Pharmacology: Block 2: Neuroeffector Systems 2, Organ Responses To Autonomic Stimulation

Front 1

Primary innervation of the GI tract

Back 1

PSNS

Front 2

Tone of the heart at rest

Back 2

PSNS

Front 3

Tone of the heart during exertion

Back 3

SNS

Front 4

What is the innervation of some sweat glands in the skin? What receptors are involved?

Back 4

The sweat glands (and some blood vessels) in the skin are innervated by cholinergic sympathetic fibers. The M2, M3 receptors are involved.

Front 5

c/c the SNS and the PSNS effects on the three muscles of the eye.

Back 5

Radial muscle iris: The SNS constricts the radial muscle iris via an α1 --> Gq --> IP3, DAG response.

Sphincter muscle iris: The PSNS contracts the sphincter muscle iris producing miosis via a M3 --> Gq --> IP3, DAG response.

Ciliary muscle: The SNS relaxes the ciliary muscle via a β receptor --> Gs --> Adenyl cyclase up response. This adjusts the lens for far vision This response is weak compared to the PSNS response (the SNS tone is not high).

The PSNS constricts the ciliary muscle via a M3 --> Gq --> IP3, DAG response. This adjusts the lens for near vision (accomodation)

Front 6

What drugs will have effects on the eye? (2 main groups, each with 2 divisions)

Back 6

1. Muscarinic agonists (bethanechol) will produce constriction and near-vision.

2. Muscarinic antagonists (atropine) will produce dilation and far-vision.

3. α1 agonists (phenylephrine) will produce dilation.

4. α1 anatgonists (prazosin) will produce constriction.

Front 7

Contraction of the ciliary muscle has what effect on the tension on the lens?

Back 7

It decreases the tension on the lens. Allows to see things up close (accomodation).

Front 8

What is the response of the bronchial smooth muscle and the bronchiole glands to autonomic stimulation?

Back 8

Bronchial smooth muscle:
SNS: β2 receptors --> Gs --> relaxation (weak response)
PSNS: M3 receptors --> Gq --> IP3, DAG --> contraction.

Bronchial glands:
PSNS: M3 receptors --> Gq --> IP3, DAG --> increased Ca release from the SR --> increased secretion from gland cells via Ca-gated K and Cl channels.

Front 9

The autonomic innervation of the lungs is primarily what?

Back 9

PSNS.

Front 10

PSNS has what effect on the airways?

SNS has what effect on the airways?

Back 10

Constricts the smooth muscles of the airway.

SNS only weakly relaxes the airways.

Front 11

Primary innervation of the GI tract

Back 11

PSNS

Front 12

Tone of the heart at rest

Back 12

PSNS

Front 13

Tone of the heart during exertion

Back 13

SNS

Front 14

What is the innervation of some sweat glands in the skin? What receptors are involved?

Back 14

The sweat glands (and some blood vessels) in the skin are innervated by cholinergic sympathetic fibers. The M2, M3 receptors are involved.

Front 15

c/c the SNS and the PSNS effects on the three muscles of the eye.

Back 15

Radial muscle iris: The SNS constricts the radial muscle iris via an α1 --> Gq --> IP3, DAG response.

Sphincter muscle iris: The PSNS contracts the sphincter muscle iris producing miosis via a M3 --> Gq --> IP3, DAG response.

Ciliary muscle: The SNS relaxes the ciliary muscle via a β receptor --> Gs --> Adenyl cyclase up response. This adjusts the lens for far vision This response is weak compared to the PSNS response (the SNS tone is not high).

The PSNS constricts the ciliary muscle via a M3 --> Gq --> IP3, DAG response. This adjusts the lens for near vision (accomodation)

Front 16

What drugs will have effects on the eye? (2 main groups, each with 2 divisions)

Back 16

1. Muscarinic agonists (bethanechol) will produce constriction and near-vision.

2. Muscarinic antagonists (atropine) will produce dilation and far-vision.

3. α1 agonists (phenylephrine) will produce dilation.

4. α1 anatgonists (prazosin) will produce constriction.

Front 17

Contraction of the ciliary muscle has what effect on the tension on the lens?

Back 17

It decreases the tension on the lens. Allows to see things up close (accomodation).

Front 18

What is the response of the bronchial smooth muscle and the bronchiole glands to autonomic stimulation?

Back 18

Bronchial smooth muscle:
SNS: β2 receptors --> Gs --> relaxation (weak response)
PSNS: M3 receptors --> Gq --> IP3, DAG --> contraction.

Bronchial glands:
PSNS: M3 receptors --> Gq --> IP3, DAG --> increased Ca release from the SR --> increased secretion from gland cells via Ca-gated K and Cl channels.

Front 19

The autonomic innervation of the lungs is primarily what?

Back 19

PSNS.

Front 20

PSNS has what effect on the airways?

SNS has what effect on the airways?

Back 20

Constricts the smooth muscles of the airway.

SNS only weakly relaxes the airways.

Front 21

What drugs have effects on the lungs?

Back 21

1. Muscarinic agonists (methacholine) will constrict the airways.

2. Muscarinic antagonists (atropine) will relax bronchiole smooth muscles.

3. β2 agonists (epinephrine, albuterol) will relax the smooth muscles of the airway.

4. β2 antagonists (butoxamine) can constrict the airways

Front 22

Methacholine

Back 22

(Provocholine®)

Muscarinic agonist

Front 23

What are the three muscles that are involved with the filling and emptying of the bladder?

Back 23

1. Detrusor muscle.
2. Internal sphincter.
3. External sphincter.

Front 24

c/c the effects of the SNS and the PSNS on the bladder

Back 24

SNS:
Relaxes the detrusor (β2)
Constricts the internal sphincter (α1)
FACILITATES FILLING

PSNS:
Contricts the detrusor (M3)
Relaxes the internal sphincter (M3) *** this is an exception to the rule that M3 causes constriction.
FACILITATES EMPTYING

Front 25

What drugs have effects on the bladder?

Back 25

1. Muscarinic agonists (bethancholine) promote emptying

2. Muscarinic antagonists (atropine) promote filling (primarily by acting on the detrusor muscle.

3. α1 agonists (phenylephrine) increase filling by contracting the internal sphincter.

4. α1 antagonists (prazosine) relax the internal sphincter, promoting emptying.

Front 26

What effect does the SNS have on the GI tract?

Back 26

Promotes a weak reduction in GI smooth muscle tone and slight increase in saliva production.

Front 27

What drugs affect the GI tract?

Back 27

1. Muscarinic agonists (bethanechol) stimulate the mechanical and secretory activity of the GI tract.

2. Muscarinic anatagonists (like atropine) inhibit GI motility and secretory activity.

Note: adrenergic receptor agonists and antagonists have weak effects upon G.I. function.

Front 28

What is the primary source of innervation of the GI tract?

Back 28

The PSNS (M3 receptors)

Front 29

What aspects of the cardiovascular system are innervated by the PSNS? What receptors are involved?

Back 29

The PSNS innervates the atria and nodes via M2 receptors

Front 30

Where are non-innervated M2 receptors located?

Back 30

In the ventricles.

Front 31

What type of special receptors are present in the ventricles of the heart?

Back 31

Non-innervated M2 receptors

Front 32

c/c the different types of innervation of the peripheral vasculature.

Back 32

Arterioles and venules: α1 receptors cause contraction, β2 receptors cause relaxation. M2/M3 receptors cause relaxation (innervated by cholinergic sympathetic fibers).

Front 33

What receptors are located on the endothelium? Describe them.

Back 33

M3 receptors:

Not innervated by autonomic nerves (NO PS tone)

Respond to circulating agonists by releasing EDRF (= NO) --> vasodilation.

Do not respond to muscarinic antagonists (because there is no tone???)

Remember, there is also local control of dilation of the arterioles due to production of metabolites.

Front 34

What type of adrenergic receptor is the most abundant in the heart?

Back 34

β1 receptors.

Front 35

What is the general effect of SNS stimulation on the heart?

Back 35

Heart Rate up
Contractility up
Constriction of peripheral vessels up

Front 36

What is the general effect of PSNS stimulation of the heart?

Back 36

Heart rate down
Atrial contractility down

Front 37

Contractility correlates directly with what?

Back 37

Intercellular calcium concentration.

Front 38

c/c the molecular effects of beta adrenergic stimulation vs. muscarinic stimulation on the heart.

Back 38

β1 receptors --> increased PKA activity --> Inc P of:
- Ca channel --> increased trigger Ca --> greater Ca release from SR --> increased contractility.
- Phospholamban (--> increased Ca uptake to SR) --> increased contractility (more Ca for subsequent beats), increased rate of relaxation.

NOTE: β1, β2 receptors in smooth muscle promote relaxation.

M2 receptors --> decreased Ca current --> less Ca for contraction --> decreased contractility. Also more outward K current, SHORTENING the plateau phase.

Front 39

What effect do β1 and β2 receptors have on smooth muscle?

Back 39

They promote relaxation.

Front 40

c/c the effects of the SNS vs. the PSNS on heart rate.

Back 40

SNS: β1/β2 --> PKA inc --> adenyl cyclase increased --> increased "funny" Na current --> reaches threshold faster --> increased HR

PSNS: M2:
--> decreased PKA activity --> inhibition of adenyl cyclase --> reduced "funny" Na current --> reduced heart rate.

--> Inc outward K current (Gi binds K channel) --> hyperpolarization --> reaches threshold more slowly --> decreased HR

Front 41

What autonomic reflexes are illicited when mean arterial blood pressure drops?

Back 41

SNS activity increases
PSNS activity decreases.

Front 42

c/c the effects of giving a β antagonist vs a muscarinic anatagonist on heart rate AT REST.

Back 42

At rest, giving a β antagonist will cause only a slight decrease in the heart rate, because tone is mainly PS.

Giving a muscarinic antagonist will greatly increase heart rate because heart rate tone at rest is mainly PS.

Front 43

c/c the effects of giving a β antagonist vs. a muscarinic anatagonist on heart rate durng exertion.

Back 43

Giving a β antagonist during exertion will lower heart rate (because tone is S), giving a muscarinic anatagonist during exertion will not have much effect (a slight increase).

Front 44

What are the prevailing receptors/innervations of the peripheral vessels?

Back 44

SNS fibers and non-innervated M3 receptors.

Front 45

What are the prevailing receptors/innervations of the ventricles?

Back 45

SNS fibers and non-innervated M2 receptors.

Front 46

What effect does a muscarinic agonist have on the peripheral vessels?

Back 46

It produces vasodilation (greater effect during exercise)

Front 47

What effect does a muscarinic antagonist have on the peripheral vessels?

Back 47

Little effect because there is little PS tone.

Front 48

What effect does a muscarinic agonist have on the ventricles?

Back 48

Reduces contractility (greater effect during exercise; aka accentuated antagonism???)

Front 49

What effect does a muscarinic antagonist have on the ventricles?

Back 49

Has little effect because there is little PS tone.

Front 50

What is the prevailing tone of the arterioles and veins?

Back 50

S

Front 51

What is the prevailing tone of the heart?

Back 51

S/PS

Front 52

What is the prevailing tone of the iris?

Back 52

S/PS

Front 53

What is the prevailing tone of the ciliary muscle?

Back 53

PS

Front 54

What is the prevailing tone of the GI tract?

Back 54

PS

Front 55

What is the prevailing tone of the urinary bladder?

Back 55

S/PS

Front 56

What is the prevailing tone of hte salivary glands?

Back 56

PS

Front 57

What is the prevailing tone of the sweat glands?

Back 57

S