Autonomic Pharmacology Principles Flashcards
On what basis is the ANS divided? Why is this important?
the division is entirely anatomical, which means that the two do overlap with regards to neurochemistry at times
What are the various divisions of the ANS?
- the sympathetic nervous system, including the adrenal medulla
- the parasympathetic nervous system
- the enteric nervous system
Describe the basic anatomy of the sympathetic nervous system.
- it has thoracolumbar outputs
- shorter preganglionic fibers terminate in ganglia called the paravertebral chains)
- longer postganglionic fibers innervate peripheral tissues
- furthermore, it is important to remember that the sympathetic system, unlike the parasympathetic, is diffuse, meaning that one preganglionic fiber may innervate several postganglionic fibers
How does the adrenal medulla connect to the autonomic nervous system?
- it can be equated to a postganglionic sympathetic neuron
- it receives sympathetic preganglionic fibers and releases epinephrine and norepinephrine into the blood
Describe the basic anatomy of the parasympathetic nervous system.
- it has craniosacral outputs
- long preganglionic fibers terminate in parasympathetic ganglia
- short postganglionic fibers originate in those ganglia and innervate organs
- these connections tend to be more discrete than those of the sympathetic system, meaning that, for the most part, there is a 1:1 connection between pre and postganglionic fibers
Describe the basic anatomy of the enteric nervous system.
- it innervates the walls of the GI system, forming the myenteric plexus and the sub mucous plexus (aka plexus of Meissner)
- it receives parasympathetic preganglionic fibers and sympathetic postganglionic fibers
Which division of the autonomic nervous system has diffuse connections? What does this mean?
a single sympathetic preganglionic fiber may innervate numerous postganglionic fibers, there isn’t a 1:1 relationship as there is in the more “discrete” PNS
What NT system mediates the synapse between pre- and postganglionic sympathetic fibers? What about those the parasympathetic system?
both the SNS and PNS utilize ACh and nicotinic receptors at the preganglionic-postganglionic synapse
Postganglionic sympathetic neurons utilize what NT system?
most utilize adrenergic receptors, however, a few utilize acetylcholine and some, mostly in the CNS, utilize DA
Postganglionic parasympathetic neurons utilize what NT system?
most utilize acetylcholine, however, a few utilize nitric oxide or peptide neurotransmitters
What NT mediates the NMJ?
acetylcholine
Most autonomic nerves release a co-transmitter in addition to ACh or NE. What are these co-transmitters? Why are they released?
- vasointestinal peptide alongside ACh
- neuropeptide Y with NE
- they provide long lasting, slowly developing activation of the postsynaptic target tissue
Describe acetylcholine synthesis, release, and catabolism.
- acetyl-Co is synthesized in the mitochondria and choline is transported into the neuron from the synaptic cleft (recycled)
- choline acetyltransferase (ChAT) synthesizes acetylcholine
- ACh is then transported into a synaptic vesicle via vesicular acetyl transporter (VAT)
- an action potential triggers a calcium influx, which induces vesicular fusion and NT release
- in the synaptic cleft, ACh is catabolized by AChE into choline and acetate
- the choline is recycled by the presynaptic cell
What is butyrylcholinesterase?
a non-neuronal AChE expressed by RBCs that essentially eliminate all ACh that reaches the blood stream
Describe adrenergic synthesis, release, and catabolism.
- tyrosine hydroxylase converts tyrosine to dopa in the rate-limiting step
- dopa is then converted to dopamine by dopa decarboxylase
- dopamine is packaged into a synaptic vesicle by VMAT where it is converted to NE by dopamine-B-hydroxylase
- an action potential triggers a calcium influx, which induces vesicular fusion and NT release
- it is primarily cleared form the synaptic cleft via uptake 1, which transports it back into the presynaptic terminal, and uptake 2, which transports it into the postsynaptic terminal,
- MAO and COMT are responsible for turnover and catabolism, generating the end product VMA (3-methoxy-4-hydroxymandelic acid), which undergoes renal excretion
What is VMA (aka 3-methoxy-4-hydroxymandelic acid) and how is it clinically useful?
it is the end product of NE catabolism by MAO and COMT, which is excreted in the urine and can be used as a measure of sympathetic activity
What class of receptor is the muscarinic acetylcholine receptor?
it is a GPCR
What class of receptor is the nicotinic acetylcholine receptor?
it is an ion channel
What class of receptor are the adrenergic receptors?
they are all GPCRs
What are nonadrenergic, noncholinergic neurons? Where are they important?
- neurons in the ANS that are neither cholinergic nor adrenergic
- instead they primarily use NO, peptides, and purines
- they are particularly important in the GI and GU systems
Generally speaking, what are the functions of the parasympathetic and sympathetic nervous systems?
- the PNS produces energy conservation (slowing of heart rate, stimulation of digestive activity)
- the SNS is recruited at times of stress (cardiac stimulation, increased blood glucose, cutaneous vasoconstriction)
Is the parasympathetic or sympathetic system responsible for most of the underlying tone at most organs? Where is this not true?
- the PNS is responsible for the underlying tone of most organs
- the primary exception is peripheral vasculature, which has only sympathetic tone and does not receive any innervation by the PNS
Describe the ANS innervation of endothelial cells.
- the entirety of their underlying tone is sympathetic because they receive no parasympathetic innervation
- however, they do express muscarinic cholinergic receptors, which can be activated pharmacologically but don’t experience endogenous activation, resulting in NO release and vasodilation
What is the function of muscarinic cholinergic receptors found on endothelial cells?
while they have no endogenous activation, they can be activated pharmacologically, which causes the release of NO and subsequent vasodilation
Describe autonomic control of cardiovascular function, particularly their mechanism and effect on MAP.
- the sympathetic system has the biggest impact on MAP by increasing peripheral vascular resistance
- the parasympathetic system functions to reduce MAP by reducing the heart rate, which lowers the cardiac output
- the sympathetic system, however, can also increase contractile force and thus stroke volume, while also increase venous tone and thus increasing venous return
Describe autonomic control of the eye. What receptor is expressed by each important structure?
- the radial muscle has alpha-adrenergic receptors and increases the diameter of the pupil
- the secretory epithelium of the ciliary body has beta-adrenergic receptors and is stimulated to form more aqueous humor
- the sphincter muscle has muscarinic receptors and reduces the diameter of the pupil
- the ciliary muscle has muscarinic receptors and contracts, rounding the pupil for near vision and enhancing the outflow of aqueous humor via the canal of Schlemm
How can you use the autonomic innervation of the eye to treat glaucoma?
- an beta-adrenergic receptor inhibitor will reduce secretion of aqueous humor
- a muscarinic agonist will increase the outflow of aqueous humor via the canal of Schlemm
What are alpha2 receptors?
presynaptic receptors on postganglionic sympathetic neurons that tend to inhibit the release of NE
Presynaptic auto receptors tend to have what function?
they tend to inhibit vesicular release
