DSA: Autonomic Pharmocology

Question 1

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 __________.

Answer 1

Oppose each other.

Question 2

ANS actions

Answer 2

CO

Blood flow

Digestion

Question 3

Parasympathetic NS

NT: _____

Receptors: _____ and _____

Answer 3

NT: ACh

Receptors: nAChR and mAChR

Question 4

Sympathetic NS

NT: _________

Receptors: _________

Answer 4

NT: ACh, NE*, EPI, DA,

Receptors: Adrenergic (alpha and beta), DA, nAChR and mAChR

Question 5

What is the primary mediator of all ganglionic NSs?

Answer 5

ACh

Question 6

What is the major NT of the PNS?

Do post-ganglionic NT sympathetic fibers release them?

Answer 6

ACh

Released by a few post-ganglionic sympathetic fibers onto sweat glands.

Question 7

_________ is the major NT of the sympathetic NS.

Answer 7

NE

Question 8

________ is released by a vast majority of the post-ganglionic sympathetic fibers.

Answer 8

NE

Question 9

Where is EPI made?

Answer 9

1. Adrenal medulla
2. Few pathways of the brainstem

Question 10

DA is the precursor to what?

What does it act on.

Answer 10

EPI and NE

Acts on CNS and renal vascular muscle

Question 11

nAChR (ionotropic receptors)

1. Found in:
2. Fx:
3. Agonists:

Answer 11

1. Found in: CNS, autonomic ganglia, adrenal medulla
2. Fx: Excitatory and causes the release of catecholamines from the adrenal medulla via the sympathetic NS
3. Agonists: ACh and nicotine

Question 12

mAChR (metabotropic receptors)

1. Found in:
2. Fx:
3. Agonists:

Answer 12

mAChR (metabotropic receptors)

1. Found in: CNS, autonomic ganglia, effector organs such as cardiac, smooth muscle, glands), sweat glands
2. Fx: Excitatory and inhibitory; causes sweat secretion from sweat glands
3. Agonists: ACh and muscarine

Question 13

M1 receptors

Located:

Structure:

Fx:

Answer 13

M1 receptors

Located: CNS and ganglia

Structure: Gq/11 GCPR

Fx: + PLC –> + IP3 and DAG

Question 14

M2 receptors

Located:

Structure:

Fx:

Answer 14

Located: heart, nerves, smooth muscle

Structure: Gi GCPR

(-) AC–> (-) cAMP production–> activates K+ channels

Question 15

M3 receptors

Located:

Structure:

Fx:

Answer 15

M3

Located: Glands, smooth muscle, endothelium

Structure: Gq GCPR

+PLC–> + IP3 and DAG

Question 16

M4 receptors

Located:

Structure:

Fx:

Answer 16

Located: CNS

Stucture Gi/o GCPR

(-) AC–> (-) cAMP production–> activates K+ channels

Question 17

M5 receptors

Located:

Structure:

Fx:

Answer 17

Located: CNS

Structure: Gq GCPR

+PLC–> + IP3 and DAG

Question 18

Primary M receptors in the parasympathetic NS?

Answer 18

M2 and M3

Question 19

How is NE made in the nerve terminal?

Answer 19

1. Tyrosine enters nerve cytoplasm via Na+ dependent tyrosine transporter:
2. Tyrosine–> DOPA–> Dopamine
3. 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

Question 20

How is NE released from vesicle?

Answer 20

AP and influx of Ca2+

Question 21

Termination of catecholamines?

Answer 21

• 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

Question 22

Reserpine

Answer 22

blocks VMAT-2; prevents DA from getting into vesicles.

Question 23

Cocaine

Answer 23

blocks NET; increases NE in synapses

Question 24

Catecholamines activate 2 subsets of adrenergic receptors; what are they?

Answer 24

Alpha (1 and 2) and beta1, 2 and 3, which are GCPRs

Question 25

Binding onto alpha-1 receptors causes what?

Answer 25

Binding causes: 1. Contraction of all smooth muscle 2. If vascular--\> vasoconstriction

Question 26

Binding onto **beta-2 receptors** causes what?

Answer 26

**Relax smooth muscle--\> vasodilation**

Question 27

Binding to muscarinic receptors causes?

Answer 27

Contraction of muscle

Question 28

Primary receptors in the **heart**: B1 receptors Sympathetic activation of B1 receptors--\> \_\_\_\_\_\_\_\_\_\_\_\_ Parasympathetic activation of M2 receptors--\> \_\_\_\_\_\_\_\_\_

Answer 28

Sympathetic activation of B1 receptors: **increase HR, contraction, conduction velocity** Parasympathetic activation (primary receptor is M2): **opposite**

Question 29

What receptors do we bind to on blood vessels to cause vasoconstriction? How do we vasodilate the BV?

Answer 29

A1 ## Footnote 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.

Question 30

**Lungs** Sympathetic activation of **B2**--\> \_\_\_\_\_\_\_\_\_\_ Parasympathetic activation of **M2/M3**--\> \_\_\_\_\_\_\_\_\_\_

Answer 30

**Lungs** Sympathetic activation of **B2**--\> bronchodilation Parasympathetic activation of **M2/M3**--\> contraction

Question 31

**Bronchial glands** Sympathetic activation of **alpha-1**--\> \_\_\_\_\_\_\_\_ Sympathetic activation of **beta-2**--\> \_\_\_\_\_\_\_\_\_ Paraympathetic activation of **M2 and M3**--\> \_\_\_\_\_\_\_

Answer 31

Bronchial glands Sympathetic activation of **alpha-1**--\> decrease secretion Sympathetic activation of **beta-2**--\> increase secretion Paraympathetic activation of **M2 and M3**--\> stimulation

Question 32

Pheylephrine

Answer 32

A1 receptor agonist. Increases BP via baroreceptor; increasing parasympathetic NS and decreasing sympathetic NS

Question 33

Histamine causes a decrease in blood pressure via baroreceptor reflex, which leads to?

Answer 33

a decrease in para NS activation and increase in sympathetic NS activation

Question 34

What are cholinomimetic agents?

Answer 34

drugs that mimic ACh (AChR agonists or AChE inhibitors.

Question 35

What are cholinoceptor-blocking drugs?

Answer 35

AChR antagonists

Question 36

What are sympathomimetic agents?

Answer 36

drugs that mimic or enhance a/b receptor stimulation

Question 37

What are adrenoceptor blocking drugs?

Answer 37

a/b receptor antagonists