Corticosteroids, asthma prevention

Rowe BH, Spooner CH, Ducharme EM, Bretzlaff JA, Bota GW. Corticosteroids for preventing relapse following acute exacerbations of asthma. Cochrane Database Syst Rev 2001. 

There is at least one published analysis related to asthma based on a policy model. This model examined the relative clinical and economic impact of as-needed relievers (e.g. short-acting p-agonists) versus inhaled corticosteroid therapy in adults with a forced expiratory volume in 1 s >60% of predicted normal [49]. That model estimated that over a 10-year period, use of inhaled corticosteroids increased the costs, and improved clinical outcomes, at a cost of USD 7.50 per symptom-free day gained. Such a health policy model that focuses on primary prevention, rather than secondary control, might help guide economic and policy decisions for asthma prevention. 

Corticosteroids are the most potent anti-inflammatory agents available for the treatment of asthma. The efficacy of corticosteroids is due to their ability to affect multiple inflammatory pathways, resulting in the suppression of inflammatory cell activation and function, prevention of microvascular leakage, decreased mucus production, and upregulation of P2-adrenergic receptors.10,18 Clinically, corticosteroids decrease airway inflammation, decrease AHR, decrease mucus production and secretion, and improve the response to P2-agonists.18 Corticosteroids for the treatment of asthma are available in inhaled, oral, and injectable dosage forms. 

In persistent asthma, inhaled corticosteroids provide the most comprehensive control of the inflammatory process and are the cornerstone of therapy.2 Inhaled corticosteroids are more effective than cromolyn, leukotriene modifiers, nedocromil, and theophylline in reducing markers of inflammation and AHR, improving lung function, and preventing emergency department visits and hospitalizations due to asthma exacerbations.2,25 The primary... 

Corticosteroids (e.g., beclomethazone, flunisolide, triamcinolone) have anti-inflammatory and immunosuppressant actions. These drugs are used prophylactically to prevent the occurrence of asthma in patients with frequent attacks. Because they are not useful during an acute attack, corticosteroids are prescribed along with maintenance bronchodilators. These drugs are also administered by inhalation. Cromolyn is another anti-inflammatory agent used prophylactically to prevent an asthmatic attack. The exact mechanism of action of cromolyn is not fully understood however, it is likely to involve the stabilization of mast cells. This prevents the release of the inflammatory mast cell mediators involved in inducing an asthmatic attack. Cromolyn has proven effective in patients with exercise-induced asthma. 

LTB4 is a potent bronchoconstrictor, as are several other leukotrienes. A 5-lip-oxygenase inhibitor, Zileuton, is approved for therapy of asthma (though it is not much used for this purpose) as is a leukotriene blocker, montelukast, marketed as Singulair. Singulair is widely used by asthmatics as a preventive for asthma attacks. Certain corticosteroids are employed for the same purpose. Neither montelukast nor the steroids are effective in terminating an established asthmatic attack. Beta agonists are employed for that purpose (see chapter 17). 

Urgent treatment is often begun with an oral dose of 30-60 mg prednisone per day or an intravenous dose of 1 mg/kg methylprednisolone every 6 hours the daily dose is decreased after airway obstruction has improved. In most patients, systemic corticosteroid therapy can be discontinued in a week or 10 days, but in other patients symptoms may worsen as the dose is decreased to lower levels. Because adrenal suppression by corticosteroids is related to dose and because secretion of endogenous corticosteroids has a diurnal variation, it is customary to administer corticosteroids early in the morning after endogenous ACTH secretion has peaked. For prevention of nocturnal asthma, however, oral or inhaled corticosteroids are most effective when given in the late afternoon. 

Asthma is best thought of as a disease in two time domains. In the present domain, it is important for the distress it causes—cough, nocturnal awakenings, and shortness of breath that interferes with the ability to exercise or to pursue desired activities. For mild asthma, occasional inhalation of a bronchodilator may be all that is needed. For more severe asthma, treatment with a long-term controller, like an inhaled corticosteroid, is necessary to prevent symptoms and restore function. The second domain of asthma is the risk it presents of future events, such as exacerbations, or of progressive loss of pulmonary function. A patient s satisfaction with his or her ability to control symptoms and maintain function by frequent use of an inhaled 32 agonist does not mean that the risk of future events is also controlled. In fact, use of two or more canisters of an inhaled 3 agonist per month is a marker of increased risk of asthma fatality. 

This context accounts for the interest in reports that instructing patients with mild but persistent asthma to take inhaled corticosteroid therapy only when their symptoms worsen is as effective in maintaining pulmonary function and preventing attacks as is taking the inhaled corticosteroid twice each day. 

Salmeterol Selective B2 agonist Slow onset, primarily preventive action potentiates corticosteroid effects Asthma prophylaxis Aerosol inhalation duration 12-24 h Toxicity Tremor, tachycardia, overdose arrhythmias... 

Suissa S et al Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med 2000 343 332. [PMID 10922423]... 

If patients need to use the reliever more than three times a week, they are usually also prescribed a preventer inhaler containing a corticosteroid, such as beclometasone diproprionate, budesonide or fluticasone proprionate. Corticosteroids decrease airway inflammation, reducing airway oedema and mucus production. When used regularly they are prophylactic and reduce the frequency of asthma. 

Patients with asthma are usually treated with a reliever , usually a shortacting / 2-agonist, and a preventer inhaler containing a corticosteroid. 

THEOPHYLLINE CORTICOSTEROIDS Risk of hypokalaemia Additive effect. The CSM notes that this effect occurs with beta-2 agonists, theophyllines and corticosteroids, all of which may be given during severe asthma hypoxia exacerbates this effect Monitor blood potassium levels prior to concomitant administration and during therapy (monitor 1—2-hourly during parenteral administration). Administer potassium supplements to prevent hypokalaemia, which may also be worsened by hypoxia during severe attacks of asthma... 

Chlorine. Lacrimation. Rhinorrhea. Conjunctival irritation. Cough. Sore throat. Hoarseness Laryngeal edema. Dyspnea. Stridor. ARDS. Pulmonary edema Decontamination Copious water irrigation of the skin, eyes, and mucosal membranes to prevent continued irritation and injury Symptomatic care (no antidote) Warm/moist air, supplemental oxygen, positive pressure O2 for pulmonary edema Bronchospasm Beta-agonists (albuterol) Severe bronchospasm Corticosteroids (prednisone) (also used for PTS with H/0 asthma but use unproven) Analgesia and cough Nebulized lidocaine (4% topical solution) or nebulized sodium bicarbonate (use unproven)... 

The second group of antiasthmatics are ANTIINFLAMMATORY Or ANTIALLERGIC AGENTS. SUCh aS the CORTICOSTEROIDS and sodium cromoglycate. These drugs prevent the release of local inflammatory mediators, which contribute to attacks, so preventing asthma attacks, and also provide symptomatic relief. 

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