Drugs Affecting The Autonomic Nervous System(ANS)

Transcription

1 Drugs Affecting The Autonomic Nervous System(ANS) ANS Pharmacology Lecture 1 Dr. Hiwa K. Saaed College of Pharmacy, University of Sulaimani AUTOMATIC NERVOUS SYSTEM (ANS) The ANS is the major involuntary portion of the NS, responsible for automatic, unconscious bodily function, such as control of HR and BP and both GIT and GUT functions Autonomic Drugs: produce their primary therapeutic effect by Mimicking (stimulating) or altering (blocking) the functions of the ANS. Learning Objectives of This Lecture: outlines the fundamental physiology of the ANS, describes the role of neurotransmitters in the communication between extracellular events and chemical changes within the cell. 2

2 NERVOUS SYSTEM (NS) Two main divisions I. CNS: Brain & spinal cord: receives and processes incoming sensory information and responds by sending out signals that initiate or modify a process II. PNS 1. Afferent (sensory): carry sensory input from the periphery to the CNS and modify motor output through the reflex arc. 2. Efferent (motor): carry motor signals from the CNS to the peripheral areas of the body. Somatic ANS Parasympathetic Sympathetic Enteric brain of the gut 3 Efferent Neurons The efferent portion of the PNS is divided into two major functional subdivisions, 1. somatic (SNS): one motor neuron innervates the skeletal muscles and control voluntary (consciously) functions; movement, respiration and posture. 2. ANS; is divided into 2 main divisions: Parasympathetic ANS (PANS) dominates in sleep, Sympathetic ANS (SANS) dominates during activity; fight & flight. 3. Enteric NS brain of the gut located in the GIT, send sensory input to both PANS & SANS and receive motor output from them -Myenteric plexus (plexus of aurbach) -Submucous plexus (plexus of Meissner) 4

3 Location of Ganglia Both the PANS and SANS have relay station (ganglia) between the CNS and the end organ, but the somatic system does not; The ANS, carries nerve impulses by: a preganglionic fiber that leaves the CNS, a postganglionic fiber that innervates the effector. Adrenal medulla The Adrenal medulla, like the sympathetic ganglia, receives preganglionic fibers from the sympathetic system. Lacking the axons, in response to stimulation by Ach, influences other organs by secreting the epinephrine and lesser amounts of NEP into the blood. 5 Parasympathetic Division craniosacral The preganglionic fibers arise from the cranial nerve nuclei III (oculomotor), VII (facial), IX (glossopharyngial), X (vagus) (90%) and sacral region S2-S4 of the spinal cord, They synapse in ganglia close to the effector organ. the preganglionic fibers are long, and the postganglionic ones are short. In most instances, there is a one-to-one connection between the preganglionic and postganglionic neurons, enabling discrete response of this system. Sympathetic Division thoracolumbar The preganglionic fibers arise from the thoracic (T1-T12) and lumbar (L1-L2) regions of the spinal cord, they synapse in two cord-like chains of ganglia that run close to and in parallel on each side of the spinal cord. Postganglionic axons lead to an effector organ. the preganglionic fibers are short, and the postganglionic ones are long. In most cases, the preganglionic are highly branched, enabling one preganglionic neuron to interact with many postganglionic neurons. 6

4 SYMPATHETIC AND PARASYMPATHETIC NS & EFFECTOR ORGANS 7 SYMPATHETIC AND PARASYMPATHETIC NS & RECEPTORS ON EFFECTOR ORGANS 8

5 Functions of the Autonomic Nervous System Sympathetic Nervous System Is normally active, even at rest; however, it assumes a dominant role when the body becomes stressed (trauma, fear, hypoglycemia cold or exercise). Fight or Flight Protective mechanisms designed to help person cope with the stress or get away from it. For example, if you sense danger: Your heart rate increase, BP rises, eyes dilates, blood sugar rises, bronchioles expand, and blood flow shift from skin to skeletal muscles. Parasympathetic Nervous System Rest and digest: maintains essential body functions; digestive process and elimination of wastes. Save energy. Dilation of blood vessels in skin. Decrease heart rate (bradycardia). Increase secretion of digestive enzymes. Constriction of smooth muscle of bronchi. Increase in sweat glands. Contraction of smooth muscles of urinary bladder. 9 Functions of the Autonomic Nervous System Sympathetic Parasympathetic Opposite effects on... Myocardium Tachycardia Bradycardia Intestinal smooth muscle Decreased motility Increased motility Pupil muscles of iris Mydriasis (radial muscle) Miosis (circular muscle) Innervated by one division of ANS Blood vessels Constriction Sweat glands Increased secretion Ciliary muscle Accommodation reflex Stomach & Pancreas increased secretion

6 Sympathetic NS The sympathetic NS function as a unit and it often discharge as a complete system. These reactions are triggered both by 1. direct sympathetic activation of the effector organs, 2. stimulation of the adrenal medulla to release epinephrine. Parasympathetic NS The Parasympathetic NS is not a functional entity as such, and never discharges as a complete system. If it did it would produce massive, undesirable and unpleasant symptoms. Instead, discrete parasympathetic fibers are activated separately, and the system functions to affect specific organs, such as stomach or eye. Similarities & differences between ANS & endocrine system: The ANS, along with the endocrine system, coordinates the regulation and integration of body function. Nervous system has several: # Properties in common with the endocrine system: 1. High level integration in the brain 2. The ability to influence processes in distant regions of the body 3. Extensive use of negative feedback 4. Both systems use chemical for the transmission of information # Differences between ANS & endocrine system ANS characteristics Rapid response Brief duration Transmission of electrical impulses over nerve fibers Endocrine system characteristics Slower response Long duration Sends signals to target tissue by varying the level of blood borne hormone 12

7 Drugs affecting the ANS The cholinergic drugs act on receptors activated by acetylcholine. The adrenergic drugs act on receptors stimulated by norepinephrine or epinephrine. Cholinergic Neurons: All preganglionic fibers of both sympathetic and parasympathetic divisions. All parasympathetic postganglionic. Few sympathetic postganglionic fibers (sweat gland). All Somatic (non autonomic) fibers to skeletal muscle Adrenergic Neurons: Most sympathetic postganglionic fibers release norepinephrine; are noradrenergic or simply adrenergic. Some peripheral sympathetic fibers release dopamine (dopaminergic). The adrenal medulla, releases epinephrine (~85%) and to a lesser amount norepinephrine (15%) into the blood. 13 Parasympathetic cholinergic receptors: Muscarinic (M1 to M5) Nicotinic (Nn, Nm) Sympathetic adrenergic receptors Alpha (α1, α 2), Beta (β1 to β 3), Dopamine (D1 to D5) 14

8 Muscarinic receptors: Locations of muscarinic receptors: these receptors have been found on: Ganglia of the PNS The autonomic effector organs: heart, smooth muscle, brain and exocrine glands. M1 :gastric parietal cells, M2 : cardiac cells and smooth muscle, M3 : bladder, exocrine gland, and smooth muscle. Neurons: all five subtypes (M1-M5) have been found on neurons, Mechanisms of Ach signal transduction: M1, M3 & M5:interacts with a Gq protein, which in turn activates phospholipase C this leads to the hydrolysis of PIP2 to yield IP3, DAG, which cause an increase in intracellular Ca +2 this cation can then interact to: stimulate or inhibit enzymes, or cause hyperpolarization, secretion, or contraction. M2 : stimulates a Gi that inhibits adenylyl cyclase and increase K + conductance. 15

9 Nicotinic receptors: (NN, NM) Locations of nicotinic receptors: nicotinic receptors are located in the: CNS, adrenal medulla, autonomic ganglia, neuromuscular junction. Mechanisms of action: Ligand-gated ion channel. Binding of two Ach molecules elicits a conformational change that allows the entry of Na + ions, resulting in the depolarization of the effector cells. Nicotine initially stimulates and then blocks the receptors 17 Cholinergic Neurotransmission Synthesis of Ach, Storage, Release, Binding, Degradation of Ach, Recycling of choline