Asthma Management Drugs: Theophylline, Leukotriene Antagonists, Corticosteroids, and Mast Cell Stabilizers

Theophylline (Dansenes)

• Mechanism of Action:

  • Phosphodiesterase (PDE) is an enzyme considered a "bad guy" because it destroys cyclic AMP (cAMP), a "good guy."

  • Cyclic AMP is essential for bronchodilatation; its absence leads to bronchoconstriction.

  • Theophylline inhibits phosphodiesterase, thus increasing cellular concentrations of cyclic AMP.

  • Increased cyclic AMP results in relaxation of the bronchial tree muscles, leading to bronchodilatation and relief from bronchospasm.

• Other Actions:

  • Acts as a central nervous system (CNS) stimulant, similar to caffeine found in tea, leading to increased alertness.

• Indications:

  • Used for chronic management of mild to moderate asthma, not for acute asthma attacks.

  • An adjunct drug for Chronic Obstructive Pulmonary Disease (COPD).

  • Its use is not frequent due to potential drug interactions and significant adverse effects.

• Adverse Effects (Crucial to memorize):

  • Palpitations: Awareness of one's own heartbeat.

  • Dysrhythmia: Irregular heartbeat.

  • Tremors: Shakiness, often in the hands (e.g., from excessive tea consumption).

  • Nausea and Vomiting.

  • Peptic ulcer and Gastritis.

  • Enhancement of respiratory drive in infants (however, not recommended as medication for infants).

• Therapeutic and Toxic Levels:

  • The therapeutic drug level for Theophylline in the blood is $15 ext{ mcg/mL}$.

  • Levels above $15 ext{ mcg/mL}$ can lead to toxicity, indicated by symptoms such as repeated vomiting, tremors, palpitations, and dysrhythmia.

  • The instructor emphasizes that any medication given in microgram dosages ($1 ext{ microgram} = 1/1000 ext{ of a milligram}$) is generally considered dangerous and requires careful monitoring.

Leukotriene Receptor Antagonists

• Mechanism of Action:

  • Leukotrienes are substances (e.g., chemicals released from cat fur if allergic) that bind to specific leukotriene receptors and cause bronchoconstriction.

  • These medications act as antagonists, meaning they occupy the leukotriene receptors, preventing leukotrienes from binding and causing airway constriction.

  • By blocking leukotriene action, they prevent smooth muscle contraction in the airways, leading to bronchodilatation.

  • They also decrease mucus secretion and prevent vascular permeability, which reduces the influx of neutrophils and leukocytes, thereby decreasing the inflammatory process.

• Examples:

  • Montelukast (Singulair).

  • Zafirlukast.

  • Zileuton.

• Indications:

  • Prophylaxis and long-term prevention of asthma.

  • Not for management of acute asthma attacks.

  • Montelukast (Singulair) is also effective in treating allergic rhinitis.

• Onset of Action:

  • Improvement typically occurs after one week of continuous use. Patients should be advised to wait at least one week to observe efficacy.

• Adverse Effects:

  • Headache, nausea, and dizziness are common and generally acceptable side effects.

  • Zafirlukast and Montelukast can elevate liver enzymes, necessitating regular monitoring of liver enzymes in patients on long-term therapy.

• Contraindications:

  • Allergy to inactive ingredients of the drug, such as povidone, lactose, titanium dioxide, or cellulose derivatives, as these could still trigger an allergic reaction.

Corticosteroids

• Mechanism of Action:

  • Their primary action in bronchial asthma is anti-inflammatory, reducing the inflammation in the airways.

• Examples of Inhaled Corticosteroids:

  • Beclomethasone

  • Budesonide

  • Flunisolide

  • Fluticasone

  • Ciclesonide

  • Triamcinolone

  • Many end with "-solone" or "-lone."

• Systemic Corticosteroids vs. Inhaled:

  • Systemic corticosteroids are taken orally (e.g., tablets) or by injection.

  • Systemic use, especially long-term, carries a greater risk of adverse effects compared to inhaled corticosteroids.

• General Adverse Effects (especially with systemic use):

  • Immune suppression (compromises the immune system).

  • Flushing of the face.

  • High blood pressure (mentioned generally).

• Contraindications (for systemic corticosteroids):

  • Patients with a history of chronic infection (e.g., vaginal candidiasis, thrush) should generally not take systemic corticosteroids due to their immune-suppressing effects.

Mast Cell Stabilizers

• Mechanism of Action:

  • Mast cells are connective tissue cells that can release inflammatory substances.

  • Mast cells produce two main substances: heparin (a "good boy" anticoagulant) and histamine (a "bad boy" inflammatory mediator).

  • Mast cell stabilizers prevent the mast cells from releasing histamine, thereby inhibiting the inflammatory process and bronchoconstriction.

  • (Analogy used by instructor): Imagine histamine as a boy throwing stones. Instead of directly confronting him (like police), the mast cell stabilizers metaphorically give money to his "mother" (the mast cell) to keep him at home, preventing the release of histamine.

• Examples:

  • Cromolyn.

  • Nedocromil.

• Indications:

  • Used for the chronic management of bronchial asthma.

  • Not for acute asthma attacks.