Bronchodilators: Leukotriene antagonists and methylxanthines

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.