AUTONOMIC PHARMACOLOGY Flashcards
T1 - T12
L1 - L5
Sympathetic/Thoracolumbar
CN 3,7,9,10
S2-S4
Parasympathetic
Craniosacral
SYMPATHETIC (SANS)
Preganglionic fibers originate from
Thoracic (T1 -T12) segments of the cord
Lumbar (L1 -L5) segments of the cord
PARASYMPATHETIC (PANS)
Preganglionic motor fibers originate from
Cranial nerve nuclei III, VII, IX and X Sacral segments (S2-S4)
Preganglionic fibers are short and the
postganglionic fibers are long
SYMPATHETIC
Few (prevertebral) on the anterior aspect of the
aorta
SYMPATHETIC
Most of the ganglia are located in 2 paravertebral
chains that lie along the spinal cord
SYMPATHETIC
Most of the ganglia are located in the organs
innervated, most distant from the spinal cord
PARASYMPATHETIC
Preganglionic fibers are long and the
postganglionic fibers are short
PARASYMPATHETIC
NEUROTRANSMITTERS (NTAs)
4 FEATURES
- Synthesis
- Storage
- Release
- Termination of action
NEUROTRANSMITTERS
TERMINATION OF ACTION
By metabolism
-Monoamine oxidase (MAO)
-Cathecol-o-methly transferase (COMT)
Diffuse away from the synaptic cleft and get metabolized elsewhere
A nerve ending that releases acetylcholine as
the primary transmitter
Also a synapse in which acetylcholine is the
primary transmitter
CHOLINERGIC
A nerve ending that releases norepinephrine as
the primary transmitter
Also a synapse in which norepinephrine is the
primary transmitter
ADRENERGIC
All preganglionic fibers are
cholinergic
All postganglionic parasympathetic fibers are
cholinergic
A few postganglionic sympathetic fibers are
cholinergic
Most postganglionic sympathetic fibers are
adrenergic
Exception: Postganglionic sympathetic fibers
are
cholinergic
Adrenal cortex and medulla
Ductless gland that functions as a ganglion
Postganglionic fibers are cholinergic
ADRENAL GLAND
Inhibits transport/synthesis of ACh into the cell
HEMICHOLINIUM
Inhibits storage of ACh into the vesicle
VESAMICOL
Inhibits the release of ACh
BOTULINUM TOXIN
These drugs (Hemicholinium, vesamicol, botulinum toxin) are not very useful for systemic therapy because their
effects are not sufficiently selective
Inhibits the synthesis of NE
METYROSINE
Inhibits the storage of NE
RESERPINE
These drugs (METYROSINE, RESERPINE, GUANETHEDINE, MAO I) have been used in several diseases because
they block sympathetic but not parasympathetic functions
Inhibits release of NE
GUANETHEDINE
Inhibits metabolism of NE
MAO I
Other transmitter molecules in addition to the
primary agents (ACh or NE)
Contained in many autonomic nerves
Localized in the same vesicle as the primary
transmitter or in a separate population of vesicles
Involved in the modulation of synaptic
transmission
COTRANSMITTERS
ATP Enkephalins VIP Neuropeptide Y Substance P Somatostatin Neurotensin
COTRANSMITTERS
RECEPTOR CHARACTERISTICS
Also referred as cholinergic receptors
Respond to ACh and its analogs
A. CHOLINOCEPTORS
A. CHOLINOCEPTORS
Subdivided into
- MUSCARINIC receptors
2. NICOTINIC receptors
A. CHOLINOCEPTORS
Respond to muscarine (an alkaloid)
Respond to ACh
Mimics the effects of parasympathetic
G-protein coupled
- MUSCARINIC receptors
Located primarily on autonomic effector cells Heart Blood vessels Smooth muscles Presynaptic nerve terminals Exocrine glands
- MUSCARINIC receptors
3 subtypes of muscarinic receptors are important in peripheral autonomic
transmission
M1-nerve endings
M2-heart, some nerve endings
M3-effector cells, smooth muscle, exocrine
glands, endothelium
A. CHOLINOCEPTORS
2. NICOTINIC receptors
Respond to ACh
Respond to nicotine (another ACh mimic)
Do not respond to muscarine
Ligand-gated
A. CHOLINOCEPTORS
2. NICOTINIC receptors
2 major subtypes:
Nn-neuronal (ANS ganglia)
Nm-neuromuscular endplate (skeletal muscle)
TYPE OF CHOLINOCEPTORS
Nerve endings
G-coupled
Increase IP3
M1
TYPE OF CHOLINOCEPTORS Heart, some nerve endings G-coupled Decrease cAMP, activates K+ channel
M2
TYPE OF CHOLINOCEPTORS Effector cells, smooth muscle, glands, endothelium G-coupled Increase IP3
M3
TYPE OF CHOLINOCEPTORS ANS ganglia Ion channel Depolarizes, evokes action potential
Nn
TYPE OF CHOLINOCEPTORS Neuromuscular end plates Ion channel Depolarizes, evokes action potential
Nm
RECEPTOR CHARACTERISTICS
Also referred as adrenergic receptors
Respond to NE
G-protein coupled
B. ADRENOCEPTORS
B. ADRENOCEPTORS
Subdivided into
- ALPHA receptors
2. BETA receptors
ALPHA receptors
Located in
Blood vessels Presynaptic nerve terminals Blood platelets Fat cells (lipocytes) Neurons in the brain
ALPHA receptors
2 subtypes
effector tissues, smooth muscles, glands
ALPHA1-
ALPHA receptors
2 subtypes
nerve endings, some smooth
muscles
ALPHA2-
ADRENOCEPTORS
2. BETA receptors
Located on
Most types of smooth muscle Cardiac muscle Some presynaptic nerve terminal Lipocytes Brain
BETA receptors
3 major subtypes
BETA1-heart and kidney
BETA2-lungs, uterus, liver, heart
BETA3-fat or adipose tissue
Type of Adrenoceptor Effector tissues, smooth muscle,glands G- Increase IP3 Increase Ca2+ ,causes contraction, secretion
Alpha1
Type of Adrenoceptor Nerve endings, some smooth muscle G- Decrease cAMP Decrease transmitter release, causes contraction
Alpha2
Type of Adrenoceptor Cardiac muscle, kidney G- Increase cAMP Increase heart rate, force, increase renin release
Beta1
Type of Adrenoceptor Lungs, uterus, heart G- Increase cAMP Relax smooth muscle, increase glycogenolysis, increase HR, force
Beta2
Type of Adrenoceptor Adipose cells G- Increase cAMP Increase lipolysis
Beta 3
Predominant state in any situation
CENTRAL INTEGRATION
CENTRAL INTEGRATION
Ergotrophic (energy expenditure)
”Fight or flight” response
SYMPATHETIC
CENTRAL INTEGRATION
Tropotrophic (energy saving)
Leading to growth
”Rest and digest
PARASYMPATHETIC
Principle of negative feedback control
Alpha receptors located on noradrenergic
terminals which are activated by NE and other
similar molecules
Activation diminishes further the release of NE
from these nerve endings
PRESYNAPTIC REGULATION
PRESYNAPTIC REGULATION
Presynaptic receptors that respond to
transmitter substances released by the
nerve endings and thereby regulate its
release
AUTORECEPTORS
Up- and down-regulation are known to occur in response to decreased or increased activation of the receptors Up regulation (agonist) Down regulation (antagonist)
POSTSYNAPTIC REGULATION
Transmission involves different mechanisms
in different segments of the ANS
Some drugs produce highly specific effects
Others drugs are much less selective in their
actions
PHARMACOLOGIC MODIFICATION OF
AUTONOMIC FUNCTION
PHARMACOLOGIC MODIFICATION OF
AUTONOMIC FUNCTION
Drug that block action potential
Very nonselective
Act on the process that is common to all
neurons
LOCAL ANESTHETICS
PHARMACOLOGIC MODIFICATION OF
AUTONOMIC FUNCTION
Drugs that act on the biochemical processes
involved in transmitter synthesis and storage
are more —-
selective
Promote the release of NE
Effect is sympathetic
TYRAMINE AND AMPHETAMINE
Blocks uptake of ACh
Slows synthesis of ACh
HEMICHOLINIUM
Prevents storage of ACh
VESAMICOL
Prevents release ACh
BOTULINUM TOXIN
Binds alpha receptors Causes activation (agonist)
NOREPHINEPHRINE
Binds alpha receptors Prevents activation (antagonist)
PHENTOLAMINE
Binds beta receptors
Activates adenyl cyclase (agonist)
ISOPROTERENOL
Binds to beta receptors Prevents activation (antagonist)
PROPRANOLOL
Causes skeletal muscle contraction
agonist
NICOTINE
Prevents skeletal muscle contraction
antagonist
TUBOCURARINE
Binds muscarinic receptors
Activates (agonist)
BETANECHOL
Binds muscarinic recepto
Prevents activation
ATROPINE
Inhibits enzyme acetylcholinesterase
Prolongs and intensifies transmitter action
NEOSTIGMINE
Inhibits MAO
Increases stored transmitter pool
TRANYLCYPROMINE
