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Pharmacology Test #4 > Respiratory Pharmacology I > Flashcards

Respiratory Pharmacology I Flashcards

1
Q

Three components influencing bronchoconsriction

A
  1. activation of mast cells
  2. local inflammation
  3. vagal stimulation
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2
Q

What is central to bronchoconstriction and airway inflammation

A

mast cell activation

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3
Q

What do agents that increase bronchoconstriction activate?

A

7-spanning transmembrane receptors linked to internal G-proteins

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4
Q

Activation of Gq subunits results in

A

phospholipase C activation, increases in IP3, and influx of Ca2+, influx of Ca2+ results in actin-myosin coupling and smooth muscle contraction

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5
Q

Activation of Gi subunits results in

A

decrease in adenylate cyclase activity and cAMP, incrase in PLC; resulting in bronchoconstriction

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6
Q

Activation of Gs subunits results in

A

increased adenylate cyclase activity and increases in cAMP; resulting in actin-myosin dissolution

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7
Q

What do bronchodilators do?

A

induction of smooth muscle relaxation
inhibit smooth muscle contraction
block actions of other inflammatory mediators

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8
Q

Agents that reduce bronchoconstriciton and increase smooth muscle relaxation share which common feature

A

increase intracellular cAMP concentrations

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9
Q

How do sympathomimetics work

A

increase cAMP through Gs subunit of GRPRC; relax smooth muscle contraction; decrease release of mediators from mast cells

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10
Q

Sympathomimetics act through?

A

act through adenoreceptors on smooth muslce (not sympathetic innervation)

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11
Q

Name some sympathomimetics

A

epinephrine, ephedrine, isoproterenol, albuterol/salbutamol

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12
Q

Specificity of ephinephrine

A

both alpha and beta effects and cardiac effects preclude its use except in emergencies

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13
Q

Specificity of ephedrine

A

has more central effects and lower efficacy; has been replaced by selective beta-adrenergic agents

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14
Q

Selective beta-adrenergic agents

A

albuterol, terbutaline, metaproterenol, pirbuterol

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15
Q

How are selective beta-adrenergic agents delivered

A

delivered via airway using metered dosing devices (albuterol and terbutaline also available in oral forms)

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16
Q

Difference between airway delivery and oral delivery of selective beta-adrenergic agents

A

little cardiac side effects with airway delivery; side effects minimal with airway delivery; oral forms associated with tremor, nervousness, and weakness

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17
Q

How may beta-adrenergic agents lead to increased perfusion-ventilation mismatch and decreased oxygenation

A

beta-adrenergic agents may act on pulmonary vascular beds resulting in vasodilation; this leads to a perfusion of poorly ventilated areas (previously vasoconstricted due to hypoxemia)

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18
Q

How can you avoid an increased perfusion-ventilation mismatch with beta-adrenergic agents

A

they’re given with oxygen

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19
Q

Long-acting beta-agonists

A

salmeterol and formoterol

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20
Q

How are long-acting beta-agonists used

A

used only in combination with inhaled corticosteroids for maintenance therapy; not used alone; not used for acute exacerbations

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21
Q

How do antimuscarinic agents work

A

reverses vagal contribution to bronchoconstriction; competitively inhibitis muscarinic receptor (block acetylcholine activation)

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22
Q

The effectiveness of antimuscarinic agents is related to

A

muscarinic contribution to bronchospasm; limited effectiveness in allergic asthma; greater effectiveness in non-allergic conditions such as COPD

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23
Q

Antimuscarinic agents may be an alternative to

A

long-acting beta-agonists in combination with steroids

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24
Q

Atropine

A

antimuscarinic agent; effective, but has systemic side-effects even when delivered by inhalation

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25
Q

Ipratropium bromide

A

antimuscarinic agent; quaternary ammonium derivative with decreased absorption

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26
Q

Tiotropium

A

longer-acting selective anti-muscarinic approved for COPD

27
Q

Methylxanthines

A

theophylline, caffeine, theobromine

28
Q

Not used very commonly but remains an inexpensive alternative to other therapies

A

Methylxanthines

29
Q

Mechanism of action of methylxanthines

A

relates to inhibition of phosphodiesterase; blocks inactivation of cAMP; results in increased intracellular levels of cAMP

30
Q

What do methylxanthines do

A

cause bronchodilation and smooth muscle relaxation; also inhibits activation of inflammatory cells, including mast cells

31
Q

What can low dose methylxanthines potentiate?

A

may also potentiate the action of corticosteroids in COPD

32
Q

Systemic effects of methylxanthines mimic

A

mimic beta-adrenergic stimulation: cortical arousal and increased alertness, nervousness and tremor, tachycardia, increased CO, rare arrhythmias, stimulation of gastric acid and digestive enzyme secretion, increased diaphragmatic function and ventilatory effort

33
Q

Theophylline

A

once commonly used as a mainline asthma drug; now used primarily in combination with steroids; less expensive than many other maintenance therapies

34
Q

Aminophylline

A

theophylline-ethylenediamine complex

35
Q

roflumilast

A

selective PDE4 inhibitor

36
Q

Main issues with theophylline

A

wide variation in blood levels, narrow window of therapeutic range; must closely monitor blood levels to avoid toxicity

37
Q

Side effects/toxicity symptoms with theophylline

A 
tremor nervousness (therapeutic range)
anorexia, nausea, vomiting, abdominal discomfort, headache anxiety (upper therapeutic range)
seizures and arrhythmias (>40 mg/L)
38
Q

Intracellular signaling in mast cells

A

increased GTP stimulates secretion

increased ATP inhibits secretion

39
Q

Mast cell mediator blockers

A 
Anti-IgE
beta agonists, methylxanthines
cromolyn sodium
leukotriene synthesis inhibitors
leukotriene receptor blockers
anti-histamines
40
Q

Omalizumab (Xolair)

A

monoclonal antibody that targets the Fc portion of IgE, preventing its attachment to the FcE receptor on mast cells and basophils

41
Q

MOA of cromolyn sodium and nedocromil sodium

A

appear to inhibit mast cell degranulation by a poorly understood mechanism; also inhibits other clel types such as eosinophils

42
Q

How is cromolyn sodium used?

A

Used prophylactically to inhibit asthma caused by allergen inhalation and exercise because it has no effect on bronchoconstriction; neither as potent or predictable as steroids; used as an adjunct to inhaled steroid therapies

43
Q

How are anti-histamines used

A

used prophylactically, especially for allergy-induced asthma; not useful for acute exacerbations of asthma or late phase reactions

44
Q

LTB C, D, and E act through

A

Cys-LT1 and Cys-LT2 (7-spanning membrane receptors with g-proteins)

45
Q

What do leukotriene modifiers do?

A

cause bronchoconstriction that is slower and more persistent than histamine or cholinergic stimulation; potentiate bronchial reactivity to histamine; increase mucosal edema, hypersecretion of mucous

46
Q

Two approaches of leukotriene modifiers

A
  1. inhibition of 5-lipoxygenase (zileuton)

2. LTD4 receptor antagonists (zafirlukast and montelukast)

47
Q

Pros and cons of leukotriene modifiers

A

less effective against inflammation than steroids, but reduce exacerbations of bronchoconstriction; particularly effective in aspirin-induced asthma

48
Q

What has Zileuton been associated with

A

liver toxicity

49
Q

What are anti-inflammatory medications useful for

A

maintenance therapy of asthma not controlled by periodic use of beta-agonist inhalers

50
Q

Mainstay of anti-inflammatory therapy

A

corticosteroids

51
Q

Corticosteroids inhibit

A

inflammatory cell activation and cytokine production (NFk-b signaling)

52
Q

What are steroids used

A

used early in an exacerbation to decrease late phase reactions

53
Q

How are steroids best delivered

A

due to systemic anti-inflammatory and endocrine effects, best delivered in airway; oral and parenteral use limited to urgent cases where bronchodilators are insufficient

54
Q

Inhaled steroids

A

beclomethasone, budesonide, ciclesonide, fluinisolide, fluticasone, mometasone, and triamcinolone

55
Q

What can inhaled steroids be associated with

A

oropharyngeal candidiasis; may increase risk of osteoporosis and cataracts long term; may slow growth in children

56
Q

short-acting bronchodilators

A

epinephrine, isoproterenol, albuterol, terbutaline, metaproterenol

57
Q

long-acting bronchodilators

A

salmeterol and formoterol

58
Q

muscarinic inhibitors

A

ipratropium bromide, tiotropium

59
Q

methylxanthines

A

theophylline, aminophylline, dyphylline, roflumilast

60
Q

Anti-IgE

A

omalizumab

61
Q

Cromolyn

A

cromolyn sodium, nedocromil sodium

62
Q

Anti-leukotrienes

A

zileuton, zafirlukast, montelukast

63
Q

steroids

A

prednisone, beclomethasone, fluticasone, ciclesonide

Pharmacology Test #4 (9 decks)

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