01.10 Pulmonary - Inhalation

Drugs used for effects on the pulmonary system are often administered by inhalation to give the highest concentrations of the drug in the lung. The human respiratory tract has a considerable surface area, which should aid absorption, but most of this is deep in the alveolar region of the lung and it is difficult to deliver drugs deep into the lung. Inhalation is not actually a very good way of delivering drugs to the lung, as only about 10% of a drug that is inhaled actually goes to the lungs, the rest is swallowed, and may be absorbed from the gastrointestinal tract.

With inhalation, predominant local effects are achieved in pulmonary diseases (e.g. bronchial asthma) by having the highest concentration of the drug in the lung. In asthma, metered-dose inhalers are used. These have an inert propellant gas, and require good hand-breath co-ordination to achieve inhalation, rather than swallowing. An example of a drug that is used in a metered-dose inhaler is salbutamol for the treatment of bronchial asthma. Another way to deliver drugs to the airways is to use a nebulisers. Nebulisers produce fine droplets in the air (aerosol), and are used to deliver large doses of drugs in an emergency. Thus, in the emergency treatment of asthma, large doses of salbutamol can be delivered by a nebuliser.

Local pulmonary effects can be achieved by using drugs that are poorly absorbed. For example, the glucocorticoid beclomethasone is poorly absorbed from the pulmonary epithelium in bronchial asthma. Thus, it remains in the lung to have an anti-inflammatory effect in asthma. Localised pulmonary effects without major systemic adverse effects can also be achieved by inhaling drugs that undergo extensive liver metabolism. For example, after inhalation, the glucocorticoid budesonide has anti-inflammatory effects on the lung. As budesonide is rapidly metabolised by liver this prevents it from having serious systemic adverse effects.

After inhalation, when a drug is deep into the lung, access to the circulation is rapid because the lung has a large surface area. Thus, inhalation can also be used for widespread effects, including central effects. For instance inhalation is used for gaseous and volatile anaesthetics, which are rapidly absorbed through the pulmonary epithelium and mucous membranes of the respiratory tract, and have their anaesthetic effect within the central nervous system.

Methoxyflurane was introduced as an inhalation anaesthetic, but was withdrawn because of toxicity. Lower less toxic doses of methoxyflurane are analgesic and are used for the treatment of acute pain in the emergency situation. The analgesic effect of methoxyflurane is mediated by the central nervous system.