Autonomic Nervous System

Autonomic Nervous SystemSukamto S M1

Nervous SystemNervous systemPeripheral Nervous systemCentral Nervous systemAfferent DivisionEfferent DivisionSpinal CordBrainAutonomic Nervous SystemSomatic Nervous SystemParasympathetic Nervous SystemSympathetic Nervous SystemEnteric Nervous System2

Efferent NeuronsCNS

Ganglionic transmitterCell body

Neuroeffector transmitter

Effector organ

Preganglionic neuronsPostganglionic neurons

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Differences between PNS and SNSComparisonsParasympatheticSympatheticSources of neuronsNeurotransmitter (neuroeffector transmitter)Preganglionic fiberReceptorsResponse

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Differences between PNS and SNSComparisonsParasympatheticSympatheticSources of neuronsCraniosacralThoracolumbalNeurotransmitter (neuroeffector transmitter)AcetylcholineEpinephrine/ NorepinephrinePreganglionic fiberLongShortReceptorsMuscarinic (M1-5) and nicotinic (Nn & Nm) receptors Adrenergic (1-2 & 1-3) and nicotinic receptorsResponseRest & digestFight or flight

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Sources of Neurons

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Neurotransmitters, ganglionic fibers and receptors

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Neurotransmitters, ganglionic fibers and receptors

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Sympathetic Alpha () receptors (1-2) Beta () receptors (1-2) Nicotinic receptors (Nn & Nm)Parasympathetic Muscarinic receptors (M1-5) Nicotinic receptors (Nn & Nm)

Autonomic Nervous System Receptors

Highlights!! Alpha receptors have subtypes: 1A 1B 1D 2A 2B 2C Another beta receptor has been identifies as 3 located in fat tissue9

NeurotransmitterSynthesisStorageReleaseInteractionRemoval/ DegradationRecovery

Acetylcholine10

NeurotransmitterSynthesisStorageReleaseInteractionRemoval/ DegradationRecovery

Epinephrine

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Receptor Bindings

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Agents Acting on Sympathetic Nervous System

(Sympatomimetics/ Adrenomimetics/ Adrenergic agonists)

(Sympatolytics/ Adrenolitics/ Adrenergic antagonists)

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Sympatomimetics/ Adrenomimetics/ Adrenergic AgonistsDirect acting (The drugs bind directly to the receptors leading to responses)Indirect acting (The drugs stimulate the release of norepinephrine rather than binding to the receptors)Mixed acting (The drugs have both direct- and indirect acting mechanisms)

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Direct Acting Sympatomimetics1 (Post synaps)

2 (Post synaps)

1(Post synaps)

2(Pre synaps)

SalbutamolTerbutalineRitodrineFormoterolSalmeterolIndacaterolPhenylephrinePseudoephedrineTetrahydrozolineMetaraminolMidodrineMethoxamineClonidineMehtyldopaGuanabenzGuanfacineGuanethidineDobutamineDenopamineXamoterol

OxymetazolineNaphazoline

Isoproterenol

Norepinephrine

Epinephrine

Highlight!!Pseudoephedrine is an alpha-1 agonist and used as nasal decongestant. However, it has property as a stimulant leading to special restriction by the government.16

Sympathetic Specific Responses17 Vasoconstriction Increased peripheral resistance Increased blood pressure Midriasis Increased closure of internal sphincter of the bladder 1

Inhibition of norepinephrine release Inhibition of acetylcholine release Inhibition of insulin release2

Tachycardia Increased of lypolisis Increased myocardial contractility Increased release of renin1

Vasodilation Slightly decreased peripheral resistance Bronchodilation Increased muscle and liver glycogenolisis Increased release of glucagon Relaxed uterine smooth muscle

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Indirect and Mixed Acting Sympatomimetics

Highlight!!!Substances derived from AMPHETAMINE/ METAMPHETAMINE is related to drug abuses such as DOPING. It is caused by the property of amphetamine that can enter blood brain barrier leading to DECREASED SENSE OF HUNGER OR FATIGUE.18

Releasing agents

COMT Inhibitors

MAO Inhibitors

Reuptake InhibitorsHighlight!!!The use of MAO inhibitors not only increases the concentration of NOR/EPINEPHRINE in synapse but also SEROTONIN and DOPAMIN leading to potency to be used as ANTIDEPRESSANT and ANTIPARKINSON.

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Clinical Use of Sympatomimetics

ClonidineAlong with other alpha-2 agonists, Clonidine has been used clinically as antihypertensive agent.

Phenylephrine Decongestant Midriaticum20

Salbutamol Like other beta-2 agonists, this drug is an asthma therapy Short acting drugClinical Use of SympatomimeticsDobutamine Cardiogenic shock Heart failure

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Epinephrine Anaphylactic shock Cardiac arrest Local anaesthetic preparationClinical Use of Sympatomimetics

OxymetazolineNasal decongestant

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Sympatolitics/ Adrenolitics/ Adrenergic Antagonists 23

Sympatolitics1 (Post synaps)

2 (Post synaps)

1(Post synaps)

2(Pre synaps)

ButoxaminePrazosinDoxazosinTerazosinBunazosinAlfuzosinTamsulosinYohimbineAtenololMetoprololAcebutololBisoprololEsmololBetaxololNebivololPhenoxybenzaminePhentolaminePropranololNadololPindololTimololPenbutololOxprenolol

LabetalolCarvedilol

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Sympathetic Specific Responses25 Vasoconstriction (Vasodilation) Increased peripheral resistance (Decreased) Increased blood pressure (Decreased) Midriasis (Miosis) Increased closure of internal sphincter of the bladder 1

Inhibition of norepinephrine release (Stimulation) Inhibition of acetylcholine release (Stimulation) Inhibition of insulin release (Stimulation)2

Tachycardia (Bradycardia) Increased of lypolisis (Decreased) Increased myocardial contractility (Decreased) Increased release of renin (Decreased)1

Vasodilation Slightly decreased peripheral resistance Bronchodilation Increased muscle and liver glycogenolisis Increased release of glucagon Relaxed uterine smooth muscle

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Several Substances Acting on NE Production26

MethyltyrosineCarbidopa

Clinical Use of SympatoliticsAlpha 1 blocker27Alpha 2 blocker

Libido performance. Not widely used.

Hypertension

Clinical Use of Sympatolitics28

Hypertension, angina, myocardial infarction & cardiac dysrhythmias

GlaucomaBeta 1 blocker

Parasympathomimetics/ Cholinomimetics/ Cholinergic Agonists29

Parasympathetic ReceptorsNicotinicNeuromuscular junction at skeletal muscleAutonomic gangliaMuscarinic (M1 - M5)M1 ganglia and secretory glandsM2 myocardium and smooth musclesM3 smooth muscles and secretory glands30

Parasympathetic ResponsesMiosisCopious; watery salivationBronchoconstriction; increased secretionBradycardiaGastric acid secretionIncreased gastric motilityDiuresisErection31

Parasympathomimetic Acting on Nicotinic Receptors32TypesNeuromuscular JunctionAutonomic GangliaAgonists/ Depolarizing agentsAChAChNicotineNicotineSuxamethoniumDecamethoniumAntagonists/ Non depolarizing agentsTubocurarineTrimetaphanPancuroniumMecamylamineVecuroniumHexamethoniumAtracurium

Clinical Use of Drugs Acting on Nicotinic Receptors33

Muscle relaxantMuscle relaxant

Parasympathomimetic Acting on Muscarinic ReceptorsDirect Acting Cholinomimetic (Choline ester)AcetylcholineMethacholineBethanecholCarbacholMuscarinePilocarpine

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GlaucomaMioticum/ GlaucomaUrine retention/ increase GIT motility

Parasympathomimetic Acting on Muscarinic ReceptorsIndirect Acting Cholinomimetic (Anticholinesterase)35Reversible, short-acting anticholinesterases Edrophonium TacrineReversible, intermediate-acting anticholinesterases (carbamylating agents) Physostigmine Neostigmine PyridostigmineIrreversible, long-acting anticholisterases (phosphorylating agents) Parathion Malathion Diazinon SarinAChCholine + AcetateCholinesterase

Clinical Use of Drugs Acting on Muscarinic Receptors36

Myasthenia gravisAlzheimer diseaseAnticholinergic toxicity/ Glaucoma

Parasympatholytics/ Anticholinergic/ Cholinergic Antagonists37

AnticholinergicAtropineHyoscine/ ScopolaminePirenzepinePropanthelineBenzatropineIpratropiumTiotropiumTrihexyphenidylTropicamide38Highlight!!!Antimuscarinic agents were of plant origin: Atropa belladonna Atropine Datura stramonium Atropine Hyoscyamus niger Hyoscyamine Scopolia carniolica ScopolamineHighlight!!!Several antihistamines have anticholinergic effects. Diphenhydramine Dimenhydrinate Doxylamine

Clinical Uses of Anticholinergics39

MidriaticumAsthmaAntispasmodicSinus bradycardia/ premedication in surgery

Thank You40