Nursing Pharmacology Autonomic (ANS) Pharmacology: Introduction
ANS regulates organs/processes not under conscious control including:
Some endocrine gland secretions
Sympathetic system is most active when the body needs to react to changes in the internal or external environment.
The requirement for sympathetic activity is most critical for:
Regulation of glucose levels
Rapid vascular response to hemorrhage
Reacting to oxygen deficiency
During rage or fright the sympathetic system can discharge as a unit--affecting multiorgan systems.
Sympathetic fibers show greater ramification.
Sympathetic preganglionic fibers may traverse through many ganglia before terminiating at its post-ganglionic cell. Synaptic terminal arborization results in a single preganglionic fiber terminating on many post-ganglionic cells.
This anatomical characteristic is the basis for the diffuse nature of sympathic response in the human and other species.
Heart rate increases
Blood pressure increases
Blood is shunted to skeletal muscles
Blood glucose increase
Slows heart rate
Protects retina from excessive light
lowers blood pressure
Empties the bowel and bladder
Increases gastrointestinal motility
Promotes absorption of nutrients
Lefkowitz, R.J, Hoffman, B.B and Taylor, P. Neurotrasmission: The Autonomic and Somatic Motor Nervous Systems, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.108.
Neurotransmitters and the Autonomic Nervous System
To support the idea that a chemical is a neurotransmitter, several conditions must be satisfied
Enzymes that are involved in "transmitter" synthesis should also be present.
Where possible (as in autonomic transmission), recovery of the "transmitter" in higher quantities following nerve stimulation than in the absence of stimulation.*
Externally applied (e.g. iontophoretically applied) chemical produces the same effect as stimulation. For example, the reversal potential is the same.
Effects of antagonists influence the response to externally applied chemical in the same manner as antagonists modify responses following nerve stimulation.
* may not be possible in many instances
Depolarization of the axonal membrane potential results in an action potential.
The upstoke of the action potential is a sodium current flowing through voltage-activated sodium channels
As the membrane potential decreases, activation occurs of an outgoing potassium current, which opposes further depolarization and initiates repolarization.
Longitudinal spread of local depolarizing sodium currents results in progressive, longitudinal activation of sodium channels and new sites of depolarization. The rate of conduction is dependent on the number and synchrony of sodium channel activation.
Number and synchrony of sodium channel activation is membrane potential dependent.
As the resting membrane potential decrease (towards 0), fewer sodium channels will be activated by a depolarizing influence and conduction velocity slows.
In myelinated fibers, depolarization occurs at the Nodes of Ranvier.
Synaptic (Junctional) Activity
Small molecule neurotransmitters (e.g. acetylcholine, norepinephrine) are synthesized at axonal terminals and stored in synaptic vesicles.
Isolated neurotransmitter "quanta", perhaps corresponding to single vesicle neurotransmitter quantity, is randomly released in the basal state.
This level of release, generating miniature end-plate potentials (mepp's), is necessary for resting skeletal muscle tone.
Action Potentials, promoting calcium influx, induce large, synchronous release of several hundred quanta .
Calcium facilitates vesicular membrane-synaptic membrane fusion, resulting in vesicular content discharge into the synaptic cleft.
Many chemical can inhibit norepinephrine or acetylcholine release through receptor interactions at the appropriate terminal. Examples:
Norepinephrine + presynaptic α2-adrenergic receptor (autoreceptor) inhibits norepinephrine release
α2 receptor antagonists increase release of norepinephrine
Neurally-mediated acetylcholine release from cholinergic neurons is inhibited by α2-adrenergic receptor agonists
Stimulation of presynaptic β2 adrenergic receptors increases slightly norepinephrine release
These agents Inhibit neurally-mediated norepinephrine released by interacting with presynaptic receptors
Neurotransmitter diffuses across the synaptic cleft and bind to post-junctional receptors causing an increase in membrane conductance (ions flow).
Three primary types of changes in conductance (permeability to ions) may occur:
Increase in Na+ (usually) or Ca+ conductance which depolarizes the membrane (EPSP), membrane potential LESS negative, towards threshold.
Increase in Cl- permeability: inward hyperpolarizing flow: membrane potential MORE negative) (IPSP)
Increase in K+ permeability; K+ leaves the cells, resulting in hyperpolarization (membrane potential is MORE negative), (IPSP)
If the EPSP is of sufficient magnitude to cause the membrane potential to reach the threshold potential, an action potential results (e.g. in skeletal or cardiac muscle).
In gland cells an EPSP may cause secretion; in other cells, an EPSP may increase the rate of spontaneous depolarization.
An IPSP (produced in neurons and smooth, but not skeletal muscle) opposes EPSPs.
Definitions: EPSP: excitatory postsynaptic potential; IPSP: inhibitory postsynaptic potential
Cholinergic: Termination of action of acetylcholine is acetylcholine hydrolysis. (acetylcholinesterase-catalazed)
If acetylcholinesterase is inhibited, the duration of cholinergic effect is increased.
Adrenergic: Termination of action of adrenergic neurotransmitters is by reuptake and diffusion away from receptors.
Amino Acids: Termination of action of amino-acid neurotransmitters is by active transport into neurons and glia
Basal, quantal release of transmitter in quantities insufficient to generate an EPSP may have other actions.
These effects may include:
Regulation of neurotransmitter biosynthetic and degradative enzymes and
Pre- and post-synaptic receptor density.