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Main Classes of Drugs
Published in Jerome Z. Litt, Neil H. Shear, Litt's Drug Eruption & Reaction Manual, 2017
Mast cell stabilizerCromolynLodoxamideNedocromilPemirolast
Mast Cell Activation and Leukocyte Rolling Responses
Published in Bruce S. Bochner, Adhesion Molecules in Allergic Disease, 2020
Using intravital video microscopy, investigators have demonstrated that exposure of rat mesentery to Tx-A results in an increased adherence and emigration of leukocytes, enhanced albumin leakage in postcapillary venules, and the degranulation of perivenular mast cells (72). Although leukocyte rolling per se was not documented in this study, the recruitment of leukocytes elicited by Tx-A was dependent on P-selectin and sialyl-Lewisx (sLex), a selectin counter-receptor. Both of the reagents (mAb to P-selectin and soluble sLex) were also effective in blunting the enhanced albumin leakage normally elicited by the toxin, suggesting that the recruitment of leukocytes was an essential prerequisite for the microvascular alteration. Lodoxamide, a mast cell stabilizer, effectively prevented the mast cell degranulation in rat mesentery that was elicited by Tx-A exposure, and this particular therapy also attenuated leukocyte recruitment and the corresponding reduction in albumin leakage. Similar protective effects were noted following treatment with either diamine oxidase (histaminase) or an H1-receptor antagonist. These observations suggested that histamine represents an important mast cell-derived mediator of Tx-A-induced leukocyte recruitment. Based on these data, it is thought that Tx-A rapidly induces mast cell degranulation, leading to release and accumulation of histamine in the perivenular compartment. The mast cell-derived histamine appears to mediate at least part of the leukocyte–endothelial cell interactions by engaging H1-receptors on endothelial cells to perhaps increase the expression of P-selectin. The expression of this adhesion molecule would recruit rolling leukocytes that would directly contribute to the leukocyte recruitment elicited by C. difficile toxin A.
Pharmacotherapeutic management of atopic keratoconjunctivitis
Published in Expert Opinion on Pharmacotherapy, 2020
Ibtesham T Hossain, Priyanka Sanghi, Bita Manzouri
Cromones, such as sodium cromoglycate, are the oldest therapeutic agent for the treatment of allergic eye disease. Due to their delayed onset of action, they are not useful in the acute phase of the disease and are therefore reserved for the prevention of symptoms [11]. Lodoxamide is approximately 2500 times more potent in the prevention of histamine release compared to sodium cromoglycate based on in-vitro assays [25]. Lodoxamide and is used for both the acute and chronic phases of the disease by acting on eosinophil chemotaxis in addition to preventing histamine release from mast cells [24]. If single agents fail to control symptoms then dual-acting agents (olopatadine, ketotifen, azelastine, epinastine, and bepotastine) can be effective. These agents exert multiple pharmacological effects such as stabilization of mast cell degranulation, histamine receptor antagonist action, and inhibition of eosinophil activation and infiltration [26,27]. Olopatadine is a selective H1 receptor antagonist and demonstrates significant effectiveness in comparison to placebo in clinical trials [28,29]. These agents are well tolerated and have minimal side effects, although they are seldom effective in isolation.
Efficacy and Tolerability of Ketotifen in the Treatment Of Seasonal Allergic Conjunctivitis: Comparison between Ketotifen 0.025% and 0.05% Eye Drops
Published in Ocular Immunology and Inflammation, 2019
Andrea Leonardi, Decio Capobianco, Nicola Benedetti, Antonio Capobianco, Fabiano Cavarzeran, Tania Scalora, Rocco Modugno, Oren Mark Feuerman
Ocular allergies (OA), either seasonal/intermittent or perennial/persistent, are characterized by a clinical reaction involving the conjunctiva and the eyelids always associated with ocular itching, the quintessential symptom of allergy consequence of mast cell degranulation. In fact, IgE-mediated mast cell activation and release of the main mediator, histamine, has been described in all allergic ocular diseases: seasonal allergic conjunctivitis (SAC), perennial conjunctivitis (PAC), vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC).1 In addition to histamine, conjunctival mast cells have been shown to release several mediators and cytokines, and to be heterogeneous in phenotype, biochemical properties, and functional responses.2 Histamine release is a rapid process accompanied by immediate ocular itching,2 with tear histamine values peaking 5 minutes after conjunctival allergen challenge.3 Redness and chemosis have a slower onset after challenge but persist for a longer period of time. Therefore mast cells and histamine receptors are the main targets for anti-allergic treatment in all forms of OA. Mast cell stabilizers inhibit mast cell degranulation by blocking calcium-mediated release of inflammatory mediators, including histamine, from mast cells.4 The first approved drug in its class was cromolyn sodium 4%, approved in 1984 for use in VKC. Others that followed include lodoxamide tromethamine 0.1%, nedocromil sodium 2%, and permirolast potassium 0.1% and N-spaglumic acid 4%, are beneficial because they can target both early and late phase allergic reactions. However, they are only effective if mast cells are deactivated prior to an allergic response. Thus, therapy must be initiated at least 2 weeks prior to antigen exposure.
Ocular Surface Disorders in Patients with Human Immunodeficiency Virus (HIV) Infection
Published in Ocular Immunology and Inflammation, 2020
Matthew Ong Beng Seng, David Meyer, Stephen Gichuhi, Louis Tong, Sridharan Sudharshan, Jyotirmay Biswas, Ilaria Testi, Rupesh Agrawal
Topical mast cell stabilizers, including cromolyn sodium, nedocromil sodium, and lodoxamide, are usually administered in combination with topical antihistamines, in mild forms of the disease. High pulse dose topical corticosteroids followed by fast tapering and administration of low-absorptions steroid eye drops, such as fluorometholone or loteprednol, is effective in more severe disease. Immunosuppressive agents, such as cyclosporine and tacrolimus, are often needed on the long-term basis and have been proven to decrease inflammatory cytokines, leading to improvement of signs and symptoms.