piperidines and lodoxamide-ethyl

Topical ocular allergy drugs are indicated for the treatment of allergic conjunctivitis after more conservative measures have been employed. Antihistamines, vasoconstrictors, nonsteroidal anti-inflammatory drugs, mast cell stabilizers and corticosteroids are available. Levocabastine and ketorolac tromethamine are new drugs for the treatment of allergic conjunctivitis. Lodoxamide is currently indicated only for the treatment of vernal keratoconjunctivitis, although treatment efficacy has been demonstrated in patients with giant papillary conjunctivitis and atopic keratoconjunctivitis. As a general rule, topical ocular allergy drugs are well tolerated by most patients except for transient stinging and burning on instillation. Ocular steroids should be reserved for severe cases and should be prescribed by an ophthalmologist, who can monitor the patient for possible ocular side effects.

Topics: Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Ketorolac Tromethamine; Oxamic Acid; Piperidines; Tolmetin; Tromethamine

Recent decades have been marked by an increasing number of patients suffering from ocular allergic-like symptoms without being associated with an increase in IgE levels. These symptoms include heaviness of the lid, foreign body sensation, burning, stinging and photophobia. Both epidemiological studies and controlled human exposure clinical studies have shown cause-effect relationships between allergic-like symptoms and environmental factors such as outdoor air pollutants or poor indoor air quality. An ocular surface subclinical inflammation is thought to be responsible for pseudoallergic, pollution-related conjunctivitis. The complement system is considered as one of the major effector mechanisms involved in initiation of the subclinical inflammation that leads to IgE-independent eye irritation.. To study the capability of nine antiallergic eyedrops commonly used in the treatment of allergic conjunctivitis to inhibit complement activation induced in vitro by pollutants.. Normal human serum obtained from healthy individuals was used as a source of complement. Activation of complement was assessed using the complement hemolytic 50% (CH50) assay, in the absence or the presence of antiallergic eyedrops and in the absence or the presence of various stimuli, including sand, common house dust, eye mascara, and Dactylis glomerata pollen extract. Zymosan was used as a standardized complement activator. The following eyedrops were studied: Naabak (4.9% N-acetyl aspartic acid-glutamic acid, NAAGA, sodium salt), Almide (lodoxamide 0.1%), Levophta (0.05% levocabastine), Emadine (0.05% emedastine), Tilavist (2% nedocromil), Allergodil (0.05% azelastine), Patanol (olopatadine), and Zaditen (0.025% ketotifen). Effects of preservative-free lodoxamide and ketotifen were also assessed and compared to those of the preserved formulations. A solution of 0.01% benzalkonium chloride (BAC), the most widely used preservative in topical eyedrops, was also tested.. Zymosan-induced activation of complement (30+/-6%) was significantly lowered by preincubation of serum with unpreserved NAAGA (16.6+/-4%, p=0.0026) or benzalkonium-preserved nedocromil (20+/-2%, p=0.022). Preserved levocabastine, emedastine, olopatadine and ketotifen did not interfere with zymosan-induced complement activation, whereas preserved azelastine, lodoxamide and benzalkonium chloride significantly aggravated complement activation induced by zymosan. Similar results were obtained when complement activation was triggered by sand, common house dust, mascara, or by an allergenic extract of Dactylis glomerata pollen. In the absence of complement activator, none of the antiallergic eyedrops induced a significant change in CH50 titer, indicating that the deleterious pro-inflammatory effect of preserved azelastine and lodoxamide may occur only once complement activation has been initiated, i.e., on an inflamed ocular surface.. Among the antiallergic eyedrops tested in this study, only Naabak and Tilavist were found to significantly inhibit complement activation triggered by particulate matters or pollen allergenic extract. Such an anticomplement activity confers these two molecules a potential in the therapeutic management of pollution-related pseudoallergic conjunctivitis.

Topics: Air Pollutants; Anti-Allergic Agents; Benzalkonium Compounds; Benzimidazoles; Complement Activation; Conjunctivitis; Cosmetics; Dibenzoxepins; Dipeptides; Drug Evaluation; Dust; Humans; In Vitro Techniques; Ketotifen; Nedocromil; Olopatadine Hydrochloride; Ophthalmic Solutions; Oxamic Acid; Phthalazines; Piperidines; Pollen; Silicon Dioxide; Zymosan

Leukocytes from ten allergic patients (five allergic to dust-mites and five allergic to pollen) were treated with N-acetyl aspartyl glutamic acid (NAAGA) 4.9%, disodium cromoglycate (DSCG) 2%, lodoxamide (LODO) 1%, and levocabastine (LEVO) 0.5% (concentrations representing the pharmaceutical eyedrop preparations) for 20 minutes. Degranulation was then induced with Complement (rHu5Ca). Histamine was measured in the supernatant with ELISA. LODO and LEVO were inactive in blocking histamine released from human cells, and paradoxical unexpected effects were found with these two agents. They both induced significant histamine release in almost 100% of the samples. DSCG was able to block histamine release in seven patients out of nine (ranging between 5 and 34%). NAAGA was the most active agent on human cells and was able to block basophil degranulation in nine patients out of nine (inhibition ranging between 4 and 66% of total histamine pool).

Topics: Allergens; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Basophil Degranulation Test; Basophils; Cell Degranulation; Complement C5; Cromolyn Sodium; Dipeptides; Enzyme-Linked Immunosorbent Assay; Histamine; Histamine H1 Antagonists; Histamine Release; Humans; Hypersensitivity, Immediate; Ophthalmic Solutions; Oxamic Acid; Piperidines; Recombinant Proteins

Topics: Anti-Inflammatory Agents, Non-Steroidal; Conjunctivitis, Allergic; Drug Combinations; Histamine H1 Antagonists; Humans; Ketorolac Tromethamine; Ophthalmic Solutions; Oxamic Acid; Piperidines; Tolmetin; Tromethamine

Topics: Anti-Inflammatory Agents, Non-Steroidal; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Ophthalmic Solutions; Oxamic Acid; Piperidines; United States; United States Food and Drug Administration