Pharmacological approaches to COPD/Asthma

Question 1

Beta-2 Agonists: Short Acting

Answer 1

• Prototype: salbutamol
• Onset within minutes (for acute use)
• Side Effects: Generally Well tolerated, tachycardia/palpitations, tremor
  Long Acting Beta-2 Agonists
• Prototype: salmeterol
• Dissociates (releases) from the receptors more slowly
• Advantages: longer duration (12 hours)
• However – slower onset of action (not for acute use)
• Note that it usually not used alone and is paired with a corticosteroid

Question 2

salbutamol

Answer 2

Beta-2 Agonists: Short Acting

Question 3

Methyxanthines

Answer 3

• Prototype: theophylline
• Discovered when people noticed strong coffee cured asthma

Methylxanthines

• Narrow margin of safety
• Side effects: nasea, vomiting
• Stimulatory: insomnia, tremor, restlessness
• Serious: Cardiac arrhythmias
• Drug Interactions are common

Question 4

theophylline

Answer 4

Methyxanthines

Question 5

Inhaled Corticosteroids

Answer 5

• Prototypes: budesonide fluticasone
• Localized deliver helps minimize systemic side effects
• Side effects: oral thrush (overgrowth of candida, occurs due to deposition of steroid in the oral cavity) dysphonia
  Novel Drugs
• Prodrug activated by esterases in the airways (ciclesonide)

Question 6

budesonide fluticasone

Answer 6

Inhaled Corticosteroids

Question 7

Leukotriene Receptor Antagonist (LTRA)

Answer 7

• Protype: Montelukast
• Advantage: Allow oral dosing
• Disadvantage: likely not as efficacious as other agents

Question 8

Montelukast

Answer 8

Leukotriene Receptor Antagonist (LTRA)

Question 9

Monoclonal Antibodies

Answer 9

• Prototype: omalizumab
• Mechanism: prevents interaction of allergen with IgE
• Administered by subcutaneous injection
• Advantage: administered every few weeks
• Disadvantages: immune reactions / cost
  Future Directions
• Extending drug action (ultra long acting beta agonists)
• Selective PDE4 inhibitors
• Interleukin 5 inhibitors (mepolizumab)

Question 10

omalizumab

Answer 10

Monoclonal Antibodies

Question 11

Anticholinergics

Answer 11

• Atropine is the prototypical anticholinergic
• Ipratropium is a modified version of atropine, designed to minimize systemic absorption
• M1, M3 receptors mediate: bronchoconstriction and bronchial secretion
• Therefor blocking these receptors with an antagonist leads to bronchodilation and reduced bronchial secretion (?)
• Short-acting muscarinic antagonist (SAMA) = Ipratropium
• Long-acting muscarinic antagonist (LAMA) = Tiotropium
  Side effect is dry mouth as there is muscarinic receptors in the salivary glands

Question 12

Ipratropium

Answer 12

• Short-acting muscarinic antagonist (SAMA) =

Question 13

Tiotropium

Answer 13

Long-acting muscarinic antagonist (LAMA)