Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chemistry, antimicrobial spectrum, mechanism of action, pharmacology and pharmacokinetics, clinical use, adverse effects, dosage and administration, place in therapy, cost-effectiveness, and formulary considerations of imipenem-cilastatin sodium are reviewed. Imipenem is the first carbapenem antibiotic of the thienamycin class to be used clinically. Imipenem has the widest spectrum of antimicrobial activity of currently available beta-lactam agents and, in contrast to other beta-lactam antibiotics, lacks cross resistance with recently introduced extended-spectrum penicillins and third-generation cephalosporins. Against gram-positive and gram-negative aerobic and anaerobic organisms, imipenem demonstrates excellent activity. Pseudomonas maltophilia, some strains of Pseudomonas cepacia, and Streptococcus faecium are resistant. Strains of methicillin-resistant staphylococci should also be considered resistant to imipenem. For clinical use imipenem is coadministered in equal parts with cilastatin. Cilastatin is a renal dehydropeptidase inhibitor that inhibits the metabolism of imipenem by renal brush-border enzymes, thus increasing imipenem concentrations in urine. Imipenem-cilastatin is administered by the intravenous route only. The adverse reaction profile of imipenem-cilastatin is similar to t that of other beta-lactam antibiotics. Recommended dosage reductions appropriate for renal impairment should be guided by periodic assessments of renal function, with close adherence to recommended dosage schedules, particularly among patients who are predisposed to seizures or receiving anticonvulsant medication. Imipenem-cilastatin performed well in both comparative and noncomparative trials of clinical efficacy and safety. For infections with multiple organisms (e.g., pelvic, intra-abdominal, or soft-tissue infections), imipenem-cilastatin may be a cost-effective and less toxic single-agent alternative to "standard" combination (e.g., aminoglycoside-penicillin plus an antianaerobic agent) therapy. However, in patients with serious pseudomonal infections (e.g., pneumonia), isolates may rapidly acquire resistance to imipenem or be replaced by resistant strains of Ps. aeruginosa when imipenem is used alone. Therefore, when the recovery of Ps. aeruginosa is anticipated or documented, treatment with imipenem-cilastatin should include an aminoglycoside to reduce the likelihood of the emergency of resistant organisms during therapy.
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PMID:Imipenem-cilastatin sodium, a broad-spectrum carbapenem antibiotic combination. 353 Jun 14

The behavioural and convulsant effects of imipenem and meropenem were studied after intraperitoneal administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizure, and in C57 mice, a strain not prone to seizure. DBA/2 mice were more susceptible than C57 mice to seizures induced by imipenem-cilastatin or meropenem. Imipenem was also 1.9 times more potent than meropenem in inducing clonus in DBA/2 mice. To investigate the possibility that the seizure-inducing activity of imipenem might be due to a probenecid-like effect of cilastatin, animals were treated with imipenem alone. No significant differences were observed between imipenem-cilastatin and imipenem-treated animals. Thus, it is reasonable to exclude a probenecid-like effect of cilastatin. Although the main mechanism for seizure-like activity of imipenem cannot be easily determined, we believe that several mechanisms may be involved. An increased excitation of the central nervous system (CNS) by inhibition of GABA binding to receptors and a slow clearance of imipenem from the CNS may be postulated. Cilastatin did not induce seizures. In addition, meropenem, a compound structurally related to imipenem, showed weak or no convulsant effects.
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PMID:Comparative convulsant potencies of two carbapenem derivatives in C57 and DBA/2 mice. 779 Oct 26