ans nuclei in cns sympathetic nervous system parasympathetic nervous system preganglion growth...

ANS

Nuclei

in

CNS

Sympathetic

Nervous

System

Parasympathetic

Nervous

System

PREGANGLION

GROWTHPOSTGANGLION

END ORGAN

Flight

Fright

Fight

Parasympathetic

Somatic

gut

Sympathetic O

O

ACh

Noradrenaline

ACh

Nicotinic

Ach

Nicotinic

Stimulation of Stimulation of muscarinicmuscarinic

Circular muscle eye Circular muscle eye ((miosismiosis))

ciliary muscle ciliary muscle ((accommodation)

bronchial smooth musclebronchial smooth muscle

GIT wall bladder wallGIT wall bladder wall

venous sphincters (penis)venous sphincters (penis)

contractcontract

Stimulation Stimulation muscarinicmuscarinic

SecretionsSecretions GIT GIT

BronchiBronchi

Heart rateHeart rate AV ConductionAV Conduction

increaseincrease

decreasedecrease

Parasympathetic organ

MiosisContract ciliary

muscle

EyeEye

Open canal of SchlemmOpen canal of Schlemm

GlaucomaGlaucoma

accommodationaccommodation

Aqueous humour outflowAqueous humour outflow


GITcontract musclecontract muscle

relax sphinctersrelax sphincters

increase secretionsincrease secretions

digestiondigestion


Bladder contract musclecontract muscle

relax sphincterrelax sphincter

Urine voidingUrine voiding

metabolismmetabolismCVS Inhibit Inhibit

AV / SA nodeAV / SA node


metabolismmetabolism

Respiratory Respiratory systemsystem

BronchoconstrictionBronchoconstriction

Mucous secretionMucous secretion

Parasympathomimeticdrugs

muscarinic agonistsmuscarinic agonists

bethanecolbethanecol

pilocarpinepilocarpine

Indirect Indirect actingacting

acetylcholine acetylcholine esterase esterase inhibitorsinhibitors

neostigmineneostigminepyridostigminepyridostigmineedrophoniumedrophonium

long acting pesticides

malathionmalathion

reversiblereversible irreversibleirreversible

direct actingdirect acting

Therapeutic usesTherapeutic uses

EyeEye

GITGIT

Bladder

CVS

GlaucomaGlaucoma pilocarpinepilocarpine

bethanecolbethanecol

neostigmineneostigmine

Post surgical

ileus

Urine retentionUrine retention

End supra-End supra-Ventricular Ventricular tachycardiatachycardia

neostigmineneostigmine

edrophoniumedrophonium

Therapeutic usesTherapeutic usesPoisoningPoisoning

Alzheimer

Atropine-likeAtropine-like neostigmineneostigmine

donepezildonepezil

rivastigminerivastigmine

diagnosis

Increase CNSIncrease CNSACh levelsACh levels

pyridostigminepyridostigmine

Myasthenia Myasthenia gravisgravis treatment

edrophoniumedrophonium

Therapeutic uses muscarinic Therapeutic uses muscarinic blockersblockers

EyeEye

GITGIT

Bladder

Surgical

Ophthalmic examOphthalmic examCycloplegicCycloplegic, ,

atropineatropine

homatropinehomatropine

oxybutininoxybutinin

amitriptylineamitriptyline

Irritable bowel Syndromediarrhoea

enuresisenuresis

bradycardiabradycardiadry secretionsdry secretions

mebeverinemebeverine

diclominediclomine

atropineatropine

glycopyrrolateglycopyrrolate

Therapeutic uses muscarinic Therapeutic uses muscarinic blockersblockers

CNSCNS

Respiratory

N & V

Pesticidepoison

TremorTremorParkinson'sParkinson's

orphenadrineorphenadrine

biperidinebiperidine

scopolaminescopolamine

antihistaminesantihistamines

Asthma COPD

Stabilize vestibularStabilize vestibularMotion sicknessMotion sickness

Block parasympBlock parasympover stimulateover stimulate

ipratropium ipratropium bromidebromide

atropineatropine

Parasympathetic effectsParasympathetic effects

Terminate bradycardia

SurgerySurgery

CVSCVS

acetylcholine on AV node

edrophoniumedrophoniumatropineatropine

glycopyrrolateglycopyrrolate

Terminate SV Tachycardia

digoxindigoxin

Location of receptors Location of receptors Sympathetic Nervous Sympathetic Nervous

SystemSystem

VascularVascular

SmoothSmooth

MuscleMuscle

Presynaptic

inhibitionGIT

Pancreasplatelets

Alpha Alpha 11

Alpha Alpha 22

eyeeye

BetaRespiratory

Uterus SA node

myocardiumJG CellsAdipose

Vascular Smooth MuscleLiver

Location of receptors Location of receptors Sympathetic Nervous Sympathetic Nervous

SystemSystem

22

noradrenaline noradrenaline

releaserelease

InsulinInsulin

Sympathetic Nervous Sympathetic Nervous SystemSystem

11 VSM VSM arterioles arterioles

Radial muscle Radial muscle eyeeye

IncreaseIncreaseresistanceresistance

InhibitInhibitpresynapticpresynaptic

Renin releaseRenin release

increaseincrease

HRHR contractilitycontractility

Liver Liver

glucoseglucose

Sympathetic Nervous System

11

Pregnant Pregnant

uterusuterus

bronchibronchi

BloodBlood vesselsvessels

Sympathetic Nervous System

22 relaxrelaxdilatedilate

Sympathetic Sympathetic agonistsagonists

phenylephrine / oxymetazolinephenylephrine / oxymetazoline

alpha-2

alpha-1

alpha-methyldopa / clonidinealpha-methyldopa / clonidine

dopamine / dobutaminedopamine / dobutaminebeta-1

beta-2 dopamine / dobutaminedopamine / dobutamine

Multi receptor agonists

alpha 1+2 / beta 1+2alpha 1+2 / beta 1+2

reuptake inhibitor (nor)adrenaline / dopaminecocainecocaine

strong release adrenaline / noradrenaline

amphetamineamphetamine

adrenalineadrenaline

pseudoephedrine Weak release adrenaline / noradrenaline

Sympathomimetic agents

Depends onDepends on

Location of adrenergic receptor

Specificity for alpha / beta receptors

Reflexes

Sympathetic agonists Sympathetic agonists on organ systemson organ systems

conductionconduction(+ve(+ve dromotropic) dromotropic)

Heart

amphetamineamphetaminecocainecocaine

dopaminedopamine

Stroke volumeStroke volume(+ve(+ve inotropic) inotropic)

Heart rateHeart rate(+ve(+ve chronotropic) chronotropic)

beta-1 receptors

adrenalineadrenalinenoradrenalinenoradrenaline


mydriasismydriasis

(contract radial (contract radial

musclemuscle))

Eye

Decrease blood Decrease blood flow to ciliary flow to ciliary bodybody

(constrict))(constrict))

(nor)adrenalinealpha 1 receptors

dipivefrinedipivefrineapraclonidineapraclonidine

phenylephrinephenylephrine

Sympathetic Sympathetic agonistsagonists

bronchibeta 2 receptors (dilate)Relieve asthma

Respiratory Respiratory

↓ ↓ Blood flow to nasal Blood flow to nasal mucosamucosa

alpha 1 receptors (constrict)alpha 1 receptors (constrict)decongestiondecongestion

adrenaline

phenylephrinephenylephrineoxymetazolineoxymetazoline

pseudoephedrinepseudoephedrine

salbutamolsalbutamol

salmeterolsalmeterol


Adipose tissuebeta 3 receptors Increase lipolysis

Metabolic Metabolic (nor) adrenaline

Liverbeta 2 receptors Increase glycogenolysis

JG (renal)beta receptors Increase renin

B cells pancreas alpha 2 (Inhibit insulin)

Sympathetic Nervous Sympathetic Nervous SystemSystem

Blood Blood

PressurePressure

ConstrictConstrictDilateDilate

2211

Arterioles - VSM

Sympathetic effects on blood Sympathetic effects on blood vesselsvessels

skeletal muscle VSMskeletal muscle VSM skinskin

splanchnicsplanchnic

11

22

dilatedilateluminalluminal

(not innervated)(not innervated)

constrictconstrictInnervated SNSInnervated SNS

Sympathomimetic agents

specificity / receptor

adrenalinenoradrenaline

dopaminedobutamine

phenylephrinepseudoephedrine

amphetaminecocaine

1 2 1 2

Sympathetic effects on

chronotropicchronotropic

HeartHeart

inotropicinotropic

1 2 reflexes

1

Arterioles - VSM


EyeEye

Nasal Nasal congestion

CNS

GlaucomaGlaucoma

dipivefrinedipivefrine

apraclonidineapraclonidine

Constrict blood vessel

Decrease fatigueAppetite suppressant


pseudoephedrinepseudoephedrine

pseudoephedrinpseudoephedrinee

amphetamineamphetamine


EyeEye

LRT

labour

red eyered eyeallergyallergy


oxymetazolineoxymetazoline


hexoprenalinehexoprenaline

AsthmaCOPD

prematureprematurerelax uterusrelax uterus


salmeterolsalmeterol

Therapeutic Therapeutic usesuses

CVS

adrenalineadrenalineanaphylaxisanaphylaxis

Acute heart failureVentricular

fibrillation

dopaminedopamine

adrenalineadrenaline

alpha-methyldopaalpha-methyldopahypertensionhypertension

ShockShockRenal failureRenal failure

Adrenoreceptor blocking agents

alpha1 + alpha2 - blockers

alpha1 selectiveselective

irreversible(phenoxybenzamine)

reversible(phentolamine)

prazosinprazosin

doxazosindoxazosin

Beta – adrenoreceptor blocking agents

Block agonist on beta-receptorBlock agonist on beta-receptor

ACGs

Ca2+ATP cAMP

Kinase

Contraction

Ca2+

SR

V

Beta - adrenergic Beta - adrenergic blockersblockers

beta1 + beta2 (non – selective)

beta1 (cardiac – selective)

beta1 beta2 + alpha 1

carvedilolcarvedilol

propranolol / timololpropranolol / timolol

atenolol / bisoprololatenolol / bisoprolol

Adrenergic antagonists on Adrenergic antagonists on organsorgans

CVSDecrease heart rate

dilate VSM (alpha)

block (nor)adrenaline

LiverBlock sympathetichypoglycaemia

JG (renal)decrease renin

bronchiincrease airway resistance

Eyemydriasis (alpha)decrease aqueous

Therapeutic uses - blockersTherapeutic uses - blockers

CVS

Heart Heart failurefailure

hypertension

Angina Angina pectorispectoris

atenololatenolol

bisoprololbisoprolol

ArrhythmiaArrhythmiaPost MIPost MI

bisoprololbisoprolol

carvedilolcarvedilol

AnxietyAnxiety

Migraine

EyeEye

Decrease Decrease CVSCVS atenololatenolol

propranololpropranololprophylaxis

GlaucomaGlaucomaTopical reduce Topical reduce aqueous humouraqueous humour

timololtimolol

metipranololmetipranolol

BPHBPH Reduce massImprove voiding

prazosinprazosin

doxazosindoxazosin

Therapeutic uses - blockersTherapeutic uses - blockers

Beta blockers - MOABeta blockers - MOA

CNSdecrease SNS out put

renaldecrease renin

lowerlowerblood pressureblood pressure

heartdecrease heart

ratedecrease SV / SBP

VSMPresynapticdecrease NA

Beta - blockersBeta - blockersCO = SV x HR

NonselectiveNonselective propranololpropranololtimolol timolol Short half lifeShort half life

Blocks (cardiac) Blocks (cardiac) 11 and and 22 receptor receptor

Beta - blockersBeta - blockers

CO = SV x HR

CardioselectiveCardioselective atenololatenololbisoprololbisoprolol Blocks Blocks mainlymainly cardiac cardiac 1 1 - -

receptor receptor

Cardioselective beta - Cardioselective beta - blockersblockers

Advantage Advantage in diabetesin diabetes

asthmaasthma

PVDPVD

Side effects and CI

Other beta - blockers

AcebutololAcebutololIntrinsic sympathomimetic (ISA)Intrinsic sympathomimetic (ISA)

partial agonistspartial agonists

TPR?TPR?

prevent bradycardiaprevent bradycardia

CO = SV x HR

Mixed Mixed / / blocker blockercarvedilolcarvedilol3:1 3:1 / / blocker blockerTPRTPRHeart failureHeart failureImproves morbidity and Improves morbidity and

mortalitymortality

Adverse effects beta Adverse effects beta blockersblockers

BradycardiaAV blockHeart failurePVDLimit

exercise

Cardiovascular

block (nor)adrenaline

diabetesBlock sympathetichypoglycaemia

Asthma COPD

respiratory

CNSVivid dreamsdepression

11 - adrenergic - adrenergic blockersblockers

prazosin / doxazosinprazosin / doxazosin

Post-synaptic 1 receptors

antagonist

Block NA induced vasoconstriction

CO / HR unaltered

Benefit HDL:LDL

Now in BPH

11 - adrenergic blockers - adrenergic blockers

First dose low BP

Postural hypotension

Impotence

Urinary incontinence

CNS depression

Tolerance?

Safety in hypertension?

Centrally acting - receptor agonists

alpha-methyldopa – alpha-methyldopa – 22 agonistagonist

Post - Post - synapticsynaptic

(locus coreleus)(locus coreleus)medullamedulla

- presynaptic- presynapticreceptorreceptor

NANA

Preferred in hypertension Preferred in hypertension pregnancypregnancy

Reduce central Reduce central sympathetic sympathetic

outputoutput

alpha-methyldopa Convert to Convert to alphaalpha- -

methylnoradrenalinemethylnoradrenaline

Reduce TPRReduce TPR

/ r/ reflexes intacteflexes intact

++veve Coombs Test Coombs Test

SedationSedation

HepatitisHepatitis

Fluid retentionFluid retention

Reserpine

PeripheralPeripheral

Depletes NA vesicles Depletes NA vesicles (centrally)(centrally)

blocks DA entryblocks DA entry Decreases sympathetic Decreases sympathetic

activity activity Increases venous toneIncreases venous tone

ReserpineReserpine

side effectsside effects Postural hypotension

Rebound PSNS(diarrhoea, bradycardia, peptic ulcer depression, drowsiness

Na+ + H2O retention Effect + 3 weeks

t½ = + 75 days

HeartHeartResistance Resistance CentralCentralReninRenin

Sympathetic blockersSympathetic blockersin hypertensionin hypertension

Classes of anti-hypertensives

ResistanceResistance Diuretics - Na+/volumeDiuretics - Na+/volume Calcium channel Calcium channel

blockersblockers Direct vasodilators Direct vasodilators Angiotensin inhibitorsAngiotensin inhibitors

ResistanceResistanceNa/waterNa/water

ans nuclei in cns sympathetic nervous system parasympathetic nervous system preganglion growth...

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