Adverse Reactions to Fluoroquinolones. An Overview on Mechanistic Aspects

Abstract

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 occur, 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 undesirable 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 gamma-aminobutyric acid (GABA) and excitatory amino acid (EAA) neurotransmission and the kinetics of quinolones distribution in brain tissue are discussed. In addition, quinolones may interact with other drugs--theophylline and nonsteroidal antiflammatory 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.

Monitoring, evaluation and comparison of adverse effect profile of ciprofloxacin and ofloxacin in acute bacterial exacerbation of chronic bronchitis patients attending pulmonology department of tertiary care teaching hospital: a prospective observational study

“…5 However, few studies had reported more gastrointestinal than neurological ADRs. 6 Our findings are contrasting to postmarketing surveillance of ciprofloxacin alone, as well as those of ciprofloxacin, norfloxacin, and ofloxacin showed a preponderance of ADR reporting to skin and appendages, followed by neurological and gastrointestinal disorders.…”

Ciprofloxacin enhances the stimulation of matrix metalloproteinase 3 expression by interleukin‐1β in human tendon‐derived cells

“…The reported side effects associated with the use of these antibiotics include tendon pain and/or rupture in a small proportion of patients, principally affecting the Achilles tendons (1). Although other adverse reactions, which have been observed in the central nervous system and gastrointestinal tract, may involve antagonism of amino acid neurotransmitter receptors (2), the cellular interactions underlying the effects of fluoroquinolones on the tendons are not clear. Inflammation of the paratenon and degenerative changes in tendon cells have been noted in studies of fluoroquinolone-treated animals (3,4).…”

A comparative experimental study of proconvulsive potential of ciprofloxacin and ofloxacin and assessment of proconvulsive potentiating action of caffeine coadministration with fluoroquinolones in rats

“…Proconvulsant activity of ciprofloxacin and ofloxacin is due to inhibition of GABA-A channels and lowering of seizure threshold as reported by De Sarro and De Sarro 2001. [4] Caffeine acts by blocking adenosine receptor in the brain. [22] Potentiation of proconvulsive action of fluoroquinolone is seen on addition of caffeine.…”

“…Adverse effects on central nervous system (CNS) also need to be explored as some CNS effects have been observed in some animal and clinical studies. [2][3][4][5] A headache and dizziness are common symptoms in humans. Hallucinations, delirium, and seizures have been observed in 0.9-11% of patients.…”