Cromolyn blocked

The facet of cromolyn s activity profile on which we concentrated was the compound s reported tachyphylactic action in both the rat PCA screen and in producing a Bezold-Jarisch reflex induced fall in blood pressure in the anaesthetised dog flO. 141. In essence, a high dose of the compound administered to a rat 30 - 60 minutes before a second dose, given in the normal manner at the time of antigen challenge, inhibits or abolishes the protective effect of the latter dose on the rat PCA reaction. In the anaesthetised dog, we have found that a fifteen minute infusion of a low dose of cromolyn blocks the normal depressor activity of a subsequent bolus injection of the compound. The blocking action of the infused dose diminishes with time as shown in Figure 1. The loss of activity with time in these experiments probably reflects the rate of elimination of the cromolyn from the sensory receptors in the left ventricle of the heart which have been shown to be involved in the... 

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... 

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. 

The term antihistamine, without a modifying adjective, refers to the classic Hi receptor blockers. These compounds do not influence the formation or release of histamine, but rather they competitively block the receptor-mediated response of a target tissue. [Note This contrasts with the action of cromolyn (see p. 220), which inhibits the release of histamine from mast cells and is useful in the treatment of asthma.] The H receptor blockers can be divided into first- and second generation drugs.(Figure 40.5). The first generation drugs are still widely used because they are effective and inexpensive. 

Cromolyn sodium (sodium cromoglycate) inhibits exocytosis of mast cells, thus blocking the release of histamine and leukotrienes. It is used mainly to prevent attacks (e.g. those triggered by exercise). 

Even though various antileukotriene drugs have been synthesized, none has reached clinical acceptability. Inhibition of histamine release by an apparent mast cell stabilizing mechanism (in lung tissue, but probably not elsewhere) is achieved with the carboxy-chromone derivative cromolyn sodium. The mechanism is believed to involve inhibition of histamine release from pulmonary mast cells by blocking Ca2+ movement through membrane channels. 

Diethyl dithiocarbamate, the major metabolite of dis-ulfiram has recently been shown to block dopamine p-hydroxylase, and may be the reason for the hypotensive effects characteristic of the disulfiram-mediated modulation of ethanol metabolism. The antioxidant probucol lowers the cholesterol level in blood. Cromolyn, a chromone heterocycle, is useful in the inhalation treatment of bronchial asthma. 

The most commonly used bronchodUators are the beta-adrenoceptor agonists. In some patients, a muscarinic blocking drug (eg, ipratropium) has a useful bronchodilating effect. Cromolyn and nedocromil inhibit the degranulation of mast cells and are useful as prophylactic agents in some patients. They are not useful in an acute attack. Systemic corticosteroids are reserved for patients with severe asthma who do not respond adequately to other agents, but inhaled steroids (eg, beclomethasone) are standard prophylactic therapy for aU individuals with moderate or severe recurrent asthma... 

The bronchodilatory activity of khellin, a chromone obtained from a plant source Ammi visnaga) used by ancient Egyptians for spasmolytic activity, stimulated the search for related compounds with similar pharmaoological properties (14). From a study of many bischromones, cromolyn sodium was developed and marketed (Fig. 37.5). Although it prevents bronchospasm, it does not reverse antigen-induced bronchiolar constriction. Thus, it and other agents like it that followed prevent the release of histamine and do not block the effects of histamine at its reoeptors. 

This is the correct explanation for administering a cromolyn inhaler it prevents the asthma attack by blocking the release of mast cell mediators. 

Initial studies showed that the IgE-mediator ja imate respiratory response was partially inhibited by antihistamines, partially reversed by beta adrenergic blocking agents (20) and partially inhibited by cromolyn sodium when it was given either intravenously or by aerosol prior to antigen challenge (21). 

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