Updated: 3/30/2017

Asthma Drugs

Topic
Review Topic
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Questions
11
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Evidence
16
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Overview
  • Therapeutic strategies for treating asthma include:
    • decreasing inflammation
    • increasing sympathetic tone
  • There are 7 families of drugs that are commonly used:
    1. corticosteroids
    2. β-agonists
    3. muscarinic antagonists
    4. methylxanthines
    5. cromolyn
    6. antileukotrienes
    7. omalizumab
Corticosteroids
  • Inhaled corticosteroids are first line therapy for chronic asthma 
  • Examples
    • mometasone
    • fluticasone 
    • budesonide
    • beclomethasone
    • triamcinolone
    • flunisolide
  • Mechanism
    • inhibiting the synthesis of virtually all cytokines
    • inactivating NF-κB
      • NF-κB is the transcription factor that induces the production of TNF-α and other inflammatory agents
  • Toxicity
    • oral candidiasis
      • use spacers or post-inhalation mouth rinse to prevent 
β2-agonists
  • Drugs
    • short acting -- used for breakthrough symptoms and during acute exacerbation
      • albuterol 
        • known internationally as salbutamol
      • levalbuterol 
      • Others used much less commonly
        • terbutaline
        • metaproterenol (β2, minor β1)
        • isoproterenol (nonselective)
          • tachycardia
          • may lead to cardiac death
    • long acting -- used for maintenance in combination with inhaled corticosteroid (never without)
      • salmeterol 
        • tremors, arrhythmia
      • formoterol 
  • Mechanism
    • β2 receptors are activated on bronchial smooth muscle to achieve bronchodilation
    • stimulation of adenylate cyclase leading to closing of calcium channels and ultimately the relaxation of smooth muscles
Methylxanthines
  • Drugs
    • theophylline (rarely used)
  • Mechanism
    • inhibition of phosphodiesterase leading to decreased cAMP hydrolysis
      • causes bronchodilation
    • metabolized by P-450
    • blocks actions of adenosine
  • Toxicity
    • seizures 
    • narrow therapeutic index
    • nausea/vomiting
    • arrhythmia
Muscarinic antagonists
  • Drugs
    • ipratropium 
    • tiotropium
  • Mechanism
    • competitive inhibition of muscarinic receptors 
      • prevents bronchoconstriction
  • Also used for COPD
Cromolyn
  • Prophylaxis only!
    • ineffective during an acute asthma attack
  • Mechanism
    • prevents release of mediators from mast cells
  • Toxicity
    • rare
Antileukotrienes
  • Drugs
    • zileuton
      • 5-lipoxygenase pathway inhibitor
        • blocks conversion of arachidonic acid to leukotrienes 
    • zafirlukast, montelukast
      • blocks leukotriene receptors
      • particularly effective in aspirin-induced asthma
Omalizumab
  • Clinical use
    • severe uncontrolled asthma with elevated IgE
      • symptoms and activity refractory to standard therapies and oral glucocorticoids
  • Mechanism
    • anti-IgE antibody  
      • inhibits action of IgE with inflammatory cells 
    • asthma can be caused by uncontrollably high IgE response
 

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Questions (11)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.PL.33) In patients with chronic obstructive pulmonary disease, stimulation of muscarinic acetylcholine receptors results in an increase in mucus secretion, smooth muscle contraction and bronchoconstriction. The end result is an increase in airway resistance. Which of the following pharmacologic agents interferes directly with this pathway? Review Topic

QID: 100836
1

Epinephrine

0%

(0/3)

2

Theophylline

0%

(0/3)

3

Ipratropium

100%

(3/3)

4

Albuterol

0%

(0/3)

5

Metoprolol

0%

(0/3)

M1

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(M1.PL.126) A new drug is designed to treat asthma by inhibiting bronchoconstriction. Experimental assays show that treated animals had markedly reduced acetylcholine binding to muscarinic receptors relative to untreated controls. The drug is most similar to which of the following: Review Topic

QID: 100929
1

Theophylline

6%

(1/16)

2

Cromolyn

0%

(0/16)

3

Zafirlukast

19%

(3/16)

4

Prednisone

0%

(0/16)

5

Ipratropium

75%

(12/16)

M1

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PREFERRED RESPONSE 5
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(M1.PL.106) An 8-year-old female is given omalizumab for the treatment of bronchial asthma. Omalizumab treats asthma through which mechanism? Review Topic

QID: 100909
1

Inhibition of IgE binding to mast cells

55%

(6/11)

2

Binding to nuclear receptors

0%

(0/11)

3

Inhibition of leukotriene binding to receptor

36%

(4/11)

4

Inhibition of phosphodiesterase breakdown of cAMP

9%

(1/11)

5

Mediating type IV hypersensitivity reaction

0%

(0/11)

M1

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PREFERRED RESPONSE 1
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(M1.PL.91) A 12-year-old female presents to her pediatrician with an asthma exacerbation. Upon physical examination, the physician notes the finding shown in Figure A. This presentation is a common side effect of which of the following pharmacologic agents used in the treatment of asthma? Review Topic

QID: 100894
FIGURES:
1

Salmeterol

6%

(1/16)

2

Albuterol

0%

(0/16)

3

Inhaled beclomethasone

81%

(13/16)

4

Ipratropium

6%

(1/16)

5

Theophylline

6%

(1/16)

M1

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(M1.PL.41) A 7-year-old boy is brought to your office with complaints of wheezing and dyspnea. Laboratory work reveals eosinophilia and positive skin tests for allergens. Which of the following types of drugs would be an effective treatment in this patient? Review Topic

QID: 100844
1

Beta-2 antagonist

19%

(17/89)

2

Histone deacetylase inhibitor

4%

(4/89)

3

VEGF inhibitor

4%

(4/89)

4

Muscarinic antagonist

71%

(63/89)

5

Anticoagulant

0%

(0/89)

M1

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