Pulmonary pharm – Asthma drugs

a) Short-acting beta-2 agonist.

b)

• First-line treatment for acute attacks.
• Patient uses inhaler when feeling asthmatic symptoms.
• Used as a nebulizer (face mask) in the emergency setting.

a) Inhaled corticosteroid (ICS).

b)

• Used to prevent recurrences of asthma.
• Added second-line to albuterol for outpatient treatment – i.e., if patient has weekly occurrences of asthma, rather than just receiving an albuterol inhaler to abort acute episodes, a preventative ICS can be added to the regimen.
• Has no utility in the acute setting.
• In the acute setting, IV steroids (methylprednisolone) can be given, but ICS have no role.

a) Long-acting beta-2 agonist.

b)

• Can be added third-line for outpatient asthma management for patients already using an albuterol and fluticasone inhaler but who still have occurrences.
• In other words, the first three drugs for outpatient management are: albuterol –> fluticasone –> salmeterol.

a) Lipoxygenase inhibitor (enzyme that normally synthesized leukotrienes, which cause bronchoconstriction).

b)

• Patients already on albuterol, fluticasone, and salmeterol inhalers but who still have intractable asthma.
• Good for patients with history of NSAID/aspirin-induced asthma (i.e., Samter triad –> NSAID/aspirin hypersensitivity, NSAID/aspirin-induced asthma, nasal polyps):
  • Arachidonic acid is a precursor molecule of both leukotrienes and prostaglandins.
  • Lipoxygenase catalyzes synthesis of leukotrienes.
  • Cyclooxygenase catalyzes synthesis of prostaglandins.
  • NSAIDs (including aspirin) inhibit cyclooxygenase (COX), thereby preventing prostaglandin synthesis. Arachidonic acid is then shunted down the lipoxygenase pathway toward leukotrienes –> bronchoconstriction.

a)

• Leukotriene receptor antagonists.
• Leukotrienes cause bronchoconstriction, so antagonizing these receptors decreases bronchoconstriction.

b)

• Same as zileuton.
• Patients already on albuterol, fluticasone, and salmeterol inhalers but who still have intractable asthma.
• Good for patients with history of NSAID/aspirin-induced asthma (i.e., Samter triad –> NSAID/aspirin hypersensitivity, NSAID/aspirin-induced asthma, nasal polyps):
  • Arachidonic acid is a precursor molecule of both leukotrienes and prostaglandins.
  • Lipoxygenase catalyzes synthesis of leukotrienes.
  • Cyclooxygenase catalyzes synthesis of prostaglandins.
  • NSAIDs (including aspirin) inhibit cyclooxygenase (COX), thereby preventing prostaglandin synthesis. Arachidonic acid is then shunted down the lipoxygenase pathway toward leukotrienes –> bronchoconstriction.

a)

• Mast cell stabilizers.
• Mast cells normally degranulate to release histamine –> stimulate H1 receptors on bronchioles  + stimulation of afferent vagal fibers in the airways –> bronchoconstriction.

b)

• Patients who have persistent attacks despite already using albuterol, fluticasone, and salmeterol.

a) Phosphodiesterase inhibitor –> prevents breakdown of cAMP.

b) Not used due to neuro- and cardiotoxicity.

a) Monoclonal antibody against the Fc region of IgE.

b)

• Intractable asthma refractory to multi-drug regimens, including patients already on oral prednisone.
• Patients who qualify for use have high serum IgE levels.

a) Monoclonal antibodies against IL-5. IL-5 normally promotes eosinophil maturation.

b) -Lizumab agents –> Benlizumab, Reslizumab, Mepolizumab –> “Ben Really likes Maple.” –> Benlizumab, Reslizumab, Mepolizumab

c) Intractable asthma in patients with eosinophilia, similar to omalizumab.

a) Muscarinic receptor agonist

b)

• To diagnose asthma. Not used in the treatment of asthma.
• Causes bronchoconstriction –> reproduces asthma symptoms and obstructive spirometry profile in patients with asthma.
• Patients who do not have asthma will not get symptom production with methacholine.
• Never used during acute attacks; used between attacks to merely reproduce symptoms.

Salmeterol

MOA of salmeterol?

• Long-acting beta-2 agonist.

How is it used?

• Can be added third-line for outpatient asthma management for patients already using an albuterol and fluticasone inhaler but who still have occurrences.
• In other words, the first three drugs for outpatient management are: albuterol –> fluticasone –> salmeterol.

-Lizumab agents –> Benlizumab, Reslizumab, Mepolizumab –> “Ben Really likes Maple.” –> Benlizumab, Reslizumab, Mepolizumab

MOA of -lizumabs?

• Monoclonal antibodies against IL-5.
• IL-5 normally promotes eosinophil maturation.

When are they used?

• Intractable asthma in patients with eosinophilia, similar to omalizumab.

Theophylline

MOA of theophylline?

• Phosphodiesterase inhibitor –> prevents breakdown of cAMP.

What are its side-effects?

• Not used due to neuro- and cardiotoxicity.
• Just know MOA + toxicities for USMLE.

Nedocromil, cromolyn sodium

MOA of nedocromil and cromolyn sodium?

• Mast cell stabilizers.
• Mast cells normally degranulate to release histamine –> stimulate H1 receptors on bronchioles  + stimulation of afferent vagal fibers in the airways –> bronchoconstriction.

When are they used?

• Patients who have persistent attacks despite already using albuterol, fluticasone, and salmeterol.

Fluticasone

MOA of fluticasone?

• Inhaled corticosteroid (ICS).

How is it used?

• Used to prevent recurrences of asthma.
• Added second-line to albuterol for outpatient treatment – i.e., if patient has weekly occurrences of asthma, rather than just receiving an albuterol inhaler to abort acute episodes, a preventative ICS can be added to the regimen.
• Has no utility in the acute setting.
• In the acute setting, IV steroids (methylprednisolone) can be given, but ICS have no role.

Omalizumab

MOA of omalizumab?

• Monoclonal antibody against the Fc region of IgE.

When is it used?

• Intractable asthma refractory to multi-drug regimens, including patients already on oral prednisone.
• Patients who qualify for use have high serum IgE levels.

Methacholine

MOA of methacholine?

• Muscarinic receptor agonist

When is it used?

• To diagnose asthma. Not used in the treatment of asthma.
• Causes bronchoconstriction –> reproduces asthma symptoms and obstructive spirometry profile in patients with asthma.
• Patients who do not have asthma will not get symptom production with methacholine.
• Never used during acute attacks; used between attacks to merely reproduce symptoms.

Montelukast, zafirlukast

MOA of montelukast and zafirlukast?

• Leukotriene receptor antagonists.
• Leukotrienes cause bronchoconstriction, so antagonizing these receptors decreases bronchoconstriction.

When are they used?

• Patients already on albuterol, fluticasone, and salmeterol inhalers but who still have intractable asthma.
• Good for patients with history of NSAID/aspirin-induced asthma (i.e., Samter triad –> NSAID/aspirin hypersensitivity, NSAID/aspirin-induced asthma, nasal polyps):
  • Arachidonic acid is a precursor molecule of both leukotrienes and prostaglandins.
  • Lipoxygenase catalyzes synthesis of leukotrienes.
  • Cyclooxygenase catalyzes synthesis of prostaglandins.
  • NSAIDs (including aspirin) inhibit cyclooxygenase (COX), thereby preventing prostaglandin synthesis. Arachidonic acid is then shunted down the lipoxygenase pathway toward leukotrienes –> bronchoconstriction.

Zileuton

MOA of zileuton?

• Lipoxygenase inhibitor (enzyme that normally synthesized leukotrienes, which cause bronchoconstriction).

When is it used?

• Patients already on albuterol, fluticasone, and salmeterol inhalers but who still have intractable asthma.
• Good for patients with history of NSAID/aspirin-induced asthma (i.e., Samter triad –> NSAID/aspirin hypersensitivity, NSAID/aspirin-induced asthma, nasal polyps):
  • Arachidonic acid is a precursor molecule of both leukotrienes and prostaglandins.
  • Lipoxygenase catalyzes synthesis of leukotrienes.
  • Cyclooxygenase catalyzes synthesis of prostaglandins.
  • NSAIDs (including aspirin) inhibit cyclooxygenase (COX), thereby preventing prostaglandin synthesis. Arachidonic acid is then shunted down the lipoxygenase pathway toward leukotrienes –> bronchoconstriction.

a) NSAID/aspirin hypersensitivity, NSAID/aspirin-induced asthma, nasal polyps

b) Drugs that target the lipoxygenase pathway are notably effective (zileuton, montelukast, zafirlukast).

• Arachidonic acid is a precursor molecule of both leukotrienes and prostaglandins.
• Lipoxygenase catalyzes synthesis of leukotrienes.
• Cyclooxygenase catalyzes synthesis of prostaglandins.
• NSAIDs (including aspirin) inhibit cyclooxygenase (COX), thereby preventing prostaglandin synthesis. Arachidonic acid is then shunted down the lipoxygenase pathway toward leukotrienes –> bronchoconstriction.

Nasal polyps

16M + takes aspirin for sore muscles after snowboarding + gets wheezing. Q asks: what is most likely to be seen on physical exam? –> answer = nasal polyps.

16M + takes aspirin for sore muscles after snowboarding + gets wheezing. Q asks: which drug should most likely be avoided in this patient? –> answer = ibuprofen; wrong answer = acetaminophen (not an NSAID).

Theophylline

MOA of theophylline?

• Phosphodiesterase inhibitor –> prevents breakdown of cAMP.

What are its side-effects?

• Not used due to neuro- and cardiotoxicity.
• Just know MOA + toxicities for USMLE.