Mast-cell stabilizers

Given the routine use of mast cell stabilizers in the clinic, for example in the setting of asthma treatment, these preclinical results may stimulate clinical evaluation in humans. 

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,... 

Along with the bronchodilators, several types of dragp are effective in Hie treatment of asthma. These include corticosteroids, leukotriene formation inhibitors, leukotriene receptor agonists, and mast cell stabilizers. 

Mast cell stabilizers include cromolyn sodium (Intal) and nedocromil sodium (Tilade). 

The more common adverse reactions associated witii die mast cell stabilizers include headache, dizziness, nausea, fatigue, hypotension, or unpleasant taste in the mouth. These dm may cause nasal or throat irritation when given intranasally or by inhalation. A more complete listing of the adverse reactions associated with the mast cell stabilizers is found in the Summary Drug Table Antiastiima Dru i. 

The mast cell stabilizers are contraindicated in patients with known hypersensitivity to the drugp. The mast cell stabilizers are contraindicated in patients during attacks of acute astiima because they may worsen bron-chospasm during tiie acute asthma attack. 

It is important to use the mast cell stabilizers cautiously in patients witii impaired renal or hepatic function and during pregnancy (Pregnancy Category B) and lactation. No significant drug interactions have been reported. 

The mast cell stabilizers currently for ophthalmic use are nedocromil and pemirolast. These drugp are used for the prevention of eye itching caused by allergic conjunctivitis. The mast cell stabilizers act by inhibiting the antigen-induced release of inflammatory mediators (eg, histamine) from human mast cells. 

Nedocromil, a mast cell stabilizer, has not been adequately tested in COPD patients and is not included in the GOLD recommendations. 

Antihistamines and intranasal corticosteroids are considered first-line therapy for allergic rhinitis, whereas decongestants, mast cell stabilizers, leukotriene modifiers, and systemic corticosteroids are secondary treatment options. 

Pharmacotherapy has an important role in managing AR symptoms (Table 59-2). Intranasal corticosteroids, systemic and topical antihistamines and decongestants, mast cell stabilizers, and immunotherapy all are beneficial in treating symptoms of AR.9 Antihistamines and intranasal corticosteroids are considered first-line therapy for AR, whereas decongestants, mast cell stabilizers, leukotriene modifiers, and systemic corticosteroids are secondary treatment options10-12 (Fig. 59-2). Whenever exposure to allergens can be predicted (e.g., SAR or visiting homes with a pet), medications should be used pro-phylactically to maximize effectiveness.11... 

Treatment of ocular allergy is aimed at slowing or stopping these processes. Antihistamines block the histamine receptors and some prevent histamine production and/or inhibit mediator release from the mast cells.15 Mast cell stabilizers inhibit the degranulation of mast cells, preventing mediator release. Some topical agents have multiple mechanisms of action, combining antihistaminic, mast cell stabilization, and antiinflammatory properties (Tables 60-3 and 60-4).16... 

Ketotifen Hrreceptor antagonist, mast cell stabilizer, eosinophil inhibitor, platelet-activating factor inhibitor May inhibit eosinophil chemotaxis... 

Nedocromil Mast cell stabilizer, Hrreceptor antagonist May inhibit eosinophils... 

Lodoxamide Mast cell stabilizer May be used for up to 3 months... 

If insufficient relief is obtained from these products, either a mast cell stabilizer or a multiple-action agent is appropriate.17 Use mast cell stabilizers prophylactically throughout the allergy season. Full response may take 4 to 6 weeks. 

If mast cell stabilizers or multiple-action agents are not successful, a trial of a topical NSAID is appropriate. Ketorolac is the only approved topical agent for ocular itching. NSAIDs do not mask ocular infections, affect wound healing, increase intraocular pressure, or contribute to cataract formation like the topical corticosteroids. However, for allergic conjunctivitis, topical ketorolac is not as effective as olopatadine or emedas-tine in trials.15 Full efficacy of ketorolac takes up to 2 weeks.17... 

Cromolyn sodium (Nasalcrom), a mast cell stabilizer, is available as a nonprescription nasal spray for symptomatic prevention and treatment of allergic rhinitis. 

Recently, NGF has been shown to cause a significant proliferation of connective tissue mast cells when injected subcutaneously into newborn (day 1) rats [122]. This effect of NGF is blocked by DSCG, which suggests that products released from NGF-stimulated mast cells are responsible (directly or indirectly) for the proliferation or recruitment of other mast cells. In adult rats, a similar proliferation of mucosal mast cells in the small intestine is known to accompany an infection by intestinal nematode, N. brasilensis [123] and has also been reported to accompany the repeated injections of compound 48/80 [ 124], It may be relevant in this regard that mast cells are frequently prominent in a wide variety of fibrotic conditions such as neurofibromatosis where itching around the growing neurofibroma is a common symptom [125]. Treatment of neurofibromatosis with ketotifen, a mast cell stabilizer similar to DSCG, results... 

Lodoxamide (Alomide) Mast cell stabilizer Ophth soln 0.1% [10 mL] ... 

Nedocromil (Tilade) Mast cell stabilizer Aerosol [16.2gm] Nefazodone (Serzone) Antidepressant Tab 100,150, 200, 250... 

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. 

Inhibitors of histamine release One of the effects of the so-called mast cell stabilizers cromoglycate (cromolyn) and nedocromil is to decrease the release of histamine from mast cells (p. 72, 326). Both agents are applied topically. Release of mast cell mediators can also be inhibited by some Hi antihistamines, e.g., oxatomide and ketotifen, which are used systemically. 

Initial observations on khellin (32), a furochromone-type compound from Ammi visnaga L., showed a mast-cell stabilizing effect. This led to the synthesis of many derivatives of this lead for the potential treatment of allergy and asthma, most notably the approved preventive antiasthma drug, cromolyn sodium (33). The precise molecular mechanism of this class of drugs is not yet clearly imderstood. ... 

Pharmacology Lodoxamide is a mast cell stabilizer that inhibits the in vivo Type I immediate hypersensitivity reaction. Although lodoxamide s precise mechanism of action is unknown, the drug may prevent calcium influx into mast cells upon antigen stimulation. 

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