วััตถุุประสงค · PDF fileณัฐัิยา ... • Central nervous system (CNS) –Brain –Spinalcord • Peripheral nervous system (PNS) –Autonomic

Introduction to ANS PharmacologyIntroduction to ANS Pharmacologyพญพญ.. ณัฐิณัฐิยายา ไกรวไกรวพันธุพันธุ

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Introduction to ANS - CVS Drugs

พญ. ณัฐิยา ไกรวพันธุภาควิชาเภสัชวิทยา คณะแพทยศาสตร

มหาวิทยาลัยเชียงใหม

พญพญ.. ณัฐิณัฐิยายา ไกรวไกรวพันธุพันธุภาควิชาเภสัชวิทยาภาควิชาเภสัชวิทยา คณะแพทยศาสตรคณะแพทยศาสตร

มหาวิทยาลัยเชียงใหมมหาวิทยาลัยเชียงใหม

วัตถุประสงควัตถุประสงค สามารถบอกบทบาทและหนาที่ของระบบ

sympathetic และ parasympathetic nervous systems สามารถบอกชนิดของ cholinergic และ

adrenergic receptors


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NervousNervous SystemSystem• Central nervous system (CNS)

– Brain– Spinal cord

• Peripheral nervous system (PNS)– Autonomic nervous system (ANS)– Somatic nervous system

Autonomic nervous system• control visceral function, involuntary• innervate

smooth musclecardiac muscleexocrine glands

Somatic nervous system• voluntary• innervate skeletal muscle


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AutonomicAutonomic NervousNervous SystemSystem((ANSANS))

Parasympathetic NS. (PSNS)• Craniosacral (CN III,VII,IX,X and 3rd &

4th sacral spinal roots)

Sympathetic NS. (SNS)• Thoracolumba


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Innervation of ANS• อวัยวะสวนใหญมีท้ังระบบ sympathetic,

parasympathetic มาควบคุมโดยผลลัพธท่ีเกิดกับอวยัวะโดยมากมักมีผลตรงขามกนั

Parasympathetic nerves

Sympathetic nerves

preganglionic

preganglionic

postganglionic

postganglionic

ACh

ACh

ACh Effectortissues

Effectortissues

NE

Ganglia

Ganglia

CNS

CNS

long

long

short

short


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NeurotransmittersNeurotransmitters

1. Acetylcholine: Cholinergic fiber2. Norepinephrine: Adrenergic fiberกระตุน alpha1-2, beta1

3. Epinephrine: Adrenal medullaกระตุน alpha1-2, beta1-2

4. Dopamine: Dopaminergic fiber

• Synthesis - nerve terminal• Storage - vesicle• Release - exocytosis• Inactivation - Acetylcholinesterase,

Esterases- Re-uptake, MAO, COMT

Steps of Neurotransmitter


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ACETYLCHOLINE 1

2

3

4

ACETYLCHOLINE


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NOREPINEPHRINE2

1

3

4

NOREPINEPHRINE


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Step Sympathetic Parasympathetic

Synthesis: precursor Tyrosine Acetyl CoA, Choline Major mech. of inactivation

Uptake and recycling of NE

Enzymatic degradation of ACh

Degradation enzyme

MAO, COMT (intracellular)

Acetylcholinesterase (postsynaptic mb)

MAO: monoamine oxidaseCOMT: catechol-o-methyltransferaseButyrylcholinesterase (Pseudocholinesterase)

Acetylcholine1. Preganglionic fibers - both sympathetic

and parasympathetic2. Parasympathetic postganglionic nerves4. Sympathetic fibers to sweat glands4. Somatic motor fiber (skeletal muscle)


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Norepinephrine- Most postganglionic sympathetic nerves(ยกเวน postganglinonic fiber ที่ไป sweat glands)

- Adrenal medullaEpinephrine

- Adrenal medulla


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DopamineBrain, vasodilator transmitter,splanchnic vessels and renal vessels


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AutonomicAutonomic ReceptorsReceptors

1. Cholinoceptors1.1 Muscarinic receptors

M1 : CNS neurons, some presynapticsites

M2 : Myocardium smooth muscle,some presynaptic sites

M3 : Exocrine glands, smooth muscle and endothelium


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1.2 Nicotinic receptors (NN, NM)

NN: autonomic glanglia: adrenal medulla

NM: Somatic nerve endplate

2. Adrenoceptors

พบที่ :effector tissues ที่ถูกinnervate Postjunctionalโดย sym. nerve (postsynaptic)

:adrenergic nerve terminal Prejunctional(presynaptic)

แบงไดเปนα--adrenergic receptors sm.muscle---contractβ--adrenergic receptors sm.muscle---relax

heart ---stimuation+ GI smooth muscle: α & β - relaxation +


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2.1 Alpha (α) adrenergic receptorsalpha1 : vascular smooth muscle

alpha2 : CNS: platelets, lipocytes,: smooth muscle: presynaptic adrenergic

nerve terminals (ยับยั้ง transmitter release)

2.2 Beta (β) adrenergic receptorsbeta1: cardiac muscle, brain,lipocytes,

presynaptic adrenergic and cholinergic nerve terminal

beta2: bronchial smooth muscle: vascular smooth muscle

beta3: lipocytes


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Adrenoceptor ActivationEpinephrine(Epi)

alpha และ beta receptors ทั้งหมดNorepinephrine(NE)

alpha และ beta1 receptors

2.3. Dopamine receptorsD1,D5: brain; smooth muscle of renal

vascular bedD2: Brain; smooth muscle; presynaptic

nerve terminalD3: BrainD4: Brain, cardiovascular system


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FunctionFunction ofof ANSANS

• Parasympathetic= “Rest and Digest”

• Sympathetic= “Fight or Flight”

Cardiovascular function

• Blood vesselsSympathetic nerves–NE alpha1 contraction–Epinephrine beta2- relaxation(skeleton muscle)

BP = CO x TPR


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• HeartParasympathetic– Postganglionic fibers terminate in SA

node, atria and AV node– Causes (-)ve chronotropic effect;

decreased heart rate– Causes ↑ AV conduction time– Causes ↓ contractility of atrium

↓ CO ↓ BP

• HeartSympathetic– Postganglionic nerves innervated S-A node,

atria, AV node and ventricle– Causes (+)ve chronotropic effect;beta1&2

increased heart rate– Causes (+) inotropic effect;beta1&2

increased contractility↑ CO ↑ BP


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• Baroreceptor Reflex

การปรับตัวของรางกายเมื่อ BPเปลี่ยนแปลง– When BP ↓

↑ Sympathetic tone- Heart : rate & force เพิ่ม- Blood vessel : vasoconstriction

↓ Parasympathetic tone

• Baroreceptor Reflex

– When BP ↑

↓ Sympathetic tone- Heart : rate & force ลด - Blood vessel : vasodilatation

↑ Parasympathetic tone


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• EyeParasympathetic– contract of circular muscle miosis– Ciliary m. contraction

accommodationopening pores of trabecularmeshwork

• EyeSympathetic–alpha: contraction of radial m.-> mydriasis–beta: ↑ secretion of aqueous humorBeta-blocker (treatment of glaucoma)

↓ secretion and ↓ intraoccular pressure


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•Lung

Parasympathetic– Bronchoconstriction– increased secretionSympathetic– Bronchodilatation (beta2)

•GI tract

Sympathetic–smooth m.wall relaxes (alpha2,beta2)–sphincters contracts (alpha1)Parasympathetic–smooth m.wall contracts–sphincters relaxes–secretion increases


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•Genitourinary smooth muscle

Sympathetic

– bladder wall relaxes (beta2)– sphincter contracts (alpha1)– uterus relaxes (beta2)– penis ejaculation (alpha)

Parasympathetic– bladder wall contracts– sphincter relaxes– uterus contracts– penis erection

• Genitourinary smooth muscle


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•SkinSympathetic nervous system–pilomotor smooth m. contracts(alpha)

•Sweat glandsSympathetic nervous system–Thermoregulatory increases(M)– Apocrine(stress) increases (alpha)

•Metabolic functionsSympathetic nervous system–Liver gluconeogenesis+glycogenolysis

(beta2&alpha)–Fat cells lipolysis (beta3)–Kidney renin releases (beta1)


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•Endocrine glandsSympathetic nervous system–Renin release

beta1 Increasealpha2 Decrease

–Insulin releasebeta Increasealpha2 Decrease

The EndThe End

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วััตถุุประสงค · PDF fileณัฐัิยา ... • Central nervous system (CNS) –Brain –Spinalcord • Peripheral nervous system (PNS) –Autonomic