Cromolyn cells

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,... 

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

CBP Cromolyn-binding protein CCK Cholecystokinin CCR Creatinine clearance rate CD Cluster of differentiation (a system of nomenclature for sur ce molecules on cells of the immune system) cluster determinant CDl Cluster of differentiation 1 also known as MHC class I-like surfitce glycoprotein... 

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... 

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. 

When stored under increasing relative humidities (RH), cromolyn sodium absorbed water, resulting in a continuous series of interstitial solid solutions [11]. The amount of water absorbed was proportional to the relative humidity of the environment and could be up to about nine molecules of water per molecule of drug. Such an unusual system was characterized by combining XPD with single-crystal x-ray studies. The unit cell parameters of cromolyn sodium were obtained from single-crystal x-ray studies, and this permitted the authors to index the powder pattern. The b axis spacing was found to increase dramatically as a function of the relative humidity up to 20% RH (Table 2). Above 40% RH, the unit cell dimensions were nearly constant. 

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. 

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

Cromolyn sodium and nedocromil sodium have beneficial effects that are believed to result from stabilization of mast cell membranes. They inhibit the response to allergen challenge as well as EIB but do not cause bronchodilation. 

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. 

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. ... 

One of the early steps in an allergic reaction consists in the release of a series of endogenous compounds referred to as mediators from sensitized cells. The finding in the early 1960s that cromolyn sodium, still the only approved drug of this class, blunts this reaction has led to an intense search for additional examples. It is of interest that a relatively simple anthranilic acid derivative has shown mediator-release inhibiting activity. Reaction of 3,4-dimethoxybenzalde-hyde (167) with isatoic anhydride 168 gives the condensation product 169, which, upon hydrolysis, affords tranilast (170) (43]. 

Cromolyn stabilizes the membranes of mast cells, stopping the release of allergy mediators and suppressing activation of eosinophiles, neutrophilis, thrombocytes, and macrophages, which take part in the formation of bronchospasms. 

Cromolyn Sodium (Intal, NasalCrom, Opticrom, Others) [Antiasthmatic/Mast Cell Stabilizer] Uses "Adjunct to the Rx of... 

IgE-medlated release of mast cell contents. Inset, Intact mast cell with histamine stored In granules. An IgE antibody molecule Is depicted adjacent to the mast cell. Two IgE molecules combine with a mast cell (sensitization). The attachment of an antigen (allergen) to the sensitized mast cell Initiates release of histamine (and other substances) from the mast cell. This degranulation can be prevented by such agents as isoproterenol, theophylline, epinephrine, and cromolyn sodium. H antihistamines do not interfere with degranulation but instead prevent actions of histamine at various pharmacological receptors. 

Cromolyn sodium and nedocromil sodium attenuate bronchospasm induced by various stimuli, including antigen, exercise, cold dry air, and sulfur dioxide. They suppress inflammatory cell influx and chemotactic activity along with antigen-induced bronchial hyperreactivity. Also inhibited is C-flber sensory nerve activation in animal models, which may in turn suppress reflex-induced bronchospasm. 

The chromone cromolyn sodium (5-5) was at one time considered the forerunner of a novel class of antiallergic and antiasthmatic drugs that act at one of the earliest stages of the allergic reaction. Detailed experiments, acmally conducted after the dmg s clinical effectiveness had been confirmed, suggested that the compound inhibited the release of mediators of the allergic reaction from mast cells. The dmg is not very active when taken orally and is usually applied topically to the lung by insufflation as its sodium salt. Considerable efforts to uncover additional structurally related mediator release inhibitors have had only limited success. 

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, 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... 

Mast cell stabilizers Intal (Aventis) Cromolyn sodium Solution for inhalation 20 mg/2 mL None... 

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. 

Mast cell stabilizers. Cromoglycate (cromolyn) and nedocromil decrease, by an as yet unknown mechanism, the capacity of mast cells to release of histamine and other mediators during allergic reactions. Both agents are applied topically (p.338). 

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