Over-the-Counter Expectants Overview

Guaifenesin

• Widely used over-the-counter (OTC) expectorant.
• Increases bronchial fluid secretion.

Other Expectorants

• Traditional expectorants include ammonium chloride and tincture of ipecac.
• Efficacy of many OTC cough mixtures is considered doubtful, especially at typical dosages.

Bronchial Asthma

• Chronic inflammatory disorder of airways causing airflow obstruction.
• Symptoms include wheezing, breathlessness, chest tightness, and coughing.
• Pathogenesis involves frequent exposure to allergens leading to inflammatory cell infiltration.

Predisposing Factors for Asthma

• Respiratory infections are the most significant trigger.
• Genetic factors may contribute to asthma, particularly in families with allergic histories.
• Psychological factors impact 40% of asthmatics.

Clinical Presentation of Chronic Asthma

• Symptoms range from mild intermittent requiring minimal treatment to severe cases necessitating multiple medications.
• Acute severe asthma can lead to uncontrolled inflammation, airway edema, and severe bronchospasm.
• Patients may experience significant difficulty breathing, cyanosis, and can only speak a few words at a time.

Management of Asthma

Bronchodilators

• Three main classes: β-adrenergic agonists, muscarinic receptor blockers (like ipratropium), and xanthines (such as theophylline).

β-Adrenergic Agonists

• Non-selective agonists: adrenaline, isoprenaline, and ephedrine (rarely used).
• Selective β2 agonists:
  • Short-acting (e.g., salbutamol; duration 3-4 hours).
  • Long-acting (e.g., salmeterol; duration 12 hours).

Mechanism of Action

• Stimulation of bronchial β2 receptors increases cAMP, leading to bronchodilation and reduced histamine release.

Administration

• Short-acting β2 agonists used in acute asthma via inhalation or intravenous infusion.
• Long-acting β2 agonists are taken orally or by inhalation for chronic asthma.

Adverse Effects

• Possible tachycardia and arrhythmias due to hypotension or loss of selectivity at high doses.
• Tremors and nervousness may occur.
• Tolerance can develop with prolonged use, leading to potential hypokalemia.

Therapeutic Uses of Xanthines

• Acute severe asthma: aminophylline via slow intravenous infusion.
• Chronic asthma: sustained release theophylline tablets or rectal aminophylline.

Central Nervous System (CNS) Uses

• Reverses CNS depression and delays physical/mental fatigue (e.g., caffeine).
• Used in migraines and neonatal apnea syndrome.

Cardiovascular System (CVS) Uses

• Addresses acute pulmonary edema from left-sided heart failure.

Precautions

• Administer aminophylline slowly to avoid sudden cardiac complications.
• Monitor for interactions with enzyme inhibitors or in patients with pre-existing conditions.

Asthma and Its Characteristics

• Hypertrophy of airway smooth muscle contributes to airway obstruction.
• Excessive mucus secretion leads to difficulty in mucus expulsion.
• Congestion and edema of the respiratory mucosa may occur.

Predisposing Factors

• Recurring respiratory infections: Most significant risk factor for asthma.
• Genetic factors: Family history of asthma and allergies increases risk.
• Psychological factors: Present in 40% of asthmatic patients.

Clinical Presentation of Asthma

• Chronic asthma: Characterized by dyspnea, chest tightness, nighttime coughing, and expiratory wheezing.
• Symptom variability: Patients may experience mild intermittent symptoms or severe symptoms needing multiple medications.

Acute Severe Asthma

• Can escalate to uncontrolled inflammation, airway edema, mucus accumulation, and severe bronchospasm.
• Symptoms include severe dyspnea, inspiratory wheezing, cyanosis, and limited ability to speak.

Management of Asthma

• Bronchodilators: Key medications used to treat asthma.

β-Adrenergic Agonists

• Divided into three groups: non-selective, selective β2 agonists, and muscarinic receptor blockers.
• Selective β2 agonists:
  • Short-acting: Salbutamol, terbutaline, fenoterol (3-4 hours duration).
  • Long-acting: Salmeterol, formoterol (12 hours duration).
• Mechanism of action: Stimulating bronchial β2 receptors increases cAMP, leading to bronchodilation and reduced inflammation.
• Administration: Short-acting for acute asthma via inhalation or IV; long-acting for chronic asthma orally or via inhalation.
• Adverse effects: Tachycardia, arrhythmia, tremors, tolerance development, hypokalemia.

Muscarinic Antagonists

• Ipratropium bromide: Blocks M3 receptors, leading to bronchodilation but is not the first choice in treating asthma.
• More selective than atropine; does not cross the blood-brain barrier, reducing CNS side effects.
• Often combined with β2 agonists for synergistic effect.

Methylxanthines

• Classification: Include natural (caffeine, theophylline) and semi-synthetic forms (aminophylline).
• Mechanism of action: Adenosine A receptor antagonists leading to bronchodilation and CNS stimulation.
• Inhibit phosphodiesterase enzymes, increasing cAMP and affecting cardiac contractility.
• Precautions: Slow IV administration to avoid complications; caution in patients with cardiac/renal diseases.

Drug Interactions

• Enzyme inhibitors: Increase serum levels of methylxanthines, risking toxicity.
• Enzyme inducers: Decrease levels and reduce effectiveness of methylxanthines.

Asthma Overview

• Chronic asthma leads to hypertrophy of airway smooth muscle and increased mucus secretion, causing difficulty in expelling mucus.
• Congestion and edema of the respiratory mucosa affect airflow and breathing.

Predisposing Factors

• Recurrent respiratory infections: Major contributing factor to asthma development.
• Genetic factors: Asthma has a familial component, commonly seen in individuals with a history of allergies.
• Psychological factors: Present in about 40% of asthmatics, potentially influencing the severity of symptoms.

Clinical Presentation

• Chronic asthma symptoms: Include dyspnea, chest tightness, cough (often at night), and expiratory wheezing.
• Patients exhibit varying degrees of symptom severity, from mild to severe, requiring either little to no medication or multiple treatments.

Acute Severe Asthma

• Uncontrolled asthma can escalate into an acute phase characterized by inflammation, airway edema, mucus accumulation, and severe bronchospasm resistant to bronchodilators.
• Symptoms include severe dyspnea, inspiratory wheezing, cyanosis, and limited verbal communication due to breathlessness.

Management of Asthma

• Treatment involves bronchodilators classified into three groups:
  • β-adrenergic agonists
  • Muscarinic receptor blockers (e.g., ipratropium)
  • Xanthines (e.g., theophylline)

β-adrenergic Agonists

• Classification:
  • Non-selective (e.g., adrenaline, ephedrine) rarely used.
  • Selective β2 agonists:
    • Short-acting: Salbutamol (3-4 hours), Terbutaline, Fenoterol.
    • Long-acting: Salmeterol, Formoterol (12 hours).
• Mechanism: Stimulate bronchial β2 receptors, increasing cAMP, leading to bronchodilation and reduced bronchial inflammation.
• Administration:
  • Short-acting for acute asthma via inhalation or IV.
  • Long-acting for chronic asthma orally or via inhalation.
• Adverse Effects: Tachycardia, arrhythmias, tremors, tolerance, and hypokalemia due to potassium shifts.

Muscarinic Antagonists: Ipratropium Bromide

• Blocks M3 receptors in airway smooth muscle for bronchodilation; however, not used solely for asthma treatment due to side effects (dry mouth, urine retention).
• More selective and less central nervous system effects than atropine.

Methylxanthines

• Classification:
  • Natural (e.g., caffeine, theophylline) and semisynthetic (e.g., aminophylline).
• Mechanism: Adenosine receptor antagonism leads to bronchodilation, CNS stimulation, decreased mediator release from mast cells, and increased AV conduction.
• Therapeutic Uses:
  • Severe asthma: Aminophylline IV infusion for acute attacks.
  • Chronic asthma: Sustained-release theophylline tablets or rectal suppositories.

CNS and CVS Uses of Methylxanthines

• CNS: Reverses depression, delays fatigue, treats migraines, and neonatal apnea.
• CVS: Used in acute pulmonary edema due to heart failure.

Adverse Effects of Methylxanthines

• CNS: Irritability, headaches, insomnia, nervousness, and convulsions.
• CVS: Palpitations, tachycardia, and arrhythmias.

Bronchodilators

• Adrenaline, isoprenaline, and ephedrine are rarely used as bronchodilators.
• Selective β2 agonists are categorized into short-acting (e.g., salbutamol, terbutaline, fenoterol) with a duration of 3-4 hours and long-acting (e.g., salmeterol, formoterol) with a duration of 12 hours.

Mechanism of Action

• Stimulation of bronchial β2 receptors increases cAMP levels, leading to bronchodilation.
• β2 receptor stimulation in mast cells decreases histamine release.
• Reduces bronchial inflammation and wall edema.

Administration

• Short-acting β2 agonists are typically administered via inhalation or intravenous infusion for acute asthma.
• Long-acting β2 agonists are given orally or by inhalation for chronic asthma.

Adverse Effects

• Common side effects include tachycardia and arrhythmias due to reflex hypotension and direct activation of cardiac β1 receptors at high doses.
• Tremors and nervousness can occur.
• Tolerance may develop with prolonged use, necessitating a temporary cessation of the drug.
• Hypokalemia results from potassium shift from blood to cells.

Muscarinic Antagonists

• Ipratropium bromide is a non-selective M3 blocker which leads to bronchodilation.
• Side effects include dry mouth, urine retention, increased sedation, and excessive dryness of bronchial secretions.
• Ipratropium is preferred over atropine: it is a more selective muscarinic blocker, a quaternary ammonium compound unable to cross the blood-brain barrier, and does not excessively dry bronchial secretions.
• Commonly combined with β2 agonists for a synergistic effect.

Methylxanthines

• Classifications include natural (caffeine, theophylline, theobromine) and semi-synthetic (aminophylline, a salt of theophylline).
• Mechanism involves antagonizing adenosine A receptors, leading to bronchodilation, CNS stimulation, reduced mediator release from mast cells, and increased AV conduction.
• Inhibition of phosphodiesterase enzymes (PDE3 and PDE4) results in bronchodilation, increased cardiac contractility, smooth muscle relaxation, and diuresis.

Therapeutic Uses

• Acute severe asthma: aminophylline can be administered via slow intravenous infusion (250 mg at least over 15 minutes) followed by maintenance infusion (0.7 mg/kg/h).
• Chronic bronchial asthma: sustained-release theophylline tablets (100-300 mg/day) or rectal suppositories of aminophylline can be used.
• CNS applications include reversing CNS depression, delaying fatigue (caffeine), and treating migraines (caffeine with ergotamine).
• Neonatal apnea syndrome: caffeine is the preferred treatment.
• CVS applications involve treating acute pulmonary edema due to left-sided heart failure.

Adverse Effects of Methylxanthines

• CNS: irritability, headache, insomnia, nervousness, and convulsions.
• CVS: palpitations, tachycardia, and arrhythmias; rapid IV injection can cause hypotension and syncope.
• GIT: nausea, anorexia, increased acidity, and activation of peptic ulcers.

Precautions

• Aminophylline should be administered slowly (at least over 15 minutes).
• Caution is required in patients with severe cardiac disease, hypoxemia, renal and hepatic conditions, and in elderly or neonate populations.
• Avoid use in patients with peptic ulcers.

Drug Interactions

• Co-administration with enzyme inhibitors (e.g., cimetidine, erythromycin) may increase serum levels of methylxanthines, posing a risk for toxicity.
• Enzyme inducers (e.g., smoking, rifampin) may decrease serum levels and effectiveness of these drugs.

Asthma Overview

• Chronic asthma leads to hypertrophy of airway smooth muscle and increased mucus secretion, causing difficulty in expelling mucus.
• Congestion and edema of the respiratory mucosa affect airflow and breathing.

Predisposing Factors

• Recurrent respiratory infections: Major contributing factor to asthma development.
• Genetic factors: Asthma has a familial component, commonly seen in individuals with a history of allergies.
• Psychological factors: Present in about 40% of asthmatics, potentially influencing the severity of symptoms.

Clinical Presentation

• Chronic asthma symptoms: Include dyspnea, chest tightness, cough (often at night), and expiratory wheezing.
• Patients exhibit varying degrees of symptom severity, from mild to severe, requiring either little to no medication or multiple treatments.

Acute Severe Asthma

• Uncontrolled asthma can escalate into an acute phase characterized by inflammation, airway edema, mucus accumulation, and severe bronchospasm resistant to bronchodilators.
• Symptoms include severe dyspnea, inspiratory wheezing, cyanosis, and limited verbal communication due to breathlessness.

Management of Asthma

• Treatment involves bronchodilators classified into three groups:
  • β-adrenergic agonists
  • Muscarinic receptor blockers (e.g., ipratropium)
  • Xanthines (e.g., theophylline)

β-adrenergic Agonists

• Classification:
  • Non-selective (e.g., adrenaline, ephedrine) rarely used.
  • Selective β2 agonists:
    • Short-acting: Salbutamol (3-4 hours), Terbutaline, Fenoterol.
    • Long-acting: Salmeterol, Formoterol (12 hours).
• Mechanism: Stimulate bronchial β2 receptors, increasing cAMP, leading to bronchodilation and reduced bronchial inflammation.
• Administration:
  • Short-acting for acute asthma via inhalation or IV.
  • Long-acting for chronic asthma orally or via inhalation.
• Adverse Effects: Tachycardia, arrhythmias, tremors, tolerance, and hypokalemia due to potassium shifts.

Muscarinic Antagonists: Ipratropium Bromide

• Blocks M3 receptors in airway smooth muscle for bronchodilation; however, not used solely for asthma treatment due to side effects (dry mouth, urine retention).
• More selective and less central nervous system effects than atropine.

Methylxanthines

• Classification:
  • Natural (e.g., caffeine, theophylline) and semisynthetic (e.g., aminophylline).
• Mechanism: Adenosine receptor antagonism leads to bronchodilation, CNS stimulation, decreased mediator release from mast cells, and increased AV conduction.
• Therapeutic Uses:
  • Severe asthma: Aminophylline IV infusion for acute attacks.
  • Chronic asthma: Sustained-release theophylline tablets or rectal suppositories.

CNS and CVS Uses of Methylxanthines

• CNS: Reverses depression, delays fatigue, treats migraines, and neonatal apnea.
• CVS: Used in acute pulmonary edema due to heart failure.

Adverse Effects of Methylxanthines

• CNS: Irritability, headaches, insomnia, nervousness, and convulsions.
• CVS: Palpitations, tachycardia, and arrhythmias.

This quiz covers the essential information about a common over-the-counter expectorant, guaifenesin, and contrasts it with other traditional expectorants found in various cough mixtures. Understand the mechanisms by which these expectorants work and their relevance in treating coughs effectively.