Therapy and Management | Treatment | Non-Inhalation

Oral or parenteral medications

The therapeutic index (effect vs. side effect ratio) of long-term inhaled corticosteroids generally exceeds the one of orally applied steroids. Therefore the use of oral glucocorticosteroids is limited and may only be necessary in the control of severe persistent asthma. Substances with short half-life and only minor mineralcorticoid effects like prednisone should be preferred. Although onset of action starts only 4 to 6 hours after application oral steroids are also indicated in severe acute exacerbations preventing progression and early relapse as well as reducing morbidity and the incidence of hospitalisation.

In addition to the side effects observed with inhaled orally administered corticosteroids may cause for example arterial hypertension, peptic ulcer, diabetes, cataracts, glaucoma, mood alterations, obesity and muscle weakness. Preventive treatment for osteoporosis is obligatory in patients receiving long-term systemic glucocorticosteroids. In patients exposed to herpes or varicella viruses discontinuation of steroid treatment and prophylactic therapy should be considered.

Methylxanthines including theophylline and aminophylline act as bronchodilators at high concentrations and have anti-inflammatory effects at lower concentrations. In patients with milder disease methylxanthines can be applied as monotherapy whereas in more severe asthma they serve as an add-on therapy to inhaled corticosteroids. Sustained-release preparations are especially useful in controlling nocturnal symptoms.

Due to the risk of adverse effects treatment with theophylline must be monitored carefully. Toxic effects usually does not occur at serum levels below 15 µg/ml. Symptoms of intoxication include nausea and vomiting, central nervous stimulation and seizures, tachycardia and arrythmias and sometimes central respiratory stimulation.

Sustained-release formulations of β2-agonists like salbutamol or terbutaline are used to treat nocturnal symptoms when they are not controlled sufficiently by inhaled glucocorticosteroids. In contrast short-acting oral β2-agonists are only indicated in patients unable to inhale. Compared to inhalation side effects like anxiety or muscle tremor occur more often with orally applied β2-agonists. In combination with theophylline adverse cardiovascular effects are more likely.

The role of orally applied leukotriene modifiers, like montelukast or zileuton, in asthma management is still under investigation. They have a small bronchodilator effect and reduce allergen- exercise- and sulfur-dioxide-induced bronchoconstriction. Leukotriene modifiers may serve to reduce the dose of inhaled corticosteroids in patients with moderate to severe asthma. Except single reports of Churg-Strauss syndrome leukotriene modifiers are usually well tolerated.

In patients with severe allergic asthma subcutaneously administered IgE antibodies are used to reduce corticosteroids. Therapy with anti-IgE also results in fewer exacerbations, symptoms and need of rescue medication and appears to be safe.

Literature:

Drazen JM, Israel E, O'Byrne PM. Treatment of asthma with drugs modifying the leukotriene pathway. 1999. New England Journal of Medicine , 340: 197-206

Mash B, Bheekie A, Jones PW. Inhaled vs oral steroids for adults with chronic asthma. 2000. Cochrane Database Syst Rev , 2

Milgrom H, Fick RB Jr, Su JQ, Reimann JD, Bush RK, Watrous ML, Metzger WJ for the RhuMAb-E25 Study Group. Treatment of allergic asthma with monoclonal anti-IgE antibody. New England Journal of Medicine , 341: 1966-1973

O'Byrne P. GINA Executive Commitee. Global strategy for asthma management and prevention. 2004. National Institutes of Health. Publication No 02-3659

Reed CE, Offord KP, Nelson HS, Li JT, Tinkelman DG. Aerosol beclomethasone dipropionate spray compared with theophylline as primary treatment for chronic mild-to-moderate asthma. The American Academy of Allergy, Asthma and Immunology Beclomethasone Diproprionate-Theophylline Study. 1998. J Allergy Clin Immunol , 101: 14-23

Mode of action of non-inhaled drugs in asthma therapy

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