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HLTH 2511 > Module H > Flashcards

Module H Flashcards

1
Q

Describe why acetylcysteine is no longer recommended as a mucolytic, but pulmozyme is

A

Acetylcysteine causes too much liquification of mucus, causing breakdown of both infected and protective mucus. Dornase Alfa (pulmozyme) breaks down DNA only in infected mucus and therefor maintains protective mucus in the lungs

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2
Q

Mucus in the lungs is produced by _____ and _____. It is composed of two layers: the _____ and the _____.

A

Mucus in the lungs is produced by goblet cells and mucus glands . It is composed of two layers: the sol layer and the gel layer.

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3
Q

The _____ layer of pulmonary mucus makes up 95% of the total volume. the _____ layer contributes viscosity and elasticity. Cilia are primarily located in the _____ layer.

A

The sol layer of pulmonary mucus makes up 95% of the total volume. the gel layer contributes viscosity and elasticity. Cilia are primarily located in the sol layer.

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4
Q

List three factors that are important in changing the transport of mucus

A
  • changes in mucus volume
  • changes in mucus composition
  • the hydrationn state of the individual
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5
Q

Define sputum

A

sputum is expectorated secretions, including mucus and saliva, from the oropharynx, nasopharynx, and lower airways

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6
Q

Compare and contrast the MOA of mucomyst (acetylcysteine) and pulmozyme (dornase alpha).

A

Both are mucolytic agents

acetylcysteine cleaves disulfide bonds in mucus, reducing mucus viscosity. It is no longer recommended due to it’s non-specific liquification of mucus

pulmozyme cleaves DNA in infected mucus, selectively reducing viscosity of infected mucus. it is a recombinant form of DNAse

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7
Q

Describe a use of acetylcysteine not related to mucolysis

A

it is used to reverese acetominophen overdose

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8
Q

What is the role of pulmonary surfactant in normal respiration

A

it reduces surface tension at the liquid-air interface of the lungs, aiding in full lung expansion. Increased surface tension leads to increased work of breathing

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9
Q

Describe the etiology of respiratory distress syndrome (RDS) in premature neonates, and list another cause of RDS

A

neonates at <35 weeks gestation produce insufficient surfactant so alveolar surface tension is too great and their work of breathing is excessively high

RDS also occurs with meconium aspiration, which inactivates pulmonary surfactant

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10
Q

BLES (Bovine Lipid Extracted Surfactant)

A
  • Natural surfactant extracted from bovine lungs
  • First choice treatment for managment of RDS
  • Reduces pulmonary gas-liquid interface surface tension and work of breathing
  • Instilled through endotracheal tube
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11
Q

What are the two types of antitussive, and give examples of each

A
  1. Locally-acting: Menthol, other related sprays and lozenges
  2. Centrally acting: Codeine, Dextromethorphan, Hydrocodone
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12
Q

Describe the use of opioids as antitussives

A

All opioids have some antitussive effects. Opioids for antitussive therapy are selected based on ratio of antitussive to other effects (ex: codeine, hyrocodone). Dextromethorphan is an opioid that has strong antitussive effect with little to no euphoric, analgesic, or sedative effects at therapeutic doses and is often given OTC.

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13
Q

Describe the general MOA and clinical use of expectorants

A

Expectorants are generally hypertonic solutions that draw moisture into mucus to facilitate clearing of secretions.

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14
Q

Prolastin

A
  • Alpha1 Proteinase Inhibitor
  • Used in patients with alpha1 antitrypsin deficiency to reduce alveolar damage due to elastin degradation
  • alpha1 antitrypsin usually inhibits elastase and protease, preventing damage from these endogenous enzymes.
  • Used in management of alpha1 antitrypsin-associated emphysema
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15
Q

Describe pharmacologic treatment of Interstitial Pulmonary Fibrosis (IPF)

A

usually treated with Esbriet (perfenidone). MOA is unclear but is though to interfere with production of inflammatory proteins like TGF-Beta and TNF

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16
Q

Esbriet (Perfenidone)

A
  • Anti-fibrotic, anti-inflammatory
  • Used in management of IPF
  • thought to interfere with production of inflammatory proteins like TGF-Beta and TNF
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17
Q

List 4 potential stimuli of asthma exacerbation

A
  • cold air
  • exercise
  • allergens
  • emotional stress
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18
Q

List three causes of airway obstruction in asthma

A
  • Bonchoconstriction
  • Airway inflammation
  • Lumen obstruction by mucus, inflammatory cells, and epithelial debris
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19
Q

The three leukocytes most involved in asthma pathogenesis are:

A

TH2 cells (mainly in atopic asthma), mast cells and eosinophils

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20
Q

The two main types of asthma are:

A

Allergic/extrinsic/atopic/TH2

Non-allergic/intrinsic/non-atopic/non-TH2

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21
Q

The mainstays of pharmacological asthma care are:

A

Inhaled corticosteroids (ICS)

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22
Q

Describe important asthma control criteria

A
  • FEV1 and PEF should be ≥90% of personal best
  • PEF variation throughout the day should be limited to 15% (normal decrease is expected due to circadian rhythm of corticosteroid production)
  • Rescue inhalers should not be used more than 3 times per week
  • There should be no absenteeism due to asthma
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23
Q

Describe general features of a continuum of care for asthma

A
  • begins with environmental control, education, written action plan, etc.
  • All pts. receive ICS (to reduce hyperreactivity) and fast-acting bronchodilators for symptom control
  • Add-on therapy starts with LABA if ICS does not maintain control
  • Moderate ICS dosage increase or LTRA may be added if low-dose ICS and LABA does not control
  • Difficult-to-control asthma may require Anti-IgE, anti-IL-5, or macrolide treatment
  • Severely uncontrolled asthma may require systemic corticosteroids (prednisone)
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24
Q

What are two ways in which ICSs are useful in asthma therapy?

A
  • they act as anti-inflammatory agents
    • reduce airway responsiveness, prevent persistent symptoms, improve lung function, reduce mortality
  • they potentiate the effects of beta-agonists
    • reduce uncoupling and down-regulation of beta agonists. Also inhibit uptake of exogenous catecholamines, prolonging their effect
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25
Q

ICSs usually require a _____ (high/low) dose to maintain asthma control

A

low

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26
Q

list concerns with chronic use of ICS

A
  • decreased bone density/osteoporosis
  • HPA suppression with very high doses
  • Fungal infections
  • Dysphonia
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27
Q

What property of ICS allows them to be used on a long-term basis with minimal adverse effects

A

they have high high first-pass metabolism and are administered by the inhalational raoute, so there are limited systemic effects

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28
Q

Which ICS can only be administered by way of turbuhaler DPI

A

Pulmicort (Budesonide)

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29
Q

Which ICSs can be given QD instead of BID, and what are their available delivery devices?

A

Alvesco (Ciclesonide) - MDI

Pulmicort (Budenoside) - DPI Turbuhaler

Arnuity (fluticasone furoate) - DPI

Asmanex (Mometasone) - MDI or twisthaler

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30
Q

QVAR (Beclomethasone dipropionate)

A
  • Inhaled Corticosteroid (ICS)
  • Used as an anti-inflammatory and to potentiate beta-agonists effects in asthma control
  • MDI only given BID
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31
Q

Flovent (Fluticasone propionate)

A
  • Inhaled Corticosteroid (ICS)
  • Used as an anti-inflammatory and to potentiate beta-agonists effects in asthma control
  • MDI or Diskus DPI given BID
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32
Q

Alvesco (Ciclesonide)

A
  • Inhaled Corticosteroid (ICS)
  • Used as an anti-inflammatory and to potentiate beta-agonists effects in asthma control
  • MDI only, given QD
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33
Q

Pulmicort (Budesonide)

A
  • Inhaled Corticosteroid (ICS)
  • Used as an anti-inflammatory and to potentiate beta-agonists effects in asthma control
  • Turbuhaler DPI only, given BID
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34
Q

ICS drugs have generic names ending in _______ or _______

A

-asone or -sonide

ex: beclomethasone, fluticasone, ciclesonide, budesonide

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35
Q

Describe two uses of systemic corticosteroids in asthma management

A
  • management of acute exacerbations of asthma
  • long-term managment of the difficult to control asthmatic. Systemic steroids should be avoided if possible
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36
Q

Describe the MOA and how LTRAs are used in asthma management

A
  • Competitive antagonists to leukotriene receptors, producing an anti-inflammatory effect
  • Have no effect on the leukotrienes involved in the most severe asthma exacerbations, so never indicated for “rescue” use
  • Generally given as an adjunct to low-dose ICSs in moderate to severe asthma
  • may be given as monotherapy in patients that can or will not take ICSs
  • given orally
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37
Q

Singulair (Montelukast)

A
  • Leukotriene Receptor Antagonist (LTRA)
  • second-line asthma controller
  • given as adjunct with ICS or as second-line monotherapy where ICS not tolerated
  • not useful in severe exacerbations of asthma
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38
Q

Accolate (Zafirlukast)

A
  • Leukotriene Receptor Antagonist (LTRA)
  • second-line asthma controller
  • given as adjunct with ICS or as second-line monotherapy where ICS not tolerated
  • not useful in severe exacerbations of asthma
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39
Q

Describe the use of anti-IgE agents in asthma management

A
  • used when combination ICS and LABA is not sufficient to control asthma
  • antibody given to inhibit IgE binding to mast cells
  • prevents release of mediators in allergic response
  • given SQ every 2-4 weeks for 3-4 months
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40
Q

Xolair (Omalizumab)

A
  • Anti-IgE antibody
  • inhibits inflammatory mediator release from mast cells
  • used to treat asthma that is not controlled by med/high ICS/LABA combination therapy
  • given SQ every 2-4 weeks for 3-4 months
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41
Q

Describe the use of anti-IL-5 agents in asthma management

A
  • used when med/high ICS/LABA does not control asthma
  • IL-5 is involved in recruitment, activation, differentiation, and growth of eosinophils
  • Anti-IL-5 agents inactivate interleukin-5, reducing the number of activated eosinophils in blood and sputum
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42
Q

Cinquair (Rexlizumab)

A
  • Anti-IL-5 agent
  • Inactivates interleukin-5 (IL-5) which is involved in recruitment, activation, differentiation, and growth of eosinophils. Cinquair reduces number of activated eosinophils in blood and sputum
  • used in management of refractory asthma, reduces inflammation and airway remodelling
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43
Q

Nucala (Mepolizumab)

A
  • Anti-IL-5 agent
  • Inactivates interleukin-5 (IL-5) which is involved in recruitment, activation, differentiation, and growth of eosinophils. Nucala reduces number of activated eosinophils in blood and sputum
  • used in management of refractory asthma, reduces inflammation and airway remodelling
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44
Q

Describe use of macrolides in asthma management

A
  • used for both anti-inflammatory and anti-microbial effects
  • may reduce frequency of exacerbations for severe asthmatics
  • prolonged use may lead to bacterial resistance and hearing damage
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45
Q

Why should LABAs never be used as monotherapy for asthma control?

A

They only counter bronchoconstriction and do not address the underlying issue of inflammation and airway hyper-reactivity. They can therefore mask the underlying problem

46
Q

How are LABAs useful in controlling nocturnal exacerbations of asthma?

A

They have a long duration of action and also potentiate the effects of both exogenous and endogenous CSs when they are at theire lowest (at night)

47
Q

What property of LABAs is primarily responsible for their long duration of action?

A

They have a highly lipohillic structure, allowing them to remain embedded in the membrane-bound receptor for longer

48
Q

LABAs have ______ (greater / less) Beta-2 selectivity than SABAs

A

greater

49
Q

Salmeterol is given ____ (QD / BID / PRN)

A

BID

not to be given PRN! Salmeterol is only used as a controller in combination with an ICS, not reliever

50
Q

The LABA that can be used as both a controller and reliever of asthma is ________

A

Formoterol

Formoterol has a fast onset of action and long duration of action (12 hrs.) so it is classed as both a LABA and a FABA.

51
Q

2 advantages of formoterol over salmeterol are:

A
  • Faster onet, so may be used as a rescue inhaler (both a controller and reliever)
  • Better bronchoprotector; i.e. prevents airway reactivity against common irritants
52
Q

What are the main advantages of giving ICSs and LABAs as a combined inhaler? Does this improve effectiveness?

A
  • increased ease of administration
  • Reduces risk of taking LABA without ICS
  • No evidence that this is more effective then giving the agents as seperate formulations
53
Q

Serevent (Salmeterol)

A
  • Long-acting Beta Agonist (LABA)
  • 12hr duration of action with relatively slow onset
  • Used always as combination therapy with an ICS for asthma control
  • causes bronchodilation and potentiates anti-inflammatory effects of ICS
  • never to be used as monotherapy or as a rescue inhaler
54
Q

Oxeze (Formoterol)

A
  • Long-acting Beta Agonist (LABA), Fast-acting Beta Agonist (FABA)
  • 12hr duration of action with relatively fast onset
  • Used always as combination therapy with an ICS for asthma control
  • causes bronchodilation and potentiates anti-inflammatory effects of ICS
  • may be used for asthma control or relief
55
Q

Describe how and why LABAs and ICSs are given as combination therapy

A
  • often given as a single combination inhaler (symbicort, advair, zenhale, etc.)
  • provides asthma control where low-dose ICS monotherapy is insufficient
  • ICSs and LABAs potentiate each others’ effects so that both anti-inflammatory and bronchodilatory effects are exagerated
  • May be given as separate inhalers if flexibility in dosing is required (i.e. need to increase LABA without increasing ICS)
56
Q

Advair (Fluticasone + Salmeterol)

A
  • Combination ICS and LABA
  • used to control asthma that is not adequately controlled with low-dose ICS alone
  • ICS and LABA potentiate each others’ effects, improving both anti-inflammatory and bronchodilatory actions
  • Should NOT be used as a reliever
57
Q

Symbicort (Budesonide+ Formoterol)

A
  • Combination ICS and LABA
  • used to control asthma that is not adequately controlled with low-dose ICS alone
  • ICS and LABA potentiate each others’ effects, improving both anti-inflammatory and bronchodilatory actions
  • May be used as a reliever for brief exacerbations of asthma
58
Q

Zenhale (Mometasone + Formoterol)

A
  • Combination ICS and LABA
  • used to control asthma that is not adequately controlled with low-dose ICS alone
  • ICS and LABA potentiate each others’ effects, improving both anti-inflammatory and bronchodilatory actions
  • May be used as both controller and reliever
59
Q

Spiriva (Tiotropium)

A
  • Long-Acting Anti-Muscarinic
  • Used as combination therapy with ICS for “ultra” long-acting control of asthma symptoms
  • also used in COPD management
  • most useful where there is parasympathetic/vagal mediated bronchoconstriction and mucus production
60
Q

Describe the use of methylxanthines in asthma control

A
  • includes caffeine and theophylline
  • central and peripheral stimulants. Theophylline is most potent bronchodilator, caffeine is more potent central stimulant
  • less common now in asthma therapy with advent of more effective, safer, and more convenient bronchodilators
  • caffeine still commonly used in apnea of prematurity
  • MOA unclear, but involves PDE inhibition, adenosine receptor blockage, and increased catecholamine production
61
Q

What is one of the major disadvantages of theophylline for asthma control in terms of administration?

A
  • serum levels need to be monitored to maintain a therapeutic dosage
  • metabolism is highly patient-dependent and therapeutic index is narrow
62
Q

what are common adverse effects of methylxanthines?

A
  • nausea
  • cardiac arrhythmias
  • tachypnea
  • seizures
63
Q

List the three common classes of asthma relievers

A
  • Short-Acting Beta Agonists (SABAs) ex: salbutamol
  • fast, Long-Acting Beta Agonists (LABAs): ex: formoterol
  • Short-Acting Anti-Muscarinics (SAAMs) ex: ipratropium
64
Q

Asthma relievers are given on a _____ basis

A

prn

65
Q

What are some restrictions on use of asthma relievers

A
  • should never be given as monotherapy because they can mask underlying disease progression
  • Frequent use may lead to desensitization and loss of asthma control. Frequent use should be adressed with escalating control medications
66
Q

The two most common SABAs are:

A

ventolin (salbutamol) and bricanyl (terbutaline)

67
Q

what is airomir?

A

airomir is an auto-inhaler delivery mechanism for ventolin

68
Q

What are two common clinical uses of SABAs?

A
  • relief of acute bronchospasm
  • short-term prevention of exercise-induced bronchospasm
69
Q

What are common side effects of SABAs?

A
  • tremors
  • cardiac stimulation; tachycardia
  • headache & anxiety
  • metabolic effects
    • increased blood glucose and insulin
    • hypokalemia due to cotransport of potassium and glucose
  • tolerance and loss of asthma control
70
Q

explain how SABA use may lead to a pardoxical decrease in PaO2

A
  • ventolin promotes pulmonary vasodilation, which may lead to a V/Q mismatch as poorly ventilated alveoli are perfused
71
Q

The preferred method of administration for SABAs is _______ (MDI/nebulizer)

A

MDI

72
Q

What are the medications present in symbicort and how is it used?

A
  • symbicort = formoterol (FLABA) + budesonide (ICS)
  • used for asthma control in the traditional manner since the ICS and LABA potentiate each others’ activities
  • may be used as a reliever because of formoterol’s fast onset, which is a unique property of this drug
  • Always given by turbuhaler DPI
73
Q

Why is ipratropium not recommended as a first-line asthma reliever?

A

it has a slower onset than SABAs

74
Q

Describe the clinical use of ipratropium

A
  • quaternary antimuscarinic that is used as a second-line bronchodilator
  • often used in combination with a SABA for improved bronchodilation due to synergistic effect
  • may be used as primary relief in patients that are unable to tolerate a SABA
75
Q

Describe the MOA of ipratropium

A
  • blocks the muscarinic GPCR in lungs, preventing ACh binding
  • prevents influx of Ca2+ and therefore reduces bronchoconstriction
76
Q

How is MgSO4 used in asthma management?

A
  • used for relief of acute bronchoconstriction in combination with SABA, LABA, and ICS
  • generally given in emergency setting
  • may be given IV or nebulized
77
Q

how does MgSO4 aid in treatment of acute bronchoconstriction?

A
  • has synergistic effects with SABAs
  • exact MOA is unknown, but blocks influx of Ca2+ into bronchial smooth muscle cells
  • has anti-inflammatory effects that are not well understood
78
Q

The objective flow measurement that is most indicative of COPD is:

A

reduced FEV1 / FVC ratio; generally less than 0.7 in COPD

79
Q

describe long term systemic consequences of COPD

A
  • Persistent inflammation of lung parenchyma leads to fibrosis and air trapping, increasing WOB
  • hypoxemia
  • Pulmonary hypertension due to compensatory vasoconstriction
  • Eventual cor pulmonale
80
Q

List risk factors for developing COPD

A
  • smoking or second-hand smoke exposure
  • alpha-1-antitrypsin deficiency
  • History of childhood viral infections
81
Q

The single most effective way to prevent COPD is:

A

smoking cessation

82
Q

Three pharmacologic interventions to aid in smoking cessation are:

A
  • Nicotine replacement therapy (NRT)
  • Zyban (Buproprion): antidepressant
  • Champix (Verenicline): Partial nicotine agonist
83
Q

describe the function of Zyban (bupropion) in smoking cessation therapy

A
  • antidepressant (atypical, norep and dopamine reuptake inhibitor)
  • increases dopamine concentration when ceasing smoking
  • more effective when combined with NRT
84
Q

Describe the function of Champix (verenicline) in smoking cessation therapy

A
  • partial nictone receptor agonist
  • acts as a competitive antagonist in presence of nicotine while maintaining baseline dopamine release
85
Q

Drug dosages commonly ______ (are / are not) titrated down in copd patients who are well managed

A

are not!

typically drug dosages are maintained or more drugs are added

86
Q

The basis of COPD pharmacotherapy is:

A

bronchodilators

87
Q

All COPD patients at risk of AECOPD should carry:

A

salbutamol

88
Q

define SABD and LABD and describe the types of drug in each class

A
  • SABD = short acting bronchodilator
    • includes SABAs and SAACs (AKA SAAMs)
    • used for relief of acute exacerbation
  • LABD = long acting bronchodilator
    • includes LABAs and LAAMs
    • used for maintenance/control and to improve long-term outcomes (LAAMs)
89
Q

Describe how ipratropium is used in COPD and contrast to use in asthma

A
  • SAAM/SAAC used to reduce bronchoconstriction and improve respiratory function
  • Used as combination therapy with salbutamol with synergistic effects
  • unlike in asthma, is used as a daily maintence bronchodilator (QID)
  • appears to be more effective for bronchodilation in COPD than asthma
    • greater improvement in FEV1 % change than SABAs
90
Q

Compare and contrast SABAs and SAAMs in COPD management

A
  • both used as relief bronchodilators. SAAMs also used for daily maintenance (QID)
  • SABAs have faster onset and shorter duration
  • SAAMs have fewer adverse effects (tremor, paradoxical PaO2 fall, tolerance)
  • SAAMs mostly affect larger, central airways. SABAs affect both central and peripheral airways
91
Q

Describe use of LAAMs in COPD management and give an example

A
  • used as daily maintenance (QD)
  • generally given when COPD is no longer managed with QID SAAM
  • prototype of class is spiriva (tiotropium)
92
Q

Tiotropium _______ (does / does not) lead to formation of tolerance with prolonged use

A

does not!

93
Q

___________ (LABAs / LAAMs / both) are shown to reduce mortality in COPD

A

LAAMs

LABAs are used for maintenance bronchodilation but have not been shown to decrease mortality

94
Q

how are formoterol and salmeterol used in COPD management?

A
  • both are long-acting beta agonists (LABAs)
  • used for maintenance bronchodilation
  • combination therapy with LAAM preferred due to synergistic effects and reduced mortality vs. monotherapy
95
Q

ICSs _____ (are / are not) used as monotherapy in COPD management. Why is this?

A

are not!

ICSs have their most pronounced effects on eosinophils, which are primarily implicated in asthma pathogenesis. Inflammatory cells, macrophages, and neutrophils are not as responsive.

There is also increased risk of pneumonia with ICSs in COPD due to immunosupression

96
Q

Systemic CSs _____ (are / are not) used for management of COPD

A

are not!

97
Q

Describe “triple therapy” for COPD management

A
  • triple therapy = ICS + LABA + LAAM
  • improves lung function and reduces exacerbation risk
98
Q

What are three classes of drugs other than ICS, LABA, and LAAM that are used in COPD therapy

A
  • PDE4 inhibitors
  • Antibiotics (macrolides)
  • Mucolytics
99
Q

How are PDE4 inhibitors (ex: Daxas/roflumilast) used in COPD management?

A
  • used in combination with LABA/ICS to reduce inflammation
  • prevents cAMP breakdown in smooth muscle cells
  • causes severe diarrhea as a side effect
100
Q

How are macrolides used in COPD management?

A
  • given intermittentently to reduce AECOPD in pts. at risk of exacerbation due to pneumonia
  • increased risk of drug resistance
101
Q

Describe use of acetylcysteine in COPD

A
  • used as a mucolytic and anti-oxidant
  • reduces number of exacerbations and improves health status
  • not combined with ICS
102
Q

What class of asthma does not require treatment with an ICS (SABA prn only)

A

Very mild (even mild asthma should receive ICS treatment)

103
Q

What frequencies of daytime and night time symptoms are considered controlled for asthma?

A

Daytime symptoms <4 days/week

Night time symptoms <1 night/week

104
Q

If asthma is not controlled by ICS alone, the next step should be to ______ (increase ICS dosage / add a LABA)

A

add a LABA

most ICSs have a flat does-response relationship, so increasing dosage is not very effective. Adding a LABA is more effective and potentiates the effects of the ICS

105
Q

Describe the various methods by which ICSs exert therapeutic effects in asthma

A
  • Increase lipocortin expression which inhibits phospholipase A2 activity
  • Inhibit recruitment, maturation, and differentiation of inflammatory cells
  • cause vasoconstriction of microvasculature
  • inhibit synthesis and release of histamine
  • inhibit synthesis and release of inflammatory mediators
106
Q

Describe how ciclesonide is unique as an ICS

A
  • designed intentionally as an “ultra” drug in that it can be given QD effectively
  • it is given as a prodrug which is converted into the active drug by enzymes in the respiratory mucosa which is hypothesized (but not confirmed) to reduce adverse effects (esp. growth retardation in children)
107
Q

What is considered a “controlled” FEV1 and PEF diurnal variation in asthma

A

FEV1 at least 90% of best and PEF variation less than 10-15%

108
Q

What is considered appropriate use of relief inhalers for controlled asthma?

A

<4 uses per week

109
Q

Systemic steroids are administered for ______ (range) days in asthma for ________ or _________. They _____ (do / do not) require tapering upon discontinuance if ICSs are continued afterwards

A

7-14 days

acute exacerbations or chronic management of difficult to control asthma

do not

110
Q

ICSs demonstrate maximal anti-inflammatory response after _______ (duration) of therapy

A

2-3 months

HLTH 2511 (11 decks)

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