1.
Short-Acting β2 Agonists (SABAs)
❖ SABAs “Quick relief”:
➢ Examples: Albuterol (Salbutamol), Levalbuterol (Levosalbutamol).
❖ Mechanism of Action:
✓ Direct-acting β2-selective agonists.
✓ Provide significant bronchodilation with little of the undesired effect of α or β1 stimulation.
✓ Directly relax airway smooth muscle.
❖ Therapeutic Uses:
✓ Symptomatic treatment of bronchospasm.
✓ Monotherapy for intermittent asthma or exercise-induced bronchospasm.
✓ All patients with asthma should be prescribed a SABA inhaler.
✓ Have no anti-inflammatory effects, and they should never be used as the sole therapy for persistent asthma.
1. Short-Acting β2 Agonists (SABAs)
❖ Pharmacokinetics:
✓ Rapid onset of action (5 to 30 minutes).
✓ Provide relief for 4 to 6 hours.
❖ Adverse Effects:
✓ Tremors (dose related).
✓ Tachycardia.
✓ Hyperglycemia.
✓ Hypokalemia.
✓ Hypomagnesemia.
2. Long-Acting β2 Agonists (LABAs)
❖ LABAs “Long-term control”:
➢ Examples: Salmeterol, Formoterol.
❖ Mechanism of Action:
✓ β2 Agonists.
❖ Therapeutic Uses:
✓ Useful adjunctive therapy for asthma (LABA monotherapy is contraindicated).
❖ Pharmacokinetics:
✓ Long duration of action, providing bronchodilation for at least 12 hours.
✓ Salmeterol and formoterol should not be used for quick relief of an acute asthma attack.
❖ Adverse effects are similar to SABAs.
3. Corticosteroids: Inhaled Corticosteroids (ICS)
❖ ICS: Tissue Injury
➢ Examples: Beclomethasone, Budesonide, Fluticasone, Mometasone.
Phospholipids
❖ Mechanism of Action: Corticosteroids Phospholipase A2
✓ Inhibit the release of arachidonic acid through phospholipase A2 inhibition. Arachidonic Acid
Lipoxygenase
❖ Therapeutic Uses: Leukotrienes
(LTB, LTC, LTD, LTE)
✓ Drugs of choice for long-term control in patients with persistent asthma.
✓ Should be used regularly.
Cysteinyl leukotrienes
✓ Appropriate inhaler technique is critical to the success of therapy.
Cysteinyl leukotrienes 1 receptor
Airway smooth muscle constriction
3. Corticosteroids: Inhaled Corticosteroids (ICS)
❖ Reduce the hyperresponsiveness of the airway smooth muscle to bronchoconstrictor stimuli, such as allergens,
irritants, cold air, and exercise (after months of regular use).
❖ ICS therapy directly targets underlying airway inflammation by:
✓ Inhibiting the release of leukotrienes.
✓ Decreasing the inflammatory cascade.
✓ Decreasing capillaries permeability.
✓ Decreasing mucus production.
✓ Reversing mucosal edema.
3. Corticosteroids: Oral/Systemic
❖ Oral/Systemic Corticosteroids:
➢ Examples: Methylprednisolone, Prednisone.
✓ Severe persistent asthma may require a short course of oral glucocorticoid treatment.
✓ Patients with a severe exacerbation of asthma (status asthmaticus) may require intravenous methylprednisolone or
oral prednisone to reduce airway inflammation.
✓ Long-term therapy with systemic corticosteroids should be reserved for patients who are not controlled on an ICS.
3. Corticosteroids: Adverse Effects
4. Long-acting β2 Agonist + Inhaled Corticosteroid Combination
❖ LABAs + ICS Combination:
➢ Examples: Formoterol/Budesonide, Formoterol/Fluticasone and Salmeterol/Fluticasone.
✓ The preferred therapy for patients who do not achieve optimal control of asthma with ICS monotherapy.
✓ Addition of a LABA to ICS therapy is clinically more effective than increasing the dose of ICS.
✓ LABAs has steroid-sparing effect.
✓ LABAs + ICS is a superior to leukotriene modifiers + ICS.
✓ Single inhalers that contain LABAs + ICS provide improved efficacy.
5. Leukotriene Modifiers
❖ Leukotriene Modifiers: Tissue Injury
➢ Examples: Zileuton, Zafirlukast, Montelukast.
Phospholipids
❖ Mechanism of Action: Corticosteroids Phospholipase A2
➢ Zileuton: Arachidonic Acid
✓ Selective inhibitor of 5-lipoxygenase. Zileuton Lipoxygenase
Leukotrienes
(LTB, LTC, LTD, LTE)
➢ Zafirlukast and Montelukast:
✓ Selective antagonists of the cysteinyl leukotriene-1 receptor.
Cysteinyl leukotrienes
Zafirlukast
Montelukast
❖ Therapeutic Uses: Cysteinyl leukotrienes 1 receptor
✓ Prevention of asthma symptoms.
✓ Prevention of exercise induced bronchospasm. Airway smooth muscle constriction
5. Leukotriene Modifiers
❖ Pharmacokinetics:
✓ All the three drugs are orally active and metabolized extensively by the liver.
✓ Food impairs the absorption of zafirlukast.
✓ Zileuton and its metabolites are excreted in urine.
✓ Zafirlukast and Montelukast undergo biliary excretion.
❖ Adverse Effects:
✓ Elevations in serum hepatic enzymes.
✓ Headache.
✓ Dyspepsia.
6. Alternative Drugs Used to Treat Asthma: Cromolyn
❖ Cromolyn (Cromoglicic acid):
✓ Mast cell stabilizer.
✓ Prophylactic anti-inflammatory agent.
❖ Mechanism of Action:
✓ Inhibits mast cell degranulation and release of histamine.
❖ Therapeutic Uses:
✓ Alternative therapy for mild persistent asthma.
✓ Exercise induced asthma
✓ Not useful in managing an acute asthma attack, because it is not a bronchodilator.
❖ Adverse Effects:
✓ Cough, irritation and unpleasant taste.
6. Alternative Drugs Used to Treat Asthma: Ipratropium
❖ Ipratropium:
❖ Mechanism of Action:
✓ Cholinergic Antagonists block vagally mediated contraction of airway smooth muscle and mucus secretion.
❖ Therapeutic Uses:
✓ Useful in patients who are unable to tolerate a SABA or patients with concomitant COPD.
❖ Adverse Effects:
✓ Xerostomia.
✓ Bitter taste.
6. Alternative Drugs Used to Treat Asthma: Theophylline
❖ Theophylline:
❖ Mechanism of Action:
✓ Competitively inhibits type III and type IV phosphodiesterase (PDE).
✓ Adenosine A2B receptor antagonist, blocks adenosine mediated bronchoconstriction.
✓ Activates histone deacetylase to prevent transcription of inflammatory genes.
❖ Therapeutic Uses:
✓ Chronic asthma.
❖ Adverse Effects:
✓ Has narrow therapeutic window and potential drug interactions.
✓ Overdose may cause insomnia, seizures or potentially fatal arrhythmias.
✓ Higher dose is required in smokers to reach therapeutic plasma concentration.
6. Alternative Drugs Used to Treat Asthma: Omalizumab
❖ Omalizumab:
❖ Mechanism of Action:
✓ Selectively binds to human IgE reducing IgE binding to its receptor on surface of mast cells and basophils.
✓ Reduction in surface-bound IgE limits the release of mediators of the allergic response.
❖ Therapeutic Uses:
✓ Moderate to severe persistent asthma.
❖ Adverse Effects:
✓ Serious anaphylactic reaction (rare), cancer, arthralgias, fever, and rash.
✓ Use is limited by the high cost, route of administration (subcutaneous), and adverse effect profile.
