Bronchodilators: Leukotriene antagonists and methylxanthines

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Bronchodilators: Leukotriene antagonists and methylxanthines

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USMLE® Step 1 style questions USMLE

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USMLE® Step 2 style questions USMLE

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A 32-year-old woman is brought to the emergency department because of a generalized tonic-clonic seizure. She does not have a prior history of seizure disorder. Past medical history is significant for severe persistent asthma, hypertension, and hyperlipidemia. Five days ago, the patient was started on ciprofloxacin for a urinary tract infection. Her other medications include inhaled fluticasone/salmeterol combination, theophylline, lisinopril, and hydrochlorothiazide. Her BMI is 37 kg/m2. Her temperature is 37°C (98.6°F), pulse is 115/min, respirations are 15/min, and blood pressure is 110/65 mmHg. Physical examination is unremarkable. Which medications is the most likely cause of this patient’s presentation?

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Theophylline p. 706

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In obstructive lung diseases like asthma, individuals suffer from reversible narrowing of the airways, medications like bronchodilators are helpful in keeping the airways open.

Now, based on their mechanism of action, bronchodilators can be broadly divided into four main groups; β2-agonists, muscarinic antagonists, leukotrienes antagonist and methylxanthines.

In this video, we’ll focus on the leukotriene modifying agents and methylxanthines.

So, if we take a look at the lungs, you’ve got the trachea, which branches off into right and left bronchi, and then continues to branch into thousands of bronchioles.

In the bronchioles you’ve got the lumen, the mucosa, which includes the inner lining of epithelial cells, as well as the lamina propria which contains many cells like the type 2 helper T cells, B cells, and mast cells.

Surrounding the lamina propria, there is a layer of smooth muscles and submucosa.

The submucosal layer contains mucus-secreting glands and blood vessels.

Now, the molecular pathway that leads to asthma is actually pretty complex but it is often initiated by an environmental trigger.

Allergens from environmental triggers, like air pollutants or cigarette smoke, are picked up by dendritic cells which present them to a type 2 helper T cell or Th2 cell in the lamina propria. These cells then produce cytokines like IL-4 and IL-5 which causes the inflammatory response.

IL-4 is especially important because it leads to the production of IgE antibodies by B cells, and these antibodies bind to FcεR1 receptors on mast cells to activate them.

These mast cells use an enzyme called phospholipase A2 to take membrane phospholipids and make a 20 carbon polyunsaturated fatty acid called arachidonic acid.

Sources

  1. "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
  2. "Rang and Dale's Pharmacology" Elsevier (2019)
  3. "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
  4. "Triple therapy (ICS/LABA/LAMA) in COPD: time for a reappraisal" International Journal of Chronic Obstructive Pulmonary Disease (2018)
  5. "Exacerbations of COPD" International Journal of Chronic Obstructive Pulmonary Disease (2016)
  6. "Medication Regimens for Managing Acute Asthma" Respiratory Care (2018)
Elsevier

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