Corticosteroids: use in respiratory diseases
introduction
Corticosteroids are widely used in the treatment of asthma and other respiratory diseases to reduce bronchial inflammation and hyper-responsiveness. They are thought to reduce the synthesis and secretion of a variety of inflammatory mediators (such as prostaglandins and leukotrienes) and cytokines, which are implicated in the pathogenic process underlying asthma.
Corticosteroids are used in the management of acute severe asthma, as well as in the preventive management of asthma. The most commonly used oral corticosteroid is prednisolone. Commonly used parenteral corticosteroid preparations are hydrocortisone, dexamethasone and methylprednisolone.
Use of inhaled corticosteroids in respiratory diseases
Inhaled corticosteroids currently marketed in Australia include beclomethasone dipropionate, budesonide and fluticasone propionate. Inhaled corticosteroids are used as preventive therapy in asthma and are known as ‘preventers’. They have a delayed onset of clinical effect and should be used regularly. They are not sufficiently potent and do not have a sufficiently rapid effect to be of use in acute severe asthma.
Adverse effects, interactions and precautions: Inhaled corticosteroids do not generally produce systemic adverse effects until large doses are administered. Systemic effects are dependent on a complex interplay between:
potency of the corticosteroid
absorption of the drug deposited in the airway, which is related to formulation (suspension, solution, dry powder) and delivery device used (MDI with or without spacer, powder inhaler)
absorption of drug deposited in the pharynx and swallowed, and first-pass hepatic metabolism (to a minor degree).
The dose at which systemic effects are observed is product-specific and may be patient-specific. Using the currently available devices, estimated dose equivalent ratios of inhaled corticosteroids are 1:2:1 for beclomethasone, budesonide and fluticasone respectively. In adults, doses at which systemic adverse effects may become manifest are those greater than 1000 to 1500 micrograms daily of budesonide or 500 to 750 micrograms daily of beclomethasone or fluticasone. In children, doses at which systemic adverse effects may become manifest are those greater than 800 micrograms daily of budesonide or 400 micrograms daily of beclomethasone or fluticasone. Systemic adverse effects occur at lower doses in some patients, and the possibility of cataracts should be considered, particularly in those receiving therapy of extended duration. The dose at which the hypothalamic-pituitary-adrenal (HPA) axis is suppressed has not yet been established for any corticosteroid, so the lowest effective dose should always be recommended.
The effect of inhaled corticosteroids on long-term growth in children is unclear. Most studies have focused on short-term growth velocity and have failed to show any reduction in final height. In fact, children with severe asthma may have improved growth velocity after starting inhaled corticosteroids, perhaps by eliminating the growth-suppressive effects of poorly-controlled asthma.
In low doses adverse effects are uncommon, but include hoarse voice and oral and oesophageal Candida albicans infection (candidiasis/thrush). To minimise oropharyngeal thrush and absorption of inhaled corticosteroids, patients should be advised to rinse their throat and mouth with water and spit out after inhalation. Patients using an MDI should also be advised to use a spacer. Dry powder devices are an appropriate alternative to MDI plus spacer delivery.
Corticosteroid nasal sprays may cause sneezing, nasal irritation and nosebleeds.
Use of oral corticosteroids in respiratory diseases
Prednis(ol)one is frequently given as a short course lasting several days to weeks with the aim of disease control without exposing the patient to the corticosteroid for a long enough period for significant adverse effects to develop or for significant adrenal suppression to occur. After long-term use (more than 2 weeks), dose reduction must be slow to enable the hypothalamic-adrenal feedback system to re-equilibrate
Use of parenteral corticosteroids in respiratory diseases
Dexamethasone and hydrocortisone are used intravenously for the acute treatment of asthma. The exact time course of action is not well established, but response takes at least some hours to develop.
Approximate dose equivalents of oral and parenteral corticosteroids are:
Oral prednisolone or prednisone | IV dexamethasone | IV hydrocortisone |
25 mg | 4 mg | 100 mg |
Evidence suggests that moderate- to high-dose oral corticosteroids may be as effective as parenteral corticosteroid treatment for the management of acute asthma.
Very few acute adverse effects are seen, but psychoses, mood changes, hypokalaemia and hyperglycaemia can occur.
Use of nebulised corticosteroids in respiratory diseases
Budesonide is available for nebulisation via high-flow nebuliser. This form of treatment should be reserved for severe chronic asthma in patients who are unable to use other forms of inhaled therapy.
Some patients develop a rash on the face following nebulised treatment. It is important to protect the eyes and face from the effects of drug deposition.
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