sympathetic nervous system
Post on 30-Dec-2015
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Dual Innervation
Predominant Tone
Exceptions
Primarily parasympathetic NS
- blood vessels
Exceptions
- blood vessels (sympathetic)
- sweat glands (sympathetic cholinergic)
(only sympathetic)
- bronchioles (only parasympathetic)
- ciliary muscles (only parasympathetic)
Denervation Supersensitivity
Before Denervation After Denervation
+ Effect+ Effect +++ Effect+++ Effect
NTNT NTNT
NENE
EPIEPI
DADA
Catecholamines
PRESYNAPTICPRESYNAPTIC POSTSYNAPTICPOSTSYNAPTIC
NE
Re-uptake 1Re-uptake 1
Metabolic RemovalMetabolic Removal
ActionAction /
ReceptorBinding
ReceptorBinding
NE synthesisNE synthesis
NE
COMTCOMT
MAOMAO
Re-uptake 2
(-)
NE - predominately removed from synapse via ‘re-uptake 1’
2
SITE EFFECT
EFFECTS OF STIMULATING ADRENERGIC RECEPTORS
BRONCHORELAXATION (2)
TACHYCARDIA and INCREASED CONTRACTILITY (1)
VASODILATION
DECREASED URINATION (2)
DECREASED GI MOTILITY and SECRETIONS (2)
GI TRACT
BLADDER
IRIS
AIRWAYS
VASCULATURE
HEART
(2)VASOCONSTRICTION
(1, 2)
UTERUS RELAXATION (2)
MYDRIASIS (1)
MIXED ADRENERGIC AGONISTSMIXED ADRENERGIC AGONISTS
NorepinephrineNorepinephrine
EpinephrineEpinephrine
1, 2, 1, 2
1, 2, 1
DopamineDopamine
DA1, 1, 1
MIXED ADRENERGIC AGONISTSMIXED ADRENERGIC AGONISTS
Norepinephrine Norepinephrine ((1, 2, 1)
Epinephrine Epinephrine ((1, 2, 1, 2)
Dopamine Dopamine ((DA, 1, 1)
Tx: ● Asthma (but there are better drugs)
Tx: ● CHF
● Anaphylactic shock
● Cardiogenic shock
● Prolong action of local anesthetics
● Topical hemostatic agent
ALPHA AGONISTSALPHA AGONISTS
- - PhenylephrinePhenylephrine ( (11))
- - Oxymetazoline Oxymetazoline ( (11 and and 2 in periphery2 in periphery))
- - Ephedrine/PseudoephedrineEphedrine/Pseudoephedrine ( (11))
- - Clonidine Clonidine ( (22, Tx site of action is CNS), Tx site of action is CNS)
- - MethoxamineMethoxamine ( (1)1)
- - Tetrahydrozoline Tetrahydrozoline ((1)1)
- - NaphazolineNaphazoline ((1)1)
Alpha-1 agonistsAlpha-1 agonists
Alpha-2 agonists Alpha-2 agonists
Tx: ● Nasal decongestion
Tx: ● Hypertension
● Hypotensive states
● Used in eye drops to ‘get the red out’
Tx uses for ALPHA AGONISTSTx uses for ALPHA AGONISTS
BETA AGONISTS BETA AGONISTS and Tx usesand Tx uses
Non-selective 1/2
- - Isoproterenol
Selective 1
- - Dobutamine
Non-selective 1/2
- - Isoproterenol
Selective 1
- - Dobutamine
Selective Selective 22
- - Albuterol- - Albuterol
- - Terbutaline- - Terbutaline
- - Isoetharine
- - Metaproterenol
- - Bitolterol
- - Ritodrine
Tx: Cardiac stimulant
Tx: Inotropic agent
Tx: COPD, Asthma
Tx: Uterine
relaxation
CNS ADRENERGIC AGENTSCNS ADRENERGIC AGENTS
- - Clonidine Clonidine ((2 agonist)2 agonist)
- - MethyldopaMethyldopa
- - GuanfacineGuanfacine ( (2 2 agonist)agonist)
CNS : Tx antihypertensive effectCNS : Tx antihypertensive effect
Converted in CNS to methylnorepinephrine Converted in CNS to methylnorepinephrine (low efficacy (low efficacy 2 agonist)2 agonist)
- - Guanabenz Guanabenz ( (2 agonist)2 agonist)
ALPHA ANTAGONISTS ALPHA ANTAGONISTS and Tx usesand Tx uses
- - PhentolaminePhentolamine
- - PrazosinPrazosin - - Terazosin Terazosin (water soluble)(water soluble)
- - PhenoxybenzaminePhenoxybenzamine Non-competitive actionNon-competitive action
Tx: - DOC for overdose of alpha agonists Tx: - DOC for overdose of alpha agonists - Management of pheochromocytoma- Management of pheochromocytoma - Dental use for reversal of local anesthetic action- Dental use for reversal of local anesthetic action
Nonselective Nonselective 1 and 1 and 2 receptor antagonists2 receptor antagonists
Selective Selective 1 receptor antagonists1 receptor antagonists
Tx: Antihypertensive agents,Tx: Antihypertensive agents,Management of benign prostatic hypertrophy Management of benign prostatic hypertrophy
Competitive action Competitive action
NE VasoconstrictionVasoconstriction1
NE
(-)
Adrenergic Influence onVascular Smooth Muscle Tone
2
VSMCVSMC
2
NE VasoconstrictionVasoconstriction1
NE
(-)2
VSMCVSMC
2
EPI
VasoconstrictionVasoconstriction
Adrenergic Influence onVascular Smooth Muscle Tone
NEVasodilationVasodilation
1
NE
(-)
Marked hypotensive response produced by dual 1 and 2 - Receptor Blockade on VSMC
2
VSMCVSMC
2
EPI
VasodilationVasodilation
Phentolamine - 11 and 2 2 blockade blockade
X
XX
VasodilationVasodilation1
NE
(-)
Moderate hypotensive response produced by dual 1 and 2 - Receptor Blockade 0n VSMC
2
VSMCVSMC
2
EPI
Prazosin - selective 11 blockade ockade
XNE
VasoconstrictionVasoconstriction
● ● Non-selective Non-selective 1, 1, 22
BETA ANTAGONISTSBETA ANTAGONISTS
● ‘● ‘Cardio’- Cardio’- Selective Selective 11
PropranololPropranolol
NadololNadolol
TimololTimolol
PindololPindolol
CarteololCarteolol Intrinsic Intrinsic Sympathomimetic Sympathomimetic
ActivityActivity
AtenololAtenolol
MetropololMetropolol
EsmololEsmolol
AcebutololAcebutolol (ISA)(ISA)
●● Non-selective1, 1, 2, 2, 11
LabetalolLabetalol
CarvedilolCarvedilol
Beta Blocker Tx Uses:Beta Blocker Tx Uses:
● Hypertension
● Migrane ● Arrhythmias
● Anxiety
● Angina
● Congestive heart failure
● Stage fright
● Myocardial infarction
AmphetamineAmphetamine
INDIRECT ACTING ADRENERGICINDIRECT ACTING ADRENERGICAGONISTSAGONISTS
TyramineTyramine (dietary substance)(dietary substance)
PseudoephedrinePseudoephedrine
EphedrineEphedrine
PRESYNAPTICPRESYNAPTIC POSTSYNAPTICPOSTSYNAPTIC
NE
Re-uptake 1Re-uptake 1
ActionAction /
ReceptorBinding
ReceptorBinding
NE
AmphetamineAmphetamine
PRESYNAPTICPRESYNAPTIC POSTSYNAPTICPOSTSYNAPTIC
Re-uptake 1Re-uptake 1
ActionAction /
ReceptorBinding
ReceptorBinding
NE
AmphetamineAmphetamine
NE
amphetamineamphetamine
(+)
• CocaineCocaine
• Tricyclic AntidepressantsTricyclic Antidepressants
Uptake BlockersUptake Blockers
PRESYNAPTICPRESYNAPTIC POSTSYNAPTICPOSTSYNAPTIC
NE
Re-uptake 1Re-uptake 1
ActionAction /
ReceptorBinding
ReceptorBinding
NE
CocaineCocaine
PRESYNAPTICPRESYNAPTIC POSTSYNAPTICPOSTSYNAPTIC
Re-uptake 1Re-uptake 1
ActionAction /
ReceptorBinding
ReceptorBinding
NE
CocaineCocaine
NE
XXcocainecocaine
• GuanethadineGuanethadine
Neuronal BlockersNeuronal Blockers
• ReserpineDepletes NE stores by inhibiting Depletes NE stores by inhibiting vesicular uptake of NE; NE then vesicular uptake of NE; NE then metabolized by intra-neuronal metabolized by intra-neuronal MAOMAO
Inhibits NE release, also causes Inhibits NE release, also causes NE depletion, and can damage NE NE depletion, and can damage NE neuronsneurons
• PargylinePargyline
Monoamine Oxidase (MAO) InhibitorsMonoamine Oxidase (MAO) Inhibitors
• Tranylcypromine• Tranylcypromine
Tyramine (or other drugs that promote NE release) Tyramine (or other drugs that promote NE release) may cause markedly increased blood pressure in may cause markedly increased blood pressure in patients taking MAO inhibitorspatients taking MAO inhibitors
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