respiratory pathophysiology Flashcards
chemicals that contribute to increased airway resistance include (3)
inositol triphosphate (CN10–>Ach–>M3–>Gq–>PLC–>IP3–>Ca2+–>MLCK–>bronchoconstriction)
phospholipase C
leukotrienes
which nerve supplies parasympathetic innervation to airway smooth muscle
vagus nerve
how M3 receptor in airway smooth muscle creates bronchoconstriction (PSNS)
- cholinergic nerve endings release Ach to M3 receptors (a Gq protein)
- Gq protein activated, which activates phospholipase C (PLC)
- PLC activates ionsitol triphosphate (IP3), which is the second messenger
- IP3 stimulates calcium release from SR
- myosin light chain kinase activates and bronchoconstriction occurs
how M3 receptor in airway smooth muscle is inactivated
when IP3 phosphatase deactivates IP3 to IP2
are there sympathetic nerve endings in airway smooth muscle?
no, so B2 receptors are activated via catecholamines circulating systemically
how B2 receptors in airway smooth muscle creates bronchodilation (SNS)
- B2 receptor activation is via circulating catecholamine
- B2 (Gs receptor) activates adenylate cyclase
- adenylate cyclase activates cAMP
- along with protein kinase A, cAMP reduces Ca2+ release from SR
- this reduces smooth muscle contraction and produces bronchodilation
how B2 receptor in airway smooth muscle is inactivated
PDE3 turns off cAMP by converting it to AMP
pathway that NO follows to create bronchodilation
- non cholinergic PNS nerves release vasoactive intestinal peptide into airway smooth muscle
- this increases NO production
- NO stimulates cGMP, which fosters smooth muscle relaxation and bronchodilation
beta 2 agonists (3)
albuterol
metaproterenol
salmeterol
MOA of beta 2 agonists
stimulate B2, increase cAMP, decrease iCa2+
-stabilizes mast cell membranes and decreases mediator rerlease
SE of B2 agonists (5)
increased HR
dysrhythmias
hypokalemia (stimulates Na/K pump)
hyperglycemia
tremors
anticholinergics
atropine, glycol, iatropium*
MOA of anticholinergics
M3 antagonism, decreased IP3, decreased iCa2+
SE of anticholinergics (5)
inhibits secretions (dry mouth)
urinary retention
blurred vision
cough
increased IOP with narrow angle glaucoma
corticosteroid examples (5)
beclomethasone
budesonide
flunisolide
fluticasone
triamcinolone
MOA of corticosteroids (4)
stimulates intracellular steroid receptors
regulates inflammatory protein synthesis
decreases aw inflammation
decreases aw hyperresponsiveness
SE of corticosteroids (4)
dysphonia
myopathy of laryngeal muscles
oropharyngeal candidiasis
possible adrenal suppression
cromolyn MOA
stabilizes mast cell membranes (negligible SE’s)
leukotriene modifiers (4)
zileuton
monteuklast
pranlukast
zafirlukast
MOA of leukotriene modifiers
inhibits lipoxygenase enzyme, decreases leukotriene synthesis (negligible SE’s)
theophylline (methylxanthine) MOA
inhibits PDE, increases cAMP available
increases endogenous catecholamine release, inhibits adenosine receptors
SE’s of theophyllin (depending on plasma concentration)
-at a plasma concentration of 20mcg/mL: n/v/d, HA, disrupted sleep
-at a plasma concentration of 30mcg/mL: sz, tachydysrhythmias, CHF
most sensitive PFT for small airway disease (obstruction)
FEV 25-75%
FEV1 measurement and normal value
volume of air that can be exhaled after maximum inhalation in 1 second (declines with age)
>80% predicted value