Respiratory System Overview and Cough Remedies

Respiratory System Overview

• The respiratory system comprises the upper and lower respiratory tracts.
• The upper tract includes the nose, pharynx, larynx, and trachea.
• The lower tract includes the bronchial tree and alveoli.
• Inflammation in the upper respiratory tract can cause common cold, seasonal rhinitis, sinusitis, pharyngitis, and laryngitis.
• Inflammation of the lower tract can lead to serious conditions like bronchitis and pneumonia, impacting gas exchange.
• Obstructive disorders hinder gas delivery to alveoli due to airway blockages (e.g., asthma, COPD).
• Drugs affecting the respiratory system maintain open airways and efficient gas movement.

Cough Remedies (Antitussives)

• Antitussives suppress the cough reflex by acting on the brain's cough center.
• These drugs are often used for nonproductive coughs (e.g., common cold, sinusitis).
• Persistent coughing can cause muscle strain and further respiratory irritation.
• Examples of antitussives include benzonatate (Tessalon), codeine, dextromethorphan (Benylin), and hydrocodone (Hycodan).

Pharmacokinetics (Antitussives)

• Codeine, hydrocodone, and dextromethorphan are rapidly absorbed, metabolized in the liver, and excreted in urine.
• They cross the placenta and enter breast milk.
• Benzonatate is also metabolized in the liver and excreted in urine.

Contraindications/Cautions (Antitussives)

• Antitussives should be used carefully in patients requiring a cough to clear airways.
• Patients with asthma or emphysema may develop secretion buildup with cough suppression.
• Use caution in patients with hypersensitivity to narcotics or a history of addiction to narcotics.
• Avoid use during pregnancy and lactation.

Adverse Effects (Antitussives)

• Traditional antitussives dry mucous membranes and increase respiratory tract secretions' viscosity.
• Central nervous system (CNS) effects like drowsiness and sedation can occur due to brain center impact.
• Dry mouth, nausea, constipation, and GI upset are other associated side effects.
• Local antitussives may cause headaches, congestion, and dizziness.

Expectorants (e.g., Guaifenesin)

• Expectorants reduce respiratory tract fluid adhesiveness and surface tension, improving secretion movement and thus facilitating a more productive cough.
• Expectorants are indicated for symptomatic relief of dry, nonproductive coughs (e.g., common cold, acute bronchitis, influenza).
• Guaifenesin is rapidly absorbed (onset 30 minutes), with a duration of 4-6 hrs.

Adverse effects (Expectorants)

• Common adverse effects include gastrointestinal (GI) symptoms (nausea, vomiting, anorexia).
• Less common effects include headache, dizziness, and a possible mild rash.

Mucolytics (e.g., Acetylcysteine, Dornase Alfa)

• Mucolytics increase or liquefy respiratory secretions to aid in airway clearance.
• Acetylcysteine affects mucoproteins to decrease secretion viscosity.
• Dornase alfa selectively breaks down respiratory mucus by separating DNA from proteins and used in cystic fibrosis cases (characterized by thick tenacious mucus).

Pharmacokinetics (Mucolytics)

• Mucolytic administration may be via nebulization or direct tracheal instillation.

Contraindications/Cautions (Mucolytics)

• Mucolytics should be used cautiously in acute bronchospasm, peptic ulcer, esophageal varices as increased secretions worsen these problems.

Bronchodilators/Antianthmatics (Asthma/COPD)

• Bronchodilators/Antianthmatics relax airway smooth muscle, enhancing breathing and preventing/treating bronchospasm associated with asthma and COPD.
• Some are administered orally, leading to increased systemic effects.
• Others (e.g., nebulizers) are administered directly into the airways, reducing systemic effects.
• Include xanthines, sympathomimetics, and anticholinergics.

Xanthines (e.g., Aminophylline, Caffeine, Theophylline)

• Xanthines directly affect smooth muscle in the respiratory tract and blood vessels.
• They inhibit slow-reaction substance (SRS-A) and histamine release. Reducing airway swelling and narrowing.
• Aminophylline, caffeine, dyphylline, theophylline are examples.

Pharmacokinetics (Xanthines)

• Rapidly absorbed from the gastrointestinal (GI) tract (oral) and via intravenous (IV) injection.
• Widely distributed, metabolized in the liver, excreted in urine.
• Cross placenta, enter breast milk.

Contraindications/Cautions (Xanthines)

• Use caution in patients with GI problems, coronary disease, respiratory dysfunction, renal/hepatic disease, alcoholism, or hyperthyroidism.
• Systemic side effects can exacerbate these conditions.

Adverse Effects (Xanthines)

• Adverse effects are related to theophylline blood levels.
• Therapeutic levels range from 10-20 mcg/mL.
• Adverse effects increase with higher levels, including GI upset, nausea, irritability, tachycardia, seizures, and even death.
• Nicotine increases xanthine metabolism in the liver. Increase doses may be necessary in smokers if treatment continues.

Sympathomimetics (e.g., Epinephrine, Albuterol, Formoterol)

• Act directly on beta2-receptors in bronchi (increasing respiration rate and depth).
• Beta2-selectivity is lost at higher levels, leading to systemic effects.

Anticholinergics (e.g., Ipratropium, Tiotropium)

• Anticholinergics block neurotransmitter acetylcholine actions at vagus-mediated receptor sites.
• Prevents smooth muscle contraction and thus improve airflow.
• These medications are often used when patients cannot tolerate sympathetic effects of sympathomimetics.

Drugs Affecting Inflammation (e.g., Inhaled Steroids, Leukotriene Receptor Antagonists, Mast Cell Stabilizer)

• Steroids, leukotriene inhibitors, mast cell stabilizers target inflammatory processes.
• These affect airway inflammation, mucus production, and bronchoconstriction that arises from inflammation.

Inhaled Steroids

• Inhaled steroids effectively treat bronchospasm by reducing airway inflammation.
• They decrease the inflammatory cells' effectiveness.

Leukotriene Receptor Antagonists

• These block or antagonize leukotriene receptors responsible for asthma symptoms like constriction, edema, mucus secretion, and neutrophil aggregation.

Mast Cell Stabilizer (e.g., Cromolyn Sodium)

• Mast cell stabilizers prevent the release of substances that cause inflammation and bronchoconstriction from mast cells.

Pharmacokinetics (Inhaled Steroids)

• Rapid absorption, but takes weeks to reach effective levels.
• Metabolized in the liver, excreted in urine.
• Cross placenta, enter breast milk.

Contraindications/Cautions (Inhaled Steroids)

• Not used for acute asthma attack or status asthmaticus.
• Use with caution during pregnancy and lactation (risk-benefit assessment required).
• Caution in active respiratory infections, as suppression of the inflammatory response can be dangerous.

Adverse Effects (All)

• Adverse effects are often limited, due to localized administration (inhaled).
• But possible side effects include local irritation (throat soreness), hoarseness, dry mouth, coughing, pharyngeal/laryngeal fungal infections.