Albuterol: Mechanism of Action and Uses

Albuterol Mechanism of Action

• Albuterol binds to Beta-2 adrenergic receptors on airway smooth muscle cells.
• Adenylyl cyclase is activated which then converts ATP into cyclic AMP (cAMP).
• Increased cAMP activates protein kinase A (PKA).
• PKA then inhibits myosin phosphorylation and decreases intracellular calcium levels.
• Ultimately resulting in bronchial smooth muscle relaxation.

Conditions Albuterol Treats

• Asthma, COPD, and exercise-induced bronchospasm see relief from bronchospasms when using albuterol.

Asthma Indications

• The acute relief of bronchospasms requires a "rescue inhaler" / reliever like albuterol.
• Albuterol is used as needed for wheezing, coughing, or shortness of breath.

COPD Treatment

• Albuterol is used to treat reversible airway obstruction.
• It is also used during exacerbations or before exercise.

Exercise-Induced Bronchospasm

• Albuterol should be taken 15-30 minutes before exercise.

Prescription Example

• Albuterol 2.5 mg via SVN Q4H PRN for wheezing, mixed with 3 mL NS (normal saline), with breath sounds monitored pre/post treatment.

Albuterol Drug Calculation Example - Continuous Albuterol at 25 mg/hr for 6 hours

• The LVN output is 40 mL/hr, and only concentrated albuterol is available at 2.5 mg/0.5mL.
• Calculate the total amount of albuterol needed by dividing the dose by the duration: 25 mg/hr x 6 hrs = 150 mg.
• Determine the number of vials needed by dividing the total albuterol needed by the amount per vial, where each vial contains 2.5 mg of albuterol: 150 mg / 2.5 mg/vial = 60 vials.
• Calculate the total volume of albuterol solution by multiplying the number of vials by the volume per vial: 60 vials x 0.5 ml/vial = 30 mL.
• Determine the total volume needed for nebulization by multiplying the LVN output by the duration: 40 mL/hr x 6 hours = 240 mL.
• Calculate the amount of normal saline needed by subtracting the volume of albuterol vials from the total volume needed: 240 mL - 30 mL = 210 mL.

Albuterol Delivery Methods

• Metered Dose Inhaler (MDI) is used with a spacer to improve delivery, delivering 90 mcg per puff.
• Nebulizer converts liquid albuterol into a mist, ideal for acute attacks, dose example: 2.5 mg in 3mL NS.

Aerosol Delivery Devices

• Delivery devices include: Ultrasonic Nebulizer, Small Particle Aerosol Generator (SPAG), Small Volume Nebulizers (SVN), Metered Dose Inhaler (MDI), Dry Powder Inhaler (DPI), and Small Mist Inhaler (SMI - Respimat).

Aerosol Particle Sizes

• For the low respiratory tract: 2-5 mm
• For the terminal airways and alveolar region: .08-3.0 mm
• For pulmonary applications: 1-10 mm
• Fine particle fraction: 5 mm

Aerosol Device by condition

• For the upper airway: Breath Actuated Jet Nebulizer
• For an old, debilitated patient with acute distress: Vibrating Mesh Nebulizer
• For a person who travels extensively: Ultrasonic Nebulizer
• For an infant who cannot hold their breath: Jet Nebulizer
• For a patient whose drug test may need to be modified based on their level of dyspnea: Passive Mesh Nebulizer

Medication Device Combinations

• Iloprost with Pro-Dose/I-Neb
• Pentamidine with Marquest Respirgard II
• TOBI with Pari LC
• Pulmozyme with Hudson T Up-draft II
• Ribavirin with SPAG

MDI Components

• MDI components are a canister, actuator, metering valve, actuator set, drug/propellant liquid mixture, and actuator nozzle.

MDI Spacers

• Using a valved holding chamber, a spacer device with a one-way valve, assists to contain and hold the aerosol cloud until inspiration.

Nebulizer Gas Flow Rate

• For Jet Nebulizers, the flow rate should be 6-8 liters per minute (L/min)
• The optimal flow rate yields a particle size of 1-5 microns for lower airway deposition, ensuring efficient aerosolization of medication.
• For higher flow rates of 8-10 L/min, aerosol particles may be smaller, leading to exhalation before deposition and potentially shortening treatment time with less effective delivery.
• The flow rate to disperse a DPI is 30-90 mL/min.
• While 6-8 L/min is standard, 8 L/min is often used for better mist generation.

Improving Aerosol Deposition

• Use a spacer with an MDI.
• Employ proper inhalation technique (slow, deep inhalation with breath hold).
• Rinse mouth after use when administering corticosteroids.
• Breathe through mouth with tight seal.
• For infants, use a mask.

Advantages of Aerosols

• Aerosols are cost effective.
• Aerosols provide direct delivery to lungs (local effects).
• Aerosols have a fast onset of action.
• Aerosols have lower side effects.
• Aerosols have smaller doses.

Beta-2 Agonist Effectiveness

• Pulmonary function tests measure lung capacity and airflow rates, including FEV1 (Forced Expiratory Volume in one second) and FVC (Forced Vital Capacity).
• A bronchodilator response is indicated by a significant increase in FEV1 (at least 12% of baseline) after inhaling a beta-2 agonist.
• Peak Expiratory Flow (PEF) measures of airflow out of the lungs.
• Wheezing, SOB, and chest tightness, are improvements recorded as patient-reported outcomes.
• Assess quality of life by evaluating the impact on daily activities, exercise tolerance, and overall well-being.
• Measure a patient's ability to perform physical activities and assess breathlessness during exercise to evaluate exercise tolerance.

Beta-2 Agonist Considerations

• Monitor for decreased effectiveness of B2 agonists over time with regular use due to Tachyphylaxis.
• Monitor for potential side effects like increased heart rate, hypokalemia, and hyperglycemia.
• Evaluate frequency and severity of asthma or COPD for exacerbation rates.

Beta-2 Agonist Side Effects

• Beta-2 agonists may cause tachycardia, palpitations, tremors, increased blood pressure, and nervousness.

Asthma Medications

• Anticholinergics include: Ipratropium bromide and Tiotropium.
• Mucus controlling agents include: N-Acetylcysteine (NAC) Mucomyst, Dornase Alfa (Pulmozyme), and Hyperosmolar saline.
• Catecholamines include: Epinephrine
• Inhaled corticosteroids include: Budesonide (Pulmicort), Beclomethasone Dipropionate, Flunisolide hemihydrate, Fluticasone propionate, Fluticasone Furoate, Mometasone furoate, and Ciclesonide.
• Fluticasone & Salmeterol (Advair diskus, Wixela Inhub, Advair HFA, AirDuo Respiclick), Budesonide & Formoterol (Symbicort), Mometasone Furoate & Formoterol (Dulera), Fluticasone furoate & Umeclidinium bromide & Vilanterol (Trelegy Ellipta), and Fluticasone & Vilanterol (Breo Elipta) also work as combination drugs.
• LABAs include: Salmeterol, Formoterol, Indacaterol (Arcapta neohaler), and Arformoterol (Brovana).
• SABAs include: Albuterol and Levalbuterol.
• Ultra-short acting: Racemic Epinephrine
• Anti-leukotrienes include: Montelukast (Singulair), Zafirlukast (Accolate), and Zieuluton (Zyflo).
• Monoclonal antibodies include: Omalizumab (Xolair), Benrazulimab, Mepolizumab, Mepolizumab, Relizumab, Relizumab, and Dupilumab.
• Mast cell-stabilizing agents include: Cromolyn Sodium.
• Xanthines include: Theophylline
• Corticosteroid is available as a nasal spray.

Assessing Medication Response: Pre/Post-Bronchodilator Documentation Changes

• Vital signs: HR, RR, SpO2 and BP
• Breath sounds
• Peak flow
• Patient’s report
• Color, WOB, Cough and secretions
• Assess through breath sounds, SpO2 changes, and heart rate (if using albuterol).

Inhaled Drugs and Pharmacodynamics

• Albuterol is a short acting beta-2 agonist.
• Levalbuterol is an isomer of Albuterol.
• Ipratropium is an anticholinergic bronchodilator.
• Budesonide is an anti-inflammatory corticosteroid.
• Formoterol/Salmeterol: LABAs

Sympathomimetic vs Anticholinergic Bronchodilators: Mechanism of Action

• Sympathetic bronchodilators directly stimulate beta-2 receptors to relax airway muscles.
• Parasympathetic bronchodilators block acetylcholine from binding to muscarinic receptors, preventing bronchoconstriction.

Sympathomimetic vs Anticholinergic Bronchodilators: Onset and Duration

• Sympathetic bronchodilators (especially SABAs) work quickly making them ideal for acute relief.
• Parasympathetic bronchodilators usually have slower onset but provide long-lasting relief which is beneficial for maintenance therapy.

Sympathomimetic vs Anticholinergic Bronchodilators: Side Effect Profiles

• Sympathetic bronchodilators may cause cardiovascular side effects due to beta-1 receptor stimulation.
• Parasympathetic Bronchodilation mainly causes localized side effects such as dry mouth.

Bronchodilator Clinical Applications

• SABAs are preferred for immediate relief of bronchospasm.
• LABAs and long-acting anticholinergics are used for ongoing control and prevention of symptoms in chronic conditions like COPD.
• Respiratory therapists play a crucial role in educating patients about proper use of these medications to optimize their respiratory health.

SABA Examples

• Patients experiencing an acute asthma exacerbation or sudden bronchospasm would be given SABA for rapid relief of symptoms such as wheezing, shortness of breath and chest tightness.
• SABAs are given for an Asthma attack as a rescue medication, for COPD for immediate relief of dyspnea during a flare up, and 15-30 minutes before exercise to prevent symptoms of exercise induced Asthma.

LABA Examples

• A patient with poorly controlled asthma or moderate severe COPD would be prescribed a LABA to help manage chronic symptoms and reduce the frequency of exacerbations.
• LABAs are given for Asthma as maintenance therapy (with inhaled corticosteroid) to control persistent symptoms, and for COPD to improve lung function.

Anticholinergic Examples

• A patient with COPD experiencing persistent bronchospasm (An involuntary action - AcH) would benefit from an anticholinergic bronchodilator to relax airway muscle.
• Anticholinergics are given for COPD for long term maintenance to reduce bronchoconstriction (Tiotropium or ipratropium), Asthma if severe and uncontrolled, and as Add-on therapy, they are also given for an overactive bladder to relax bladder muscles, for Bradycardia and as Pre-anesthesia to reduce salivation and respiratory secretions before surgery.

Synergystic effects of Inhaled Medications: Albuterol & Ipratropium

• Albuterol is a short acting beta 2 agonist (SABA).
• Ipratropium Bromide is a short-acting Muscarinic Antagonist (SAMA).
• This combination provides faster and more complete bronchodilation during acute exacerbations by relaxing airway smooth muscle and blocking bronchoconstriction.

Synergystic effects of Inhaled Medications: Budesonide & Formoterol

• Budesonide is an inhaled corticosteroid (ICS).
• Formoterol is a long-acting beta-2 agonist (LABA).
• This combination results in reduced airway inflammation and maintained bronchodilation, can be used for both maintenance and reliever therapy.

Synergystic effects of Inhaled Medications: Fluticasone & Salmeterol

• Fluticasone is an inhaled Corticosteroid.
• Formoterol is a LABA.
• This combination provides reduced inflammation plus long-acting bronchodilation.

Synergystic effects of Inhaled Medications: Fluticasone + Vilanterol

• Fluticasone is an ICS.
• Vilanterol is a LABA.
• This combination provides a once-daily option with anti-inflammatory and bronchodilator effects.

Synergystic effects of Inhaled Medications: Montelukast + ICS

• Montelukast is an antileukotriene.
• This combination targets Leukotriene-mediated inflammation alongside corticosteroids, useful in exercise induces or allergy driven asthma.

Synergystic effects of Inhaled Medications: ICS + Theopylline

• Theophylline is a Methylxanthine bronchodilator.
• This combination provides mild bronchodilation + anti-inflammatory effects, but is rarely used today due to side effects and monitoring requirements.