Histamine Release Mast Cell Stabilizers

INHIBITION OF HISTAMINE RELEASE MAST CELL STABILIZERS 

Cromolyn Sodium, USP. Cromolyn stxlium. dlsodium 1.3 - bis (2 -carboxychnimon - 5 - yloxy) -2-hydroxy propane (Intal). is a hygroscopic, white, hydrated crystalline powder that is soluble in water (1 10). It i.s tasteless at first but leaves a very slightly biller aftertaste. The pK of cromolyn is 2.0. It is available as a solution for a nebuliz.cr. an aerosol spray, a nasal solution, an ophthalmic solution, and an oral concentrate. 

2 ampules q.i.d.. 30 minittes before meals attd at bedtime 

Nedocromil Sodium, U5P. Nedocromil. stxlium. disodium 9-elhyl-6.9-dihydro-4.6-dioxo-IO-propyl-4W-pyrano 3.2-g quinolinc-2.8-dicarboxylale (Tilade). is available as an aerosol in a melcred-dosc inhaler. 

Usual adult dose Intriinasal. 14 mg lt v inhalations)q.i.da regular iiaervals 

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Mast Cell Stabilizer A mast cell stabilizer prevents bronchospasms and inhibits asthmatic response by blocking the release of histamine, leukotrienes, and other mediators from the mast cell that cause the inflammatory process. A mast cell stabilizer does not have an effect on inflammatory mediators that were already released. Mast cell stabilizers are administered by aerosol inhalation. The most common mast stabilizers are ... 

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. 

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... 

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. 

Mechanism of Action A mast cell stabilizer that prevents increase in cutaneous vascular permeability, antigen-stimulated histamine release, and may prevent calcium influx into mast cells. Therapeutic Effect Inhibits sensitivity reaction. Pharmacokinetics Nondetectable absorption. Half-life 8.5 hr. 

Mechanism of Action A mast cell stabilizer that prevents the activation and release of inflammatory mediators, such as histamine, leukotrienes, mast cells, eosinophils, andmonocytes.T herapeuticEffect Prevents both early and late asthmatic responses. Pharmacokinetics The extent of absorption is 7% to 9% of a single inhaled dose of 3.5 to 4 mg and 17% of multiple inhaled doses, with absorption largely from the respiratory tract. Although most of the inhaled dose is subsequently swallowed, only 2% to 3% is absorbed from the G1 tract. Less than 4% of the total dose is systemically absorbed following multiple doses of ophthalmic solution. Protein binding 89%. Not metabolized. Excreted in urine. Half-life 1.5-3.3 hr. 

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). 

Mast cell stabilizers are indicated for the treatment of inflammatory airway disease in some horses. Inflammatory airway disease is observed in yoimg horses the clinical syndrome is characterized by poor exercise performance, chronic cough and the presence of exudate in the tracheobronchial tree. A subset of horses with inflammatory airway disease will have metachromatic inflammation in bronchoalveolar lavage, with mast cells constituting 2-5% of the total cell count. This form of chronic lower airway inflammation probably represents a local pulmonary hypersensitivity reaction. There is controversy as to whether this form of inflammatory airway disease represents an early form of recurrent airway obstruction. Nebulization of sodium cromoglicate (200 mg) will improve the clinical signs of respiratory disease and will stabilize mast cell histamine release (Hare et al 1994). 

Mast cell stabilizers prevent bronchospasms and inhibit asthmatic response by blocking the release of histamines, leukotrienes, and other mediators from the mast cell that cause the inflammatory process. 

Cromones Cromones (cromolyn sodium and nedocromil sodium, Aventis see Figure 16.6) are a unique class of compounds that are known to cause mast cell stabilization, thereby preventing the histamine release involved in local hypersensitivity of the lungs. In addition, these agents are implicated in preventing the release of other inflammatory mediators and the sensitivity of myelinated nerves... 

Drugs in this group are also known as mast-cell stabilizers and they probably work by blocking the release of mediators such as histamine and serotonin in the lung, although their exact mode of action is unknown. They can be used prophylactically to reduce the incidence of asthmatic attacks and to allow reduction in the doses of other drugs. They are not used in chronic bronchitis. 

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. 

The synthesis of a series of triazolobenzopyranones carrying piperazinoalkoxy substituents on the phenyl ring demonstrated the feasibility of integrating the mast-cell-stabilizing properties of the chromone (benzopyranone) moiety and H( antihistaminic properties into one molecule. The most effective compound of a small series was BR-28390. Its antihistaminic potency (guinea pig ileum) was the same as mepyramine histamine release inhibition effectiveness (tested by rat passive peritoneal anaphylaxis) was somewhat less than cromolyn. 

Nedocromil sodium is a mast-cell stabilizer that inhibits release of mediators from inflammatory cell types associated with asthma, including histamine from mast cells and beta-glucuronidase from macrophages. It may also suppress local production of leukotrienes and prostaglandins and inhibit development of bronchoconstriction responses to inhaled antigen and other challenges such as cold air. It is... 

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). 

Hj antihistamines are the most commonly prescribed medications for AR. Hj antihistamines bind to and stabilize the Hj histamine receptor, thereby inhibiting mast cell and basophil mediator release and resulting in reduction of sneezing, itching, rhinorrhea, and ocular irritation. Antihistamines do not prevent histamine release, nor do they bind to already-released histamine. For this reason, maintenance therapy is considered optimal. However, antihistamines are also effective when taken on an as-needed basis.4,11,12 Antihistamines only minimally... 

Cromoglycate and nedocromil are known to stabilize the outer cell membrane of mast cells and thereby inhibiting the release of histamine and leukotrienes. Their antiallergic effect might be due to more than one mechanism, for example by additionally reducing the sensitivity of inflammatory cells towards histamine. 

Spanish needles have also been found to have anti-allergy action at the level of mast cells and other allergy mediators.4 Spanish needles contains quercetin and ethyl caffeate, both of which have previously been shown to possess in vitro anti-inflammatory or anti-allergic mediator action.23,24 Quercetin5 has also been shown to stabilize mast cells and basophils, decrease leukotriene formation, and reduce release of histamine and other mediators.24,25 Anti-inflammatory effects have been demonstrated in rats after receiving aqueous extracts of Spanish needles leaves and stems.26,27 A related species, Bidens parviflora, has been reported to inhibit histamine release from rat mast cells in vitro.6 Spanish needles have been shown to inhibit the inflammatory mediator nuclear transcription factor kappaB (NF-kappaB) and its downstream inflammatory mediators in vitro.23... 

There is some evidence that children under five years of age obtain benefit from use of nedocromil sodium or sodium cromoglicate. These agents are used only in prophylaxis cromoglicate is not a bronchodilator and cannot be used to treat acute episodes of asthma. Its action is not well understood but the prophylactic effect appears to be partly due to stabilization of mast cells, which reduces release of histamine and other mediators so that hyperactive bronchial muscle is less responsive to environmental triggers. 

Cromoglicate inhibits mast-ceU degranulation and histamine release induced by phosphohpase A2, but does not interfere with the interaction of antigen and reaginic antibodies. Evidence is accumulating that it has an important stabilizing action on leukocytes, apart from mast cells, such as neutrophils, eosinophils, and monocytes, and that it also affects nerve reflexes in the lung (2). 

Inhibits degranulation of mast cells also inhibits release of histamine and SRS-A (a leukotriene) from the mast cell. This inhibits the early asthmatic response by stabilizing the mast cell also inhibits the late asthmatic response. It has no intrinsic bronchodilator, antihistaminic, anticholinergic, vasoconstrictor, or anti-inflammatory activity. 

Nedocromil, 9-Etkyl-6,tFdihydrO-4,6 ioxo-IO-propyl-4H-pyrano[3,2-g]qu i notine-2, H-dicarboxylic acid 4,6-dioxo-1 -ethyl-10-propyl-4H,6H-pyrano[3,2-g]quinotlne-2,8-dicar boxy lie acid FPL 59002. C HpNO, mol wt 371.35. C 61.45%, H 4.61%, N 3.77%, O 30.16%. Anti-aller-gic compound with the ability to stabilize both mucosal and connective tissue mast cells. Prepn and pharmacology H. Cairns, D. Cox. Belg. pat. 866,622 eidem, U.S. pat. 4,474,-787 (1978, 1984 both to Fisons) H. Cairns et at, J. Med. Chem. 28, 1832 (1985). Prevention of histamine release from mast celts, inhibition of Monchoconstriction in monkeys R. P. Eady et at.. Bril. J. Pharmacol 85, 323 (1985). Early clinical trial in bronchial asthma S. Lai et al. Thorax 39, 809 (1984). 

Yes. These drugs stabilize the mast cell membrane and prevent the release of histamine. 

Corticosteroids can decrease inflanunatoty responses in the lung by several mechanisms.These include the inhibition of synthesis of inflammatory prostanoids, induction of P2-adrenergic receptors, and the inhibition of histamine release through stabilization of mast cells. 

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