PHARMACOLOGY Chapter 20 Bronchodilators & Other Drugs Used in Asthma

Beta-adrenoceptor agonists stimulate adenylyl cyclase (via the 2-adrenoceptor–Gs-coupling protein-adenylyl cyclase pathway) and increase cyclic adenosine monophosphate (cAMP) in smooth muscle cells (Figure 20–2). The increase in cAMP results in a powerful bronchodilator response.

The methylxanthines inhibit phosphodiesterase (PDE), the enzyme that degrades cAMP to AMP (Figure 20–2), and thus increase cAMP. This anti-PDE effect, however, requires high concentrations of the drug. Methylxanthines also block adenosine receptors in the central nervous system

When given by aerosol, ipratropium and tiotropium competitively block muscarinic receptors in the airways and effectively prevent bronchoconstriction mediated by vagal discharge

Mechanism is appears to involve a decrease in the release of mediators (such as leukotrienes and histamine) from mast cells. The drugs have no bronchodilator action but can prevent bronchoconstriction caused by a challenge with antigen to which the patient is allergic

Corticosteroids reduce the synthesis of arachidonic acid by phospholipase A2 and inhibit the expression of COX-2, the inducible form of cyclooxygenase

Zafirlukast and montelukast are antagonists at the LTD4 leukotriene receptor (see Table 18–1). The LTE4 receptor is also blocked. These drugs are orally active and have been shown to be effective in preventing exercise-, antigen-, and aspirin-induced bronchospasm

Zileuton is an orally active drug that selectively inhibits 5-lipoxygenase, a key enzyme in the conversion of arachidonic acid to leukotrienes. The drug is effective in preventing both exercise- and antigen-induced bronchospasm. It is also effective against "aspirin allergy

Omalizumab is a humanized murine monoclonal antibody to human IgE. It binds to the IgE on sensitized mast cells and prevents activation by asthma triggers and subsequent release of inflammatory mediators