Part 12: Asthma and COPD Flashcards
____ cells of the respiratory tract are exposed to the external environment when we inhale and are a critical first line of defense
epithelia
epithelial cells secrete ____ that protects against pathogens and irritants
mucous
resident ____ cells in the airways promptly manage any forgein particles
immune
the ____ nervous system innervates the smooth muscle of the airways
autonomic
depending on the parasympathetic and sympathetic stimuli to the smooth muscle cells will constrict or relax, this is called _____
bronchial tone
___ and ____ modulating drugs can influence the contractility of airway smooth muscle
cholinergic and adrenergic
parasympathetic stimulation increases the secretion of ___-
mucous
some mucous secretion of the airways is good becaue ___, but too much is bad becaue___
lubricates the airway and adds a barrier between the external environment and the internal organs; too much mucous can become obstructive and make it difficult to breathe
the balance between parasympathetic and sympathetic stimulation is called ___
tone
the parasympathetic and sympathetic stimulation in the lungs goes back and forth based on our ____ and ___
activity and O2 demand
bronchiole smooth muscle cells express M__ and B__ receptors
3; 2
what type of receptor are M3 and B2 receptors?
G protein coupled
parasympathetic activation causes the release of ___ into synapses
Ach
Ach stimulates which receptors in the lungs?
M3
M3 receptors are coupled to G__ proteins
q
activation of M3 receptors causes the increased production of cellular mediators like ___
IP3
IP3 is an important mediator in muscle cells bc it stimulates the release of ____ from intracellular storage
Ca
the calcium released by IP3 interacts with ___ to facilitate myosin chain phosphorylation and causes cellular contraction
calmodulin
B2 receptors are G___ coupled
s
activation of Gs pathway in B2 receptors causes an increase in ____
cAMP
key role of cAMP signalling pathways in smooth mucscle cells is the reduction of the ____ activity
myosin light-chained kinase activuty
reduction in myosin light chain activty caused by activation of B2 receptors results in ____ and ____
decreased phophorylation of myosin and relaxation of smooth muscle fiber
the pathophysiology of asthma comes down to 2 essential components: ____ and ____
constriction of airway smooth muscle and inflammation of bronchioles
together, constriction of airway smooth muscle and inflammation of bronchioles results in less _____ for air to move through and less O2 into the blood
surface area
patients with asthma have ____ airways
hyperresponsive
in asthma, ____ cells are triggered by inhaled particles or allergens
resident immune cells (mast cells and T cells )
when mast cells are stimulated they dump large amounts of pro-inflammatory mediators, this process is called _____
degranulation
what are the key mediators that can initiate contraction of smooth muscle cells, resulting in bronchoconstriction?
histamine, prostaglandins, and leukotrienes
in asthma, which mediators promote infiltration of immue cells into the airways?
interleukins and TNF
theophylline is an example of a ____ drug
methylxanthines
tiotropium is an example of a _____ drug
anticholinergic
montelukast is an example of a _____ drug
anti-leukotrienes
COPD is a _____ pulmonary disease
destructive
COPD is caused by ___
prolonged exposure to inhlaed toxins such as smoking and possibly vaping
in COPD, inhaled toxins cause damage to the ____ tissues, making them less effective at exchanging oxygen into the blood
alveolar
bronchodilators act to push the autonomic control of bronchial tone towards relaxation of smooth muscle by stimulating ____ pathways or inhibiting ____ pathways
sympathetic; parasympathetic
t/f selective B2 agonists have very little effects on cardiac cells
t
salbutamol is similar to what endogenous molecule?
epinephrine
what is the onset of action for salbutamol?
~5min
what is the duration of action for salbutamol?
3-8 hours
how can tachyphylaxis occur with SABAs?
when given repeatedly, its effect can be diminished, this relates to changes in the expression of the B2 receptors on bronchiole smooth muslce cells (downregulation)
after an agonist binds to a B2 receptor, _____ phosphorylate the intracellualr tail so another G proteins cant come stimulate the receptor. _____ binds to the phosphorylated tail and triggers internalization of the receptor where the cells decides to either break it down or recycle it
g-protein coupled receptor kinases; beta-arrestin
desensitization od B2 receptors ocurs within the first couple ___ of salbutamol dosing
hours
t/f unlike in desensitization, in downregulation, even after a period of no exposure, the full response will not be made when the agonist is reintroduced
t
what genetic variation can result in B2 receptors not being downregulatedas much?
glycine glycine at codon 16 (instead of arg arg at codon 16)
what structural feature of salmeterol allows it to act for a longer period of time?
long tail prolongs the interaction of the drug with the receptor
t/f receptor desensitization and down regulation are less prominent in salmeterol than salbutamol
t
why does salmeterol not cause as much downregulation of receptors?
study suggests it make cause less phosporylation and beta arrestin binding, preventing the receptor from being internalized
theophylline is not commonly used anymore, but it is chemically related to ____
caffeine
methylxanthines inhibit _____enzymes and have many other systemic effecst
phosphodiesterase
what is phosphodiesterase and its role in bronchodilation?
an enzyme that breaks down intracellular cAMP; if we inhibit this enzyme, cAMP can last longer to allow for bronchodilation
what are some of the ADRs of theophylline given for asthma and COPD?
tachycardia or palpitations, CNS stimulation
what is the typical dose of theophylline
?
400-600mg/day
bc theophylline is similar to caffeine, can strong coffee be used to treat an asthma attack?
may cause small change in FEV1 (not enough to help with the asthma attack, buy enough to influence spirometry test results)
blocking the M3 receptors of bronchiole smooth muscle reduces the production of ____, which decreases the levels of intracellular ___ available to activate muscle contraction
IP3; Ca
the common systemic effects of an anticholinergic are ___
the opposite of SLUDGE
tiotropium has a ____ group which allows itto stay and act at the site of administration
tertiary (charged) nitrogen
lekotrienes are released from ___ cels and act to increase ___
mast cells; vascular permeability and recruit immune cells
t/f leukotrienes are taken as preventative measures for asthma and COPD
t
are LTRAs first line for respiratory diseases?
no, more as a support therapy
montelukast is a competitive antagonist of ____
Cys LTR1 (leukotriene receptor 1)
