Adrenergic Bronchodilators for Asthma & COPD

• Adrenergic bronchodilators treat reversible airway obstruction from asthma and COPD
• Bronchodilation is produced through stimulation of Beta 2 receptors on airway smooth muscle
• Long-acting beta adrenergic bronchodilators should not be used as monotherapy for acute bronchospasms

Short-Acting Beta Adrenergic Bronchodilators

• Treat acute airflow obstruction
• Act as rescue and reliever medications in asthma and COPD
• Examples: albuterol and levalbuterol

Long-Acting Beta Adrenergic Bronchodilators

• Are used to maintain airflow obstruction, bronchodilation, control bronchospasm, and control nocturnal symptoms
• Also called "controllers"
• Examples: salmeterol, formoterol, arformoterol, olodaterol, and vilanterol

Inhalation Route

• The preferred administration because the onset of action is rapid
• Smaller doses are needed compared to oral doses
• Side effects such as tremor and tachycardia are reduced
• The drug is delivered directly to the target organ
• It is painless and safe

Clinical Effects

• Beta-2 stimulation in the lungs causes relaxation of bronchial smooth muscle (bronchodilation)
• Alpha-1 stimulation causes vasoconstriction and acts as a vasopressor (decongestant)
• Beta-1 stimulation increases myocardial conductivity and increases heart rate

Isomers

• Stereoisomers (aka enantiomers) are mirror images of each other
• (R)-isomer and (S)-isomer are examples, and are "enantiomers"
• Epinephrine is the natural form
• Racemic mixtures are synthetic formulations for inhalation
• It's a 50:50 mixture of (R)-isomer and (S)-isomers
• Levalbuterol was the first synthetic inhaled solution of the single (R)-isomer of racemic albuterol

Catecholamine Agents

• Limitations in treating bronchospasm are due to the limited duration of action, unsuitable for maintenance therapy

Epinephrine

• Clinical uses: acute asthma (inhalation), anaphylaxis (subcutaneous), and cardiac arrest (IV)
• Racemic epinephrine treats upper airway edema and controls bleeding during bronchoscopy
• It can reduce airway swelling-peripheral vasoconstriction, treats post-extubating stridor, epiglottitis, croup
• Recommended dosages for neb is 2.25% solution, 0.25-0.5mL QID
• Epinephrine onset of action: 3-5 minutes
• Duration of action: 0.5-2 hours

Non-Catecholamine Bronchodilators

• Advantages: longer duration of 4-6 hours
• They can be taken orally

Single Isomer Formulations

• Two adrenergic bronchodilators available: levalbuterol and epinephrine

Albuterol Doses

• Adult dosage, nebulized: 0.5% solution, 0.5mL (2.5mg), tid or qid

Levalbuterol vs Albuterol

• Proposed advantages: levalbuterol has less effect on heart rate

LABA Onset

• Salmeterol has the slowest onset of action (3-5 hours)

Beta-Agonist Controversy

• Also known as “asthma paradox"
• Describes an increase in mortality and morbidity despite advances in treatment
• Beta-agonists have been questioned as a possible factor in the increase in asthma mortality – This has led to the "beta-agonsit controversy", near-death emergencies and deaths, worsening clinical outcomes, and increased hyperreactivity

FDA Warning

• LABAs are contraindicated WITHOUT the use of an asthma controller medication such as an inhaled corticosteroid

Continuous Bronchodilator Therapy

• Indications: managing severe asthma, avoid respiratory failure, intubation and mechanical ventilation
• Typical dosage range: 7.5-10mg/hour

Monitoring CBT

• Monitor cardiac and electrolytes
• Observe for potential complications: cardiac arrhythmias, hypokalemia, and hyperglycemia
• Techniques involved are measured refilling of a small volume nebulizer, volumetric infusion pump with SVN, or Large reservoir nebulizer (HEART or HOPE nebulizer)

Patient Data

• Subjective: what is the patient telling you?
• Objective: breathing rate (RR) before and after, breathing pattern before and after, breath sounds by auscultation before and after, pulse rate (HR) before, during and after
  • A 20% increase from baseline may constitute a change in medications or discontinuing therapy
• Monitor peak flow and lab values: blood glucose (increase) & potassium (decrease)

Identifying Positive Clinical Responses

• Outcomes to inhaled bronchodilator therapy: open airways, making it easier to breathe
• A 12% increase in either forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC), along with a 200mL absolute increase in either

Side Effects

• Trembling, nervousness, increased heart rate, palpitations, headache, upset stomach, dry mouth, and trouble sleeping

Bronchodilator Therapy

• Modifications: If there's a 20% increase in heart rate from baseline, consider changing the medication or discontinuing it

Key Facts

• Albuterol (SABA): Available as a nebulizer solution, duration 4-6 hours
• Levalbuterol (SABA): Available as a nebulizer solution, duration 5-8 hours, medication Xopenex
• Salmeterol (LABA): NOT available as a nebulizer solution, duration 12 hours
• Formoterol (LABA): Available as a nebulizer solution, duration 12 hours, medication Perforomist
• Arformoterol (LABA): Available as a nebulizer solution, duration 12 hours, medication Brovana
• Olodaterol (LABA): NOT available as a nebulizer solution, duration 24 hours