08.14 - ANS and Bronchial Tone (Sweatman) - Questions

Question 1

Clinically, both ___ agonists and ___ antagonists are used to control bronchospasm

Answer 1

B2 agonists, Muscarinic Antagonists

Question 2

Adrenergic receptors in the lung are found in

Answer 2

Airway SM, Epithelial Cells, Mast Cells, Type 2 alveolar cells

Question 3

T/F: The SNS has no direct neural connection to bronchial SM

Answer 3

TRUE

Question 4

How does SNS modulate bronchial SM tone

Answer 4

Modulate PNS, via hetero-receptors

Question 5

Permeability advantages of lung drug delivery

Answer 5

More permeable to macromolecules than other; Most permeable to small molecules than GI tract

Question 6

The less ionized a molecule, the __ it’s absorption rate

Answer 6

Faster - Fewer interactions with proteins and lipids that line the pore

Question 7

What type of compounds can “dissove” in the lipid bilayer and rapidly be absorbed transcellular

Answer 7

Lipophilic

Question 8

How do insoluble compounds traverse lung epithelium

Answer 8

Paracellular - Aqueous pores in intercellular tight junctions

Question 9

What determes rate at which molecules pass through lung epithelium

Answer 9

MW and Degree of Ionization, and Lipophilicity

Question 10

How does ionization affect absoprtion rate

Answer 10

Less ionized is absorbed more rapidly

Question 11

Blockade of M2 Auto-receptors ___

Answer 11

increases release of endogenous ACh

Question 12

Paradoxical actions of Atropine, Ipratropium

Answer 12

Decr bronchial SM tone via M3 blockade; But blocking M2 auto-recetpors actually increases release of enodgenous ACh –> bronchial SM contraction

Question 13

M1 Receptor Locations

Answer 13

PG membrane; Nasal mucosa

Question 14

Locations of M2 receptors

Answer 14

Inhibitory autoreceptors on pre-synaptic membrane of PG fibers; Bronchial SM

Question 15

Selectivity of Atropine, Ipratopium

Answer 15

Non-selective: M2 and M3

Question 16

Selectivity of Tiotropium

Answer 16

Functional selectivity for M1 and M3 receptors

Question 17

Tiotropium

Answer 17

Functional selectivity for M1 and M3 receptors

Question 18

Most pervasive group with anticholinergic “side effects”

Answer 18

1st generation antihistamines

Question 19

Effect of Anticholinergics on secretions

Answer 19

Dry secretions

Question 20

Effect of Acetylcholinesterase inhibitors on secretions

Answer 20

Increase

Question 21

Which phase of atopic asthmatic response is Albuterol effective in?

Answer 21

Early (bronchospastic), not Late (Inflammatory)

Question 22

How might B2 agonists produce bronchoconstriction

Answer 22

Increasing PNS Tone

Question 23

Goblet Cells and Submucosal Glands receive primarily __ innervation

Answer 23

PNS

Question 24

Beta agonist effect on mucociliary clearance

Answer 24

Increase glycoportein composition; Incr cilia beat freq -> incr clearance

Question 25

Beta agonist effect on Vascular Endothelial Permeability

Answer 25

Decr microvascular leakage, Decr airways obstruction in asthma

Question 26

At high concentrations, B2 agonists produce (2):

Answer 26

CV stimulatory effects; QT prolongation (esp in hypoK)

Question 27

How does B2 agonism affect QT prolongation

Answer 27

Stimulation of Na/K pump decr serum K --> Hypokalemia --> Worsening QT prolongation

Question 28

Patients with whtat type of problems should be cautions with B2-agonists

Answer 28

Cardiovascular

Question 29

3 drug classes that also promote hypokalemia

Answer 29

Saquinavir; Loop and Thiazide Diuretics; Non-specific Beta Blockers

Question 30

Why should asthmatics not take beta-blockers

Answer 30

Can't treat with B2 Agonists

Question 31

Beta-agonists activate G-proteins, which stimulate __

Answer 31

Adenylyl Cyclase

Question 32

Beta-Arrestin

Answer 32

Binds to phosphorylated domain on B-adrenergic receptor and blocks Gs binding -> Thereby decr AC activity; Endosomal localization

Question 33

M1 is coupled to what g protein

Answer 33

Gq

Question 34

M3 is coupled to what g protein

Answer 34

Gq

Question 35

M2 is coupled to what g protein

Answer 35

Inhibitory action via Gi/o

Question 36

Beta2 agonists activate what g protein

Answer 36

Gs

Question 37

Repeated stimulation of beta adrenergic receptor results in

Answer 37

Phosphorylation --> Beta-arrestin --> internalization

Question 38

Corticosteroid effect on b2 receptors

Answer 38

Transcriptional upregulation of beta-2 receptors

Question 39

4 off-target Beta2 actions

Answer 39

Cardiostimulation, Muscle Fasciculation, Hypokalemia (QT prolongation)

Question 40

B2agonist activity is exacerbated by

Answer 40

Metabolism inhibitors

Question 41

How can you restore beta 2 receptor density

Answer 41

Corticosteroid transcriptional upregulation