Adverse Reactions to Fluoroquinolones. An Overview on Mechanistic Aspects
Angela De Sarro and Giovambattista De Sarro
Affiliation: Istituto di Farmacologia, Facolta di Medicina e Chirurgia, Torre Biologica, Policlinico Universitario, Via Consolare Valeria, 98125 Messina, ITALIA.
This review focuses on the most recent research findings on adverse reactions caused by quinolone antibiotics. Reactions of the gastrointestinal tract, the central nervous system (CNS) and the skin are the most often observed adverse effects. Occasionally major events such as phototoxicity, cardiotoxicity, arthropathy and tendinitis occurr, leading to significant tolerability problems. Over the years, several structure-activity and side-effect relationships have been developed, in an effort to improve overall antimicrobial efficacy while reducing undesiderable side-effects. In this article we review the toxicity of fluoroquinolones, including the newer derivatives such levofloxacin, sparfloxacin, graepafloxacin and the 7-azabicyclo derivatives, trovafloxacin and moxifloxacin. A special attention is given to new data on mechanistic aspects, particularly those regarding CNS effects. In recent years extensive in vivo and in vitro experiments have been performed in an attempt to explain the neurotoxic effects of quinolones sometimes observed under therapeutic conditions. However, the molecular target or receptor for such effects is still not exactly known. Several mechanisms are thought to be responsible. The involvement of g-aminobutyric acid (GABA) and excitatory aminoacid (EAA) neurotransmission and the kinetics of quinolones distribution in brain tissue are discussed. In addition, quinolones may interact with other drugs theophylline and nonsteroidal antinflammatory drugs (NSAID s )in producing CNS effects This article provides information about the different mechanisms responsible of quinolones interaction with NSAID s , methylxanthines, warfarin and antiacids.
Keywords: Adverse Reactions, Fluoroquinolones, aminomethylpyrrolidinyl agents, Mechanistic, haemolytic uraemic syndrome, CNS effect, glutamergic receptors, proconvulsant potency
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