08.14 - ANS and Bronchial Tone (Sweatman) - Questions Flashcards
Clinically, both ___ agonists and ___ antagonists are used to control bronchospasm
B2 agonists, Muscarinic Antagonists
Adrenergic receptors in the lung are found in
Airway SM, Epithelial Cells, Mast Cells, Type 2 alveolar cells
T/F: The SNS has no direct neural connection to bronchial SM
TRUE
How does SNS modulate bronchial SM tone
Modulate PNS, via hetero-receptors
Permeability advantages of lung drug delivery
More permeable to macromolecules than other; Most permeable to small molecules than GI tract
The less ionized a molecule, the __ it’s absorption rate
Faster - Fewer interactions with proteins and lipids that line the pore
What type of compounds can “dissove” in the lipid bilayer and rapidly be absorbed transcellular
Lipophilic
How do insoluble compounds traverse lung epithelium
Paracellular - Aqueous pores in intercellular tight junctions
What determes rate at which molecules pass through lung epithelium
MW and Degree of Ionization, and Lipophilicity
How does ionization affect absoprtion rate
Less ionized is absorbed more rapidly
Blockade of M2 Auto-receptors ___
increases release of endogenous ACh
Paradoxical actions of Atropine, Ipratropium
Decr bronchial SM tone via M3 blockade; But blocking M2 auto-recetpors actually increases release of enodgenous ACh –> bronchial SM contraction
M1 Receptor Locations
PG membrane; Nasal mucosa
Locations of M2 receptors
Inhibitory autoreceptors on pre-synaptic membrane of PG fibers; Bronchial SM
Selectivity of Atropine, Ipratopium
Non-selective: M2 and M3
Selectivity of Tiotropium
Functional selectivity for M1 and M3 receptors
Tiotropium
Functional selectivity for M1 and M3 receptors
Most pervasive group with anticholinergic “side effects”
1st generation antihistamines
Effect of Anticholinergics on secretions
Dry secretions
Effect of Acetylcholinesterase inhibitors on secretions
Increase
Which phase of atopic asthmatic response is Albuterol effective in?
Early (bronchospastic), not Late (Inflammatory)
How might B2 agonists produce bronchoconstriction
Increasing PNS Tone
Goblet Cells and Submucosal Glands receive primarily __ innervation
PNS
Beta agonist effect on mucociliary clearance
Increase glycoportein composition; Incr cilia beat freq -> incr clearance
Beta agonist effect on Vascular Endothelial Permeability
Decr microvascular leakage, Decr airways obstruction in asthma
At high concentrations, B2 agonists produce (2):
CV stimulatory effects; QT prolongation (esp in hypoK)
How does B2 agonism affect QT prolongation
Stimulation of Na/K pump decr serum K –> Hypokalemia –> Worsening QT prolongation
Patients with whtat type of problems should be cautions with B2-agonists
Cardiovascular
3 drug classes that also promote hypokalemia
Saquinavir; Loop and Thiazide Diuretics; Non-specific Beta Blockers
Why should asthmatics not take beta-blockers
Can’t treat with B2 Agonists
Beta-agonists activate G-proteins, which stimulate __
Adenylyl Cyclase
Beta-Arrestin
Binds to phosphorylated domain on B-adrenergic receptor and blocks Gs binding -> Thereby decr AC activity; Endosomal localization
M1 is coupled to what g protein
Gq
M3 is coupled to what g protein
Gq
M2 is coupled to what g protein
Inhibitory action via Gi/o
Beta2 agonists activate what g protein
Gs
Repeated stimulation of beta adrenergic receptor results in
Phosphorylation –> Beta-arrestin –> internalization
Corticosteroid effect on b2 receptors
Transcriptional upregulation of beta-2 receptors
4 off-target Beta2 actions
Cardiostimulation, Muscle Fasciculation, Hypokalemia (QT prolongation)
B2agonist activity is exacerbated by
Metabolism inhibitors
How can you restore beta 2 receptor density
Corticosteroid transcriptional upregulation
