The Autonomic Nervous System Introduction Autonomic Nervous ...

The Autonomic Nervous System
Introduction
Edward JN Ishac, Ph.D.
Professor
Smith Building, Room 742
eishac@vcu.edu
828 2127
Department of Pharmacology and Toxicology
Medical College of Virginia
Campus of Virginia Commonwealth University
Richmond, Virginia, USA
Autonomic Nervous System - Overview
www2.courses.vcu.edu/ptxed/ptx/
1. Tissues / Organs: - receptors present,
tissue / organ response
2. Transmitters: - NE, Ach, synthesis, storage,
release, regulation
3. Drugs: - receptor selectivity,
mechanism of action
4. Can predict: - clinical application, side effects,
toxicity, treatment of toxicity
5. Eye Anatomy: - miosis, mydriasis, cycloplegia,
wide- vs narrow-angle, Horner’s syn.
6. General: - learn by drug classes, important
adverse reactions, not dosage
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ANS – Overview Tissues/Organs
Sympathetic NS
Parasympathetic NS
Cardiovascular System
Organ
Action
Receptor
Action
Receptor
BP = CO X TPR,
CO = SV X HR
Eye: Radial m.
Mydriasis
α 1
Reflexes oppose direct action to correct BP
change (not HR change)
Circular m.
Miosis
M 2 , M 3
Ciliary m.
Contract
M 3
Receptor
Action
Heart:
↑HR, ↑force
β 1
↓HR
M 2
α 1
vasoconstriction→↑TPR →↑BP
Vascular muscle
Constrict
α 1
Relax
M 3 (NO)
β 1
↑HR → ↑CO → ↑BP
Relax
β 2 , D 15 renal
β 2
vasodilation →↓TPR → ↓BP
Bronchial m.
Relax
β 2
Contract
M 3
M 2
(vagus) ↓HR → ↓CO → ↓BP
GI-tract
↓ motility
α 1 , β 2
↑ motility
M 3
M 3
(NO) relaxation→ ↓TPR → ↓BP
Sphincter m.
Contract
α 1
Relax
M 3
Genitourinary m.
Relax
β 2
Contract
M 3
Cardiovascular Drug Effects
Penis
Ejaculation
α
Erection
M
Norepinephrine
↑BP,
↓HR (reflex)
Uterus
Relax
β 2
NO = Nitric oxide
Isoproterenol
BP (o/-), ↑HR,
↑PP
Pilomotor
Contract
α
2 nd Messengers
Epinephrine
↑BP, ↑HR, ↑PP
Sweat glands
↑ secretion
M 3
β 123 D 15
↑cAMP
Mecamylamine
↓BP,
(o/+) HR
Liver
↑ glucose
β 2
α 1 M 135
↑IP 3 / Ca 2+
Propranolol
BP (o/-), ↓HR
Kidney
↑ renin
β 1
α 2 M 24 D 234
↓cAMP
Atropine
BP (o/-), ↑HR
Fat cell
Lipolysis
β 3
N n
N m
Na + in
K+ out
Phentolamine
↓BP, ↑HR (reflex),
↑PP
Summary Table
Indented = similar action to parent compound Most important agent, important, least important [ ] = questionable therapeutic value
I =drug interactions S = side effects T = toxicity CV = cardiovascular system CNS = central nervous system
Agent (trade name®)
Adrenoceptor Agonists
Therapeutic Use
Notes
MAOI = Monoamine oxidase inhibitors TCA = Tricyclic antidepressants
Norepinephrine
(Levarterenol)
Hypotension, pressor agent
α / β 1 β 3 (β 2 ) neuronal, non-circulating, I: MAOI, TCA
Epinephrine
(generic)
Allergic reactions (DOC), shock, CPR
α / β 1 β 2 (β 3 ) adrenal medulla, circulating; I: MAOI, TCA
Dopamine
(Intropin)
Shock (DOC)
α 1 / β 1 / D, NE precursor, renal vasodilatation? I: MAOI
Isoproterenol
(Isuprel)
Asthma, cardiac stimulant
β, synthetic, not endogenous; BP(↓, --) HR↑
Phenylephrine
Methoxamine
(Neosynephrine)
(Vasoxyl)
Nasal decongestant, hypotension
Hypotension, pressor agent
α 1 Not commonly used for hypotension; S: CV, reflex
bradycardia
Metaraminol
(Aramine)
Hypotension, pressor agent
α, orally active; NE or DA better choice
Clonidine
Guanfacine
α-methyl-dopa
(Catapres)
(Tenex)
(Aldomet)
Hypertension
α 2 , ↓ cns sympathetic outflow, inhibit NE release, rebound
HT; S: dry mouth, sedation, impotence.
α-methyl-dopa is metabolized to α-methyl-NE (α 2 -agonist,
positive Coombs test)
Dobutamine
(Dobutrex)
CHF, cardiac stimulant
β 1, iv infusion, tolerance, desensitization
Prenalterol
Albuterol
Ritodrine
Metaproterenol
(Proventil, Ventolin)
(Yutopar)
(Alupent)
Asthma - bronchodilator
Premature labor
Asthma
β 2 --selective, Oral 1-2 hrs onset 4-6 hrs duration,
Inhalation 5-10 min onset 3-4 hrs duration;
S: cardiovascular; less via inhalation
Note: Terbutaline not FDA approved for premature labor
(cheaper, longer lasting than Ritodrine)
Terbutaline
(Brethaire)
Asthma, (premature labor)
2

Autonomic Nervous System
Autonomic Nervous System
SYMPATHETIC
Thoracolumbar
T1-12, L1-3
PARASYMPATHETIC
Craniosacral
Cranial N. III, VII, IX, X
Sacral S2-3
“Flight or Fight”
↑BP, ↑HR, ↓GIT
“Feeding & Breeding”
↓BP, ↓HR, ↑GIT
FUNCTIONS CONTROLLED
Respiration
Circulation
Body Temperature
Metabolism
Sweating
Secretions
CENTRAL INVOLVEMENT
Hypothalamus - Integration, body
temp & water balance
Medulla - BP, respiration
Cerebral cortex - somatic NS & ANS
integration
3

Activation of SNS and release
of NE & EPI from nerve
endings and adrenal gland
Increase blood flow, BP, HR,
glucose, pupil dilation
Decrease activity of digestive
& immune system
Fight or Flight
Exam Stress
Normal BP: 120 / 80 mmHg HR: 72 bpm
Before exam: 140 / 99 mmHg HR: 97 bpm
During exam: 179 / 149 mmHg HR: 110 bpm
End of exam: 111 / 74 mmHg HR: 76 bpm
4

Neurons of the ANS
Key Points
Preganglionic fibers
– mylinated
Postganglionic fibers
– non mylinated
SNS pre : post 1:20
PNS pre : post 1:1
(exception 1:10,000
Auerbachs plexus)
Key role of Ach
Motor fiber not part of ANS
Neurons of the ANS
5

Adrenoreceptors
Alpha
Beta
Dopamine
α 1
-
α 2
-
β 1
-
β 2
-
β 3
-
D 1-5 -
Vascular smooth muscle
Nerve terminals
Cardiac muscle
Bronchial smooth muscle
Fat cells
Renal, vascular smooth
muscle (D 1 -)
Cholinoreceptors
Muscarinic
M 1
-
M 2
-
M 3
-
Ganglia cells
Cardiac muscle
Sweat glands
Nicotinic
M 4
/M 5
N N
-
N M
-
Ganglia cells
Neuromuscular junction
6

ANS Diagram
Key Points
Division – Anatomical
Usually dual innervation
Usually antagonistic
Usually some ANS “tone”
Usually one dominates
Role of reflex responses
Raynaud’s Syndrome
• Excessive sympathetic tone in nerves
supplying hands and feet. Minor cold,
or even thought of cold, causes
pronounced vasoconstriction that can
be severe enough to cause necrosis of
tissues
• Discoloration of the fingers and/or toes
when the patient is exposed to changes
in temperature (cold or hot) or
emotional events
• Abnormal spasm of blood vessels
causes diminished blood supply
• Initially, the digit(s) turn white because
of diminished blood supply.
• Then turn blue because of prolonged
lack of oxygen
• Finally turn red, the blood vessels
reopen, causing a local "flushing"
• Three-phase color sequence (white to
blue to red) is typical
• Treatment: Ca++ blockers if severe
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