11. DSA Autonomic Pharmacology Flashcards
What are common targets of drugs?
Proteins such as GF receptors, hormone receptor, NT receptors
DNA
What are the major NT and receptors for parasympathetic nervous system?
NT: Ach
Receptors: muscarinic (nicotinic)
What are the major NTs and receptors for sympathetic?
Norepinephrine, Epinephrine, (ACh) dopamine
Receptors adrenergic alpha/beta, nicotinic muscarinic
What is the same for all preganglionic fibers NTs in autonomic fibers?
Acetylcholine
What are the postganglionic sympathetic and parasympathetic NTs?
Symp: norepinephrine
Para: acetylcholine
Where does the sysnthesis of epinephrine occur?
mainly in the adrenal medulla
nAChR (ionotropic) and mAChR (metabotropic) are both receptors. where can each be found?
N: CNS, adrenal medulla, autonomic ganglia
FX: excitatory
M:CNS autonomic ganglia, effector organs
FX: excitatory and inhibitory
Muscarinic receptors are coupled to GPCRs which when acitvated do what?
a downstream event. either via activation of PLC (M1/3/5) or inhibition of adenylyl cyclase (M2/4)
Parasympathetic NS M2 and M3 receptors are mainly found where?
M2 are found in heart, nerves, smooth muscles
M3 are found in glands, smooth muscle and endothelium
What are the 4 main steps at the adrenergic nerve terminal?
- Synthesis (dopamine)
- Storage (dopamine converted to norepinephrine)
- Release (by AP)
- Reuptake (norepinephrine/epinerphrine instead o ACh)
How is norepinephrine made in the nerve terminal?
In cytoplasm, tyrosine becomes dopa which becomes dopamine
Dopamine transferred to vessicle where covereted to norepinephrine (can become epinephrine if in adrenal medulla
Na dependent tyrosine transporter brings it into nerve terminal cytoplasm. Once converted, transported into vesicle via vesicular monoamine transporter (VMAT-2). Then what happens?
The VMAT2 tranports anything into vesicles, NE released upon AP and CA influx, the NE transport or dopamine transporter (NET/DAT) reuptakes back into nerve terminal for reuse
What can block VMAT2?
Reserpine
What can block norepinephrine trasnporter (NET)?
Cocaine, increasing NE in synapse
What do monoamine oxidase and catechol o methyltransferase do along with NET and DAT?
Metabolize catecholamines (NE/E/Dope)
Catecholamines activate two subsets of adrenergic receptors, what are they and what kinds are there?
Alpha receptors (GPCR) types one and two Beta receptors (GPCR) types one two and three
Whats the one thing to remember about alpha-1 receptors?
Stimulates contraction of all smooth muscle
Vasuclar smooth muscle-vasoconstriction
What is the one thing to remember about beta2receptors?
relax smooth muscle, vasodilation
What is the one thing to remember about muscarinic receptors?
contract smooth muscle (different signal than alpha 1 receptors)
The key thing to remember in autonomics is that smooth muscles in blood vessels have no parasympathetic innervation, however the endothelium does what?
The endothelium via M3 activates NO synthase in response to ACh which acts as a vasodialtor, to oppose the sympathetic A1 response and vasoconstriction
Activation of mAChRs on endothelial cells causes production and release of endothelium-derived relaxing factor EDRF, also known as nitric oxide (NO). How does this occur?
ACh activates M3 receptors in intact endothelial cells, increasing Ca2+ levels, which increases NO, which diffuses to smooth muscles and causes vasodilation
Pheylphrine is an A1 receptor agonist. Which increases?
Increases blood pressure via baroreceptor, increasing parasympathetic NS, 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
