Asthma

Question 1

SABA drugs

Answer 1

Albuterol and terbutaline

Question 2

Inhaled corticosteroids drugs

Answer 2

Beclomethasone
Budesonide
Mometasone
Fluticasone
Ciclesonide

Question 3

Leukotriene pathway inhibitor drugs

Answer 3

Zileuton
Zafirlukast
Montelukast

Question 4

LABA drugs

Answer 4

Formoterol and salmeterol

Question 5

Antimuscarinic drugs

Answer 5

Ipratropium and tiotropium

Question 6

Methlxanthine drugs

Answer 6

Theophylline

Question 7

Sympathomimetic agents MOA

Answer 7

• Primary mechanism: relax airway smooth muscle via b2-adrenergic activation; increase cAMP
• Inhibit the release of bronchoconstricting mediators from mast cells
• May inhibit microvascular leakage and increase mucociliary transport by increasing ciliary activity

Question 8

Why do nebulizers require a higher dose versus an inhaler?

Answer 8

The particles are larger

Question 9

Beta2-agonists adverse effects of inhaled

Answer 9

Tremulousness
Heart palpitations/arrhythmias
Cough/throat irritation
Contraindications: Cautiously use in patients with CV disease

Question 10

Corticosteroids MOA

Answer 10

• Presumed to act by their broad anti-inflammatory actions
  
  • Inhibits production of inflammatory cytokines
  • Inhibits the infiltration of asthmatic airways by lymphocytes, eosinophils, and mast cells

Question 11

Corticosteroids clinical use

Answer 11

• Aerosol controller therapy (minimal systemic absorption)
• Improves severity of symptoms, tests of airway caliber and bronchial reactivity, frequency of exacerbations, and quality of life

Question 12

Corticosteroids adverse drug reactions

Answer 12

Oropharyngeal candidiasis, hoarseness, adults - possible risk of osteoporosis and cataracts
Children - slight delay in rate of growth

Question 13

Leukotriene pathway inhibitors MOA

Answer 13

Block leukotriene D4 receptor (except zileuton)

Question 14

LTC4 and LTD4 exert many effects in asthma, including…

Answer 14

Bronchoconstriction
Increased bronchial reactivity
Mucosal edema
Mucus hypersecretion

Question 15

Leukotriene pathway inhibitors are less effective than inhaled corticosteroids for…

Answer 15

Airway caliber, bronchial reactivity, airway inflammation

Question 16

Zileuton has been linked to…

Answer 16

Severe hepatotoxicity

Question 17

Principal advantage for leukotriene pathway inhibitors

Answer 17

Oral formulations

Question 18

Ingestion of aspirin causes…in some asthmatics

Answer 18

Profound bronchoconstriction and symptoms of systemic histamine release (flushing and abdominal cramping)

Question 19

Leukotriene inhibitors ____ the response to aspirin challenge

Answer 19

Reduce

Question 20

Cromolyn and nedocromil MOA

Answer 20

• Altering the function of delayed chloride channels in the cell membranes&raquo_space;inhibiting cell activation
  
  • Mast cells&raquo_space; inhibition of degranulation
  • Eosinophils&raquo_space; inhibition of the inflammatory response to inhaled allergens

Question 21

Cromolyn and nedocromil clinical use

Answer 21

• Non-seasonal asthma symptoms and reduced need for bronchodilators
• Allergic rhinoconjunctivitis
• Adverse drug reactions are minimal due to poor drug absorption
• Usage has diminished due to low-dose corticosteroid

Question 22

LABA

Answer 22

• Potent selective agonists with a long duration of action (12+ hours; high lipid solubility)
  
  • Can dissolve in the smooth muscle cell membrane in high concentrations
  • Interact with inhaled corticosteroids to improve asthma control
  • Have no anti-inflammatory actions of their own; not used as monotherapy
• Salmeterol (a partial agonist)
• Formoterol (a full agonist)

Question 23

LABA adverse effects

Answer 23

Asthma-related death (black box) + SABA effects

Question 24

Antimuscarinic agents clinical use

Answer 24

-Limited use (used for patients intolerant of beta-agonists)

Question 25

Iprotropium

Answer 25

Aerosolized or nasal spray emergency addon | Poorly absorbed into circulation and the CNS (minimize systemic atropine-like effects)

Question 26

Tiotropium

Answer 26

Long-acting antimuscarinic agent | Recently approved for the maintenance treatment of asthma in patients ≥6 years

Question 27

Methylxanthines (theophylline) MOA

Answer 27

At high concentrations, inhibit phosphodiesterase (PDE) enzymes >> elevated levels of cAMP (or cGMP, tissue dependent) Specifically PDE3 and PDE4 in the airway smooth muscle and on inflammatory cells Inhibition of PDE3 relaxes airway smooth muscle Inhibition of PDE4 in inflammatory cells reduces their release of cytokines and chemokines >> decreases immune cell migration and activation Inhibition of cell surface receptors for adenosine >> adenosine can cause bronchoconstriction Enhanced histone deacetylation (histone acetylation >> inflammatory gene transcription)

Question 28

Theophylline pharmacodynamics

Answer 28

CNS (primarily caffeine but all have effects) -Low doses: mild cortical arousal with increased alertness and deferred fatigue -High doses: nervousness and tremor -Very high doses: medullary stimulation and convulsions, maybe death CV (dose-dependent positive chronotropic and inotropic effects) GI tract (stimulates secretion of gastric acid and digestive enzymes) Kidney (weak diuretics) Smooth muscle ( bronchodilation) Skeletal muscle (strengthened contraction of isolated skeletal muscles in vitro; improve contractility and reverse fatigue of the diaphragm in patients with COPD)

Question 29

Theophylline clinical uses

Answer 29

Most potent bronchodilator of the methylxanthines - Relieves airflow obstruction in acute asthma - Reserved for patients in whom symptoms remain poorly controlled despite the combination of regular treatment with an inhaled anti-inflammatory and as needed use of a b2-agonist

Question 30

Theophylline cautions/adverse reactions

Answer 30

``` Narrow therapeutic window (blood levels monitored) Anorexia Vomiting Nausea Abdominal discomfort Headache and anxiety Insomnia Seizures Arrhythmias ```

Question 31

Omalizumab

Answer 31

- Anti-immunoglobulin E (IgE) monoclonal antibody - Binds free IgE >> at its constant region - Prevents IgE from binding to the receptors on mast cells and other inflammatory cells - Does NOT activate IgE already bound to these cells >> does not provoke mast cell degranulation

Question 32

Omalizumab clinical use

Answer 32

Reduction in frequency and severity of asthma exacerbations (works best with more severe disease states)

Question 33

Benralizumab

Answer 33

- IL-5 receptor alpha antibody - Clinical: add-on maintenance treatment of severe asthma in adults and children >12 with an eosinophilic phenotype - Adverse effects: antibody production, headache, pharyngitis

Question 34

Mepolizumab and Reslizumab

Answer 34

Monoclonal antibodies against IL-5 (mep = subcutaneous; res = IV) Clinical: eosinophilic severe asthma Adverse effects: Mep - hypersnsitivity, headache, site reaction Res - anaphylaxis (black box), oropharyngeal pain