Sensitization to Fluoroquinolones [8]
Fluoroquinolones are very powerful antibiotics which can be dangerous to users or previous users of benzodiazepines or Z-drugs. Throughout this discussion, any reference to benzodiazepines includes both benzodiazepines and nonbenzodiazepines.
GABA is an inhibitory neurotransmitter, and drugs which enhance its action, like benzodiazepines, cause a reduction in neural excitation and neural activity. Like benzodiazepines, fluoroquinolones bind to GABA receptors. But when a fluoroquinolone binds to a GABA receptor, the result is the polar opposite of the effect of CNS depressants like benzodiazepines. While benzodiazepines and Z-drugs enhance the function of the GABA-A receptors, fluoroquinolones are antagonists of the GABA-A receptor. They prevent the binding of GABA and can displace other molecules bound to the receptor, such as benzodiazepines.[9] The GABA receptor blockade caused by a fluoroquinolone results in a CNS stimulant effect, with neurological manifestations ranging from mild insomnia and agitation to hallucinations and seizures.[10] Anyone can suffer these side effects, but individuals prescribed benzodiazepines are notably much more prone to experiencing these adverse neuropsychiatric reactions.
Why do benzodiazepine or Z-drug users have worse reactions to fluoroquinolones than non-users? The root of the problem is the GABA receptor down-regulation imposed by benzodiazepine tolerance. When a benzodiazepine is given chronically (beyond 10 days) there are a series of downward compensatory mechanisms which seek to restore a neurological equilibrium in light of the overstimulation of GABA receptors by the drug. This results in GABA receptors becoming progressively less receptive to GABA over time following prolonged exposure to benzodiazepines.[11] Over time, the brain’s GABA-dependent systems are weakened and there is a heightened vulnerability to external influences which decrease the action of GABA, such as the GABA-A antagonist action of fluoroquinolones.
