Respiratory System Pharmacology – Comprehensive Lecture Notes Chapter 26

Overview of Respiratory Disorders

• Spectrum ranges from common, self-limiting conditions like the common cold to severe, life-threatening pathologies such as bacterial pneumonia, pulmonary embolism, and various forms of lung cancer.

• Clinical emphasis in this lecture focuses on chronic respiratory diseases (Chronic Obstructive Pulmonary Disease and asthma) and their pharmacologic management, including symptomatic control with agents like decongestants, antihistamines, and various classes of bronchodilators.

Chronic Obstructive Pulmonary Disease (COPD)

• Definition: COPD is an umbrella term encompassing two progressive, largely irreversible lung pathologies that significantly impair airflow:

  • Chronic bronchitis

    • Characterized by persistent inflammation of the bronchial tubes, leading to a chronic, productive cough for at least three months in two consecutive years.

    • This inflammation results in hypertrophy of mucus-secreting glands, persistent mucus hyper-secretion, and impaired ciliary function, making patients susceptible to recurrent respiratory infections and hypoxemia (often referred to as "blue bloaters" due to cyanosis and edema).

  • Emphysema

    • Involves the irreversible destruction and enlargement of the terminal alveolar sacs (described as "little grapes that don’t work" due to their diminished surface area for gas exchange).

    • This destruction of alveolar walls leads to loss of lung elasticity, airway collapse during exhalation, and air trapping, resulting in hyperinflation and dyspnea (often referred to as "pink puffers" due to pursed-lip breathing and lack of cyanosis).

• Disease course is aggressive, gradually worsening over time, and severely limits quality of life.

• Primary cause: Cigarette smoking is overwhelmingly the leading cause, responsible for approximately 90% of cases, due to its ability to induce chronic inflammation, oxidative stress, and an imbalance between proteases and antiproteases in the lungs.

• COPD is incurable; pharmacologic interventions aim at controlling symptoms, reducing the frequency and severity of exacerbations, and improving exercise tolerance.

Oxygen & Environmental Safety Anecdotes

• Oxygen is not flammable itself, meaning it does not burn, but it is highly combustible, meaning it vigorously supports combustion.

  • This significantly increases the risk of igniting nearby flammable materials; even small sparks from hair-dryers, electric razors, or smoldering cigarettes can lead to rapid and intense fires.

  • Case story: A patient smoking while using nasal O₂ tubing resulted in a tragic incident where the flame traveled down the oxygen cannula, causing severe "burned lungs."

• “Grass-clipping piles + summer heat” and stacks of old newspapers were cited as real-world examples of spontaneous combustion due to heat accumulation within organic materials.

• Household chemistry caution: The dangerous mixing of bleach ( ext{sodium hypochlorite}) with ammonia ( ext{ammonium hydroxide}) releases highly toxic chloramine gases, which can cause severe respiratory distress and lung damage. An example was given of accidental exposure that required Centers for Disease Control and Prevention (CDC) guidance.

Respiratory Stimulants

• Caffeine citrate (discussed in a previous chapter) and IV/oral theophylline are used for neonates and infants to stimulate their immature respiratory drive, primarily by increasing sensitivity to carbon dioxide and enhancing diaphragm contractility.

Bronchodilators – General

• Pharmacologic goal: These medications work by relaxing the smooth muscle of the bronchial tree, leading to bronchodilation and relief of bronchospasm, thereby improving airflow in conditions like asthma and COPD.

• Routes of administration:

  • Oral: Systemic absorption, slower onset, higher risk of systemic adverse effects.

  • Parenteral (IV/IM): Used for acute, severe exacerbations when rapid systemic effect is needed.

  • Inhalation – This is the preferred route due to its rapid onset of action directly at the site of constriction in the airways and a significantly minimized risk of systemic adverse effects compared to oral or parenteral routes.

Inhalation Devices

• Metered-Dose Inhaler (MDI)

  • A most common delivery device that uses a propellent to deliver a precise dose of medication with each activation.

  • Requires coordination between pressing the canister and inhaling simultaneously for optimal drug deposition.

  • Can be effectively used with a spacer (a valved holding chamber, demo with pediatric mask), which improves coordination, reduces drug deposition in the oropharynx, and enhances drug delivery to the lungs, especially beneficial for children and those with coordination difficulties.

  • Must be cleaned periodically (e.g., weekly) to prevent residue buildup, which can obstruct the valve and reduce drug delivery.

• Dry-Powder Inhaler (DPI)

  • Delivers medication as a fine powder, without a propellant.

  • Breath-actuated; medication is dispersed by the force of the patient’s inspiratory effort.

  • Requires adequate inspiratory effort to ensure the drug reaches the lungs; therefore, NOT suitable for patients during acute, severe asthma attacks where inspiratory effort may be compromised.

• Small-Volume Nebulizer (SVN)

  • Converts liquid medication into an aerosolized mist, which