Pharmacotherapeutics for Advanced Nurse Prescribers: Respiratory Medications Study Notes

Pharmacotherapeutics for Advanced Practice Nurse Prescribers

Chapter Overview

  • Focus on drugs affecting the respiratory system.

  • Objectives:

    • Discuss pharmacodynamics and pharmacokinetics of:

    • Bronchodilators

    • Leukotriene modifiers

    • Respiratory inhalants

    • Allergy medications

    • Cough and cold medications

    • Describe pharmacotherapeutics of drugs used to treat the respiratory system.

Major Drug Classes

  • Bronchodilators

  • Leukotriene Modifiers

  • Respiratory Inhalants

  • Allergy Medications

  • Cough and Cold Medications

Beta2-Receptor Agonists

Short-acting Beta2-Receptor Agonists (B2RAs)

  • Examples:

    • Albuterol (ProAir, Ventolin, Proventil)

    • Metaproterenol (Alupent)

    • Terbutaline (Brethine, Brethaire)

    • Pirbuterol (Maxair)

    • Levalbuterol (Xopenex)

Long-acting Beta2-Receptor Agonists

  • Examples:

    • Salmeterol (Serevent)

    • Formoterol (Foradil)

    • Arformoterol (Brovana)

Ultra-long-acting Beta2-Receptor Agonists

  • Examples:

    • Indacaterol (Arcapta Neohaler)

    • Olodaterol (Striverdi Respimat)

    • Vilanterol

Pharmacodynamics

  • Albuterol and Terbutaline:

    • Selective beta2 agonists with minor beta1 activity.

  • Levalbuterol:

    • Similar to albuterol but with fewer side effects.

  • Pirbuterol:

    • Structurally identical to albuterol.

  • Salmeterol:

    • More selective for beta2 with a half-life of 10-12 hours.

Pharmacokinetics

  • Albuterol:

    • Inhaled and absorbed from bronchi; oral forms well absorbed from the gastrointestinal (GI) tract.

  • Metabolism:

    • Most bronchodilators metabolized in the liver and excreted in urine.

    • Arformoterol: Metabolized in the liver by CYP2D6 and CYP2C19.

Pharmacotherapeutics

  • Precautions and Contraindications:

    • Cardiac arrhythmias, angina, ischemic heart disease (IHD), hypertension (HTN), stroke, pregnancy.

    • Diabetes: Potential drug-induced hyperglycemia.

  • Boxed Warning:

    • Salmeterol, formoterol, arformoterol, and indacaterol should not be used singly in asthma at any age; they may be used in combination with inhaled corticosteroids.

    • Increased risk of asthma-related intubations and death.

Adverse Drug Reactions (ADRs)

  • Generally transient:

    • Tachycardia, palpitations.

    • CNS effects: tremors, dizziness, shakiness, nervousness, restlessness.

    • Headaches.

    • Salmeterol and long-acting B2RAs may increase the risk of exacerbation of severe asthma symptoms if the patient is deteriorating.

Drug Interactions

  • Digitalis Glycosides:

    • Increased risk of dysrhythmia.

  • Beta Adrenergic Blocking Agents:

    • Direct competition for beta receptor sites, leading to mutual inhibition of therapeutic effects.

  • Tricyclic Antidepressants and Monoamine Oxidase Inhibitors (MAOIs):

    • Potentiate the effects of beta agonists on the vascular system.

Clinical Use and Dosing

  • Indications:

    • Bronchospasm due to asthma, bronchitis (acute or chronic), and chronic obstructive pulmonary disease (COPD).

  • Dosing:

    • Albuterol MDI: 2 puffs every 4-6 hours.

    • Nebulizer: 2.5 mg/dose, may repeat once after 5-10 mins.

    • Combined use with ipratropium is possible.

  • Levalbuterol: Nebulizer every 6-8 hours.

  • Salmeterol DISKUS: 1 puff twice daily; do not use alone for persistent asthma, combine with inhaled corticosteroid.

  • Exercise-Induced Bronchospasm (EIB):

    • Albuterol: 2 puffs 15 mins before exercise.

    • Salmeterol: if taking twice daily for asthma, do not add a dose before exercise; otherwise, 2 puffs 30-60 mins before exercise.

Rational Drug Selection

  • Short-acting beta2-agonists may be used.

  • Age Considerations:

    • Only albuterol and metaproterenol are approved for children under 4 years.

    • Albuterol is safest for infants.

  • Cost Considerations:

    • Albuterol is the least expensive.

Monitoring and Patient Education

  • Monitoring:

    • Assess pulmonary function regularly.

  • Patient Education:

    • Proper MDI use; demonstrations and return demonstrations encouraged.

    • Use a spacer with all patients.

    • Explain breath-actuated inhalers require inspiratory drive for medication delivery.

    • Inform about potential ADRs.

Xanthine Derivatives

Pharmacodynamics

  • Methylxanthines:

    • Theophylline, caffeine.

    • Promote bronchial smooth muscle relaxation and CNS stimulation.

    • Cardiovascular effects: increase heart rate (HR).

    • Increased gastric acid production and stimulation of skeletal muscle, resulting in tremors.

    • Increased renal blood flow and glomerular filtration rate.

Pharmacokinetics

  • Rapid absorption from the GI tract.

  • Wide distribution with notable variations in special populations (e.g., premature neonates, older patients).

  • Extensive metabolism in the liver via CYP450; clearance influenced by various disease states and CYP inducers.

  • Renal elimination.

Precautions and Contraindications

  • Cautious Use:

    • In patients with peptic ulcer disease, seizure disorders, hypertension (HTN), ischemic heart disease, coronary insufficiency, or a history of strokes and cardiac arrhythmias.

Toxicity

  • Theophylline Toxicity Levels:

    • Clinical toxicity at levels > 20 mcg/mL may cause seizures at 15 to 20 mcg/mL.

Adverse Reactions (ADRs)

  • Common Symptoms:

    • CNS effects: irritability, restlessness, seizures, insomnia.

    • GI issues: reflux, worsening heartburn.

    • CV events: palpitations, tachycardia, hypotension, life-threatening arrhythmias.

Drug and Food Interactions

  • Many interactions due to CYP450 metabolism.

  • Tobacco smoking increases theophylline clearance.

  • Caution with benzodiazepines, beta2-agonists, and lithium levels.

Clinical Use and Dosing

  • Theophylline for COPD:

    • Not a first-line drug for asthma and COPD.

    • Initial dose: 6 mg/kg/24 hours, increase by 25% every 3 days until levels between 10-20 mcg/mL reached.

Monitoring and Patient Education

  • Monitor signs of toxicity and check theophylline levels frequently during titration.

  • Educate patients about adherence to prescribed doses, recognizing toxicity signs, and managing lifestyle factors influencing drug metabolism.

Anticholinergics

Pharmacodynamics

  • Ipratropium Bromide (Atrovent):

    • Blocks muscarinic cholinergic receptors; used with albuterol for asthma exacerbation.

  • Tiotropium Bromide (Spiriva):

    • Inhaled anticholinergic for COPD and asthma.

  • Aclidinium Bromide (Tudorza Pressair):

    • Inhibits muscarinic M3 receptors in the lungs, treating only COPD.

Precautions and Contraindications

  • Use cautiously in known hypersensitivity cases.

  • Not recommended for acute bronchospasm.

Adverse Reactions (ADRs)

  • Most common is cough, with other potential effects being hoarseness, throat irritation, dry mouth, nausea, vomiting.

Clinical Use and Dosing

  • Ipratropium Dosing for COPD:

    • 2 puffs (36 mcg) 4 times/day, maximum 12 daily.

  • Asthma Dosing:

    • Same for adults; children < 12 years: 1-2 puffs every 6 hours.

Patient Education

  • Educate on proper inhaler use and ADRs.

  • Encourage lifestyle adjustments for self-management.

Leukotriene Modifiers (LTRAs)

Pharmacodynamics

  • Inhibits symptoms associated with allergic rhinitis by blocking the action of leukotrienes, which include smooth muscle contractions, neutrophil aggregation, and vascular permeability.

Pharmacokinetics

  • Zafirlukast:

    • Absorbed from the GI tract.

  • Montelukast:

    • Rapidly absorbed; metabolized in the liver.

  • Zileuton:

    • Metabolized in the liver; renally excreted.

Precautions and Contraindications

  • Not for acute asthma treatment or abrupt substitution for steroids.

  • Caution in hepatic dysfunction.

Adverse Reactions (ADRs)

  • Most common ADR is headache, with some reports of GI upset.

Clinical Use and Dosing

  • Montelukast:

    • Approved for persistent asthma from 12 months onward.

  • Zafirlukast:

    • Chronic asthma for patients aged 5 and older.

Monitoring and Patient Education

  • Monitor worsening asthma symptoms and potential neuropsychiatric side effects.

Corticosteroids

Overview

  • Most potent anti-inflammatory drugs, effective in reducing asthma severity and increasing peak flow readings.

Inhaled Corticosteroids

  • Examples:

    • Beclomethasone dipropionate, Budesonide, Flunisolide, Mometasone furoate, Fluticasone, Ciclesonide.

Precautions and Contraindications

  • Avoid in acute status asthmaticus and Cushing’s syndrome; caution in infectious conditions.

Adverse Reactions (ADRs)

  • Potential for oral candidiasis, dysmenorrhea, hoarseness, and others.

Clinical Use and Dosing

  • Used for managing persistent asthma and allergic rhinitis.

Patient Education

  • Administer inhaled medication correctly with spacers and provide guidelines on rinsing the mouth post-inhalation.

Anti-inflammatory Agents

Overview

  • Inhibit antigen-induced bronchospasm and block histamine release.

  • Example:

    • Cromolyn sodium

    • Administered for bronchospasm prophylaxis and allergic rhinitis.

Precautions and Contraindications

  • Not a substitute for bronchodilators.

Patient Education

  • Educate about appropriate use and common side effects.

Inhaled Antihistamines

Overview

  • Examples:

    • Azelastin, Olopatadine.

Adverse Reactions (ADRs)

  • Commonly include bitter taste, somnolence, and nasal irritation.

Clinical Use and Dosing

  • Effective for allergic rhinitis, dosed as two sprays per nostril twice daily.

Patient Education

  • Focus on administration, ADRs, and lifestyle changes.

Oxygen Therapy

Overview

  • Necessary for sustaining life in patients with hypoxia.

  • Delivery methods include nasal cannula, masks, or hoods.

Precautions and Contraindications

  • Avoid smoking and ensure the lowest concentration needed.

Adverse Reactions (ADRs)

  • Common issue: dry nasal passages, rectified with humidified oxygen.

Monitoring

  • Important to monitor oxygen saturation levels and use blood gas analyses when necessary.

Antihistamines

Overview

  • First-generation examples:

    • Diphenhydramine.

  • Second-generation examples:

    • Cetirizine, Loratadine, Fexofenadine.

Precautions and Contraindications

  • First-generation antihistamines should be avoided in certain conditions, including narrow-angle glaucoma.

Clinical Use and Dosing

  • Indicated for allergies, hypersensitivity reactions, urticaria.

Patient Education

  • Education around administration and lifestyle management.

Decongestants

Overview

  • Treat nasal congestion from colds and allergic rhinitis.

  • Examples:

    • Oral and topical forms available.

Precautions and Contraindications

  • Avoid in severe hypertension and in young children.

Adverse Reactions (ADRs)

  • CNS and CV effects including anxiety and cardiovascular issues.

Clinical Use and Dosing

  • Recommendations for short-term use with caution for prolonged application.

Patient Education

  • Stress importance of proper dosages and lifestyle changes.

Antitussives

Overview

  • Used primarily for nonproductive cough management.

  • Examples:

    • Dextromethorphan, Benzonatate, Codeine.

Precautions and Contraindications

  • Not for chronic coughs associated with smoking or asthma.

Patient Education

  • Encourage increased fluid intake and avoidance of irritants.

Expectorants

Overview

  • Example:

    • Guaifenesin; the only FDA-approved expectorant.

Precautions and Contraindications

  • Should not be used for chronic coughs or in cases with significant respiratory secretions.

Adverse Reactions (ADRs)

  • Potential GI upset and dizziness.

Patient Education

  • Emphasize hydration and awareness of adverse reactions.

Summary

  • A review of numerous medications available for treating respiratory system disorders, focusing on pharmacodynamics, pharmacokinetics, clinical use, and dosing of various drug classes including bronchodilators, leukotriene modifiers, inhaled anti-inflammatory drugs, antihistamines, decongestants, expectorants, and antitussive medications.

Knowledge Check

  • Long-acting beta2-receptor agonists have a boxed warning regarding asthma use:

    • True

  • Xanthine derivatives should be used with caution in:

    • All of the above: heart failure, seizure disorder, cardiac arrhythmias.