Table 3.
Summary of the mechanisms of neurotoxicity of particular classes of antibiotics.
| Class of Antibiotic | Mechanisms of Neurotoxicity |
|---|---|
| penicillin | GABA complex receptor inhibition via competitive or non-competitive affecting the GABAA subunits; an increase of the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazolepropionate receptors stimulation resulting in the overactivity of glutamatergic system |
| cephalosporins | |
| glycopeptides | direct damage of the auditory branch of the eighth cranial nerve; an increase of the oxidative stress leading to loss of sensory cochlear cells |
| macrolides | drug interactions (metabolism through isoenzyme CYP3A4); direct neurotoxic effect produced by the lipid-soluble active metabolites; alterations of cortisol and prostaglandin metabolism; interactions with glutaminergic and GABA pathways |
| aminoglycosides | Ototoxicity-determined by the overactivation of NMDA receptors within the cochlea with subsequent oxygen radicals formulation; neuromuscular blockade-due to the presynaptic inhibition of quantal release of acetylcholine in the neuromuscular junction and a postjunctional blockade of the acetylcholine receptor complex |
| oxazolidinones | mitochondrial injury; nonselective inhibition of monoamine oxidase leading to increased serotonin and catecholamines levels |
| polymyxins | neuromuscular blockade-due to the presynaptic decrease of acetylcholine release into the synaptic gap; induction of prolonged depolarization following the transient postsynaptic blockade, with loss of calcium from neurons and altered mitochondrial permeability; accumulation of reactive oxygen species |
| quinolones | inhibition of GABAA receptor; stimulation of NMDA receptor and ligand-gated glutamate receptors; an increase of the oxidative stress |
| sulfonamides /trimethoprim |
deficiency in the tetrahydrobiopterin synthesis resulting in disturbances in synthesis of central neurotransmitters |
| metronidazole | an increase of oxidative stress; oxidation of catecholamines and other neurotransmitters; inhibition of GABA-ergic neurotransmission |
| other anti-infective agents: nitrofurantoin, isoniazid, ethambutol |
loss of axons; decrease of GABA synthesis, NMDA receptors activation |