Asthma nedocromil

Cromones are used to prevent asthma attacks. To be effective they have to betaken continuously. Their mechanism of action is poorly understood. Cromones (cromolyn sodium, nedocromil) act as mast cell-stabilizing agents,... 

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... 

Cromolyn and nedocromil are inhaled anti-inflammatory agents that block both the early- and late-phase response. Both agents are considered alternative therapies to inhaled corticosteroids for the treatment of mild persistent asthma however, both are less effective than low doses of inhaled corticosteroids.2,30 The exact mechanism of action of these agents is not understood, but they appear to inhibit mast cell mediator release as well as modulate other inflammatory responses.3... 

Patients receiving these agents may notice improvement in 1 to 2 weeks, but maximal benefit may not be seen for 4 to 6 weeks. Cromolyn and nedocromil appear to be similar in efficacy to the leukotriene antagonists and theophylline for persistent asthma.18 Both agents are well tolerated with adverse effects limited to cough and wheezing. Bad taste and headache have also been reported with nedocromil. One dose of cromolyn or nedocromil prior to exercise or allergen exposure will provide effective prophylaxis for 1 to 2 hours. Cromolyn and nedocromil are not as effective as albuterol for prophylaxis of exercise-induced asthma. 

In patients with mild intermittent asthma, long-term control medications are not necessary, and patients should use a short-acting inhaled P2-agonist t° prevent or treat symptoms.2 This classification includes patients with exercise-induced asthma, seasonal asthma, or asthma symptoms associated with infrequent trigger exposure. Patients can pre-treat with two puffs of cromolyn or nedocromil prior to exposure to a known trigger. The treatment of choice for exercise-induced asthma is two inhalations of albuterol 5 minutes prior to exercise.1 Cromolyn and nedocromil are less effective than albuterol for prophylaxis of exercise-induced asthma. 

The majority of the marketed products are used for asthma and COPD. Typical agents that are used for these indications are fl2-agonists such as salbutamol (albuterol), Terbutalin or formoterol, corticosteroids such as budesonide, FUxotide or beclomethasone and mast-cell stabilizers such as sodium cromoglycate or nedocromil. 

Pharmacology Nedocromil is an inhaled anti-inflammatory agent for the preventive management of asthma. It inhibits the in vitro activation of, and mediator release from, a variety of inflammatory cell types associated with asthma, including eosinophils, neutrophils, macrophages, mast cells, monocytes and platelets. Nedocromil inhibits the development of early and late bronchoconstriction responses to inhaled antigen. 

Cromolyn sodium (Intal) and nedocromil sodium (Tilade) are chemically related drugs called chromones that are used for the prophylaxis of mild or moderate asthma. Both are administered by inhalation and have... 

Cromolyn sodium and nedocromil sodium are used almost exclusively for the prophylactic treatment of mild to moderate asthma and should not be used for the control of acute bronchospasm. These agents are effective in about 60 to 70% of children and adolescents with asthma. Unfortunately, there is no reliable means to predict which patients will respond. They are less effec-... 

Cromolyn sodium (disodium cromoglycate) and nedocromil sodium are stable but extremely insoluble salts (see structures below). When used as aerosols (by nebulizer or metered-dose inhaler), they effectively inhibit both antigen- and exercise-induced asthma, and chronic use (four times daily) slightly reduces the overall level of bronchial reactivity. However, these drugs have no effect on airway smooth muscle tone and are ineffective in reversing asthmatic bronchospasm they are only of value when taken prophylactically. 

In short-term clinical trials, pretreatment with cromolyn or nedocromil blocked the bronchoconstriction caused by allergen inhalation, by exercise, by sulfur dioxide, and by a variety of causes of occupational asthma. This acute protective effect of a single treatment makes cromolyn useful for administration shortly before exercise or before unavoidable exposure to an allergen. 

When taken regularly (2-4 puffs two to four times daily) by patients with perennial (nonseasonal) asthma, both agents modestly but significantly reduce symptomatic severity and the need for bronchodilator medications. These drugs are neither as potent nor as predictably effective as inhaled corticosteroids. In general, young patients with extrinsic asthma are most likely to respond favorably. At present, the only way of determining whether a patient will respond is by a therapeutic trial for 4 weeks. The addition of nedocromil to a standard dose of an inhaled corticosteroid appears to improve asthma control. 

Cromolyn or nedocromil by inhalation, or a leukotriene-receptor antagonist as an oral tablet, may be considered as alternatives to inhaled corticosteroid treatment in patients with symptoms occurring more than twice a week or who are wakened from sleep by asthma more than twice a month. Neither treatment is as effective as even a low dose of an inhaled corticosteroid, but both avoid... 

Cromolyn, nedocromil Alters function of delayed chloride channels inhibits inflammatory cell activation Prevents acute bronchospasm Asthma (other routes used for ocular, nasal, and gastrointestinal allergy) Aerosol t duration 6-8 h t Toxicity. Cough not absorbed so other toxicities are minimal... 

A 32-year-old woman s asthma regimen was changed from budesonide to fluticasone propionate 500 micrograms/day and salmeterol (44). Eight months later, she was evaluated because of excessive bodyweight gain her serum cortisol concentration was 16 nmol/1. Fluticasone propionate was replaced with nedocromil and 1 month later her serum cortisol concentration had normalized. 

The Childhood Asthma Management Program Research Group. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med 2000 343(15) 1054-63. 

Cromones such as cromolyn sodium (Intal, Nasal-crom) and nedocromil sodium (Tilade) can help prevent bronchospasm in people with asthma. These drugs are not bronchodilators and will not reverse bronchoconstriction during an asthmatic attack. Hence, these agents must be taken prior to the onset of bronchoconstriction, and they must typically be administered prophylactically to prevent asthma attacks that are initiated by specific, well-defined activities (e.g., exercise, exposure to a friend s pet, pollen).107 Likewise, the regular use of these drugs several times each day for several months may decrease airway hyperresponsiveness so that the incidence of asthmatic attacks decreases.102,113... 

Some irritation of the nasal and upper respiratory passages may occur following inhalation, but these drugs are remarkably free of serious adverse reactions. Hence, cromolyn and nedocromil are often used preferentially to treat mild persistent asthma, especially in children or in individuals who are unable to tolerate the side effects of other antiasthma drugs.102,113... 

Cromolyn or nedocromil may be considered as an alternative to inhaled corticosteroids in patients with symptoms occurring more than twice a week or who are wakened from sleep by asthma. They may also be useful in patients whose symptoms occur seasonally or after clear-cut inciting stimuli such as exercise or exposure to animal danders or irritants. In patients whose symptoms are continuous or occur without an obvious inciting stimulus, the value of these drugs can only be established with a therapeutic trial of inhaled drug four times a day for 4 weeks. If the patient responds to this therapy, the dose can be reduced. Maintenance therapy with cromolyn appears to be as effective as maintenance therapy with theophylline and, because of concerns over the possible long-term toxicity of systemic absorption of inhaled corticosteroids, has become widely used for treating children in the USA. 

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