Pharmacology ANS DSA

Question 1

What is the basis of the Somatic nervous system?

ANS?

Answer 1

Consciously controlled actions –> movement, respiration, posture

unconscious actions –> CO, blood flow to various organs, digestion

Question 2

ANS subdivisions and where its located?

Answer 2

Sympathetic = fight or flight / thoracolumbar

parasympathetic = craniosacral, rest and digest

Question 3

What is the primary neurotransmitter in the parasympathetic system? What does it activate?

same for sympathetic

Answer 3

Ach –> nAChR, mAChR

NE > Epi (DA); Ach –> alpha, beta receptors, dopamine receptors, nAChr, mAChr

Question 4

What is found at all levels of the preganglionic autonomic fibers regardless of sympathetic / parasympathetic?

Answer 4

Ach that acts on nAChr

Question 5

What is the major neurotransmitter of the SNS?

Answer 5

NE

Question 6

Epinephrine is only really occurring where?

Answer 6

the synthesis of this only in the adrenal medulla and a few epinephrine-containing neuronal pathways in the brainstem

Question 7

What is dopamine and where does it act on?

Answer 7

precursor to NE and Epi

acts on the CNS and renal vascular smooth muscle

Question 8

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?

Answer 8

nAchr –> inotropic

Autonomic ganglia (excitatory) + adrenal medula (release epinephrine)

agonists are Ach and Nicotine

========

mAChR –> metabotropic

CNS, Autonomic ganglia, effector organs (excitatory and inhibitory) + sweat glands (sweat secretion)

ACh + Muscarine

Question 9

What are the two sympathetic processes that we talked about that are kind of strange?

Answer 9

Adrenal Medulla

Sweat glands

Question 10

What are the two subtypes of Nicotinic receptors?

Answer 10

Nm = skeletal muscle neuromuscular junction ligand gated channel

Nn = postganglionic cell body, dendrites, CNS –> ligand gated channel

Question 11

What are different types of muscarinic receptors?

what’s their broad classification?

Answer 11

M1 - M5

GPCR

Question 12

Which muscarinic receptors are coupled to GQ? what does this cause?

Answer 12

1,3,5

activation of phospholipase C (PLC) –> makes IP3 / DAG cascade

Question 13

What muscarinic receptors are coupled to Gi/o? What does this cause?

Answer 13

2,4

inhibition of adenylyl cyclase (AC) –> cAMP production is lowered, which activates K+ channels

Question 14

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?

Answer 14

M2 + M3

M2

M3

Question 15

What is the difference between acetylcholine production and adrenergic production?

Answer 15

instead of destruction at the end this is mostly reuptake back into the cytoplasm

Question 16

Explain the process of Tyrosine –> effector functions

Answer 16

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

Question 17

Where does the conversion of norepinephrine to epinephrine happen?

where does tyrosine become dopamine?

Dopamine to Norepinephrine?

Answer 17

mostly in the adrenal medulla

in the nerve cytoplasm

in the vesicle

Question 18

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?

Answer 18

Sodium dependent tyrosine transporter

VMAT2 –> it’s promiscuous so it doesn’t allow only dopamine. also NE, epi, serotonin

NET and DAT (transporters)

Question 19

What does Reserpine do?

Cocaine?

Answer 19

block VMAT 2

NET, increasing the concentration of NE in the synapse

Question 20

What is the termination of catecholamine signaling?

second most common?

Answer 20

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)

Question 21

What is the final product of catecholamine metabolism?

Answer 21

VMA

Question 22

What are the two main adrenergic receptors?

what are they both?

subsets of each?

what’s the 3rd not really main adrenergic receptor?

Answer 22

Alpha and beta

GPCR

alpha 1,2
beta 1,2,3

Dopamine receptor (D1-D5)

Question 23

What is Alpha 1 coupled to?

what does it respond to?

Answer 23

Gq

respond equally to epinephrine and norepinephrine

Question 24

What is alpha 2 coupled to?

what does it respond to?

Answer 24

Gi,Go

responds equally to epinephrine and norepinephrine

Question 25

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?

Answer 25

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

Question 26

What do Alpha 1 receptors generally do?

Answer 26

Stimulate contraction of all smooth muscle, if it's vascular smooth muscle it's causing vasoconstriction

Question 27

If we block alpha 1 receptors, what are we doing? what if it's in the heart?

Answer 27

blocking smooth muscle contraction, we have smooth muscle relaxation. we lead to vasodilation

Question 28

What do Beta-2 receptors generally do? what about in the heart? lungs?

Answer 28

Relax smooth muscle --> vasodilation if that smooth muscle was in the vasculature. lung tissue? relaxation and allow air to enter the lungs.

Question 29

What do muscarinic receptors generally do?

Answer 29

contract smooth muscle

Question 30

In the heart, what happens when we activate B1 receptors (sympathetic)? what about parasympathetic activity? what molecule deals with this?

Answer 30

increase heart rate, increase contractility M2 decreases heart rate and decreases contractility

Question 31

What happens in the blood vessels with regards to sympathetic activity? parasympathetic?

Answer 31

A1 causes blood vessels --> constriction via smooth muscle NO PARASYMPATHETICS

Question 32

how is the lack of parasympathetics of the blood vessels dealt with?

Answer 32

activation of NO synthase in the endothelium by M3 receptors this causes vasodilation

Question 33

What causes sympathetic response for the lung? what about parasympathetic? glands?

Answer 33

B2 --> relaxation M2 or M3 --> contraction increase in secretion by M3 in the PNS, decrease by alpha 1 + b2

Question 34

How is NO released?

Answer 34

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

Question 35

What happens in the adrenal medulla? what is the release?

Answer 35

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

Question 36

What is the baroreceptor reflex?

Answer 36

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

Question 37

What are cholinomimetic agents? cholinoceptor-blocking drugs? Sympathomimetic drugs? Adrenoceptor-blocking drugs

Answer 37

AChR agonists / Acetylcholinesterase inhibitors AChR antagonists mimic or enhance alpha and beta receptor stimulation (agonists) (enhance release or block reuptake) alpha and beta antagonists