Autonomic Nervous System Pharmacology PDF

PHARMACOLOGY OF THE AUTONOMIC NERVOUS SYSTEM  Learning objectives List the neurotransmitters of the autonomic sympathetic nervous system and describe their anatomical location List the receptors and receptor-subtypes of the autonomic sympathetic nervous system Predict the responses to...

PHARMACOLOGY OF THE AUTONOMIC NERVOUS SYSTEM  Learning objectives List the neurotransmitters of the autonomic sympathetic nervous system and describe their anatomical location List the receptors and receptor-subtypes of the autonomic sympathetic nervous system Predict the responses to activation and inhibition of autonomic sympathetic nervous system receptors  ANS The nervous system is divided into two anatomical divisions: (i) Central nervous system (CNS) which consists of: Brain Spinal cord (ii) Peripheral nervous system (PNS; neurons outside the CNS) which consists of: Afferent division – neurons which bring signals from the periphery to the CNS Efferent (motor) division - neurons carrying signals away from the brain and spinal cord to the peripheral tissues  The efferent division is further divided into two major subdivisions: Somatic: The somatic nervous system differs from the autonomic system in that it consist of a single myelinated motor neuron, originating in the CNS; the neuron travels directly to skeletal muscle without the mediation of ganglia. The somatic nervous system is under voluntary control, whereas the autonomic nervous system is an involuntary system. Autonomic (ANS): This is also called the visceral, vegetative, or involuntary nervous system. It is largely autonomous (independent) in that its activities are not under direct conscious control and it is concerned primarily with visceral (organs in the abdominal cavity) functions that are necessary for life such as cardiac output, blood flow to various organs, digestion, etc. ANS is further subdivided into three systems, i.e: Sympathetic nervous system Parasympathetic nervous system Enteric nervous system EFFERENT DIVISION  ANATOMY OF THE There are twoANS types of efferent ANS neurons responsible for transmitting nerve impulses from the CNS to the effector organs: 1) Preganglionic neurons: They 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). Their cell bodies are located within the CNS. 2) Postganglionic neurons The latter neurons have cell bodies originating in the ganglia. They are generally non-myelinated and terminate on effector organs, such as smooth muscles of the viscera, cardiac muscle, and the exocrine glands.  It prepares the body in response to stressful situations, such as trauma, fear, hypoglycemia, cold, or exercise Stimulation of the sympathetic division increases the heart rate and blood pressure thus mobilising energy stores of the body Also increase the blood flow to skeletal muscles and the heart, while diverting the blood flow from the skin and internal organs “Fight or flight” response (in emergency) triggered both by direct sympathetic activation of the effector organs, and by stimulation of the adrenal medulla to release adrenaline (A) and lesser amounts of noradrenaline (NA) NA & A enter the bloodstream and promote responses in effector organs that contain adrenergic receptors throughout the body FUNCTIONS OF THE SYMPATHETIC NERVOUS SYSTEM  The parasympathetic division maintains essential bodily functions required for life such as the conservation of energy & maintenance of organ function during periods of minimal activity It usually acts to oppose or balance the actions of the sympathetic division It is generally dominant over the sympathetic system in "rest and digest” situations The parasympathetic division slows the heart rate, lowers the BP, stimulates the GIT movements & excretion, aids absorption of nutrients, protects the retina from excessive light, & empties the urinary bladder & rectum Functions of the parasympathetic nervous system ORGAN INNERVATION Most organs in the body are innervated by both divisions of the autonomic nervous system (sympathetic & parasympathetic) Despite this dual innervation, one system usually predominates in controlling the activity of a given organ e.g. in the heart, the parasympathetic is the predominant factor for controlling the heart rate Organs receiving only sympathetic innervation: some effector organs, such as the adrenal medulla, blood vessels, and sweat glands, receive innervation only from the sympathetic system ORGAN INNERVATION CHEMICAL SIGNALING BETWEEN CELLS Chemical communication between cells (including those of the ANS) occurs through the use of chemical mediators which are classified as follows: Local hormones: Secreted by most cells in the body They act locally and are rapidly destroyed; they do not enter the bloodstream e.g. histamine secreted by the mast cells during inflammation Hormones: Secreted by the endocrine glands into the bloodstream distributed throughout the body Neurotransmitters: Released from the nerve terminals - triggered by the arrival of the action potential at the nerve ending They are responsible for the communication between: the nerve cells (ganglion), and nerve cell and the effector organ (neuroeffector) They rapidly diffuse across the synaptic cleft or gap (synapse) and combine with (bind to) specific receptors on the postsynaptic (target) cell. Like local hormones, they are rapidly destroyed Six most common NT are noradrenaline (NA), acetylcholine (Ach), dopamine (DA), serotonin (5-HT), histamine (H), & gama-aminobutyric acid (GABA) Each of these NT binds to a specific family of receptors Ach and NA are the primary chemical signals in the ANS; others function mostly in the CNS  NEUROTRANSMI TTER CHEMISTRY OF THE ANS Autonomic nerves are classified on the basis of their primary transmitter molecules: Acetylcholine (Ach) Noradrenaline (NA) Nerves that synthesise and release Ach are referred to as cholinergic neurons (fibers), while those synthesising and secreting NA are referred to as noradrenergic (or simply “adrenergic”) fibers Ach is a NT at autonomic ganglia in both the sympathetic and parasympathetic nervous systems Also a NT at the adrenal medulla where it modulates the sympathetic nervous CHOLINERG system IC Also act at autonomic neuroeffector junction (between postganglionic nerves TRANSMISS and the effector organs) in the parasympathetic nervous system ION In the somatic nervous system, transmission at the neuromuscular junction (that is, between nerve fibers and voluntary muscles) is also cholinergic NA is a transmitter at autonomic neuroeffector junction (between postganglionic nerves and the effector organs) in the sympathetic system, with the exception of the sweat glands where ADRENERG the neurotransmitter is Ach IC FIBERS Both NA and A are also synthesised and released by the adrenal medulla following cholinergic stimulation to control (increase) BP  All neurotransmitters are too hydrophilic to penetrate the cell membranes lipid bilayer of AUTONOM target-cell IC Instead, their signal is mediated by binding to specific receptors on the cell surface of target RECEPTO organs RS There are two main types of receptors in the ANS: Cholinergic receptors Adrenergic receptors  The primary ACh (cholinergic) receptor subtypes were named after the alkaloids originally used in their identification: 1. Muscarine - Muscarinic receptors (M) Found mostly as postsynaptic membranes of effector organs in the parasympathetic nervous system. Further subdivided into M1-4 2. Nicotine – Nicotinic receptors (N) Found autonomic ganglia of, Sympathetic, Parasympathetic nervous system, and Adrenal medulla. Also found postsynaptically in neuroeffector membrane in the somatic nervous system Further subdivided into NN & NM CHOLINERGIC RECEPTORS  Adrenoceptor or simply adrenergic receptors respond to catecholamines such as NA, A, & DA The adrenoceptors can be subdivided into two main ADRENER divisions on the basis of their agonist and antagonist selectivity: GIC RECEPTO 1. Alpha-adrenergic receptors (α-ARs) Further subdivided into α1-& α2-ARs RS The rank order of potency of agonists for α-ARs is A > NA ≥ isoproterenol 2. Beta-adrenergic receptors (β-ARs) Further subdivided into β1-, β2- & β3-ARs The rank order of potency of agonists for β-ARs is isoproterenol > A ≥ NA BLOOD PRESSURE CONTROL MECHANISMS Blood pressure (BP) is a product of the total peripheral resistance and cardiac output Both the parasympathetic as well as sympathetic nervous system are involved in control of blood pressure via feedback mechanisms Changes in BP are detected by baroreceptors, which relay the information to the cardiovascular centers in the brainstem controlling parasympathetic and sympathetic outflow E.g. and increase in BP elicits baroreceptor discharge, resulting in increased parasympathetic activity, leading to bradycardia and decreased sympathetic activity, which in turn leads to decreased heart rate, force of contraction and vasoconstriction This decreases cardiac output and total peripheral resistance and ultimately lowers BP to normal levels Conversely, a decrease in BP elicits feedback involving decreased parasympathetic outflow and increased sympathetic activity – leading to increase in cardiac output and total peripheral resistance causing an increase in BP  The sympathetic and parasympathetic divisions of the autonomic nervous system have opposing effects in many tissues Drugs that activate one division often have SUMMAR the same effect as drugs that inhibit the other division Y OF Acetylcholine (Ach) is the primary neurotransmitter at parasympathetic and IMPORTA somatic neuroeffector junctions Noradrenaline (NA) or norepepinephrine, is NT the transmitter at most sympathetic junctions Most autonomic drugs activate or block receptors for Ach or NA in smooth muscle, POINTS cardiac tissue, and glands – these are called direct-acting drugs A few drugs affect neurotransmitter synthesis, storage, release or metabolism – these are called indirect-acting drugs  Practical scenario A 47-year old woman is given a drug to treat her overactive bladder. She is told that the drug will decrease her frequency of urination. She is cautioned to be aware of the possibility of dry eyes, dry mouth, blurred vision, constipation, drowsiness, dizziness and confusion. 1. Which division of the autonomic nervous system does this drug affect? 2. Describe the organ innervation resulting in all the effects above. 3. What are the differences between the sympathetic and the parasympathetic nervous systems? 4. What is the enteric nervous system? 5. What are the steps involved in the transmission of a nerve impulse? 6. Why does this drug have such a wide range of adverse effects?