Long-term combinations and updosing of second-generation H1-antihistamines show efficacy and safety in the treatment of chronic spontaneous urticaria: a multi-center real-life pilot study

Long-term combinations and updosing of second-generation H₁-antihistamines show efficacy and safety in the treatment of chronic spontaneous urticaria: a multi-center real-life pilot study:

Publication date: Available online 16 December 2019

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): Liming Zhang, Jian Wu, Yumeng Qi, Hong Zhu, Xu Yao, Mengmeng Li, Jingyi Li, Zaipei Guo, Xiangyang Su, Wei Lai, Siyu Hao, Yuzhen Li, Yang Li, Chunli Yao, Fuqiu Li, Huiping Wang, Quanzhong Liu, Hai Long, Qianjin Lu, Xinghua Gao

Second-generation

Second-generation H₁-antihistamines are newer drugs that are much more selective for peripheral H₁ receptors as opposed to the central nervous system H₁ receptors and cholinergic receptors. This selectivity significantly reduces the occurrence of adverse drug reactions, such as sedation, while still providing effective relief of allergic conditions. The reason for their peripheral selectivity is that most of these compounds are zwitterionic at physiological pH (around pH 7.4). As such, they are very polar, meaning that they are less likely to cross the blood–brain barrier and act mainly outside the central nervous system. However, some second-generation antihistamines, notably cetirizine, can interact with CNS psychoactive drugs such as bupropion and benzodiazepines.^[9]

Examples -

Systemic:

• Astemizole (Himanshu)
• Ketotifen (Zaditor)
• Cetirizine (Zyrtec)
• Loratadine (Claritin)
• Rupatadine (Rupafin)
• Mizolastine (Mizollen)
• Acrivastine (Benadryl Allergy Relief (UK), Semprex (US))
• Ebastine (Evastin, Kestine, Ebastel, Aleva, Ebatrol)
• Bilastine (Bilaxten)
• Bepotastine (Talion, Bepreve)
• Terfenadine (Seldane (US), Triludan (UK), and Teldane (Australia))
• Quifenadine (Phencarol, Фенкарол)

Topical:

• Azelastine
• Levocabastine (Livostin)
• Olopatadine (Pazeo)

Third-generation

Third-generation H₁-antihistamines are second-generation antihistamines informally labeled third-generation because the active enantiomer (levocetirizine) or metabolite (desloratadine and fexofenadine) derivatives of second-generation drugs are intended to have increased efficacy with fewer adverse drug reactions. Fexofenadine is associated with a lower risk of cardiac arrhythmia compared to terfenadine. However, there is little evidence for any advantage of levocetirizine or desloratadine, compared to cetirizine or loratadine, respectively.^{[citation needed]}

There is some controversy associated with the use of the term "third-generation antihistamines."^[10]

Examples -

Systemic:

• Levocetirizine^[11]
• Desloratadine^[12]
• Fexofenadine (Allegra)^[13]