Corticosteriods

Corticosteroids transit the cell membrane and bind to a cytosolic receptor, displacing heat shock protein. The steroid-receptor complex translocates to the nucleus, where it binds to glucocorticoid responsive elements (GRE) in the promoter region of specific genes. GREs may either enhance or suppress gene expression.

Steroids have no direct effect on contractile responses of airway smooth muscle, and improvement in lung function results from an effect on the chronic airway inflammation. It is important to recognize that steroids suppress inflammation in the airways but do not cure the underlying disease.

Steroids can be delivered either by inhalation or systemic routes (oral, intravenous). The inhaled route is preferred primarily due to the considerable toxicity of corticosteroids when delivered by the systemic route. Systemic corticosteroids are employed for acute exacerbations of asthma or COPD or in rare cases in which adequate control of asthma cannot be achieved with inhaled steroids. Inhaled corticosteroids can be broadly divided on the basis of their affinity for the glucocorticoid receptor, into high-potency and low-potency molecules. These agents are summarized in Table 2.

Steroids inhibit corticotopin and cortisol secretion by a negative feedback effect on the pituitary gland. Hypothalamic-pituitary-adrenal (HPA) axis suppression is dependent on dose. HPA axis suppression usually occurs when a dose of oral steroid is greater than 7.5 to 10 mg daily. HPA suppression with inhaled steroids is seen only when the daily-inhaled dose exceeds 2000 цg.

Side effects of long term oral corticosteroid therapy are well described and include fluid retention, increased appetite, weight gain, osteoporosis, capillary fragility, hypertension, peptic ulceration, diabetes, cataracts, and psychosis.

Several systemic effects of inhaled steroids have been described and include dermal thinning and skin capillary fragility. There has been concern about the use of inhaled steroids in children because of growth suppression. Inhaled steroids may have local side effects due to the deposition of inhaled steroid in the oropharynx. The most common problem is hoarseness and dysphonia, which is caused by laryngeal deposition. Throat irritation and coughing after inhalation are common with metered-dose inhalers and are usually due to the additives. Oropharyngeal candidiasis occurs in 5% of patients. There is no evidence for atrophy of the lining of the airway or for an increase in lung infections after use of inhaled steroids.

Category: Pharmacology Notes