Pharmacology ANS DSA Flashcards
What is the basis of the Somatic nervous system?
ANS?
Consciously controlled actions –> movement, respiration, posture
unconscious actions –> CO, blood flow to various organs, digestion
ANS subdivisions and where its located?
Sympathetic = fight or flight / thoracolumbar
parasympathetic = craniosacral, rest and digest
What is the primary neurotransmitter in the parasympathetic system? What does it activate?
same for sympathetic
Ach –> nAChR, mAChR
NE > Epi (DA); Ach –> alpha, beta receptors, dopamine receptors, nAChr, mAChr
What is found at all levels of the preganglionic autonomic fibers regardless of sympathetic / parasympathetic?
Ach that acts on nAChr
What is the major neurotransmitter of the SNS?
NE
Epinephrine is only really occurring where?
the synthesis of this only in the adrenal medulla and a few epinephrine-containing neuronal pathways in the brainstem
What is dopamine and where does it act on?
precursor to NE and Epi
acts on the CNS and renal vascular smooth muscle
What two AchRs are we talking about for neuronal and peripheral subtypes?
what are these also called?
where are they found / function with each location?
What are their agonists?
nAchr –> inotropic
Autonomic ganglia (excitatory) + adrenal medula (release epinephrine)
agonists are Ach and Nicotine
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mAChR –> metabotropic
CNS, Autonomic ganglia, effector organs (excitatory and inhibitory) + sweat glands (sweat secretion)
ACh + Muscarine
What are the two sympathetic processes that we talked about that are kind of strange?
Adrenal Medulla
Sweat glands
What are the two subtypes of Nicotinic receptors?
Nm = skeletal muscle neuromuscular junction ligand gated channel
Nn = postganglionic cell body, dendrites, CNS –> ligand gated channel
What are different types of muscarinic receptors?
what’s their broad classification?
M1 - M5
GPCR
Which muscarinic receptors are coupled to GQ? what does this cause?
1,3,5
activation of phospholipase C (PLC) –> makes IP3 / DAG cascade
What muscarinic receptors are coupled to Gi/o? What does this cause?
2,4
inhibition of adenylyl cyclase (AC) –> cAMP production is lowered, which activates K+ channels
What are the muscarinic receptors that are part of the organs?
which one for the heart?
which one for the smooth muscle for the rest of the body?
M2 + M3
M2
M3
What is the difference between acetylcholine production and adrenergic production?
instead of destruction at the end this is mostly reuptake back into the cytoplasm
Explain the process of Tyrosine –> effector functions
Tyrosine in –> made into Dopamine –> shuttled into the vesicle through VMAT2 –> made into NE –> AP causes membrane fusion and NE spills out –> activates alpha and beta receptors on another cell
Where does the conversion of norepinephrine to epinephrine happen?
where does tyrosine become dopamine?
Dopamine to Norepinephrine?
mostly in the adrenal medulla
in the nerve cytoplasm
in the vesicle
How does Tyrosine get into the cell?
What gets dopamine into the vesicle? what’s to note about this?
after the release, what gets NE back into the nerve terminal and DA back into the terminal?
Sodium dependent tyrosine transporter
VMAT2 –> it’s promiscuous so it doesn’t allow only dopamine. also NE, epi, serotonin
NET and DAT (transporters)
What does Reserpine do?
Cocaine?
block VMAT 2
NET, increasing the concentration of NE in the synapse
What is the termination of catecholamine signaling?
second most common?
reuptake into nerve terminals is the most common (NET or DAT then stored into vesicles by VMAT2)
metabolism –> by Monoamine oxidase (MAO) and Catechol-O-methyltransferase (COMT)
What is the final product of catecholamine metabolism?
VMA
What are the two main adrenergic receptors?
what are they both?
subsets of each?
what’s the 3rd not really main adrenergic receptor?
Alpha and beta
GPCR
alpha 1,2
beta 1,2,3
Dopamine receptor (D1-D5)
What is Alpha 1 coupled to?
what does it respond to?
Gq
respond equally to epinephrine and norepinephrine
What is alpha 2 coupled to?
what does it respond to?
Gi,Go
responds equally to epinephrine and norepinephrine
What do all beta receptors couple to? what does this do?
what activates B1? B2? B3?
what’s the only beta receptor that we don’t have drugs against?
Gs –> increases adenylyl cyclase which increases cyclic amp leading to L-type Ca2+ channel opening
B1 = Epi = NE B2 = Epi >> NE B3 = NE > Epi
B3
What do Alpha 1 receptors generally do?
Stimulate contraction of all smooth muscle, if it’s vascular smooth muscle it’s causing vasoconstriction
If we block alpha 1 receptors, what are we doing? what if it’s in the heart?
blocking smooth muscle contraction, we have smooth muscle relaxation.
we lead to vasodilation
What do Beta-2 receptors generally do?
what about in the heart? lungs?
Relax smooth muscle –> vasodilation if that smooth muscle was in the vasculature.
lung tissue? relaxation and allow air to enter the lungs.
What do muscarinic receptors generally do?
contract smooth muscle
In the heart, what happens when we activate B1 receptors (sympathetic)?
what about parasympathetic activity? what molecule deals with this?
increase heart rate, increase contractility
M2 decreases heart rate and decreases contractility
What happens in the blood vessels with regards to sympathetic activity?
parasympathetic?
A1 causes blood vessels –> constriction via smooth muscle
NO PARASYMPATHETICS
how is the lack of parasympathetics of the blood vessels dealt with?
activation of NO synthase in the endothelium by M3 receptors
this causes vasodilation
What causes sympathetic response for the lung?
what about parasympathetic?
glands?
B2 –> relaxation
M2 or M3 –> contraction
increase in secretion by M3 in the PNS, decrease by alpha 1 + b2
How is NO released?
it needs an intact epithelium
Acetylcholine activates mAChR which increases calcium levels which results in the production of NO. NO then is the key component that causes vasodilation
What happens in the adrenal medulla?
what is the release?
ACh from the preganglionic fibers triggers the release of EPI and NE by binding to the Nn AChRs and produces a local depolarization
80% Epi
20% NE
What is the baroreceptor reflex?
Alpha 1 receptor agonist. causes constriction –> vasoconstriction –> increases blood pressure
the baroreceptor recognizes the increase in pressure and increases parasympathetic nervous system tone and decreases SNS tone.
histamine –> causes decrease in blood pressure
baroreceptor does the opposite
What are cholinomimetic agents?
cholinoceptor-blocking drugs?
Sympathomimetic drugs?
Adrenoceptor-blocking drugs
AChR agonists / Acetylcholinesterase inhibitors
AChR antagonists
mimic or enhance alpha and beta receptor stimulation (agonists) (enhance release or block reuptake)
alpha and beta antagonists
