New antihistamines: a critical view.
OBJECTIVE
To perform a critical evaluation of the more recent H1 antihistamines and the various terms used to describe them, based on a review of evidence on their role in the treatment of allergic disorders.


METHODS
Original articles, reviews and consensus documents published from 1998 to 2006 and indexed in the MEDLINE and PubMed databases. Keyword: antihistamines.


RESULTS
Second-generation antihistamines differ from first-generation ones because of their elevated specificity and affinity for peripheral H1 receptors and because of their lower penetration of the central nervous system (CNS), having fewer sedative effects as a result. Whilst second-generation antihistamines are in general better tolerated than their predecessors, some adverse effects, principally cardiotoxicity, have been observed with some of them. Over the last 20 years, new compounds with different pharmacokinetic properties have been synthesized. The majority of these exhibit anti-inflammatory properties that are independent of their action on the H1 receptor. More recent improvements, generally in the form of active metabolites, led to the use of the term third-generation antihistamines. This term emerged spontaneously, with no clear definition of its meaning or clinical implications, creating great confusion among healthcare professionals.


CONCLUSIONS
On the basis of the evidence on H1 antihistamines, none of them deserve the title "third-generation antihistamine." As the Consensus Group on New Generation Antihistamines concluded, to merit this definition, a new class of antihistamines would have to demonstrate distinct clinical advantages over existing compounds and fulfill at least three prerequisites: they should be free from cardiotoxicity, drug interactions and effects on the CNS.
Camelo-Nunes
Inês Cristina
IC
Departamento de Pediatria, Universidade Federal de São Paulo - Escola Paulista de Medicina (UNIFESP-EPM), São Paulo, SP, Brazil. iccamelo@uol.com.br
D018926:Anti-Allergic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000139:chemically induced; D017332:Cetirizine / Q000009:adverse effects / Q000494:pharmacology*; D002648:Child; D003533:Cyproheptadine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D006331:Heart Diseases / Q000139:chemically induced; D039563:Histamine H1 Antagonists, Non-Sedating / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy; D017336:Loratadine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000009:adverse effects / Q000494:pharmacology*; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000378:metabolism; D016593:Terfenadine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology
D018926:Anti-Allergic Agents; D039563:Histamine H1 Antagonists, Non-Sedating; D010879:Piperazines; D011969:Receptors, Histamine H1; C103639:rupatadine; D003533:Cyproheptadine; C472067:levocetirizine; D017336:Loratadine; D016593:Terfenadine; C093230:fexofenadine; C121345:desloratadine; D017332:Cetirizine