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Pulm by Minnie: AH Update > SM 180a - Pulmonary Pharmacology > Flashcards

SM 180a - Pulmonary Pharmacology Flashcards

1
Q

Which LTRA (leukotrione antagonist) most commonly used as an add-on therapy for asthma?

A

Montelukast

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2
Q

What are the indications for inhaled beta-2 agonists?

A
  • COPD
    • LABA can be used as a first line controller, but usually LAMA is slightly preferred
    • LABA would be the first thing added to LAMA if COPD is poorly controlled on LAMA alone
  • Asthma
    • LABA = add-on if poorly controlled on ICS
    • SABA is a go-to during exacerbations
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3
Q

Are beta-blockers safe to use in patients with heart failure and COPD?

A

Yes!

But make sure to use a beta-1 selective beta blocker

The patient can still use their inhaled beta-2 agonist for COPD

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4
Q

What are the 3 pathophysiologic hallmarks of asthma?

A
  1. Airway hyperreactivity
  2. Airflow obstruction
  3. Mucus secretion
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5
Q

What are the possible advese effects of inhaled muscarinic receptor antagonists?

Which patients are most at risk for these adverse effects?

A

Possible effects

  • Dry as a bone
    • Dry mouth, urinary retention
  • Red as a beet
  • Hot as a desert
  • Blind as a bat - dilated pupils
    • Unilateral: most often seen if some of the medication leaks through a mask
  • Mad as a hatter

Usually, there is little systemic toxicity because the inhaled agent is poorly absorbed. However, be aware of other anticholinergic agents the paient might be taking

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6
Q

What are the indications for PDE-4 inhibitors

A
  • COPD
    • Group 4 (late stage)
      • Exacerbations and/or severe airflow obstruction despite LAMA, LABA, and ICS
    • Used to decrease exacerbations, but nor mortality
    • Need a productive cough, chronic bronchitis phenotype
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7
Q

What are the indications for inhaled corticosteroids?

A
  • COPD
    • Add ICS to LABA + LAMA for triple therapy in group D COPD if exacerbations persist on dual therapy
  • Asthma
    • ICS = first line controller
    • Add LABA at step 2 if symptoms persist
    • Increase ICS at subsequent steps if symptoms persist
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8
Q

What are the 3 pathophysiologic hallmarks of COPD?

A
  1. Fibrosis fo the small airways (bronchiolitis)
  2. Alveolar wall destruction (emphysema)
  3. Mucus hypersecretion
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9
Q

A 38 year old male with asthma presents to pulmonary clinic for evaluation. Despite use of inhaled mometasone at a low dose, he continues to experience frequent asthma symptoms including night-time awakenings and use of his albuterol inhaler several times per day for chest tightness and wheezing. He is a non-smoker and is careful to avoid known triggers for his asthma. He demonstrates good inhaler technique in clinic. Which of the following would be the preferred “step-up” in therapy for his asthma?

  1. Switch to a mometasone/formoterol combination inhaler
  2. Add tiotropium
  3. Add roflumilast
  4. Add montelukast
  5. Switch to high-dose mometsone inhaler
A

a. Switch to a mometasone/formoterol combination inhaler

This patient has persistent asthma symptoms despite the use of a low-dose inhaled corticosteroid. The preferred step-up therapy would be transition to an inhaled ICS/LABA combination

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10
Q

When is a LAMA used for asthma control

A

Hardly ever - it is a “salvage therapy”

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11
Q

What are the possible adverse effects of Roflumilast (PDE-4 inhibitor)

A

GI effects

Adverse effects are reversible and diminish with continued use

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12
Q

What are the possible adverse effects of inhaled corticosteroids?

A
  • Thrush
    • Patients should rinse their mouths after use
  • Dysphonia
  • Skin bruising
  • Increased pneumonia insidence

ICS are ususally well-tolerated with minimal systemic side effects

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13
Q

Which muscarinic receptors do inhaled muscarinic receptor antagonists act on?

What is the effect?

A

M3 receptor

  • Normally
    • ACh binds to the M3 muscarinic receptor
  • > increaed intracellular Ca2+
  • > Bronchoconstriction
  • Inhaled muscarinic receptor antagonists prevent ACh from binding to the M3 muscarinic receptor
    • ​-> No rise in intracellular Ca2+
    • -> No bronchoconstriction
    • -> Bronchodilation
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14
Q

Describe the role of theophylline in asthma control

A
  • Used to be a mainstay of therapy
    • Nonselective PDE inhibitor and adenosine antagonist
  • However, it has a narrow therapeutic window and requires monitoring
  • Not commonly used anymore
    • Occasional use in difficult to control asthma
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15
Q

When is LABA used for COPD control?

A

First line

(although LAMA is preferred)

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16
Q

When is an ICS used for asthma control?

A

First line therapy

17
Q

What are the potential adverse effects of inhaled beta-2 agonists?

A
  • Tremors
  • Palpitations
  • Tachycardia
  • Hypokalemia
  • Hyperglycemia
  • Lactic acidosis

Due to systemic absorption of the beta-2 agonist in other tissues, with possible cross-reactivity with beta-1 receptors

18
Q

What are the indications for systemic corticosteroids

A

Use in exacerbations only

19
Q

Describe the mechanism of action of phosphodiesterase-4 inhibitors (PDE-4 inhibitors)

A
  • Normally:
    • PDEs degrade second messenger enzymes
    • PDE-4 selectively inactivates cAMP, thus increasing the inflammaotry and remodeling effects fo cells in the lung
  • PDE-4 inhibitors prevent these inflammatory and remodeling effects by preventing the inactivation of cAMP
20
Q

Describe the mechanism of action of leukotriene receptor antagonists (LTRAs)

A
  • Normally
    • Leukotrienes are released from mast cells, eosinophils, and basophils
    • They are produced during the breakdown of arachadonic acid via 5-lipooxygenase pathway
    • Contribute to asthma pathogenesis
      • Bronchoconstriction
      • SM proliferation
      • Neutrophil, eosinophil migration
      • Tissue edema
  • LTRAs block these effects​
    • ​Zileuton: 5-lipooxygenase inhibotor
    • Montelukast, Zafirlukast: Inhibit the cysteinyl leukotriene-L-receptor
21
Q

A 40 year-old female with persistent asthma presents to urgent care clinic for discomfort in the back of her mouth. She uses several inhalers but did not bring them with her to clinic and does not remember their names. On examination of her oropharynx, you notice numerous white plaques (see picture). Which of the following inhalers most likely caused her new diagnosis?

a. Mometasone
b. Tiotropium
c. Formoterol
d. Indacaterol
e. Umeclidinum

A

a. Mometasone

The patient has thrush, a potential side effect of ICS use

22
Q

Describe the mechanism of action of inhaled corticosteroids on the respiratory system

A
  • Corticosteroids bind to cytoplasmic glucocorticoid receptors
  • Receptor-steroid comlex translocates to the nucleus
  • Modulates host inflammation
    • Increases anti-inflammatory gene transcription
    • Decreases inflammatory gene transcription
  • Decreases the number of inflammatory cells in the airway
  • ​Inhibits mucus production and hypersecretion
  • Decreased capillary leak
23
Q

A 65 year-old male presents to pulmonary clinic for advice on management of his COPD. He was diagnosed with COPD 10 years ago and is a former smoker with a 45 pack-year history. He produces greenish-yellow sputum most mornings and has had three hospitalizations for COPD this year. His pulmonary function tests show obstructive physiology with an FEV1 of 35% predicted. Non-contrast computed tomography of the chest shows moderate diffuse emphysema and airway wall thickening. His current inhalers include tiotropium and budesonide/formoterol. He demonstrates good inhaler technique in clinic and is up-to-date on his recommended vaccinations. Which of the following medications may help reduce his rate of exacerbations?

a. Theophylline
b. Roflumilast
c. Montelukast
d. Cilostazole
e. Mepoluzimab

A

b. Roflumilast

A PDE-4 inhibitor

The patient has GOLD group 4 COPD, chronic bronchitis, and continued exacerbations despite maximal inhaler therapy

24
Q

Summarize the recommended therapies for the 4 COPD groups

Group A:

Group B:

Group C:

Group D:

A
  • Group A: LAMA or LABA
  • Group B: LAMA or LABA, combine if persistent symptoms
  • Group C: LAMA + LABA, add ICS if persistent symptoms or exacerbations
  • Group D: LAMA + LABA + ICS, add PDE-4 inhibitor if persistent symptoms or exacerbations
25
Q

What are the possible adverse effects of LTRAs?

A

Montelukast: Headache, but well-tolerated overall

Zileuton: Hepatic dysfunction

26
Q

When is LAMA used for COPD control?

A

First line

27
Q

When is LABA used for asthma control?

A

Only as an add-on to ICS if necessary

(ex: uncontrolled symptoms or high risk of exacerbation)

**Never use as monotherapy for control**

28
Q

Give an example of a PDE-4 inhibitor

A

Roflumilast

29
Q

When is an ICS used in for COPD control?

A

Only as a salvage therapy if max LAMA + LABA is not enough

30
Q

Summarize the recommended controller therapies for asthma

Step 1:

Step 2:

Step 3:

Step 4:

Step 5:

A
  • Step 1
    • ​Consider low-dose ICS if necessary
  • Step 2
    • ​Low-dose ICS
    • Add LTRA (montelukast) if necessary
  • Step 3
    • ​Low-dose ICS + LABA
    • Increase ICS dose, add LTRA if necessary
  • Step 4
    • Med/high ICS + LABA
  • Step 5
    • Med/high ICS + LABA, refer for add-on treatment
    • May need low-dose OCS for control

Rescue: SABA as needed at all stages, add low-dose ICS for rescue at step 3 or higher

31
Q

What are the indications for inhaled muscarinic antagonists?

A
  • COPD
    • LAMA = First line agent
  • Asthma
    • LAMA: Use as a controller only in patients with continued exacerbations despite medium/high doses of ICS + LABA
32
Q

What are the indications for LTRAs?

A
  • Asthma
    • Adjunctive to ICS for control
    • An alternative, but not preferred controller in steps 2-4
    • Montelukast is most commonly used
33
Q

Which contributors to asthma pathogenesis are produced by the 5-lipooxygenase pathway?

Which agents prevent the negative effects of these contributors?

A

Leukotrienes

Leukotriene receptor antagonists (LTRAs)

Pulm by Minnie: AH Update (34 decks)

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