Central Nervous System Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

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Cefepime-Induced Neurotoxicity

Author(s): Jose Augusto Bragatti.

Abstract:

Cefepime is a parenteral fourth-generation cephalosporin antibiotic with an extended spectrum of antimicrobial activity, active against many grampositive and gram-negative bacteria, including Enterobacteriaceae, Pseudomonas aeruginosa, and Staphylococcus aureus. It is excreted primarily unchanged in the urine, its half-life is 2 hours in normal renal function, increasing to 13.5 hours as renal function declines. Dosage adjustment for renal insufficiency has been recommended in order to prevent drug accumulation, which may result in adverse drug events. Nevertheless, cefepime can produce neurotoxic manifestations, like epileptic seizures, confusion, tremor, ataxia and agitation, probably mediated by the inhibition of gamma amino butyric acid (GABA) A-receptors. Cefepime neurotoxicity usually begins within 20 hours to 5 days ofdrug exposition. Clinical picture may resolve after withdrawal of the antibiotic, depending on the severity of signs and symptoms, and the time spent to start treatment. The role of electroencephalogram in the diagnosis of cefepime-induced encephalopathy and in the differential diagnosis with other causes of coma is remarkable. When a patient on cefepime develops progressive neurological symptoms, drug neurotoxicity should be considered, early detected and promptly managed. Future experimental studies focusing on the cefepime-GABAA receptors and transporters interactions should shed some light on the pathophysiology of this now well-known condition.

Keywords: Cefepime, Neurotoxicity, cephalosporin, antibiotic, antimicrobial activity, Pseudomonas aeruginosa, Staphylococcus aureus, epileptic seizures, gamma amino butyric acid (GABA) A-receptors, encephalopathy

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Article Details

VOLUME: 8
ISSUE: 4
Year: 2008
Page: [229 - 233]
Pages: 5
DOI: 10.2174/187152408786848139
Price: $58