Reporting Status or Progress

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Sympathetic Nervous System
2
Nervous System
CNS
PNS
Brain Spinal Cord
Somatic NS
Autonomic NS
Sympathetic
Parasympathetic
3
CNS
ACh
C
M
N
ACh
T
ACh
?1
NE
N
L
NE
?1
?2
S
ACh
SM
N
4
CNS
ACh
C
M
N
ACh
T
ACh
?1
NE
N
L
NE
?1
N
EPI
ACh
?2
S
ACh
SM
N
5
CNS
ACh
C
M
N
ACh
T
ACh
?1
NE
N
L
NE
ACh
?1
N
SG
ACh
M
?2
S
ACh
SM
N
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Sympathetic Nervous System
CNS
(-)
?2
C
M
T
ACh
?1
NE
N
L
NE
?1
N
EPI
ACh
?2
S
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Dual Innervation
Exceptions
(only sympathetic)
- blood vessels
(only parasympathetic)
- bronchioles
(only parasympathetic)
- ciliary muscles
Predominant Tone
Primarily parasympathetic NS
Exceptions
- blood vessels (sympathetic)
- sweat glands (sympathetic cholinergic)
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Denervation Supersensitivity
Effect
Effect
NT
NT
Before Denervation
After Denervation
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Catecholamines
NE
EPI
DA
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PRESYNAPTIC
POSTSYNAPTIC
NE - predominately removed from synapse via
re-uptake 1
Metabolic Removal
Re-uptake 2
Re-uptake 1
NE synthesis
COMT
MAO
NE
Action
? / ?
NE
MAO
(-)
?2
Receptor Binding
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Drug actions at presynaptic autonomic nerve
terminals
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Adrenergic Receptors
?1, ?2, ?1
NE
?1, ?2, ?1, ?2
EPI
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Adrenergic Receptors
?1, ?2, ?1
NE
?1, ?2, ?1, ?2
EPI
?1, ?1, DA1
DA
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EFFECTS OF STIMULATING ADRENERGIC RECEPTORS
SITE EFFECT
HEART
TACHYCARDIA and INCREASED CONTRACTILITY (?1)
VASCULATURE
VASODILATION
VASOCONSTRICTION
(?1, ? 2)
(?2)
BRONCHORELAXATION (?2)
AIRWAYS

IRIS
MYDRIASIS (?1)
BLADDER
DECREASED URINATION (?2)
DECREASED GI MOTILITY and SECRETIONS (?2)
GI TRACT
UTERUS
RELAXATION (?2)
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contractile force heart rate
?1
renin release
vasodilation, TPR
?2
vasoconstriction TPR
?1, ?2
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Drugs and Adrenergic Synapses
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CNS
Adrenergic Agonists
ACh
C
M
N
ACh
T
ACh
?1
NE
N
L
NE
?1
N
EPI
ACh
?2
S
ACh
SM
N
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MIXED ADRENERGIC AGONISTS
Norepinephrine
?1, ?2, ?1
Epinephrine
?1, ?2, ?1, ?2
Dopamine
DA1, ?1, ?1
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HR
BP
TPR
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MIXED ADRENERGIC AGONISTS
Norepinephrine (?1, ?2, ?1)
Epinephrine (?1, ?2, ?1, ?2)
Tx ? Asthma (but there are better drugs)
? Anaphylactic shock
? Cardiogenic shock
? Prolong action of local anesthetics
? Topical hemostatic agent
Dopamine (DA, ?1, ?1)
Tx ? CHF
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ALPHA AGONISTS
- Phenylephrine (?1)
- Methoxamine (?1)
- Oxymetazoline (?1 and ?2 in periphery)
- Tetrahydrozoline (?1)
- Naphazoline (?1)
- Ephedrine/Pseudoephedrine (?1)
- Clonidine (?2, Tx site of action is CNS)
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Tx uses for ALPHA AGONISTS
Alpha-1 agonists
Tx ? Nasal decongestion
? Used in eye drops to get the red out
? Hypotensive states
Alpha-2 agonists
Tx ? Hypertension
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BETA AGONISTS and Tx uses

• Non-selective ?1/2
• - Isoproterenol
• Selective ?1
• - Dobutamine

Selective ?2
- Albuterol
Tx Cardiac stimulant
- Metaproterenol
- Terbutaline
Tx COPD, Asthma
- Isoetharine
- Bitolterol
Tx Inotropic agent
- Ritodrine
Tx Uterine relaxation
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NE
EPI
ISO
HR
BP
TPR
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Dose-response effects produced by dopamine at
different receptors
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CNS ADRENERGIC AGENTS
CNS Tx antihypertensive effect
- Clonidine (?2 agonist)
- Guanabenz (?2 agonist)
- Guanfacine (?2 agonist)
- Methyldopa
Converted in CNS to methylnorepinephrine (low
efficacy ?2 agonist)
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Sympathetic Nervous System
CNS
(-)
?2
C
M
T
ACh
?1
(-)
NE
N
(-)
L
NE
?1
N
EPI
ACh
?2
S
?2
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CNS
Adrenergic Antagonists
ACh
C
M
N
ACh
T
ACh
?1
X
NE
N
L
X
NE
?1
N
EPI
X
ACh
?2
S
ACh
SM
N
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ALPHA ANTAGONISTS and Tx uses
? Nonselective ?1 and ?2 receptor antagonists
- Phenoxybenzamine
Non-competitive action
- Phentolamine
Competitive action
Tx - DOC for overdose of alpha agonists
- Management of pheochromocytoma -
Dental use for reversal of local anesthetic
action
? Selective ?1 receptor antagonists
- Prazosin
- Terazosin (water soluble)
Tx Antihypertensive agents, Management of
benign prostatic hypertrophy
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Adrenergic Influence on Vascular Smooth Muscle
Tone
VSMC
?2
NE
?1
NE
Vasoconstriction
(-)
?2
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Adrenergic Influence on Vascular Smooth Muscle
Tone
EPI
VSMC
?2
Vasoconstriction
NE
?1
NE
Vasoconstriction
(-)
?2
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Marked hypotensive response produced by dual ?1
and ?2 - Receptor Blockade on VSMC
EPI
VSMC
X
?2
Vasodilation
X
NE
NE
?1
Vasodilation
(-)
X
?2
Phentolamine - ?1 and ?2 blockade
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Moderate hypotensive response produced by dual
?1 and ?2 - Receptor Blockade 0n VSMC
EPI
VSMC
?2
Vasoconstriction
X
NE
?1
NE
Vasodilation
(-)
?2
Prazosin - selective ?1 blockade
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BETA ANTAGONISTS
? Non-selective ?1, ?2
? Cardio- Selective ?1
Atenolol
Propranolol
Metropolol
Nadolol

Esmolol
Timolol
Acebutolol (ISA)
Pindolol
? Non-selective ?1, ?2, ?1
Carteolol
Intrinsic Sympathomimetic Activity
Labetalol
Carvedilol
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Beta Blocker Tx Uses
? Congestive heart failure
? Hypertension
? Myocardial infarction
? Angina
? Migrane
? Arrhythmias
? Anxiety
? Stage fright
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INDIRECT ACTING ADRENERGIC AGONISTS
Tyramine (dietary substance)
Ephedrine
Pseudoephedrine
Amphetamine
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Amphetamine
PRESYNAPTIC
POSTSYNAPTIC
Re-uptake 1
NE
Action
? / ?
NE
Receptor Binding
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Amphetamine
PRESYNAPTIC
POSTSYNAPTIC
Re-uptake 1
amphetamine
NE
NE
()
Action
? / ?
Receptor Binding
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Uptake Blockers

• Cocaine
• Tricyclic Antidepressants

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Cocaine
PRESYNAPTIC
POSTSYNAPTIC
Re-uptake 1
NE
Action
? / ?
NE
Receptor Binding
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Cocaine
PRESYNAPTIC
POSTSYNAPTIC
Re-uptake 1
cocaine
X
NE
NE
Action
? / ?
Receptor Binding
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Neuronal Blockers

• Reserpine

Depletes NE stores by inhibiting vesicular uptake
of NE NE then metabolized by intra-neuronal MAO

• Guanethadine

Inhibits NE release, also causes NE depletion,
and can damage NE neurons
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Monoamine Oxidase (MAO) Inhibitors

• Pargyline

• Tranylcypromine

Tyramine (or other drugs that promote NE release)
may cause markedly increased blood pressure in
patients taking MAO inhibitors
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