Part 12: Asthma and COPD Flashcards

1
Q

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

A

epithelia

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2
Q

epithelial cells secrete ____ that protects against pathogens and irritants

A

mucous

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3
Q

resident ____ cells in the airways promptly manage any forgein particles

A

immune

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4
Q

the ____ nervous system innervates the smooth muscle of the airways

A

autonomic

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5
Q

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

A

bronchial tone

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6
Q

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

A

cholinergic and adrenergic

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7
Q

parasympathetic stimulation increases the secretion of ___-

A

mucous

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8
Q

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

A

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

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9
Q

the balance between parasympathetic and sympathetic stimulation is called ___

A

tone

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10
Q

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

A

activity and O2 demand

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11
Q

bronchiole smooth muscle cells express M__ and B__ receptors

A

3; 2

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12
Q

what type of receptor are M3 and B2 receptors?

A

G protein coupled

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13
Q

parasympathetic activation causes the release of ___ into synapses

A

Ach

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14
Q

Ach stimulates which receptors in the lungs?

A

M3

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15
Q

M3 receptors are coupled to G__ proteins

A

q

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16
Q

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

A

IP3

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17
Q

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

A

Ca

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18
Q

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

A

calmodulin

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19
Q

B2 receptors are G___ coupled

A

s

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20
Q

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

A

cAMP

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21
Q

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

A

myosin light-chained kinase activuty

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22
Q

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

A

decreased phophorylation of myosin and relaxation of smooth muscle fiber

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23
Q

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

A

constriction of airway smooth muscle and inflammation of bronchioles

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24
Q

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

A

surface area

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25
Q

patients with asthma have ____ airways

A

hyperresponsive

26
Q

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

A

resident immune cells (mast cells and T cells )

27
Q

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

A

degranulation

28
Q

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

A

histamine, prostaglandins, and leukotrienes

29
Q

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

A

interleukins and TNF

30
Q

theophylline is an example of a ____ drug

A

methylxanthines

31
Q

tiotropium is an example of a _____ drug

A

anticholinergic

32
Q

montelukast is an example of a _____ drug

A

anti-leukotrienes

33
Q

COPD is a _____ pulmonary disease

A

destructive

34
Q

COPD is caused by ___

A

prolonged exposure to inhlaed toxins such as smoking and possibly vaping

35
Q

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

A

alveolar

36
Q

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

A

sympathetic; parasympathetic

37
Q

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

A

t

38
Q

salbutamol is similar to what endogenous molecule?

A

epinephrine

39
Q

what is the onset of action for salbutamol?

A

~5min

40
Q

what is the duration of action for salbutamol?

A

3-8 hours

41
Q

how can tachyphylaxis occur with SABAs?

A

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)

42
Q

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

A

g-protein coupled receptor kinases; beta-arrestin

43
Q

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

A

hours

44
Q

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

A

t

45
Q

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

A

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

46
Q

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

A

long tail prolongs the interaction of the drug with the receptor

47
Q

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

A

t

48
Q

why does salmeterol not cause as much downregulation of receptors?

A

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

49
Q

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

A

caffeine

50
Q

methylxanthines inhibit _____enzymes and have many other systemic effecst

A

phosphodiesterase

51
Q

what is phosphodiesterase and its role in bronchodilation?

A

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

52
Q

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

A

tachycardia or palpitations, CNS stimulation

53
Q

what is the typical dose of theophylline

?

A

400-600mg/day

54
Q

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

A

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

55
Q

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

A

IP3; Ca

56
Q

the common systemic effects of an anticholinergic are ___

A

the opposite of SLUDGE

57
Q

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

A

tertiary (charged) nitrogen

58
Q

lekotrienes are released from ___ cels and act to increase ___

A

mast cells; vascular permeability and recruit immune cells

59
Q

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

A

t

60
Q

are LTRAs first line for respiratory diseases?

A

no, more as a support therapy

61
Q

montelukast is a competitive antagonist of ____

A

Cys LTR1 (leukotriene receptor 1)