Autonomic Nervous System Introduction PDF

AN INTRODUCTION Of AUTOMOMIC NERVOUS SYSTEM (ANS) & NEUROMUSCULAR JUNCTION (NMJ) Professor Nageeb A.G.M. Hassan Reference...

AN INTRODUCTION Of AUTOMOMIC NERVOUS SYSTEM (ANS) & NEUROMUSCULAR JUNCTION (NMJ) Professor Nageeb A.G.M. Hassan Reference Lippincott illustrated Reviews of Pharmacology 7th edition Chapter 3 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 1  Types of Peripheral Nervous system Autonomic Nervous System (ANS) Parasympathetic nervous system Sympathetic nervous system Somatic Nervous System Neurochemical transmission of the ANS Cholinergic NT (Synthesis, Storage vesicles, Release, Binding, Terminal action) Adrenergic NT (Synthesis, Storage vesicles, Release, Binding, Terminal action) Physiology aspects of Autonomic nerve activity Click here for more details 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 2  Nervous system (NS) Peripheral Nervous system (PNS) Central Nervous System (CNS) Autonomic Nervous System (ANS) Somatic nervous System “Efferent Fibres” “Afferent Fibres” control organs that are not under our control “viscera” (skeletal muscle) - Movement - Posture Parasympathetic NS Sympathetic NS CNS = Cranio-sacral = Thoraco-lumber division of the ANS division of the ANS 1- Origin 1- Origin 2- Nerve fibres Parasympathetic 2- Nerve fibres 3- Neurotransmitters 3- Neurotransmitters Sensory 4- Functions 4- Functions Sympathetic Motor Parasympathetic 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 3 Parasympathetic nervous system Sympathetic nervous system - Origin: midbrain, medulla oblongata, - Origin: thoracic & upper lumber regions of sacral cord. spinal cord. - Nerve fibres: - Nerve fibres: a- Short preganglionic nerve fibres, which a- Long preganglionic nerve fibres, synapse in the paravertebral ganglionic b- Short postganglionic nerve fibres. chain. Ganglia are near to organ or impeded b- Long postganglionic nerve fibres. in organ. Ganglia are near to spinal cord forming a - Neurotransmitters chain. Acetylcholine (ACh) - Neurotransmitters neurotransmitter at both a- ACh is the neurotransmitters at the a- Ganglia (nicotinic receptors -NR) & ganglia (NR) b- Noradrenaline (NA) = norepinephrine b- Effector organs (muscarinic (NE) is usually neurotransmitters at receptors - MR). effector organs (α or β receptors) ACh is a neurotransmitter found at sweat - Functions: digestion, conservation of glands. energy, maintenance of organ function. - Functions: mobilizing the body’s sources to respond to fear & anxiety.(3Fs – fear, fight, flight response). 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 4  Neurotransmitters of the ANS Sympathetic Parasympathetic CNS CNS Nicotinic Receptor ACh Nicotinic Receptor NE ACh Adrenergic Muscarinic Receptor Receptor 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 5  Comparison between Voluntary “Somatic NS” & Involuntary “ANS” {NT & Receptors} Somatic Sympathetic Sympathetic Parasympathetic CNS CNS CNS CNS ACh Adrenal Nicotinic Nicotinic medulla Receptor Receptor ACh Nicotinic Receptor Adrenaline & noradrenaline ACh NE ACh ACh Muscarinic Adrenergic Muscarinic Nicotinic Receptor Receptor Receptor Receptor General - Heart - Heart Sweat gland - Skeletal muscle circulation - Sm. muscle - Sm. muscle - Glands - Glands 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 6  Neurotransmitters of the ANS Cholinergic pathways 1- Cholinergic fibres (See before) a- Synthesis, storage, & release (see diagram) b- Receptor activation & signal transduction - ACh activates (NR or MR) c- Inactivation occurs by - Acetylcholinesterase (AChE) in the synapse. - Pseudocholinesterase in the blood & liver 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 7 Synthesis and release of acetylcholine from the cholinergic neuron. AcCoA = acetyl coenzyme A. 1. Synthesis of acetylchol 6/10/2024 8 Professor Nageeb A.G.M. Hassan - ANS Introduction 2- Drugs that affect “block” Cholinergic pathways (See later) - Synthesis Hemicholinium, Trithylcholine - Storage Vesamicol - Release Botulinum toxin, Procaine - Cholinesterase inhibitors e.g. Anticholinesterase (Neostigmine; Physostigmine) - Cholinoceptor antagonists - Muscarinic receptor antagonists: e.g. Atropine; Hyoscine - Nicotinic receptor antagonists Ganglionic blocker e.g. Trimethaphan NMJ blocker e.g. Atracurium 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 9 Adrenergic pathways 1- Adrenergic fibres (See before) a- Synthesis, storage, & release (see diagram) b- Receptor activation & signal transduction - Norepinephrine or epinephrine binds to α or β receptors on postsynaptic effector cells. c- Inactivation occurs by - Reuptake by active transport (uptake I): removal of norepinephrine from synaptic cleft. - Monoamine oxidase (MAO) enzyme is located in the mitochondria of presynaptic adrenergic neuron & liver. - Catechol-O-methyltransferase (COMT) an enzyme located in the cytoplasm of autonomic effector cells & liver. 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 10 Synthesis and release of norepinephrine from the adrenergic neuron. DOPA = dihydroxyphenylalanine; MAO = monoamine oxidase; NE = norepinephrine; SNRI = serotonin–norepinephrine reuptake inhibitor. 11 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 2- Drugs that affect “block” Adrenergic pathways (See later) - Uptake e.g. Cocaine - Synthesis e.g. Metyrosine - Storage e.g. Reserpine - Release e.g. Guanethidine; Bretylium - MAO inhibitors: e.g. Tranylcypromine - Adrenoceptor antagonists: - May be nonselective or selective (α & β receptors) - May be selective for subtype of (α & β receptors) 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 12  Normal Accommodation Ciliary Muscle Relaxed (β2) Ciliary Muscle Contracts (M3) Suspensory Ligaments Under Tension Reduced Tension on Suspensory Ligaments Lens is Flattened Lens becomes Round Focus on Distant Objects Focus on Near Objects 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 13  SYMPATHETIC PARASYMPATHETIC Organ R Effect R Effect EYE Iris Constriction ▪ Radial muscle (Dilator Pupillae Muscle) = DPM α1 (Active Mydriasis) - ------------------------------------------ (Pupil Dilatation) ▪ Circular muscle Constriction (Constrictor Pupillae Muscle)=CPM - ------------------------------------------------------ M3 (Miosis) Relaxation Contraction Ciliary muscle β2 “Accommodation for M3 “Accommodation for far vision” near vision”  Aqueous humor IOP β2 secretion M3  Aqueous humor drainage Lacrimal gland - -------------------------------------------------------- M3  secretion (tears) “Lacrimation” 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 14  Heart Atria SA node AV node Ventricles 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 15  SYMPATHETIC PARASYMPATHETIC Organ R Effect R Effect Heart  HR & Force ↓ HR & Force Tachycardia  HR Bradycardia ↓ HR - SA node (-ve chronotropic) (+ve chronotropic)  Contractility strength ↓ Contractility strength - Atrial (+ve inotropic) & Conduction (-ve inotropic) (+ve dromotropic)  RP BUT NOT Atrial conduction  Conduction velocity M2 ↓ Conduction velocity - AV node β1 (+ve dromotropic), (-ve dromotropic),  ERP. ↓ ERP  Contractility strength; CO - Ventricle; and oxygen consumption (+ve inotropic) ??? --------------------- His-Purkinje Conduction (+ve dromotropic) & automaticity 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 16  SYMPATHETIC PARASYMPATHETIC Organ R Effect R Effect Blood vessels (VSM) Constriction (VC) Skin & mucosa “Viscera” α1 “↑ TPR, ↑ diastolic pressure, ↑ afterload” Contraction (VC) Non-innervated. Veins α1 “↑ venous return, EXCEPT Male Genitalia ↑ preload” (VD and Erection). M 3 VD “Most of BVs” through Dilatation release of EDRFEndothelial Skeletal muscle BVs β2 VD derived relaxing factor.. Coronary artery Dilatation β2 VD 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 17  SYMPATHETIC PARASYMPATHETIC Organ R Effect R Effect Lung “Bronchiole” Relaxation - Airway smooth muscle Constriction (NVSM) β2 “Bronchodilation” “Bronchoconstriction” “not innervated” M3 - Bronchial secretion α1  Bronchial secretion  Bronchial secretion 6/10/2024 18 Professor Nageeb A.G.M. Hassan - ANS Introduction  SYMPATHETIC PARASYMPATHETIC Organ R Effect R Effect GIT (NVSM) Smooth muscle Contraction Relaxation - Wall α1/β2 (↓ Motility & tone) M3 (↑ Motility & tone) “Cramps” Relaxation - Sphincters α1 Contraction M3 “except lower esophageal, which contracts” ↑ Enzyme secretion Profuse water Salivary secretion α1 “Viscid saliva” M3 secretion “Salivation” Stomach (HCl) --- -------------------------------- M1 ↑ HCL secretion 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 19  SYMPATHETIC PARASYMPATHETIC Organ R Effect R Effect GUT (NVSM) Urinary bladder Smooth muscle - Wall “Detrusor muscle” α1A/β2,3 Relaxation Contraction M3 Relaxation - Trigone & Sphincter & Contraction Prostatic urethra α1A “Urinary retention” “Urine flow - voiding, urinary incontinence” β2 Relaxation Uterus; Pregnant uterus Contraction “Ring of --- --------------------------------- α1 uterus” Male sex organs “Vas deferens” α1 Ejaculation M3 Erection Kidney (JGA) β1 ↑ Renin release - --------------------------------- 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 20  SYMPATHETIC PARASYMPATHETIC Organ R Effect R Effect SKIN Contraction - Pilomotor smooth muscle α1 --- ------------------------ (erects hair) Cholinergic ↑ Sympathetic sweating - Sweat glands α1 sweating M3 “↑Thermoregulatory “Forehead & palms” sweating” Enhancement of neuromuscular Skeletal Muscle β2 transmission and - --------------------------- tremors ↓ Histamine Mast cells β2 release - --------------------------- 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 21  SYMPATHETIC PARASYMPATHETIC Organ R Effect R Effect Metabolic Function ↓ Insulin release → α2 Gluconeogenesis --- --------------------------------- - Pancreas β2 ↑ Insulin release --- --------------------------------- Liver Glycogenolysis → -------------------------------- - Liver β2 ↑ Glucose release --- “gluconeogenesis” -------------------------------- - Fat cells Β1,3 ↑ Lipolysis → ↑ FFA --- ↑ Skeletal muscle glycogenolysis → ↑ lactic - Skeletal Muscle β2 acid, and contractility --- --------------------------------- (tremor) 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 22  Blood Liver Skeletal muscle K+ α2 K+ β2 K+ Initial hyperkalemia because of Followed by hypokalemia ↑ uptake ↑ release of K+ from the liver (α2) of K+ by the skeletal muscle (β2) 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 23  SYMPATHETIC PARASYMPATHETIC Organ R Effect R Effect α2 ↓ Noradrenaline release --- --------------------------------- - Nerve terminals β2 ↑ Noradrenaline release --- -------------------------------- 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 24  Most organs receive dual sympathetic and parasympathetic innervation However, some organs only receive sympathetic innervation Suprarenal Gland Sweat Glands Most Blood Vessels Spleen Piloerector Muscles https://tmedweb.tulane.edu/pharmwiki/doku.php/introduction_to_the_ans 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 25 6/10/2024 Professor Nageeb A.G.M. Hassan - ANS Introduction 26