Antihistamines, ocular

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... 

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... 

There is still debate whether oral antihistamines control ocular allergy as well as topical antihistamines. Topical antihistamines are recommended before oral agent in step therapy because of the increased risk of systemic side effects with oral drugs. Additionally, topical antihistamines provide faster relief of ocular symptoms. Consider oral antihistamines... 

Levocabastine (Livostin) and olopatadine (Patanol) are ophthalmic antihistamines that can be used for allergic conjunctivitis that is often associated with allergic rhinitis. However, systemic antihistamines are usually effective for allergic conjunctivitis, making an ocular product unnecessary. They may be a logical addition to nasal glucocorticoids when ocular symptoms occur. 

Levocabastine (Livostin) [Antihistamine] Uses Allergic seasonal conjunctivitis Action Antihistamine Dose 1 gtt in eye(s) qid = 2 wk Caution [C,-i-/-] Disp Opthal soln SE Ocular discomfort EMS None OD Unlikely... 

Methods for Reducing Toxic Effects. Limited information is available on treatments to alleviate the symptoms of tetryl exposure. These include treatment of the dermatitis with calamine lotion and/or zinc oxide preparations, treatment of dermatitis and ocular irritation with aluminum acetate or boric acid compresses, and treatment of hypersensitivity-like symptoms (including severe dermatitis and asthma-like symptoms) with epinephrine or antihistamines (Bain and Thomson I 954 Bergman 1952 Cripps 1917 Eddy 1943 Ruxton 1917 Smith 1916 Troup 1946 Witkowski et al. 1942). The data on the pharmacokinetics of tetryl are also limited (Zambrano and Mandovano 1956). In order to develop mitigating agents, further studies are needed on its kinetics and mechanisms of action. 

Practitioners should be aware of over-the-counter (OTC) medications and folk or home remedies that patients may be using. Many patients may not consider OTC agents, especially antihistamines and decongestants for hay fever and colds, as drugs. These can affect the autonomic nervous system. OTC preparations can potentially interact with ocular drugs, such as homatropine and phenylephrine, that also influence autonomic functions. 

Among the treatment options, topical decongestants, topical and oral antihistamines, mast cell stabilizers, dual-action/multiaction drugs, and certain nonsteroidal antiinflammatory agents have proven useful for alleviating the signs and symptoms associated with ocular allergic reactions. Homeopathic preparations have also become of interest to the ophthalmic community, and their scientific... 

The first-generation Hi antihistamines, also referred to as sedating antihistamines, and the second-generation antihistamines, the less or nonsedating antihistamines, are among the most frequently used oral medications for ocular allergies. Table 13-3 lists commonly used oral antihistamines and some of their important pharmacologic properties. 

Ocular side effects relate primarily to the anticholinergic properties of the Hi antihistamine. Accordingly, one can anticipate decreased secretion of tears and mucus and mydriasis with the potential of acute angle-closure glaucoma. Continued use can bring about decreased accommodation and decreased vision. Usually the therapy can continue, because the effects typically diminish with time. 

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. 

Of the systemic antihistamines, the ethanolamines, including diphenhydramine, have significant antimuscarinic activity. In addition, the antipsychotic agents, particularly the phenothiazines such as thioridazine (Mellaril), have well-dociunented anticholinergic properties. Therapeutic doses of tricyclic antidepressants, like amitriptyline hydrochloride (Elavil) and imipramine (Tofranil), produce significant anticholinergic actions and thus have the potential for ocular side effects. 

Allergic conjunctivitis, often associated with allergic rhinitis, can be treated with an ophthalmic antihistamine such as levocabas-tine. Since systemic antihistamines usually are also effective for allergic conjunctivitis, levocabastine is a logical addition to nasal steroids when ocular symptoms occur, and is an acceptable approach in patients whose only symptoms involve the eyes. 

The most common symptoms of allergic conjunctivitis treated by ophthalmologists include ocular pruritis, erythema, edema, and tearing. The traditional drugs of choice to treat these symptoms of allergic conjunctivitis have been antihistamines alone or in combination with vasoconstrictors. Antihistamines currently employed in this area as topical solutions include pheniramine, antazoline, pyrilamine, and levocabastine. However, these drugs have some disadvantages such as low potency (antazoline), slow... 

Nephrotoxicity is the principal dose-limiting side effect of intravenous cidofovir. Proximal tubular dysfunction includes proteinuria, azotemia, glycosuria, and metabolic acidosis. Concomitant oral probenecid and saline prehydration reduce the risk of renal toxicity. On maintenance doses of 5 mg/kg every 2 weeks, up to 5Wo of patients develop proteinuria, 10-15% show an elevated serum creatinine, and 15-20% develop neutropenia. Anterior uveitis that is responsive to topical glucocorticoids and cycloplegia occur commonly and ocular hypotony occurs infrequently with intravenous cidofovir. Administration with food and pretreatment with antiemetics, antihistamines, and/or acetaminophen may improve tolerance. 

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. 

A slow rate of receptor dissociation of Fli antagonists is associated with long duration of action systemically, which occurs with the more recently available ocular antihistamines. 

Based on correlations of pKa values and lipophilicity data, it appears that compounds with a log D (the sum of the partition coefficients of both the ionized and unionized species) near 1.0 60.5 at pFI 7.4 are most efficacious, and their water-soluble salts also show a low incidence of ocular irritation. Relationships between partitioning characteristics of these and other antihistamines indicate (at least moderate) receptor affinity and that a particular range of optimal lipophilicity for topical ocular antihistamines with minimal ocular irritation (43). Some of these compounds are currently available (Table 37.9) or are being evaluated as nasal sprays, and some also are occasionally used as systemic antihistamines. 

Cook EB, Stahl JL, Barney NP, Graziano FM. Mechanisms of antihistamines and mast cell stabilizers in ocular allergic inflammation. Med Chem Revs Online 2004 1 333-347. 

Sharif NA, Hellberg MR, Yanni JM. Antihistamines, topical ocular. In Wolff ME, ed. Burger s Medicinal Chemistry and Drug Discovery. 5th Ed. New York John Wiley Sons,... 

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