The potential of active metabolites of antihistamines in the management of allergic disease

Abdelaziz, Muntasir M.; Khair, Omer; Devalia, Jagdish L.

doi:10.1034/j.1398-9995.2000.00114.x

Cited by 16 publications

(19 citation statements)

References 83 publications

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“…The pharmacodynamic effect of cetirizine on IL-6 has not been studied in detail and it is currently unknown whether this dosage was sufficient to elicit an effect of cetirizine on IL-6 production, especially in patients on high-dose IFNβ. Cetirizine has a rapid onset of action (15–180 minutes), with its effects peaking at 4–8 hours and persisting for at least 24 hours [13,24]. Thanks to these characteristics, cetirizine can be used on-demand for the treatment of clinical symptoms of allergic disorders, but it has been suggested that continuous administration (10 mg, once daily) may be necessary to achieve better efficacy by reducing also the underlying allergic inflammation [25].…”

Section: Discussionmentioning

confidence: 99%

Management of flu-like syndrome with cetirizine in patients with relapsing-remitting multiple sclerosis during therapy with interferon beta: Results of a randomized, cross-over, placebo-controlled pilot study

et al. 2017

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BackgroundFlu-like syndrome (FLS) is a common adverse event experienced by patients with relapsing-remitting multiple sclerosis (RRMS) treated with interferon beta (IFNβ). FLS can lead to poor treatment adherence and early IFNβ discontinuation. The involvement of interleukin-6 (IL-6) in the occurrence of FLS has been suggested. We hypothesized that cetirizine, a second-generation histamine H1 receptor antagonist able to reduce the levels of IL-6, might improve IFNβ-induced FLS.MethodsWe conducted a pilot, cross-over, randomized, placebo-controlled, double-blind study to evaluate the efficacy of cetirizine 10 mg added after each IFNβ injection to the standard of care for FLS (acetaminophen or nonsteroidal anti-inflammatory drugs) on FLS in patients with RRMS treated with IFNβ. Patients were randomized to two treatment sequences: 1) 4-week treatment with placebo added to the standard treatment for FLS, followed by 4-week treatment with cetirizine added to the standard of care, and 2) first addition of cetirizine, then of placebo. The primary efficacy endpoint was the mean change of FLS severity [11-point visual analog scale (VAS)] after 4 weeks of treatment within each sequence.ResultsForty-five patients (71.1% female, mean age 39.1 years, mean time from RRMS diagnosis 5.8 years) were randomized to treatment sequences 1 and 2. The differences between cetirizine and placebo in the intensity of FLS were not statistically significant: total mean VAS scores at 4 hours from IFNβ injection were 3.57 and 3.42 for cetirizine and placebo, respectively (difference –0.15; 95% confidence interval: from –0.74 to 0.44; p = 0.6029). The two treatments were similar also with regard to other efficacy measures considered and to the safety/tolerability profile.ConclusionsThe addition of cetirizine to the standard of care for IFNβ-induced FLS in patients with RRMS does not seem to provide significant benefits compared with placebo. Further effort is required to understand the mechanisms underlying IFNβ-induced FLS.Trial registrationEudraCT 2013-001055-12.

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Section: Discussionmentioning

confidence: 99%

Management of flu-like syndrome with cetirizine in patients with relapsing-remitting multiple sclerosis during therapy with interferon beta: Results of a randomized, cross-over, placebo-controlled pilot study

et al. 2017

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“…However, treatment guidelines are required to optimize the AR management. Also, in further clinical trials, it is possible to use these antihistamines by the following combinations; (i) the use of an active antihistamine metabolite, (ii) manipulation of the dosage regimen and (iii) administration by an alternative route (tropical versus oral) [38].…”

Section: Discussionmentioning

confidence: 99%

The Role of Antihistamines in the Management of Allergic Rhinitis

Ünal¹,

Hafız

2005

CMCAIAA

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Allergic rhinitis is a common disease worldwide and antihistamines remain the mainstay of pharmacotherapy for allergic rhinitis. Histamine is one of main mediators involved in the disease pathophysiology. The primary mechanism of antihistamine action is believed to be competitive antagonism of histamine receptors, specifically the H 1 -receptors. These receptors are present on nerve endings, smooth muscles, and glandular cells. However, H 1 -antagonism may not be their sole mechanism of action. Antihistamines have been used in two forms; oral and topical, in the management of allergic rhinitis. The use of the first-generation oral antihistamines (chlorpheniramine, diphenhydramine, promethazine, tripolidine, clemastine, and tripelennamine) is considerably limited by their sedative and anticholinergic effects. The secondgeneration antihistamines (acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, loratadine, mizolastine, and terfenadine) are effective in reducing nasal symptoms, and have no sedative effects. However, terfenadine, astemizole and recently, loratadine, have been found to cause prolongation of the QT interval on electrocardiogram, and can increase the risk for development of potentially lethal ventricular tachyarrhythmias, or torsades de pointes. The next-generation antihistamines (fexofenadine, desloratadine, tecastemizole, and levocetirizine) are typically the structurally modified, active metabolites or isomers of second-generation antihistamines. These agents retain the non-sedating properties of second-generation antihistamines while eliminating or limiting the cardiac risks. Topical antihistamines (azelastine and levocabastine), delivered by nasal spray, avoid or minimize systemic adverse effects. They have a rapid onset of action (less than 15 min) at low drug dosage, but their action is limited to the treated organ.

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“…Despite the high efficacy of the first-generation antihistamines in providing symptomatic relief of allergic rhinitis, urticaria and other disorders, a major limitation of these drugs was that they penetrated the blood-brain barrier readily and caused marked central nervous system side-effects, such as sedation and impaired psychomotor activity, even at therapeutic doses [14]. Despite the high efficacy of the first-generation antihistamines in providing symptomatic relief of allergic rhinitis, urticaria and other disorders, a major limitation of these drugs was that they penetrated the blood-brain barrier readily and caused marked central nervous system side-effects, such as sedation and impaired psychomotor activity, even at therapeutic doses [14].…”

Section: First Generation Antihistaminesmentioning

confidence: 99%

“…The cytochrome P450 system is also responsible for the metabolism of other drugs that compete for the active site of the enzyme. However, some members of this class of drugs, particularly astemizole and terfenadine, have been shown to be associated with serious cardiac side-effects such as altered cardiac repolarization, leading to prolongation of the QT interval on electrocardiogram which reflects delayed myocardial repolarization and serious ventricular arrhythmia (e.g., torsade de pointes) [11,14]. Also grapefruit juice may have similar effects.…”

Section: Second Generation Antihistaminesmentioning

confidence: 99%

“…The concomitant administration of azolic antifungal agents, such as ketoconazole, or macrolide antibiotics, such as erythromycin, may induce elevated concentrations of unmetabolized parent drugs. Furthermore, studies of astemizole have suggested that not only the parent compound, but also its active metabolite desmethylastemizole is associated with serious cardiac side-effects [11,14]. These interactions have been particularly shown with terfenadine, astemizole and recently loratadine [11].…”

Section: Second Generation Antihistaminesmentioning

confidence: 99%

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Use of Antihistamines in Allergic Rhinitis

Pata

2008

AIAAMC

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Allergic rhinitis is a common immun-mediated inflammatory condition of the nasal mucosa. AR occurs because of the cross linking of IgE by allergens within the upper respiratory tract. Allergy is now understood to be a systemic inflammatory disease. The symptoms caused by this allergic inflammation include sneezing, rhinorrhea, nasal pruritus, and nasal congestion; allergic conjunctivitis often accompanies AR. The interaction of histamine with the histamine H1 receptor, mediates a diversity of classical pathophysiological effects, including nasal blockage, sneezing, itching and rinorrhoea in allergic disease. Antihistamines are very important to the management of allergic disease. They can be classified in three groups. First Generation antihistamines: Promethazine, ketotifen, hydroxyzine, chlorpheniramine, deschlorpheniramine, tripelennamine, oxatomide, cyproheptadine, diphenhydramine. The use of the first-generation antihistamines is considerably limited by their sedative and anticholinergic effects.Second Generation antihistamines: Cetirizine, Loratadine, Mizolastine, ebastine, terfenadine, astemizole, acrivastine, azelastine. The second-generation antihistamines have significantly fewer undesirable CNS and anticholinergic effects than first-generation. New Generation antihistamines: Fexofenadine, levocetirizine, desloratadine, rupatadine. Because of reported cardiac toxicity related to terfenadine and astemizole, new generation antihistamines have been developed. Second and new generation antihistamines are a highly efficacious, fast-acting, and safe therapy for AR in the light of the results of the controlled clinical trials.

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The potential of active metabolites of antihistamines in the management of allergic disease

Cited by 16 publications

References 83 publications

Management of flu-like syndrome with cetirizine in patients with relapsing-remitting multiple sclerosis during therapy with interferon beta: Results of a randomized, cross-over, placebo-controlled pilot study

Management of flu-like syndrome with cetirizine in patients with relapsing-remitting multiple sclerosis during therapy with interferon beta: Results of a randomized, cross-over, placebo-controlled pilot study

The Role of Antihistamines in the Management of Allergic Rhinitis

Use of Antihistamines in Allergic Rhinitis

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