Mast cell-antihistamine combination

Mucus fishing syndrome requires treatment of the underlying condition and education about the patient s role in creating the disorder. When present, allergy must be addressed. The newer antihistamine-mast cell stabilizer combination products, such as olopatadine, have been particularly helpful in managing the disorder in these patients. 

In moderate to severe cases of allergic conjunctivitis, treatment considerations also include mast cell stabilizers, antihistamine-mast cell stabilizer combinations, oral antihistamines, NSAIDs, and, in severe cases, topical steroids. 

Surgical acute pain oral and parenteral doses of antihistamines are used as an adjunct to decrease inflammation to promote analgesia. Following noxious stimulation, an inflammatory response occurs and locally released neurotransmitters such as substance P and tachykinins promote vasodilatation and histamine release from blood cells. Additional histamine is released in response to tissue damage and activation of mast cells. Antihistamines in combination with opioids have been foimd to provide superior pain relief compared to equivalent doses of opioids alone, therefore antihistamines may have an opioid-sparing effect However, one study foimd no difference in pain relief with a single dose of terfenadine (withdrawn by FDA in 1997) after oral smgery. 

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... 

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. 

Mast cell stabilizers prevent the mast cell from degranulating and therefore the subsequent release of mediators. However, once the mast cells have already degranulated, mast cell stabilizers are ineffective against the released mediators. Combination drugs with both mast cell-stabilizing and antihistamine effects provide both longterm treatment and a more rapid relief of symptoms. Drugs with this dual-action or multiaction mechanism include azelastine, epinastine, ketotifen, and olopatadine (Table 13-7). 

Treatment of VKC depends on the severity of symptoms and the clinical presentation. In mild cases the use of cool compresses, ocular lubricants, decongestant-antihistamine combinations, and mast cell stabilizers may be sufficient. Environmental controls include maintaining a cool moist environment, for example, with air conditioning. 

Topical application of Hi antihistamines to the eye is made to relieve itching, congestion of the conjunctiva, and erythema (15,42). The density of mast cells in the conjunctiva is high, and the histamine concentrations in tear film are significant in the ocular allergic response. From eye drops, only small amounts of the antihistamine (1-5%) penetrate the cornea. More of the compound is absorbed via the conjunctiva and nasal mucosa, and still more ends up swallowed from tear duct and nasal drainage. Until recently, topical ocular antihistamines were limited to two classical agents antazoline (Table 37.2), from the ethylenediamine series, and pheniramine (Fig. 37.9), from the alkylamine series. Both are used in combination with sympathomimetic vasoconstrictors. 

I, 2,3-triazoles. 13. (Piperazinylalkoxy)-[l]benzopyrano[2,3-d]-l,2,3-triazol-9(l//)-ones with combined HI -antihistamine and mast cell stabilizing properties. J. Med. Chem. 29(ll) 2262-2267. 

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