Pharmacology: Beta-2 Agonists

• Pharmacology is difficult, as is the NCLEX and real-life practice
• Think about pharmacology at a class level
• Look at the mechanism, common and serious side effects, nursing considerations, indications and contraindications, and common medication names
• medication names often start with suffixes: Benzodiazepines (-azolam), ACE inhibitors (-pril)
• Understand expected vs unexpected symptoms to identify if a symptom is due to a medication

Objectives for each class of medications

• Class
• Mechanism
• Common medications (generic name)
• Common side effects
• Rare but serious side effects
• Common precautions, contraindications & medication interactions
• What to monitor

Beta-2 Agonists (Bronchodilators)

• Primary use is bronchodilation for asthma, COPD, and other obstructive lung diseases
• Mechanism of action: stimulating beta-2 adrenergic receptors in the lungs, relaxing bronchial smooth muscle (airway dilation), and inhibiting mast cell degranulation (reducing inflammation)
• Key clinical benefit: Relieves bronchospasm & improves airflow

Beta-2 Agonists Medication Types

• Short-Acting Beta-2 Agonists (SABA): Albuterol (Ventolin, ProAir), Levalbuterol (Xopenex) with a rapid onset (within minutes) and a duration of 3-6 hours Q4 PRN for rescue inhaler for acute bronchospasm
• Long-Acting Beta-2 Agonists (LABA): Salmeterol, Formoterol with a slower onset (15-30 minutes) and a duration of 12+ hours for maintenance therapy (NOT for acute attacks!)
• SABAs are "rescue inhalers" and LABAs are for maintenance

Short-Acting Beta-2 Agonists (SABA)

• Examples: Albuterol, Levalbuterol
• Indications are acute asthma attacks, COPD exacerbations, and exercise-induced bronchospasm (EIB) prevention
• Monitor for tachycardia, palpitations, tremors, and nervousness
• Use before inhaled corticosteroids (ICS) to open airways for better medication absorption
• Overuse (>2x/week) indicates poorly controlled asthma, which requires a controller medication

Long-Acting Beta-2 Agonists (LABA)

• Examples: Salmeterol (Serevent), Formoterol
• Indications are long-term asthma & COPD control, nighttime asthma symptoms, and preventing exercise-induced bronchospasm
• Not for acute attacks and should always be paired with an inhaled corticosteroid (ICS) in asthma
• Increased risk of asthma-related death when used alone, so always use with ICS
• fluticasone/salmeterol (Advair) or budesonide/formoterol (Symbicort)
• Monitor for tremors, tachycardia, hypokalemia, and headache
• LABA alone = increased risk of asthma related death

Beta-2 Agonist Adverse Effects

• Tachycardia & Palpitations caused by Beta-1 stimulation (mild) and requires caution in cardiac patients
• Tremors caused by Beta-2 receptor activation in skeletal muscle and are usually transient, resolving over time
• Hypokalemia is from Shifts K+ into cells and requires monitoring in patients on diuretics
• Hyperglycemia is from Stimulates gluconeogenesis and requires caution in diabetics

Beta-2 Agonist Contraindications

• Uncontrolled arrhythmias
• Severe cardiac disease
• Monoamine oxidase inhibitors (MAOIs) & tricyclic antidepressants (↑ risk of CV effects)

Beta-2 Agonist Inhaler Use

• Shake the inhaler well before use
• Use a spacer if coordination is difficult
• Wait at least 1 minute between puffs
• Rinse mouth after use to prevent thrush (especially with ICS combo inhalers)

Beta-2 Agonist Nebulizer Use

• Takes 5-10 minutes to complete a dose
• Patient should breathe slowly and deeply
• Immunosuppression from ICS can make you susceptible to fungal infections like thrush
• SMART Therapy: ICS + LABA as both maintenance and rescue (e.g., Budesonide/Formoterol)

Beta-2 Agonists: Summary Table

• SABA (Albuterol, Levalbuterol) has Minutes for onset and 3-6 hours for duration
• LABA (Salmeterol, Formoterol) has 15-30 min for onset and 12+ hours for duration
• SABA (Albuterol, Levalbuterol) is used as a rescue, and LABA (Salmeterol, Formoterol) is used as maintenance
• SABA (Albuterol, Levalbuterol) can be used alone, but LABA (Salmeterol, Formoterol) should always be paired with ICS in asthma!
• SABA and LABA both cause Tachycardia, tremors, hypokalemia as side effects, but LABA are longer-lasting

Methylxanthines

• Methylxanthines equals Theophylline
• Primary Use: Bronchodilation for asthma and COPD (less commonly used today)
• Mechanism of Action: Inhibits phosphodiesterase (PDE) → ↑ cAMP → Bronchodilation
• Non-beta agonist, PDE inhibitor
• Blocks adenosine receptors, reducing airway constriction
• Mild anti-inflammatory effects
• Narrow therapeutic index and Requires careful monitoring of serum levels

Methylxanthines Therapeutics

• Theophylline Oral, IV is used as Maintenance therapy for asthma & COPD
• Aminophylline IV is used as Emergency treatment for severe bronchospasm (rarely used)
• Therapeutic Range: 10-20 mcg/mL
• Toxicity Risk Increases >20 mcg/mL

Methylxanthines Adverse Effects by Level

• Subtherapeutic (<10 mcg/mL) has no benefit
• Therapeutic (10-20 mcg/mL) causes bronchodilation
• Toxic (>20 mcg/mL) causes toxic effects (nausea, vomiting, tremors, tachycardia)
• Life-threatening (>30 mcg/mL) causes seizures and arrhythmias (VT, VF)

Methylxanthines Key Points

• Serum drug levels must be monitored regularly!
• Not first-line due to toxicity risks and drug interactions
• Toxicity is treated with activated charcoal & antiarrhythmics if severe.

Methylxanthines Contraindications

• Cardiac disease (arrhythmias, tachycardia risk)
• Seizure disorders (lowers seizure threshold)
• Peptic ulcer disease (stimulates gastric acid secretion)

Methylxanthines Administration and Patient Education

• Oral Theophylline should be taken at the same time every day, and do not crush or chew extended-release formulations
• Avoid caffeine and report signs of toxicity (nausea, tremors, palpitations).
• IV Aminophylline should be infused slowly to prevent hypotension & arrhythmias and Continuous cardiac monitoring is required
• Metabolized by the liver (CYP1A2, CYP3A4), leading to many drug interactions
• Caution in smokers because nicotine induces metabolism, leading to lower drug levels

Key Takeaways for Methylxanthines

• Methylxanthines are bronchodilators with a narrow therapeutic index (10-20 mcg/mL)
• Early toxicity signs include Nausea, tremors, tachycardia
• Severe toxicity signs include Seizures and arrhythmias
• Many drug interactions, Smoking reduces effectiveness
• Regular serum monitoring is required to prevent toxicity
• Caution in cardiac disease, seizures, and peptic ulcer disease

Inhaled Anticholinergics (Muscarinic Antagonists)

• Primary Use: Bronchodilation for COPD, asthma (adjunct), and bronchospasm prophylaxis
• Mechanism of Action: Blocks muscarinic (M3) receptors in the lungs, prevents acetylcholine from causing bronchoconstriction, Reduces mucus secretion (drying effect)
• Key Benefit: Improves airflow, especially in COPD

Inhaled Anticholinergics Types

• Short-Acting Muscarinic Antagonists (SAMA): Ipratropium (Atrovent) with an onset within 15-30 min for 4-6 hours is indicated as Rescue therapy in COPD and for asthma adjunct
• Long-Acting Muscarinic Antagonists (LAMA): Tiotropium (Spiriva), Aclidinium, Umeclidinium with an onset within 30-60 min for 12-24 hours is indicated as Maintenance therapy in COPD & severe asthma
• SAMA = "rescue" bronchodilation for COPD, LAMA = long-term control

Inhaled Anticholinergics Contraindications

• Glaucoma (can increase intraocular pressure)
• Benign prostatic hyperplasia (BPH) or urinary retention

Short-Acting Muscarinic Antagonists (SAMA)

• Examples: Ipratropium (Atrovent)
• Indications are COPD rescue therapy (often combined with a SABA like albuterol) and Acute asthma exacerbations (adjunct to beta-2 agonists) (SABA first)
• Nursing Considerations:Slower onset than SABAs (not first-line for asthma rescue) and Can be combined with Albuterol (DuoNeb) for stronger effect
• Monitor for dry mouth, hoarseness, and urinary retention

Long-Acting Muscarinic Antagonists (LAMA)

• Examples: Tiotropium (Spiriva), Aclidinium, Umeclidinium
• Indications are Long-term COPD maintenance therapy, Severe, persistent asthma (adjunct to ICS & LABA) and Reduces COPD exacerbations
• Not for acute attacks, which is maintenance therapy only
• Once-daily dosing improves adherence
• Monitor for dry mouth, constipation, and urinary retention
• Tiotropium is the most commonly used LAMA for COPD

Glucocorticoids (Corticosteroids)

• Primary Use: Anti-inflammatory actions to treat Asthma, allergic rhinitis, and systemic inflammatory conditions
• Mechanism of Action includes: Suppress inflammation by inhibiting cytokines & inflammatory mediators (prostaglandins, leukotrienes), Reduce airway hyperresponsiveness (reduces bronchoconstriction) and prevent exacerbations in asthma/COPD, and Decrease mucus production and reduce nasal congestion in allergic rhinitis
• NOTE: Glucocorticoids do NOT provide immediate relief for acute bronchospasm

Corticosteroids Delivery Methods

• Inhaled (ICS): Fluticasone (Flovent), Budesonide (Pulmicort), Beclomethasone with an inhaler or nebulizer for first-line maintenance for asthma & COPD
• Intranasal: Fluticasone (Flonase), Mometasone, Budesonide (budesonide safest for pregnancy) with a nasal spray for allergic rhinitis & nasal polyps
• Oral (Systemic): Prednisone, Methylprednisolone (Medrol) Oral for severe asthma, COPD exacerbations, autoimmune diseases

Corticosteroids Key Points

• Inhaled corticosteroids (ICS) are preferred for long-term asthma control due to fewer systemic effects
• Inhaled Corticosteroids (ICS) include fluticasone (Flovent), budesonide (Pulmicort), beclomethasone
• Indications: First-line therapy for persistent asthma (maintenance, NOT rescue) or Adjunct therapy in COPD (combined with LABA in severe cases)

Administration Notes for Inhaled Corticosteroids (ICS)

• Rinse mouth after use to prevent oral candidiasis (thrush) because it causes immunosuppression
• Use a spacer to improve drug delivery & reduce side effects
• Takes 1-2 weeks for full effect (NOT for acute relief)
• Monitor for hoarseness, cough, and signs of adrenal suppression in high doses
• ICS is usually combined with a LABA (e.g., Fluticasone/Salmeterol = Advair)

Administration Notes for Intranasal Corticosteroids

• fluticasone (Flonase), mometasone, budesonide
• Indications Allergic rhinitis (first-line therapy) or Nasal congestion & nasal polyps
• Key Safety Considerations include Blow nose before administration and Tilt head slightly forward, avoid sniffing deeply after use to fully use the effect of the medicine

Corticosteroids Oral

• Examples: prednisone or methylprednisolone (Medrol) for acute asthma & COPD exacerbations or Severe allergic reactions (anaphylaxis adjunct)
• Note: you'll still want to give SABA for immediate rescue, oral steroid use for antiinflammatory effect)
• Indications: Autoimmune diseases (e.g., lupus, rheumatoid arthritis) or Adrenal insufficiency (Addison's disease)
• Can act as supplemental cortisol
• Short-term use (3-10 days) to prevent adrenal suppression
• Take in the morning with food to prevent Gl upset
• Taper slowly if used >10 days to prevent adrenal insufficiency
• Monitor for hyperglycemia (particularly if diabetic/taking insulin, can highly increase BG), weight gain, mood changes, and osteoporosis with long-term use
• Oral steroids have the highest risk of systemic side effects

Side Effects by Route

• Oral Thrush: Common from ICS (Inhaled), but None from Intranasal and Oral (Systemic), due to ICS deposits in mouth causing fungal overgrowth
• Hoarseness: Possible from ICS (Inhaled), but None from Intranasal and Oral (Systemic), due to Local irritation
• Nosebleeds: None from ICS (Inhaled), but Common from Intranasal and None from Oral (Systemic), due to Drying effect on nasal mucosa
• Hyperglycemia: rare (high doses) from ICS (Inhaled), but None from Intranasal and Common from Oral (Systemic), due to Increased gluconeogenesis
• Osteoporosis: Rare from ICS (Inhaled), but None from Intranasal and Long-term risk from Oral (Systemic), due to Decreased bone formation
• Adrenal Suppression: Unlikely from ICS (Inhaled), but None from Intranasal and If not tapered from Oral (Systemic), due to Suppresses HPA axis
• Weight Gain: None from ICS (Inhaled), but None from Intranasal and Common from Oral (Systemic), due to Fluid retention, fat redistribution
• Mood Changes: None from ICS (Inhaled), but None from Intranasal and Possible from Oral (Systemic), due to CNS stimulation from systemic steroids

Why Does Adrenal Insufficiency Happen?

• When patients take systemic glucocorticoids, the body stops making its own cortisol (negative feedback to HPA Axis)
• Exogenous steroids ‘trick' the brain into thinking [cortisol] is high and If steroids are suddenly stopped, the adrenal glands cannot immediately produce enough cortisol, leading to adrenal crisis
• Adrenal suppression can last weeks to months based on dose & duration of exogenous steroids

Signs of Steroid Withdrawal and Adrenal Insufficiency

• Fatigue, weakness
• Hypotension (shock in severe cases)
• Nausea, vomiting, weight loss
• Hypoglycemia
• Prevention: Taper oral steroids gradually to allow the adrenal glands to recover

Corticosteroids Patient Education

• Inhaled Corticosteroids: Use ICS regularly Not for acute attacks, Rinse mouth after use to prevent thrush, Use a spacer for better delivery and fewer side effects, and Takes 1-2 weeks for full effect, so continue use even if symptoms improve
• Oral Corticosteroids: Take in the morning with food to reduce Gl upset, Do NOT stop suddenly if taken >10 days and must taper gradually, Monitor for weight gain, mood changes, and hyperglycemia, and Long-term users should take calcium & vitamin D to prevent bone loss

Leukotriene Modifiers

• montelukast (Singulair)
• Primary Use: Anti-inflammatory therapy for asthma and allergic rhinitis
• Mechanism of Action: Blocks leukotrienes (inflammatory mediators that cause bronchoconstriction, airway edema, and mucus production), and Prevents asthma symptoms and allergic responses by reducing inflammation
• Leukotriene modifiers are NOT for acute asthma attacks

Leukotriene Modifier montelukast (Singulair)

• Used for Maintenance therapy for mild-to-moderate asthma, Exercise-induced bronchospasm prevention, and Allergic rhinitis (nasal inflammation, congestion, sneezing)
• Nursing Considerations: Take once daily in the evening for asthma (maximal efficacy), and For exercise-induced bronchospasm, take at least 2 hours before activity
• Note: NOT a rescue medication, which does not relieve acute bronchospasm
• Side Effects: Common include headache and mild Gl upset, and Serious include Depression +/- suicidal ideations, so Monitor mood closely and Caution if Hx of psychiatric disorders

Antihistamines

• Histamine is a chemical mediator released by mast cells & basophils, triggers inflammation, allergic responses, and gastric acid secretion
• H1 Receptors (Allergic & Inflammatory Response) are found in in the lungs, blood vessels, skin, CNS
• Effects: Vasodilation, increased capillary permeability, bronchoconstriction, and itching
• CNS: Wakefulness and alertness
• Blocked by: H1 antihistamines (e.g., diphenhydramine, loratadine)
• H2 Receptors (Gastric Acid Secretion) are found in the stomach (parietal cells)
• Effects: Stimulates acid production which leads to GERD and ulcers
• Blocked by: H2 blockers (e.g., ranitidine and famotidine), and helps shut down the amount of acid, which helps with GERD and ulcers
• H1 Antihistamines are used for Treatment of allergic respiratory conditions by blocking histamine (H1) receptors, which blocks histamine binding at H1 receptors, preventing vasodilation, capillary leakage, and mucus production
• Reduces symptoms of allergic rhinitis, hay fever, and anaphylaxis
• Prevents motion sickness (first-generation only)
• Note: Antihistamines DO NOT treat asthma or acute bronchospasm!

H1 Antihistamines Medications

• First-Gen H1 Blockers include diphenhydramine (Benadryl), hydroxyzine (Vistaril), doxylamine (Unisom), promethazine (Phenergan)
• note: Sedating which crosses the blood brain barrier to treat allergic reactions, anaphylaxis adjunct, motion sickness, and rhinorrhea
• Second-Gen H1 Blockers include loratadine (Claritin), cetirizine (Zyrtec), and fexofenadine (Allegra)
• note: Non-sedating and do not cross the blood-brain barrier to treat seasonal allergies, allergic rhinitis, and chronic urticaria
• H2 Antihistamines blocks H2 receptors in gastric parietal cells and Reduces acid production (treating GERD and peptic ulcers, etc.)
• note: famotidine (Pepcid) includes H2: -idine (-i dine: GI), and H2 blockers are used for acid suppression NOT for allergic reactions
• examples: H1 are -amine, -zine, and -adine
• Antitussives (Cough suppressants)
• Primary Use: Suppressing cough reflex for non-productive coughs
• Mechanism of Action where Central-acting (opioids & non-opioids) suppress cough by inhibiting the cough reflex in the medulla oblongata
• Peripheral-acting: Soothes the throat or reduces irritation in the respiratory tract
• Antitussives should only be used for dry, non-productive coughs and Avoid in productive coughs (risk of mucus buildup)
• Opioid Antitussives Medications include codeine and hydrocodone and Binds to opioid receptors to Suppresses cough reflex (medulla)
• Non-Opioid Central-Acting Medications include dextromethorphan (Robitussin DM, Delsym) and blocks NMDA receptors in medulla → Reduces cough reflex
• Peripheral-Acting Medications include benzonatate (Tessalon) and Anesthetizes stretch receptors in the lungs to Opioids are the most effective but have higher risks like Sedation and dependence

Expectorant Medications

• Primary Use: Loosening and thinning mucus to make coughing more productive
• Mechanism of Action: Stimulates respiratory tract secretions, increasing mucus hydration, Reduces mucus viscosity, making it easier to clear from the airways, and Encourages effective coughing without suppressing the reflex
• Expectorants should be used for productive coughs and not dry coughs!
• understand that expectorants help clear mucus but do NOT stop coughing immediately
• Guaifenesin (Mucinex) increases hydration of mucus (making it thinner) to treat Colds, bronchitis, pneumonia, and COPD
• Acetylcysteine (Mucomyst) is used (Also an antidote for acetaminophen overdose)
• Breaks disulfide bonds in mucus (making it less sticky) to treat conditions with Thick mucus like CF, COPD, pneumonia
• note: also used to treat acetaminophen overdose
• Guaifenesin is the most common OTC expectorant and Acetylcysteine is mainly used in severe lung diseases