The inhaled route has been developed to advantage because the undesirable effects of systemic exposure to drugs, especially glucocorticoids, are substantially reduced. The pharmacokinetic advantages of using the inhaled versus oral route are apparent from the considerable dose reductions possible: 100 micrograms of salbutamol from an aerosol inhaler, for example, will given similar bronchodilatation as 2000 micrograms given orally.
Before a drug can be inhaled, it must first be converted into particulate form and the optimum particle size to reach and be deposited in the small bronchi is around 2 pm. Such particles are delivered to the lung as an aerosol, i.e. dispersed in a gas, which can be produced in a number of different ways:
Pressurised aerosol. Drug is dissolved in a low boiling point liquid in a canister under pressure. Opening the valve releases a metered dose of liquid that is ejected into the atmosphere, carrier liquid evaporates instantly leaving an aerosol of the drug that is inhaled. Until recently the vehicle has been a CFC (chlorofluorocarbon), but due to the concerns over depletion of atmospheric ozone these are being replaced by hydrofluoroalkanes (HFAs) which are ozone-friendly.
To ensure optimal drug delivery it is necessary to coordinate activation of the inhaler with inspiration and a final hold of breath. Many patients, especially the young and the elderly, find this very difficult and 'spacer' devices are often used between the inhaler and lips; these act as an aerosol reservoir and also reduce impaction of aerosol in the oropharynx. Topical deposition can cause local side effects in the mouth, particularly Candida with inhaled glucocorticoids; a spacer abolishes this problem.
Nebulisers convert a solution or suspension of drug into an aerosol, jet nebulisers require a driving gas, usually air from a compressor unit for home use, or oxygen in hospital; the solution in the nebulising chamber is broken into droplets by the jet and the larger droplets are filtered off leaving the smaller ones to be inhaled. Ultrasonic nebulisers convert a solution into particles of uniform size by vibrations created by a piezo electric crystal.9 With either method the aerosol is delivered to the patient by a mouthpiece or facemask, so no coordination is called for, and the dose can be altered by changing the strength of the solution. Much larger doses can be administered by nebuliser than by pressurised aerosol.
Dry powder inhalers. The drug is formulated as a micronised powder and placed in a device, e.g. a spinhaler or diskhaler, from which it is inhaled. Patients can often use these when they fail with metered dose aerosols. Inhalation of powder occasionally causes transient bronchoconstriction.
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