SAMUEL AGUAZIM (MD) AUTONOMIC NERVOUS SYSTEM PHARMACOLOGY

INTRODUCTION TO AUTONOMIC NERVOUS SYSTEM (ANS) PHARMACOLOGY Human nervous system is divided into two main branches Central nervous system and Peripheral nervous system. CNS is made up of brain and spinal cord. PNS contains everything else, including all of the sensory information going to the brain and all the information flowing out of the brain.

The Peripheral nervous is further divided into 1. Somatic nervous system mainly the motor system which includes all of the nerves to the muscles( CONTROLS MOVEMENT) 2. Autonomic nervous system(ANS) is responsible for maintaining the internal environment of the body (homeostasis)

WHAT IS THE ANS A collection of nuclei, cell bodies, nerves, ganglia and plexuses that provides afferent and efferent innervations to smooth muscle and visceral organs of the body.

Within the ANS two neurons are required to reach a target organ, a preganglionic and a post ganglionic neuron. A preganglionic neuron originates in the CNS. It forms a synapse with the postganglionic neurons, the cell body of which is located in the autonomic ganglia.

Why is this system important? The ANS regulates functions that are not under conscious control, such as blood pressure, heart rate and intestinal motility. Subdivisions of ANS 1. sympathetic nervous system 2. parasympathetic nervous system

Anatomic differences between these two systems? The sympathetic nervous system originates in the thoracolumbar portion of the spinal cord. The preganglionic neurons are short and usually synapse somewhere in the paravertebral ganglia ( sympathetic chain). The postganglionic neurons are long and terminate at the visceral organs. Preganglionic axons form synapses with many postganglionic cells, thus giving this system a widespread action. Note this is consistent with the fight or flight response

Anatomic differences between these two systems? The parasympathetic nervous system originates from cranial nerve nuclei III, VII, IX and X as well as the third and fourth sacral spinal roots (craniosacral origins). The preganglionic neurons take a long path and synapse onto short postganglionic neurons in or near the target organ. Within parasympathetic system, one presynatic axon tends to form a synapse with only 1 or 2 post ganglionic cells, giving the parasympathetic system a more localized action

What are the functions of the sympathetic nervous system The sympathetic nervous system is catabolic, meaning that it burns energy. It is normally active, even at rest; however, it assumes a dominant role when the body becomes stressed in some way. For example, if you sense danger, your heart rate increases, blood pressure rises, eyes dilate, blood sugar rises, bronchioles expand and blood flows shifts from skin to skeletal muscles

The sympathetic nervous system prepares you for FLIGHT OR FIGHT situations The SNS work on ADRENERGIC RECEPTORS- alpha 1, alpha2, beta 1 receptors and beta 2 and dopamine receptors

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What are the actions of the parasympathetic system? The PNS is anabolic, meaning that it tries to conserve energy. It is predominant under tranquil conditions. It slows heart rate, lower blood pressure, increases intestinal activity, constricts the pupils and empties the urinary bladder. The parasympathetic nervous system is also know as the REST and DIGEST system The PNS acts on cholinergic receptors- muscarinic and nicotinic

GENERAL RULE All preganglionic neurons release acetylcholine as their transmitter. The acetylcholine binds to nicotinic receptors on the postganglionic cell. All of the parasympathetic postganglionic fibers release acetylcholine. At the target organ acetylcholine interacts with muscarinic receptors Most of the sympathetic post ganglionic fibers release norepinephrine. At the target organ norepinephrine interacts with a variety of receptors

What are the 2 principle neurotransmitter in the ANS? 1. Acetylcholine- cholinergic transmission 2. Norepinephrine- adrenergic transmission The ion calcium is required for the release of most neurotransmitters from their storage vesicles

How do autonomic drugs function? ANS drugs achieve their effects by acting as either agonists or antagonists at cholinergic and adrenergic receptors.

RECEPTORS There are two major classes of receptors for acetylcholine Muscarinic: found mainly in the viscera ( GI tract) Nicotinic : are found at the motor end plate, in all autonomic ganglia and in adrenal medulla

RECEPTORS The receptors for Norepinephrine are divided into alpha and beta receptors. Further division Alpha: alpha 1 and alpha 2 Beta: beta 1, beta 2 and beta 3

Location Beta 1 receptors found mainly in heart Beta 2 receptors skeletal muscle blood vessels Beta 3 receptors are found in adipose tissue. This localization of receptor type is the basis of drug therapy. In order to target drug action to the correct organ, drugs have been identified (or designed) that affect only one or two receptors types. This is a very important principle of pharmacology and drug therapy.

Actions of sympathetic and parasympathetic on the following organs EYE Sympathetic: contraction of the radial muscle causes dilation or mydriasis Parasympathetic: contraction of the circular muscle causes constriction or miosis Trachea and Bronchioles Sympathetic: dilations Parasympathetic: constriction and increases secretions

Actions of sympathetic and parasympathetic on the following organs Ureter and Bladder Sympathetic: relaxation of detrusor, contraction of the trigone and sphincter Parasympathetic: contraction of detrusor, and relaxation of trigone and sphicter Male genitalia Sympathetic: stimulation of ejaculation Parasympathetic: stimulation of erection Female genitalia Sympathetic: Relaxation of uterus

Actions of sympathetic and parasympathetic on the following organs Salivary glands Sympathetic: thick, viscous secretion parasympathetic: copious, watery secretion Heart: Sympathetic: increase heart rate, increase contractility Parasympathetic: decreased heart rate, decreased contractility

Actions of sympathetic and parasympathetic on the following organs Gastrointestinal system ( GI) Sympathetic: decreased muscle motility and tone and contraction of sphincter Parasympathetic: increase motility and tone Blood vessels( skeletal muscle) Sympathetic : dilation Blood Vessels: (skin, mucous membranes and splanchnic area) Sympathetic: constrict

chief therapeutic uses 25 vascular smooth muscle contraction…………………… …. α1 inhibition of transmitter release……………………… ……… α2

chief therapeutic uses 26 cardiac stimulation…………………………… β1 vascular smooth muscle relaxation…………………………. Β2 bronchiolar smooth muscle relaxation………………………. Β2

– SYNTHESIZES AND SECRETES EPINEPHRINE & NON-EPINEPHRINE SYMPATHETIC CONTROL » FIGHT OR FLIGHT: PUMPS OUT EPI & NE TO FIGHT » EPINEPHRINE : ADRENALINE – INCREASES CARDIAC FUNCTION & CELLULAR METABOLISM MORE EFFECTIVELY THAN NE – HIGHER AFFINITY FOR BETA RECEPTORS » NOREPINEPHRINE (NE): NORADRENALINE 27 Function of the Adrenal Medulla