Sweatman: ANS and Bronchial Tone Flashcards
In Lungs, Hypoxia induces
Vasoconstriction–> shunt blood to more well-ventilated areas
Dominant Arm of ANS in lungs
PNS
Bronchial smooth muscle tone is dominated by ____ tone
PNS
Three areas the ANS oversees in LUNGS
- bronchial smooth muscle tone
- mucous production
- Inflamtory process behind asthma
Receptors in the lungs (major)
beta 2
muscarinic
*both employed to control asthma
direct innervation of bronchial smooth muscle and glands
PG PNS fibers directly to smooth muscle
SNS to smooth muscle and glands
does not directly innervate…acts via adrenergic receptors found in these tissues: SM, Type II alveolar, mast cells, epithelial cells
*respond to nerutransmitter, and neurohormones
exampls of beta 2 agonists
isoproteronol
albuterol
epinephrine
Muscarinic antagonists
ipratroprium, hydroxyzine, atropine,
SNS modulates the activity of the PNS via
HETERORECEPTORS and beta 2 receptors responding to ciruclating epinephrine or exogenous drugs tx.
define heteroreceptor
receptor mediating the release/synthesis of mediators other than its own ligand
respond to neurotransmitter released from adjacent neurons and not NT’s relased from the cell in whose wall they are embedded
M1 receptors act via
Gq–> excitatory
M1 receptors are located
on Post ganglionic membrane
M1 receptors function
- transduce vagal signal to both sub-mucosal glands and airway smooth muscle
- increase secretions in nasal mucosa
M2 receptor function
inhibitory autoreceptors in pre-synaptic membrane of PG fibers
Ach released onto airway smooth muscle causes
bronchiconstrcition via M3
mucous secretion via M1 and M3
receptor that opposes the excitation by beta 2 stimulation
M2 receptors
*also found in bronchial smooth muscle,
M2 GPCR TYPE
Gi
*both post synaptic and pre-ganglionic (autoreceptors) can inhibit the release of more ACH
blockade of the M2 autoreceptor leads to…
increase the release of exogenous ACH and can partially offset the bronchodilatory effects
*by inhibiting negative feedback mechanisms–> you can actually potentiate more Ach being released)
atropine and ipratropium specificity
antagonize the M2 and M3 receptors equally well
more selective anticholinergic for the M1 and M3 receptor
tiotropium
1st gen antihistamines with anticholinergic activity
Chlorpheniramine
Doxylamine
Diphenhydramine
1st gen antihistamines can cause
drying of secretions–> blockade of muscarinic receptors= drying and thickening of mucus
acetylcholinesterase inhibitors MOA
increase cholinergic activity–> delay break down of Ach–> increases secretions
exampl of Ach-ase inhibitors
edrophonium
neostigimine
another drug that can increase mucouse secretions
marijuana
Beta 2 receptors
7–80% of receptors in the lung
beta agonists are effective against
early bronchospastic response to inhaled antigen
beta agonist ineffective against
late inflammatory phase
CV side effect of beta 2 agonists
QT prolongation especially in
hypokalemia
-also widened pulse pressure
-arterial dilation in pulm, skeletal, coronary muscle
beta 2 stimulation effect on K
stimulated Na/K and can result in hypokalemia–> worsening QT prolongation
musculoskeletal effect of too much Beta 2 agonism
twitching of skeletal muscle–> activity agaisnt the ATPase–> over excited tissues
D-D Interaction of beta 2 agonists with Non-specific beta blockers (propranolol)
offset each other–> less effective, removes the ability to treat acute bronchospasm with first line beta 2 agonist therapy
D-D Interaction of beta 2 agonists with Loop/thiazides
k wasting
hypokalemia, qt prolong–> arryhtmias
D-D Interaction of beta 2 agonists with saquinavir
hypoK qt prolong
D-D Interaction of beta 2 agonists with MAOI’s
block metabolism of amine by MAO-b
D-D Interaction of beta 2 agonists with Tricyclic antidepressant
block reuptake of drug & NE into nerve terminal
M1 and M3=
Gq
M2=
Gi/o
BETA 2=
Gs
over stimulation by adrenergic agonists leads to
decrease in the receptor number
corticosteroids advantages to their use
- treat the underlying inflammatous cause of asthma
- transcriptionally upregulate the expression of the beta-adrenergic receptor–> leading to renewed response to the beta 2 agonist inhaler tratment
steroid therapy can….
renew beta agonist response by restoring receptor density
beta 2 agonist effect on mast cells
stimulation reduces histamine release
Mucosilliary clearance and beta agonist
increase glycoprotein content, increase beating of cillia frequency (alpha’s incease luid secretion)
mucociliary clearance is mainly under
PNS tone
vascular endothelial permeability and beta agonisst
beta2 agonism–> decrease microvascular leakage–> decreases airway obstruction
