EXAM #1: ANS PHARMACOLOGY I Flashcards
Where do the nerve terminals of the SNS originate?
T1-L2
“Thoracolumbar”
Where do the nerve terminals of the PNS originate?
Cranial: III, VII, IX, X
Sacral: S2, 3, 4
“Craniosacral”
What are the two components of the enteric division of the ANS?
1) Myenteric plexus
- Auerbach’s
2) Submucosal plexus
- Meissner’s
Where is the myenteric plexus located? What is the alternate name for this plexus?
Between the external longitudinal muscle and deeper circular muscle
Auerbach’s Plexus
Where is the submucosal plexus located? What is the alternate name for this plexus?
Between the circular muscularis muscoe
Meissner’s Plexus
What is the function of the myentric plexus?
Motility
What is the function of the submucosal plexus?
Ion and fluid transport
What is the principle of “dual innervation?”
- Most organs receive SNS and PNS innervation
- Opposing actions
**Note that though opposing actions, these are not ANTAGONISTIC*
What organs only have SNS innervation?
1) Hair follicles
2) Thermoregulatory sweat glands
3) Liver
4) Adrenal glands
5) Kidneys
In what organs does the SNS and PNS have similar rather than opposing effects?
Salivary glands
What NT is released by all pre-ganglionic fibers?
ACh
What NT is released by post-ganglionic fibers of the SNS?
NE
“Adrenergic”
What NT is released by post-synaptic SNS fibers on thermoregulatory sweat glands?
ACh
Note that this is an EXCEPTION
What type of ACh receptor is located on the ANS ganglia?
Nicotinic ACh receptor
What NT is released by post-synaptic PNS fibers?
ACh
What NT is released from post-synaptic SNS fibers acting on renal vascular smooth muscle?
DA
What is a homotropic interaction?
- This describes a NT binding to an autoreceptor on the pre-synaptic nerve terminal from which it is being released
- Action is to INHIBIT secretion of that NT
What is the effect of blocking the autoreceptor in a homotropic interaction?
Dramatic increase of NT released from the nerve fiber
What is a heterotropic interaction?
This is when one NT affects the release of another NT via interactions on heteroreceptors
What is withdrawal rebound hyperactivity/ disuse hyperactivity?
Sustained block of ganglionic transmission leads to increased sensitivity of target organs
What are the mechanisms of withdrawal rebound hyperactivity/ disuse hyperactivity?
1) Receptor proliferation
2) Loss of transmitter removal mechanisms
3) Increased post-junctional responsiveness i.e. increased sensitivity of the receptor
What is a clinical example of withdrawal rebound hyperactivity?
Rebound HTN following withdrawal of adrengeric receptor blockers
What is cotransmission?
Release of more than one NT from a neuron upon stimulation
E.g. NE and NPY are released from separate vesicles upon stimulation
What are the five steps of NT function that provide targets for pharmacologic therapy?
1) Synthesis
2) Storage
3) Release
4) Receptor effects
5) Termination action
How does choline get from the ECF into the neuron for ACh synthesis?
Na+ dependent Choline Transporter (CHT)
What drug blocks CHT?
Hemicholiniums
Once ACh is synthesized, how is it stored in vesicles?
Transport into the storage vesicle via “vesicle associated transporter” (VAT)
What drug is a VAT blocker?
Vesamicol
What is the mechanism of action for the Botulinum toxin?
- Botulinum impaires ACh vesicle and nerve terminal fusion/release
- Specifically, removes 2 amino acids from the SNARE fusion proteins
What enzyme degrades ACh?
Acetylcholinesterase
What drug blocks Acetylcholinesterase?
Neostigmine
What are the two types of ACh receptors?
1) Nicotinic
2) Muscarinic
What type of receptor is a Muscarinic receptor?
G-protein coupled receptor
What type of receptor is a Nicotinic receptor?
Na+ channel
What receptors control secretion of aqueous humor?
Adrenergic receptors
What muscles in the eye have M3 receptors?
- Sphincter muscle
- Ciliary muscle
What does activation of M3 receptors in the eye cause?
- Miosis and opening the Canal of Schlemm (sphincter)
- Spasm of accommodation for near vision (ciliary)
*****Opens the canal of schlemm to decrease intra-ocular pressure
What type of muscarinic receptor is located on the heart?
M2
What is the effect of M2 activation in the heart? Specifically, what happens at the: SA node, AV node, Atrial muscle, and Ventricular muscle?
SA node= negative chronotrope
AV node= decreased conduction velocity (negative dromotrope)
Atrial muscle= decreased atrial contraction
Ventricular muscle= decreased ventricular contraction
Generally inhibitory*
What type of ACh receptors are located in the lung?
M3
What is the effect of M3 activation in the lung? Specifically, what happens to the Brconhi and Bronchioles/ Bronchiolar submucusal glands?
Brconhi and Bronchioles= Contraction leading to bronchospasm
Bronchiolar submucusal glands= Secretion lead to a narrower lumen
What type of ACh receptor is located in the stomach?
M3
What is the effect of M3 stimulation in the stomach?
Increased motility and cramps
What type of ACh receptor is located in the glands of the GI tract?
M1 and M3
What is the effect of ACh stimulation in the glands of the GI system?
Secretion
What type of ACh receptor is located in the intestines?
M3
What is the effect of ACh stimulation in the intestine?
Contraction leading to diarrhea and involuntary defection
What PNS receptor types control gastric acid secretion?
M1 and M3
What is the role of M3 receptors in gastric acid secretion?
- M3 receptors are located on parietal cells
- ACh stimulation of M3 receptors on parietal cells directly leads to the secretion of gastric acid
What is the role of M1 receptors in gastric acid secretion?
- M1 receptors are located on ECL cells
- ECL cells release histamine
- Histamine is a key simulator of acid secretion
What type of drugs are cimetidine or ranitidine? What is their effect on gastric acid secretion?
- Both are H2R antagonists
- Thus, they block histamine induced acid secretion AND acid secretion following a normal meal
What are the muscles of the bladder? What are their functions?
- Detrusor= contraction
- Trigone= relaxation
What ACh receptor type is located in the bladder?
M3
What is the effect of PNS stimulation of the bladder?
1) Contraction of the detrusor
2) Relax trigone and sphincter
3) Voiding and potentially urinary incontinence
What type of muscarinic receptors are located in blood vessels?
M3
What is the effect of muscarinic receptor activation in blood vessels?
Generally, vasorelaxation
Specifically,
1) Increased intracelluar Ca++
2) Activation of endothelial nitric oxide synthase
3) Production of NO
4) NO diffuses to vasular smooth muscle
5) Stimulation of guanylyl cyclase
6) Increased cGMP
7) cGMP inhibits Ca++ influx
8) VASORELAXATION
What is the difference between M3 receptor activation in intact endothelial cells vs. damaged endothelium?
Intact= Vasodilation
Damaged= Vasoconstriction
This is b/c the increase in Ca++ is unopposed by NO that would normally be released by the intact endothelium*
What type of muscarinic receptors are located in the sphincters?
M3
What is the effect of ACh on sphincters? What is the exception?
- Relaxation
Except contraction of LES*
What type of muscarinic receptor is located on the glands?
M3
What is the effect of ACh stimulation of the glands?
Secretion:
- Sweat
- Salviation
- Lacrimation
What type of ACh receptor is located in the skeletal neuromuscular junction?
Nicotinic AChR (Nm)
What type of receptor is the NAChR? What is the result of ACh binding to the NAChR?
Na+ channel
1) Na+ influx causes an EPSP
2) EPSP depolarizes the muscle membrane
3) Muscle membrane depolariation causes an action potential that triggers muscle contraction
What ACh receptors are located on the adrenal medulla?
NAChR (Nn)
What is the response of the adrenal medulla to stimulation with ACh?
Secretion of NE and Epi
What ACh receptors are located on ALL autonomic ganglia?
NAChR (Nn)
What is the net response of the autonomic ganglia to ACh?
Stimulation
Note that the net effect is dependent on whether the SNS or PNS dominates
