Ganglionic Stimulant and Blockers PDF
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UiTM Puncak Alam
Saliha Azlan
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Summary
This document provides an overview of ganglionic stimulants and blockers, including their effects on the autonomic nervous system and their pharmacological applications. The document also includes learning objectives and diagrams, but lacks sufficient detail to be identified as an exam paper.
Full Transcript
Ganglionic Stimulant and Blockers Saliha Azlan Lecturer (RPh.) Faculty of Pharmacy UiTM Puncak Alam Learning Objectives 1. Understand the role of predominant tone in autonomic nervous system 2. Describe the pharmacological effects of ganglion stim...
Ganglionic Stimulant and Blockers Saliha Azlan Lecturer (RPh.) Faculty of Pharmacy UiTM Puncak Alam Learning Objectives 1. Understand the role of predominant tone in autonomic nervous system 2. Describe the pharmacological effects of ganglion stimulants 3. Describe the pharmacological effects of ganglionic blockers 4. List the therapeutic uses of ganglionic blockers Peripheral Nervous System to Sensory or Motor of Efferent from CNS Afferent Division Division CNS perception response Motor of Efferent Division Somatic Nervous Autonomic System Nervous System Sympathetic Parasympathetic Division Division Somatic Nervous Autonomic System Nervous System Innervates Innervates skeletal muscle smooth & cardiac muscle deliberate involuntary motion motion Sympathetic Parasympathetic Division Division fight or rest and flight digest - raising heart rate - digestion of food - constrict blood vessel - expulsion of waste - glucose release - general maintenance These work together (dual innervation) Sympathetic Parasympathetic Division Division Fibers originate from the Fibers originate from thoracic and lumbar the brain and sacral region of the spinal cord region of the spinal cord short preganglionic long preganglionic long postganglionic short postganglionic (ganglia near spinal cord) (ganglia in effector organs) Note: Neurotransmitter of all preganglionic autonomic fibers, all postganglionic parasympathetic fibers, and a few postganglionic sympathetic fibers is CNS acetylcholine (ACh) All PREPOSP, some POSS ACh All PPP, PS ACh PSNS ACh ACh Various organs – heart, NN M Craniosacral smooth muscle, glands SNS Various organs – heart, αβ ACh NE NN smooth muscle, glands Thoracolumbar ACh ACh Sweat glands, piloerector NN M muscle neurohumoral transmission Various organs – ACh αβ NN EPi transported via blood Somatic Skeletal muscle NM ACh Dual Innervation Most of the effector tissues and organs have innervation from both SNS and PSNS However only one will set the predominant tone of the organ (SNS/PSNS) Heart at rest Heart rate increases (tachycardia) Predominant tone = PSNS Ganglionic blocker inhibitory effect of the parasympathetic system is blocked, allowing the sympathetic input to dominate Predominant Tone “Sets” the level of activity of a given target organ EFFECTOR SITE PREDOMINANT RECEPTOR TYPE EFFECT OF LOSS OF TONE PREDOMINANT TONE Heart SA Node Parasympathetic M2 Cholinergic ↑Heart Rate Heart Ventricle Sympathetic β1 Adrenergic ↓Contractility Arterioles Sympathetic α1 Adrenergic Hypotension Veins Sympathetic α1 Adrenergic Venodilation Iris of the Eye Parasympathetic M2, M3 Cholinergic Mydriasis Ciliary Muscle of Parasympathetic M2, M3 Cholinergic Cycloplegia the Eye GI tract Parasympathetic M2,M3 Cholinergic ↓Peristalsis, ↓Secretions, Constipation Urinary Bladder Parasympathetic M2,M3 Cholinergic Urinary retention Salivary Glands Parasympathetic M2,M3 Cholinergic Dry mouth Sweat Glands (skin) Sympathetic M2,M3 Cholinergic ↓Sweating Lobeline Nicotine (Small dose) Selective Nicotinic Dimethyl phenyl piperazinium Agonist Tetramethyl ammonium Varenicline Agonist (Stimulating) MCN 343-A Acetylcholine Non-selective/ Carbachol Muscarinic Agonist Anticholinesterases Cholinergic receptor NN Between ganglions Pilocarpine Nicotinic NM Axon - Skeletal muscle Hexamethonium Heart, smooth muscle, Muscarinic Somatic Pentolinium glands Competitive blockers Mecamylamine Antagonist (Blocking) Pempidine Nicotine (big/large dose) Persistent depolarizing blocker Anticholinesterases (big/large dose) Parts of ganglionic neurons Normal physiological function of ganglionic neurons (ACh) NN receptor Pre-ganglionic neuron Post-ganglionic neuron Ganglionic neurons – competitive blockers NN receptor Pre-ganglionic neuron Post-ganglionic neuron Normal physiological function of ganglionic neurons NN receptor (Nicotine - small dose) Pre-ganglionic neuron Post-ganglionic neuron Normal physiological function of ganglionic neurons (N) NN receptor (Nicotine - small dose) Voltage-sensitive sodium channel Pre-ganglionic neuron Post-ganglionic neuron Normal physiological function of ganglionic neurons NN receptor (Nicotine - small dose) Ca++ channel Few milliseconds K+ channel only Pre-ganglionic neuron Post-ganglionic neuron Normal physiological function of ganglionic neurons NN receptor (Nicotine - small dose) Ca++ channel Few milliseconds K+ channel only Pre-ganglionic neuron Post-ganglionic neuron Ganglionic neurons (Nicotine - big dose) NN receptor Continuous influx of Na++ causes refractoriness, unable to cause depolarization, eventually neuron become dormant Pre-ganglionic neuron Post-ganglionic neuron NN receptors requires optimum amount of neurotransmitter (ACh/N), if too low, no effect, if too high no effect (receptor being blocked) Ganglionic neurons (anticholinesterases - big dose) Ganglionic neurons (anticholinesterases - big dose) Continuous influx of Na++ causes refractoriness, unable to cause depolarization, eventually neuron become dormant Ganglionic Stimulant/ Agonist Muscarinic receptor Effector Cell Non-selective nicotinic agonist/ Muscarinic agonist Selective Nicotinic receptor nicotinic agonist Therapeutic uses of ganglionic stimulants 1. Ganglionic stimulants have extremely limited therapeutic application but used as experimental tools. 2. It is due to their broad activation of both SNS and PSNS ganglia 3. Few specific cases where they have historically been or are still used 1. Nicotine Replacement Therapy (NRT) Example: Nicotine patches, gum, lozenges, nasal spray. Use: For smoking cessation. Mechanism: Nicotine in low doses stimulates nicotinic acetylcholine receptors in autonomic ganglia and the central nervous system (CNS), mimicking the effects of smoking but without the harmful combustion byproducts of tobacco. This reduces withdrawal symptoms and cravings associated with nicotine dependence, helping individuals gradually wean off nicotine. Why it works: By providing a controlled and lower dose of nicotine, NRT allows the brain to adjust to reduced stimulation of nicotinic receptors over time. 2. Varenicline (Smoking cessation) Varenicline blocks nicotine from fully activating the receptors, which reduces the reinforcing, rewarding effects of smoking. 1. Nicotine Replacement Therapy (NRT) Example: Nicotine patches, gum, lozenges, nasal spray. Use: For smoking cessation. Mechanism: Nicotine in low doses stimulates nicotinic acetylcholine receptors in autonomic ganglia and the central nervous system (CNS), mimicking the effects of smoking but without the harmful combustion byproducts of tobacco. This reduces withdrawal symptoms and cravings associated with nicotine dependence, helping individuals gradually wean off nicotine. Why it works: By providing a controlled and lower dose of nicotine, NRT allows the brain to adjust to reduced stimulation of nicotinic receptors over time. Therapeutic uses of ganglionic blockers 1. Clinical use has diminished due to the availability of more selective agents. 2. Still have some therapeutic and clinical applications, especially in specific emergencies or rare cases. 1.Hypertensive Emergencies (Historical Use) 1.Example: Trimethaphan (used previously but now largely obsolete). 2.Mechanism: 1.By blocking sympathetic ganglia, ganglionic blockers cause vasodilation, leading to a rapid decrease in blood pressure. 2.They also inhibit reflex tachycardia by blocking parasympathetic and sympathetic input to the heart. 3.Use: 1.Historically used to manage malignant hypertension (severe hypertension with end-organ damage) or during aortic dissection to rapidly lower blood pressure. 2.Trimethaphan was administered intravenously in acute settings. However, newer drugs like nitroprusside or labetalol have replaced it due to better safety profiles and ease of use. 2.Controlled Hypotension During Surgery Example: Trimethaphan (again, historical). Mechanism: Induced hypotension by blocking sympathetic tone to decrease bleeding during surgery. Use: Used in surgical procedures where lowering blood pressure helps maintain a bloodless field. Current Status: Rarely used now due to availability of more targeted vasodilators or anesthetic agents.