Administration and modes of action

Drugs acting on the airways may be administered systemically or by inhalation. The inhaled mode allows a higher concentration of agent to be delivered directly to the bronchial tree, which minimises absorption and accompanying systemic effects. Some drugs are metabolised in the lungs, resulting in a non-hepatic first-pass effect.

Typically, only 10% of an inhalationally administered bronchodilator reaches the lungs. Most of this is deposited in the upper airways with little benefit, with about 3% reaching the alveoli. Distribution is little affected by the presence of obstructive airways disease, or by particle size.

Bronchial calibre is fundamentally affected by two opposing systems. Factors that cause an increase of intracellular cyclic AMP (such as sympathetic stimulation) result in bronchodilatation. The reverse situation involves factors that raise the intracellular concentration of cyclic GMP (such as parasympathetic stimulation) to cause bronchoconstriction. The physiological and pharmacological influences on bronchial calibre are summarised in Figure RP1.

Leukotrienes are involved in the development of bronchospasm. They are so-named because of their presence in white blood cells (the leuko component) and their chemical bonds (a triene system of double bonds). They are a group of eicosanoids (bioactive lipid derivatives of arachidonic acid). Leukotrienes are produced by the action of the enzyme 5-lipoxygenase, which is found in white blood cells (particularly eosinophils) and mast cells, among other tissues.