DSA: Autonomic Pharmocology Flashcards
NS can be separated into a somatic NS (consciously controlled actions) and ANS (unconscious actions), such as CO, blood flow, digestion.
ANS can then be divided into sympathetic (thoracolumbar; fight or flight) or parasympathetic (craniosacral; rest and digest).
The actions of these subdivisions generally __________.
Oppose each other.
ANS actions
CO
Blood flow
Digestion
Parasympathetic NS
NT: _____
Receptors: _____ and _____
NT: ACh
Receptors: nAChR and mAChR
Sympathetic NS
NT: _________
Receptors: _________
NT: ACh, NE*, EPI, DA,
Receptors: Adrenergic (alpha and beta), DA, nAChR and mAChR
What is the primary mediator of all ganglionic NSs?
ACh
What is the major NT of the PNS?
Do post-ganglionic NT sympathetic fibers release them?
ACh
Released by a few post-ganglionic sympathetic fibers onto sweat glands.
_________ is the major NT of the sympathetic NS.
NE
________ is released by a vast majority of the post-ganglionic sympathetic fibers.
NE
Where is EPI made?
- Adrenal medulla
- Few pathways of the brainstem
DA is the precursor to what?
What does it act on.
EPI and NE
Acts on CNS and renal vascular muscle
nAChR (ionotropic receptors)
- Found in:
- Fx:
- Agonists:
- Found in: CNS, autonomic ganglia, adrenal medulla
- Fx: Excitatory and causes the release of catecholamines from the adrenal medulla via the sympathetic NS
- Agonists: ACh and nicotine
mAChR (metabotropic receptors)
- Found in:
- Fx:
- Agonists:
mAChR (metabotropic receptors)
- Found in: CNS, autonomic ganglia, effector organs such as cardiac, smooth muscle, glands), sweat glands
- Fx: Excitatory and inhibitory; causes sweat secretion from sweat glands
- Agonists: ACh and muscarine
M1 receptors
Located:
Structure:
Fx:
M1 receptors
Located: CNS and ganglia
Structure: Gq/11 GCPR
Fx: + PLC –> + IP3 and DAG
M2 receptors
Located:
Structure:
Fx:
Located: heart, nerves, smooth muscle
Structure: Gi GCPR
(-) AC–> (-) cAMP production–> activates K+ channels
M3 receptors
Located:
Structure:
Fx:
M3
Located: Glands, smooth muscle, endothelium
Structure: Gq GCPR
+PLC–> + IP3 and DAG
M4 receptors
Located:
Structure:
Fx:
Located: CNS
Stucture Gi/o GCPR
(-) AC–> (-) cAMP production–> activates K+ channels
M5 receptors
Located:
Structure:
Fx:
Located: CNS
Structure: Gq GCPR
+PLC–> + IP3 and DAG
Primary M receptors in the parasympathetic NS?
M2 and M3
How is NE made in the nerve terminal?
- Tyrosine enters nerve cytoplasm via Na+ dependent tyrosine transporter:
- Tyrosine–> DOPA–> Dopamine
- Dompamine–> vesicle via VMAT-2, where it is converted to NE.
VMAT-2 is promiscuous; it can transport NE, EPI, DA and 5HT into vesicles
If in the adrenal medulla, NE–> EPI
How is NE released from vesicle?
AP and influx of Ca2+
Termination of catecholamines?
- Reuptake: occurs via NET and DAT. Catecholamines are then stored in vesicles via VMAT-2
- Metabolism via MAO and COMT (catechol-O-methyltransferase).
- *Catecholamines are not broken down by degradative enzymes
Reserpine
blocks VMAT-2; prevents DA from getting into vesicles.
Cocaine
blocks NET; increases NE in synapses
Catecholamines activate 2 subsets of adrenergic receptors; what are they?
Alpha (1 and 2) and beta1, 2 and 3, which are GCPRs
Binding onto alpha-1 receptors causes what?
Binding causes:
- Contraction of all smooth muscle
- If vascular–> vasoconstriction
Binding onto beta-2 receptors causes what?
Relax smooth muscle–> vasodilation
Binding to muscarinic receptors causes?
Contraction of muscle
Primary receptors in the heart: B1 receptors
Sympathetic activation of B1 receptors–> ____________
Parasympathetic activation of M2 receptors–> _________
Sympathetic activation of B1 receptors: increase HR, contraction, conduction velocity
Parasympathetic activation (primary receptor is M2): opposite
What receptors do we bind to on blood vessels to cause vasoconstriction?
How do we vasodilate the BV?
A1
Parasympathetics do not innervate smooth vessels on blood vessels. Thus, mAchR receptors and nAchR are not found on the smooth muscle of the BV. However, blood vessels can relax in response to parasympathetic release of ACh as long as the endothelium is intact.
-Activation of mAChR on endothelial cells causes the production of endothelium-derived relaxing factor (EDRF), also known as Nom in response to ACh release from intact endothelium.
Lungs
Sympathetic activation of B2–> __________
Parasympathetic activation of M2/M3–> __________
Lungs
Sympathetic activation of B2–> bronchodilation
Parasympathetic activation of M2/M3–> contraction
Bronchial glands
Sympathetic activation of alpha-1–> ________
Sympathetic activation of beta-2–> _________
Paraympathetic activation of M2 and M3–> _______
Bronchial glands
Sympathetic activation of alpha-1–> decrease secretion
Sympathetic activation of beta-2–> increase secretion
Paraympathetic activation of M2 and M3–> stimulation
Pheylephrine
A1 receptor agonist.
Increases BP via baroreceptor; increasing parasympathetic NS and decreasing sympathetic NS
Histamine causes a decrease in blood pressure via baroreceptor reflex, which leads to?
a decrease in para NS activation and increase in sympathetic NS activation
What are cholinomimetic agents?
drugs that mimic ACh (AChR agonists or AChE inhibitors.
What are cholinoceptor-blocking drugs?
AChR antagonists
What are sympathomimetic agents?
drugs that mimic or enhance a/b receptor stimulation
What are adrenoceptor blocking drugs?
a/b receptor antagonists
