aSLACK Incorporated newspaper
April 1998
SAN DIEGO - Not all inhaled steroids for the treatment of asthma are created equal.
"There are definite differences among the inhaled steroids in terms of their relative oral bioavailability," said Harold S. Nelson, MD, a senior staff physician in the department of medicine at the National Jewish Medical and Research Center in Denver. "It is therefore important that clinicians be able to distinguish their relative potency and appreciate the need for comparing inhaled steroids at clinically equivalent doses."
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Nelson, who spoke here at the Annual Meeting of the American College of Allergy, Asthma and Immunology, noted differences in systemic bioavailability after oral administration. For example, triamcinolone (Nasacort, Rhone-Poulenc Rorer), flunisolide (Aerobid, Forest) and beclomethasone (Beclovent, Glaxo Wellcome) are three inhaled corticosteroids with about a 20% rate of bioavailability, while budesonide (Pulmicort, Astra) has about 11%, and fluticasone (Flovent, Glaxo Wellcome) less than 1%.
"You don't want a high percentage because the agent is not contributing to any clinical effect, but only contributing to the side effect," explained Nelson.
One of the systemic complications of inhaled steroids is a slowed growth rate among prepubertal children. "However, it is not certain that this results in short-statured adults," he said. Furthermore, in medium and high doses, steroids have been linked to osteoporosis, thinning of the skin and bruising easily, cataracts and increased intraocular pressure.
"The percentage of the steroid available for potential systemic absorption from the gastrointestinal tract is markedly reduced by use of a spacer and mouth washing," said Nelson. "It is assumed that all the drug delivered to the lung is available for systemic absorption. Therefore, with proper administration, there may only be a small difference in the percent that is systemically bioavailable after inhalation of a corticosteroid."
Nelson discussed the relative potency of five inhaled corticosteroids in treating asthma. Potency was determined by vasoconstrictor assay and glucocorticoid receptor binding. "Clinical studies suggest that there are three groupings," he said. "Triamcinolone and flunisolide are the least potent, budesonide and beclomethasone are intermediate, and fluticasone is the most potent."
Nelson cautioned, however, that a confounding factor in these studies is "the flat dose-response that is often observed with inhaled corticosteroids in patients with asthma." A second confounding factor are variations in efficiency among delivery systems. "This is particularly true for budesonide delivered by the Turbohaler [Pulmicort], which delivers about twice the percentage of the dose to the lungs that is regularly achieved with metered-dose inhalers. As a result, fluticasone and budesonide may perform as if of equal potency."
"There is a broad range of potency among these drugs. Practitioners should not simply think of them as being equivalent `puff for puff' or `microgram for microgram.'," said Nelson. "There is a table in the guidelines that gives the relative potency of the inhaled steroid."
For agents that are more potent, "it will be easier to show that they have some systemic impact," said Nelson. "But you don't have to use anywhere near as high a dose."
Nelson observed that there is a tendency among doctors to carry over the prescribing practices of less potent steroids when using the more potent steroids. "This may indeed cause patients to have some side effects," he said. "No matter what inhaled steroid you use, you should always taper it down to the least amount that the patient needs to control their disease. If it's a very potent steroid, the patient may be getting much more than they need - both in the lungs and from systemic side effects."
For more information:
- Nelson HS. Safety of inhaled steroids: are they created equal? Presented at the the Annual Meeting of the American College of Allergy, Asthma and Immunology. Nov. 7-12, 1997. San Diego.
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