Flashcards - Dopamine
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
Reference Material
Autonomic Nervous System - Overview
• Basic and Clinical Pharmacology by
Katzung, 11th ed., 2009, paperback
(required text, new: $65, used: $49)
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
http://www.library.vcu.edu/
• Goodman & Gilman’s
Pharmacological Basis
of Therapeutics, 12th ed.
2010 (optional text)
(New: $170, Used: )
Paperback manual ($58,
based on 11th ed.)
Summary Table
ANS – Overview Tissues/Organs
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®)
Therapeutic Use
Sympathetic NS
Organ
Notes
Eye: Radial m.
Adrenoceptor Agonists
Action
Mydriasis
MAOI = Monoamine oxidase inhibitors TCA = Tricyclic antidepressants
Hypotension, pressor agent
α / β1 β3 (β2) neuronal, non-circulating, I: MAOI, TCA
Circular m.
Epinephrine
(generic)
Allergic reactions (DOC), shock, CPR
α / β1 β2 (β3) adrenal medulla, circulating; I: MAOI, TCA
Ciliary m.
Dopamine
(Intropin)
Shock (DOC)
α1 / β1 / D, NE precursor, renal vasodilatation? I: MAOI
Heart:
↑HR, ↑force
Parkinsons D., RLS
D-receptors agonist, SE: drowsiness
Vascular muscle
Asthma, cardiac stimulant
β, synthetic, not endogenous; BP(↓, --) HR↑
Nasal decongestant, hypotension
α1 Not commonly used for hypotension; S: CV, reflex
bradycardia
Norepinephrine
Bromocriptine,
(Levarterenol)
Pramiprexole
Isoproterenol
(Isuprel)
Phenylephrine
(Neosynephrine)
Methoxamine
Clonidine
Guanfacine
α-methyl-dopa
Dobutamine
(Vasoxyl)
(Catapres)
Hypotension, pressor agent
Hypertension
(Tenex)
α2, ↓ cns sympathetic outflow, inhibit NE release, rebound
HT; S: dry mouth, sedation, impotence.
α-methyl-dopa is metabolized to α-methyl-NE (α2-agonist,
positive Coombs test)
(Aldomet)
(Dobutrex)
CHF, cardiac stimulant
β1, iv infusion, tolerance, desensitization
Asthma - bronchodilator
β2--selective, Oral 1-2 hrs onset Æ 4-6 hrs duration,
Inhalation 5-10 min onset Æ 3-4 hrs duration;
S: cardiovascular; less via inhalation
Note: Terbutaline not FDA approved for premature labor
(cheaper, longer lasting than Ritodrine)
Prenalterol
Albuterol
Ritodrine
Metaproterenol
Terbutaline
(Proventil, Ventolin)
(Yutopar)
(Alupent)
(Brethaire)
Premature labor
Asthma
Asthma, (premature labor)
Parasympathetic NS
Receptor
Action
Receptor
α1
Cardiovascular System
BP = CO X TPR,
CO = SV X HR
Reflexes oppose direct action to correct BP
change (not HR change)
Miosis
M2, M3
Contract
M3
β1
↓HR
M2
α1
vasoconstriction→↑TPR → ↑BP
Constrict
α1
Relax
M3 (NO)
β1
↑HR → ↑CO → ↑BP
Relax
β2, D15 renal
β2
vasodilation → ↓TPR → ↓BP
Bronchial m.
Relax
β2
Contract
M3
M2
(vagus) ↓HR → ↓CO → ↓BP
GI-tract
↓ motility
α1, β 2
↑ motility
M3
M3
(NO) relaxation→ ↓TPR → ↓BP
Contract
α1
Relax
M3
Vascular β2 and M3 receptors are not innervated
and are the least important
Genitourinary m.
Relax
β2
Contract
M3
Cardiovascular Drug Effects
Penis
Ejaculation
α
Erection
M
Norepinephrine
↑BP,
Uterus
Relax
β2
Isoproterenol
BP (o/-), ↑HR, ↑PP
Sphincter m.
NO = Nitric oxide
Receptor
Action
↓HR (reflex)
Pilomotor
Contract
α
Epinephrine
↑BP, ↑HR, ↑PP
Sweat glands
↑ secretion
M3
β123 D15
↑cAMP
Mecamylamine
↓BP,
Liver
↑ glucose
β2
α1 M135
↑IP3 / Ca2+
Propranolol
BP (o/-), ↓HR
Kidney
↑ renin
β1
α2 M24 D234
↓cAMP
Atropine
BP (o/-), ↑HR
Fat cell
Lipolysis
β3
Nn
Na+in K+out
Phentolamine
↓BP, ↑HR (reflex), ↑PP
2nd Messengers
Nm
(o/+) HR
1
Autonomic Nervous System
Exam Stress
Normal BP:
Autonomic Nervous System
SYMPATHETIC
Thoracolumbar
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
Neurons of the ANS
PARASYMPATHETIC
Craniosacral
Cranial N. III, VII, IX, X
Sacral S2-3
T1-12, L1-3
“Flight or Fight”
“Feeding & Breeding”
↑BP, ↑HR, ↓GIT
↓BP, ↓HR, ↑GIT
Key Points
Preganglionic fibers
– mylinated
Postganglionic fibers
– non mylinated
SNS pre : post
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
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
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
2
Raynaud’s Syndrome
Adrenoreceptors
Alpha
Beta
Dopamine
•
α1-
Vascular smooth muscle
α2-
Nerve terminals
β 1-
Cardiac muscle
•
β 2-
Bronchial smooth muscle
•
β 3-
Fat cells
D1-5-
Renal, vascular smooth
muscle (D1-)
•
•
•
Cholinoreceptors
Muscarinic M1-
•
•
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
Eye – Miosis, Mydriasis & Cycloplegia
Miosis:
Mydriasis:
Cycloplegia:
Ganglia cells
M2 -
Cardiac muscle
M3 -
Sweat glands
pin point pupils
dilated pupils (bella-donna agents)
loss of accommodation (focus)
M4/M5
Nicotinic
NN-
Ganglia cells
NM-
Neuromuscular junction
ANS Diagram
Transmitter synthesis and release
Key Points
Division – Anatomical
Usually dual innervation
Usually antagonistic
Usually some ANS “tone”
Usually one dominates
Role of reflex responses
3