Part 12: Asthma and COPD

Question 1

____ cells of the respiratory tract are exposed to the external environment when we inhale and are a critical first line of defense

Answer 1

epithelia

Question 2

epithelial cells secrete ____ that protects against pathogens and irritants

Answer 2

mucous

Question 3

resident ____ cells in the airways promptly manage any forgein particles

Answer 3

immune

Question 4

the ____ nervous system innervates the smooth muscle of the airways

Answer 4

autonomic

Question 5

depending on the parasympathetic and sympathetic stimuli to the smooth muscle cells will constrict or relax, this is called _____

Answer 5

bronchial tone

Question 6

___ and ____ modulating drugs can influence the contractility of airway smooth muscle

Answer 6

cholinergic and adrenergic

Question 7

parasympathetic stimulation increases the secretion of ___-

Answer 7

mucous

Question 8

some mucous secretion of the airways is good becaue ___, but too much is bad becaue___

Answer 8

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

Question 9

the balance between parasympathetic and sympathetic stimulation is called ___

Answer 9

tone

Question 10

the parasympathetic and sympathetic stimulation in the lungs goes back and forth based on our ____ and ___

Answer 10

activity and O2 demand

Question 11

bronchiole smooth muscle cells express M__ and B__ receptors

Answer 11

3; 2

Question 12

what type of receptor are M3 and B2 receptors?

Answer 12

G protein coupled

Question 13

parasympathetic activation causes the release of ___ into synapses

Answer 13

Ach

Question 14

Ach stimulates which receptors in the lungs?

Answer 14

M3

Question 15

M3 receptors are coupled to G__ proteins

Answer 15

q

Question 16

activation of M3 receptors causes the increased production of cellular mediators like ___

Answer 16

IP3

Question 17

IP3 is an important mediator in muscle cells bc it stimulates the release of ____ from intracellular storage

Answer 17

Ca

Question 18

the calcium released by IP3 interacts with ___ to facilitate myosin chain phosphorylation and causes cellular contraction

Answer 18

calmodulin

Question 19

B2 receptors are G___ coupled

Answer 19

s

Question 20

activation of Gs pathway in B2 receptors causes an increase in ____

Answer 20

cAMP

Question 21

key role of cAMP signalling pathways in smooth mucscle cells is the reduction of the ____ activity

Answer 21

myosin light-chained kinase activuty

Question 22

reduction in myosin light chain activty caused by activation of B2 receptors results in ____ and ____

Answer 22

decreased phophorylation of myosin and relaxation of smooth muscle fiber

Question 23

the pathophysiology of asthma comes down to 2 essential components: ____ and ____

Answer 23

constriction of airway smooth muscle and inflammation of bronchioles

Question 24

together, constriction of airway smooth muscle and inflammation of bronchioles results in less _____ for air to move through and less O2 into the blood

Answer 24

surface area

Question 25

patients with asthma have ____ airways

Answer 25

hyperresponsive

Question 26

in asthma, ____ cells are triggered by inhaled particles or allergens

Answer 26

resident immune cells (mast cells and T cells )

Question 27

when mast cells are stimulated they dump large amounts of pro-inflammatory mediators, this process is called _____

Answer 27

degranulation

Question 28

what are the key mediators that can initiate contraction of smooth muscle cells, resulting in bronchoconstriction?

Answer 28

histamine, prostaglandins, and leukotrienes

Question 29

in asthma, which mediators promote infiltration of immue cells into the airways?

Answer 29

interleukins and TNF

Question 30

theophylline is an example of a ____ drug

Answer 30

methylxanthines

Question 31

tiotropium is an example of a _____ drug

Answer 31

anticholinergic

Question 32

montelukast is an example of a _____ drug

Answer 32

anti-leukotrienes

Question 33

COPD is a _____ pulmonary disease

Answer 33

destructive

Question 34

COPD is caused by ___

Answer 34

prolonged exposure to inhlaed toxins such as smoking and possibly vaping

Question 35

in COPD, inhaled toxins cause damage to the ____ tissues, making them less effective at exchanging oxygen into the blood

Answer 35

alveolar

Question 36

bronchodilators act to push the autonomic control of bronchial tone towards relaxation of smooth muscle by stimulating ____ pathways or inhibiting ____ pathways

Answer 36

sympathetic; parasympathetic

Question 37

t/f selective B2 agonists have very little effects on cardiac cells

Answer 37

t

Question 38

salbutamol is similar to what endogenous molecule?

Answer 38

epinephrine

Question 39

what is the onset of action for salbutamol?

Answer 39

~5min

Question 40

what is the duration of action for salbutamol?

Answer 40

3-8 hours

Question 41

how can tachyphylaxis occur with SABAs?

Answer 41

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)

Question 42

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

Answer 42

g-protein coupled receptor kinases; beta-arrestin

Question 43

desensitization od B2 receptors ocurs within the first couple ___ of salbutamol dosing

Answer 43

hours

Question 44

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

Answer 44

t

Question 45

what genetic variation can result in B2 receptors not being downregulatedas much?

Answer 45

glycine glycine at codon 16 (instead of arg arg at codon 16)

Question 46

what structural feature of salmeterol allows it to act for a longer period of time?

Answer 46

long tail prolongs the interaction of the drug with the receptor

Question 47

t/f receptor desensitization and down regulation are less prominent in salmeterol than salbutamol

Answer 47

t

Question 48

why does salmeterol not cause as much downregulation of receptors?

Answer 48

study suggests it make cause less phosporylation and beta arrestin binding, preventing the receptor from being internalized

Question 49

theophylline is not commonly used anymore, but it is chemically related to ____

Answer 49

caffeine

Question 50

methylxanthines inhibit _____enzymes and have many other systemic effecst

Answer 50

phosphodiesterase

Question 51

what is phosphodiesterase and its role in bronchodilation?

Answer 51

an enzyme that breaks down intracellular cAMP; if we inhibit this enzyme, cAMP can last longer to allow for bronchodilation

Question 52

what are some of the ADRs of theophylline given for asthma and COPD?

Answer 52

tachycardia or palpitations, CNS stimulation

Question 53

what is the typical dose of theophylline | ?

Answer 53

400-600mg/day

Question 54

bc theophylline is similar to caffeine, can strong coffee be used to treat an asthma attack?

Answer 54

may cause small change in FEV1 (not enough to help with the asthma attack, buy enough to influence spirometry test results)

Question 55

blocking the M3 receptors of bronchiole smooth muscle reduces the production of ____, which decreases the levels of intracellular ___ available to activate muscle contraction

Answer 55

IP3; Ca

Question 56

the common systemic effects of an anticholinergic are ___

Answer 56

the opposite of SLUDGE

Question 57

tiotropium has a ____ group which allows itto stay and act at the site of administration

Answer 57

tertiary (charged) nitrogen

Question 58

lekotrienes are released from ___ cels and act to increase ___

Answer 58

mast cells; vascular permeability and recruit immune cells

Question 59

t/f leukotrienes are taken as preventative measures for asthma and COPD

Answer 59

t

Question 60

are LTRAs first line for respiratory diseases?

Answer 60

no, more as a support therapy

Question 61

montelukast is a competitive antagonist of ____

Answer 61

Cys LTR1 (leukotriene receptor 1)