Rau's Chapter 6: Adrenergic Bronchodilators

Rau's Chapter 6: Adrenergic Bronchodilators

• Adrenergic bronchodilators, also known as sympathomimetics, relax smooth airway muscles, treating reversible airway obstruction.

Clinical Indications

• Used for various asthma types (acute, chronic, exercise-induced)
• Also for bronchitis, emphysema, bronchiectasis, and other obstructive airway diseases.

Indication for Short-Acting Agents (SABA)

• Treat acute reversible airflow obstruction.
• Also known as rescue or reliever agents.
• Examples: Albuterol, Levalbuterol, Metaproterenol

Indication for Long-Acting Agents (LABA)

• For maintenance bronchodilation, controlling bronchospasm, and controlling nighttime symptoms.
• Also known as controller agents.
• Examples: Salmeterol, Formoterol, Arformoterol, Indacaterol, Olodaterol

Indications for Racemic Epinephrine (RE)

• Used to control airway bleeding during endoscopy.
• Strengthens α-adrenergic vasoconstriction to reduce airway swelling.
• Applied to specific situations like post-extubation stridor, epiglottitis, croup, bronchiolitis.

Specific Adrenergic Agents and Formulations

• Ultrashort acting: Duration less than 3 hours, e.g., Racemic epinephrine
• Short acting: Duration 4 to 6 hours, e.g., Albuterol, Levalbuterol, Metaproterenol
• Long acting: Duration 12 to 24 hours, e.g., Salmeterol, Formoterol, Arformoterol, Indacaterol, Olodaterol

Catecholamines

• Sympathomimetic bronchodilators that are either catecholamines or derivatives thereof.
• Mimic epinephrine's effects.
• Cause tachycardia, elevated blood pressure, smooth muscle relaxation (bronchioles and skeletal muscle blood vessels), glycogenolysis, skeletal muscle tremor and CNS stimulation.
• Diuresis, impacting electrolyte balance, is a potential outcome.

Adrenergic Bronchodilators as Stereoisomers

• Molecules with nonsuperimposable mirror images.
• (R)- and (S)-isomers have similar physical and chemical properties but different physiological effects.
• Example: Levalbuterol

Epinephrine

• A potent catecholamine bronchodilator.
• Stimulates both α- and β-receptors.
• Side effects like tachycardia, increased blood pressure, tremor, headache, and insomnia are common.
• Available as a synthetic racemic mixture.

Prescriptive Albuterol Administration

• Confirm the order.
• Administer as directed.
• Professional consultation is needed on the medication doses.

Long-Acting β-Adrenergic Agents

• Fewer doses throughout the day are needed for extended protection, like extended-release albuterol, salmeterol, formoterol, arformoterol, indacaterol, and olodaterol.

Extended-Release Albuterol

• Available as Vospire ER 4-mg or 8-mg oral tablet.
• Effective for 8 to 12 hours.

Salmeterol (Serevent Diskus)

• Inhaled medication, available as DPI
• Slower onset than albuterol (20 minutes to peak bronchodilation).
• Peak effect after 3-5 hours.
• 12-hour duration.

Formoterol (Performist, Foradil)

• ẞ2-selective agonist with a quick bronchodilation onset (3 minutes).
• 12-hour duration.
• Available as an SVN and DPI.
• Used for asthma (5+ years) and exercise-induced bronchospasm (5+ years).

Arformoterol (Brovana)

• Single isomer of formoterol.
• Up to 12 hours of duration.
• Available as a nebulizer solution.
• Indicated for COPD maintenance treatment and asthma maintenance, where inhaled corticosteroids haven't sufficiently controlled the symptoms.

Indacaterol (Arcapta Neohaler)

• ẞ2-selective agonist, ultra-long-lasting duration (24 hours).
• Available in a DPI.
• Used for COPD maintenance treatment.

Olodaterol (Striverdi Respimat)

• ẞ2-selective agonist with ultra-long-lasting effect (24 hours).
• Available in a Respimat inhaler.
• Approved for COPD maintenance treatment.

Mechanism of Action

• α-Receptor Stimulation: Causes vasoconstriction.
• β₁-Receptor Stimulation: Increases heart rate and contractility.
• β₂-Receptor Stimulation: Relaxes bronchial smooth muscle.

β- and α-Receptor Activation

• β-Receptors bind to increase cAMP synthesis.
• α-Receptors inhibit neurotransmitter release and may reduce intracellular cAMP.

α1-Receptor Activation

• Agonists like epinephrine and phenylephrine cause vasoconstriction in peripheral blood vessels.

Long-Acting β-Agonists Mechanism of Action

• Lipophilic nature.
• Lateral approach to the β-receptor from the aqueous phase.

Routes of Administration

• Inhalation: (MDI, DPI, nebulized), effective for bronchodilators
• Oral: (tablets, syrups), less effective for catecholamines
• Parenteral: (injection), used for emergencies (e.g., SQ epinephrine or terbutaline)

Inhalation Route: Benefits

• Quick onset, smaller doses, reduced side effects, direct delivery to target organ, generally safe and painless.
• Limitations include time, public embarrassment, potential difficulty using correctly.

Continuous Nebulization of Albuterol

• Used for managing asthma.
• Reduces attendance at therapist's office.
• Typical adult dosage is 10–15 mg/hour.
• Delivery methods include refillable SVN (small volume nebulizer), volumetric infusion pump, large volume nebulizer.

Oral Route

• Advantages: easy to use, short administration time, and reproducible dosage.
• Disadvantages: slower onset of action, more systemic side effects, potential loss due to liver metabolism (first-pass effect)

Parenteral Route

• Used for emergencies to manage asthma when obstruction prevents aerosol delivery.
• Examples: SQ epinephrine (0.3 mg) and SQ terbutaline (0.25 mg).

Adverse Side Effects

• Any effect unrelated to the intended therapeutic effect.
• Includes tremor, cardiac effects, tolerance to bronchodilator effect, loss of bronchoprotection, CNS effects, fall in PaO2, metabolic disturbances, propellant toxicity, and paradoxical bronchospasm, and sensitivity to additives.

Respiratory Care Assessment of β-Agonist Therapy

• Evaluate drug efficacy based on patient's requirements.
• Monitor peak flow rates.
• Pre and post-treatment physical examinations.
• Monitor for heart rate increases (20%).
• Evaluate subjective patient responses.
• Monitoring of glucose, potassium, and PFTs.
• Correct device use education and demonstration.
• For long-acting agents, track lung function, rescue medication use, nocturnal symptoms, exacerbation frequency, and school/work absenteeism. Also, assess the possibility for reducing inhaled corticosteroid dosage.

Explore the role of adrenergic bronchodilators in treating airway obstruction in this chapter from Rau's. Understand the clinical indications for both short-acting and long-acting agents, and their specific applications in conditions like asthma and bronchitis. The quiz will cover key medications such as Albuterol and Salmeterol.