insulin and Glucagon5.6.2. Diabetes Mellitus5.7. Reproductive System Anatomy5.7.1. Female Reproductive Anatomy5.7.2. Male Reproductive Anatomy5.7.3. Sexual Development at Puberty5.7.4. Male Reproductive Endocrine Axis5.7.5. Spermatogenesis5.7.6. Female Reproductive System: Oogenesis5.7.7. Ovulation and Fertilization5.7.8. The Ovarian Cycle5.7.9. The Uterine Cycle5.7.10. PregnancyAppendix A. GenderAppendix B. The Placebo EffectB.2.1. The Placebo EffectB.2.2. Examples of the Placebo EffectB.2.3. How do Placebos Work?B.2.4. Are Placebos Ethical?B.2.5. How do we validate actual effectiveness of placebosB.2.6. Tips for evaluating scientific evidenceB.2.7. What about Faith Healings
1.5.8

Actions of the Autonomic Nervous System

Certain drugs exert their effects by binding to cholinergic and adrenergic receptors to increase or decrease the activity of effectors normally controlled by the ANS. Drugs that are agonists, bind to a specific receptor and activate it, while an antagonist binds to a receptor and prevents it from being activated, or inhibits it. In the following section, some drugs will be presented. Having an understanding of the ANS and its particular receptors located on effectors and the drugs that activate or block these receptors will assist your understanding of the actions of this system.

Eyes

The eye has multiple autonomic functions controlled by several autonomic receptors. Among these are the intrinsic muscles of the eye (those controlling the size of the pupil and the shape of the lens) and the secretory epithelium (produces aqueous humor) of the ciliary body.

Pupil-of-eye.png

Image by JS S22

Circular and radial muscles of the iris, named sphincter pupillae and dilator pupillae respectively, control how much light enters the eye. Outer iris smooth muscles - the dilator pupillae muscles express alpha 1 receptors, cause mydriasis when they contract and are controlled by sympathetic fibers. The inner, sphincter pupillae muscles are innervated by the parasympathetic division, express M3 receptors, and cause miosis when they contract.

Ophthalmologists often need to enlarge the diameter of the pupil in order to more easily examine the retina. Phenylephrine is an alpha 1 agonist and atropine is a muscarinic antagonist. Both are mydriatics and are administered as eye drops to reduce systemic effects.

Clincial Pearl - Glaucoma

The autonomic nervsous system also innervates the ciliary muscle of the eye which is behind the retina and around the lens. This tissue has beta - 2 receptors and when stimulated by the sympathetic nervous system, it causes relaxation which helps with far vision and when stimulated by the parasympathetic nervous system on M3 receptors it causes contraction which helps with near vision. 

Contraction of the ciliary muscle also puts tension on an area calle the trabecular network in the anterior eye. This action helps to open up pores in the trabecular network so that aqueous humor can drain into the canal of Schlemm and into the venous circulation. 

For this reason, eye drops that are muscarinic agonists, such as pilocarpine, can be used to treat elevated intraocular pressure (glaucoma), lowering intraocular pressure by increasing the outflow of aqueous humor. Stimulation of beta 1 receptors on the ciliary body epithelium increases the production of aqueous humor. Therefore, beta 1 antagonists such as betaxolol are also often used to treat glaucoma, since they reduce the production of aqueous humor.

Blood Vessels

Arterioles of the body mostly express alpha 1 receptors on their smooth muscle cells. Activating these receptors results in an increase in intracellular calcium causing smooth muscle contraction. This contraction narrows the diameter of the arteriole lumen thus reducing blood flow. Since arterioles express primarily alpha 1 receptors, you might imagine that an increase in sympathetic nerve firing would result in vasoconstriction of most arterioles. Arterioles of certain organs including skeletal muscle and cardiac muscle express beta 2 receptors in addition to alpha 1 receptors. Beta 2 receptors are activated primarily by circulating epinephrine and their stimulation causes relaxation of smooth muscle and vasodilation. The degree of vasodilation is dependent on the density of alpha 1 vs. beta 2 receptors expressed on arterioles in a particular tissue as well as on the concentration of epinephrine in the blood. During a "fright, flight, or fight" response, vasodilation of certain arterioles supplying skeletal tissue is essential. Ample oxygen and nutrients are critical when running away from ferocious bears or scary dating situations.

Since alpha 1 receptors are so important in regulating the size of arterioles, activating or blocking them can greatly influence blood pressure. Prazosin is an alpha 1 antagonist used to treat high blood pressure. It can also be used to treat Raynaud's disease which results from excessive vasoconstriction particularly in the fingers, cutting off the blood supply leading to cold fingers and in severe cases gangrene.

While it is true that there are some blood vessels (very few) that have parasympathetic cholinergic innervation that will cause vasodilation, the vast majority of blood vessels have no parasympathetic innervation.

Sweat Glands

Sweat glands are exclusively innervated by the sympathetic division. Postganglionic neurons of the sympathetic division that innervate glands responsible for generalized sweating secrete ACH. This is the exception to the rule since postganglionic sympathetic neurons usually secrete norepinephrine. After its release from the postganglionic cell, ACH crosses the neuroeffector junction and binds to muscarinic receptors expressed on sweat glands for generalized sweating. Localized sweat glands are activated by stress and are those located in the palms, soles, genitalia, and armpits and express alpha 1 receptors. Terazosin is another alpha 1 antagonist that is sometimes used to treat excessive sweating (hyperhidrosis).

Heart

Activation of the sympathetic division and release of catecholamines from the adrenal medulla leads to increased heart rate and force of contraction. This stimulatory effect is due to a high concentration of beta 1 receptors in the myocardium and cells in the SA node. Selective beta 1 antagonists like atenolol are often used to treat high blood pressure by decreasing heart rate and force of contraction.

Parasympathetic stimulation or administration of a muscarinic agonist has an opposing effect on the heart, decreasing heart rate. Injectable atropine, a muscarinic antagonist, is often used with other drugs in emergency medicine to start the heart back up after cardiac arrest. This action blocks parasympathetic activity which normally slows the heart rate.

Lungs

Activation of muscarinic receptors located in the smooth muscle lining the bronchiole tree results in constriction of air passageways, while activation of beta 2 receptors by circulating epinephrine causes smooth muscle relaxation and dilation of the bronchioles (Note: beta 2 receptors are not innervated by postganglionic fibers and therefore respond to circulating epinephrine secreted by the adrenal medulla). Pharmacological treatment aimed at opening up the airways focuses on blocking parasympathetic actions or augmenting actions of the sympathetic division.

A muscarinic antagonist such as ipratropium, or a beta 2 agonist like albuterol, can be administered via an inhaler and cause bronchodilation. This relaxation of the smooth muscle in air passageways is very important in the treatment of asthma and chronic obstructive pulmonary disease (COPD) when ventilation of the lungs is compromised.

Stomach and Intestines

Activity of the enteric nervous system can be modified by activity of the ANS. The gastrointestinal tract is dually innervated by both divisions, but regulation is not equal. Recall that the parasympathetic division is most active under "rest and digest" conditions. Parasympathetic fibers leading to the gastrointestinal tract are much more extensive and have a much greater influence on digestion compared to the sympathetic division. The parasympathetic division increases the secretions from glands, promotes mixing of food with digestive enzymes and bile, and propels material down the digestive tract. Many muscarinic receptors and fewer adrenergic (alpha 1 and beta 2) receptors are located in the smooth muscle of the digestive tract wall. Activation of the muscarinic receptors and blocking of adrenergic receptors leads to increased motility and relaxation of sphincters which augments material propulsion.

Postoperative ileus is a condition which sometimes results after surgery in which there is a disruption in the normal peristaltic activity of the GI tract. To re-establish normal gut motility, a muscarinic agonist such as bethanechol may be given to offer a "jump start."

For a summarized list of the effects of autonomic nervous activity, receptors in specific tissues, and drugs used to modify ANS activity, please review the tables below.

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