Asthma cromolyn

The discovery of the utility of the bis-chromone carboxylic acid derivative cromolyn sodium in the treatment of asthma and related allergies has led to an intensive, and thus far not very fruitful, effort to discover analogues which would show oral activity in contrast to the lead which must be administered by inhalation. Preparation of a typical analogue, proxicromil (63), starts with the O-allylated phenol 57. Claisen rearrangement leads to the corresponding C-allylated product 58. 

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,... 

Cromolyn—When taken to prevent exercise-induced asthma, this drug should be taken approximately 15 minutes before activity but no earlier than 1 hour before the expected activity. 

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. 

In mild persistent asthma, daily use of a low-dose inhaled corticosteroid is the preferred treatment in all age groups. Cromolyn,... 

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. 

A 10-year-old female with allergy-induced asthma is treated with cromolyn. What is the mechanism of action of cromolyn ... 

The answer is d. (Katzung, pp 336-3373 The inhibitory effect of mediator release of cromolyn is cell specific In mast cells exposed to cromolyn, inhibition of the early response occurs to antigen challenge, while in eosinophils, it affects the late response, and in basophils it has almost no effect on mediator release. Cromolyn is effective in anti gen-induced asthma, occupation-exposure asthma, and in some cases of intrinsic asthma. Administration of cromolyn by inhalation is most effective in treating patients. 

Stabilization of mast cells. Cromolyn prevents IgE-mediated release of mediators, although only after chronic treatment. Moreover, by interfering with the actions of mediator substances on inflammatory cells, it causes a more general inhibition of allergic inflammation. It is applied locally to conjunctiva, nasal mucosa, bronchial tree (inhalation), intestinal mucosa (absorption almost nil with oral intake). Indications prophylaxis of hay fever, allergic asthma, and food allergies. 

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. ... 

Bronchial asthma (inhalation solution, aerosol) As prophylactic management of bronchial asthma. Cromolyn is given on a regular, daily basis in patients with frequent symptomatology requiring a continuous medication regimen. 

Acute asthma Cromolyn has no role in the treatment of acute asthma, especially status asthmaticus it is a prophylactic drug with no benefit for acute situations. Hypersensitivity reactions Severe anaphylactic reactions may occur rarely. Renal/Hepatic function Impairment. Decrease the dose or discontinue the drug in these patients. 

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-... 

B. Status asthmaticus is a dangerous exacerbation of asthma symptoms. It requires immediate and aggressive treatment with oxygen, inhaled bronchodilators, and systemic corticosteroids. Hospitalization of the patient is often indicated. By definition, status asthmaticus is not a condition in which symptoms are well controlled. Neither cromolyn sodium nor a leukotriene modulator is indicated for the treatment of status asthmaticus, as their onset of action is too slow. Status asthmaticus often does not resolve without aggressive intervention. Indeed, the patient s condition can deteriorate rapidly to death. Upper respiratory tract infection or excessive exposure to an allergen often precedes status asthmaticus, as does increased use of inhaled bronchodilators. 

It is a cromolyn analogue. It is an antihistaminic (H antagonist) and probably inhibits airway inflammation induced by platelet activating factor (PAF) in primate. It is not a bronchodilator. It is used in asthma and symptomatic relief in atopic dermatitis, rhinitis, conjunctivitis and urticaria. It is absorbed orally and well tolerated. Bioavailability is 50% due to first pass metabolism and is primarily metabolized. The common side effects include dry mouth, sedation, dizziness and nausea. 

Corticosteroids and cromolyn are also useful in asthma. Corticosteroids inhibit eicosanoid synthesis and thus limit the amounts of eicosanoid mediator available for release. Cromolyn appears to inhibit the release of eicosanoids and other mediators such as histamine and platelet-activating factor from mast cells. 

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. 

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... 

Disodium cromoglycate (724), marketed as Intal or Cromolyn Sodium, bears some structural resemblance to khellin (457), the spasmolytic component of seeds of Ammi visnaga. Intal is one of the more successful drugs for the prevention of asthmatic attacks, though it is not effective in the treatment of an acute attack of asthma. It appears to prevent the release of histamine and other substances which mediate hypersensitivity reactions but is ineffective once these substances have been released. The chemistry and pharmacology of Intal have been reviewed (B-70MI22402). 

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... 

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