Asthma cromolyn/nedocromil release

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... 

Stabilization of mast cells. Cromolyn prevents IgE-mediated release of mast cell mediators, although only after chronic treatment. It is applied locally to conjunctiva, nasal mucosa, the bronchial tree (inhalation), and intestinal mucosa (absorption is almost nil with oral intake). Indications prophylaxis of hay-fever, allergic asthma, and food allergies. Nedocromil acts similarly. 

Nedocromil was developed as a result of research for compounds to control asthma. Its activity has been studied in vitro in a variety of inflammatory cells, including mast cells, eosinophils, and polymorphonuclear leukocytes. Nedocromil appears to be more potent than cromolyn in its ability to inhibit immimologic release of mast cell mediators. It can also modify the actions of eosinophils, neutrophils, monocytes, macrophages, and platelets. Pharmacokinetic studies indicate that ocular penetration of nedocromil is slow, and clearance from the eye is relatively rapid. Nedocromil differs from the other mast cell stabilizers in that it is effective within 15 to 30 minutes. 

Cromones. Cromolyn sodium was first available for use as a therapeutic agent in the United States in 1973. Administered as an aerosol, it is widely used for the prophylactic treatment of asthma, with the onset of activity manifesting after several weeks, and it causes few side effects. Nedocromil sodium possesses cromolyn-like activity [51] and is efficacious in the treatment of asthma when administered as an aerosol [52,53]. Despite a concerted research effort, the mechanism by which cromones exert their therapeutic activity remains enigmatic. Inhibition of mediator release from mast cells and a direct suppressive action on other inflammatory cells appear to be features of their clinical actions [54,55],... 

The most important anti-inflammatory drugs in the treatment of asthma are the corticosteroids and dmgs such as cromolyn and nedocromil that inhibit release of mediators from mast cells and other inflammatory cells. The lipoxygenase inhibitor zileuton probably also exerts an anti-inflammatory effect in asthma. 

Mast cells release histamines, leukotrienes and other mediators of the inflammatory process. Mast cell stabilizer drugs inhibit the early asthmatic response and the late asthmatic response. They have no bronchodilator effect nor do they have any effect on any inflammatory mediators already released in the body. They are indicated for the prevention of bronchospasms and bronchial asthma attacks. They are administered by aerosol inhalation. The exact action of the drugs have not been determined. However, they are believed to have a modest effect in lowering the required dose of corticosteroids. The most common mast stabilizer dmgs are cromolyn (Intal) and nedocromil (Tilade). 

In delivering aerosolized steroidal and nonsteroidal anti-inflammatory drugs to patients with asthma, one cell population that should be targeted is the eosinophil. This is because asthma is generally believed to involve an eosinophilic type of inflammatory reaction (25). Steroids reduce the number of eosinophils in circulation, the recruittnent of eosinophils to local tissue sites, the survival of eosinophils in the presence of cytokines, and the production of cytokines responsible for or involved in aU of these processes (25). Cromolyn inhibits the ability of eosinophils to kill complement-coated schistosomula organisms and to express, upon stimulation, complement C3b and Fey receptors (26). Nedocromil inhibits the release of proteins from eosinophil granules and leukotriene (LTC ) formation by eosinophils (27,28). 

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