CARBAPENEM INDUCED NEURO TOXICITY A REVIEW Sneha M C 1*,Paul Sunny1,Ms.Sujisha Surendran2, Dr.R.Venkatanarayanan3 1 Pharm D IVth year, RVS College Of Pharmaceutical Sciences, Coimbatore 2Lecturer, RVS College Of Pharmaceutical Sciences, Coimbatore 3 Principal, RVS College Of Pharmaceutical Sciences, Coimbatore.

AbstractSimilar to other beta-lactam antibacterials, carbapenems have a neurotoxic potential that seems to be higher than that of the penicillins and cephalosporins. Seizures have been reported in several large studies of patients treated with imipenem/cilastatin. However, it seems clear that the main factor increasing the risk of neurotoxicity with imipenem/cilastatin is administration of excessive dosages relative to bodyweight and/or renal function. If the manufacturer's dosage recommendations are followed, the risk of seizures in patients receiving this combination is minimal. With meropenem, a newly registered carbapenem, the safety margin with respect to neurotoxic reactions has been increased compared with imipenem and meropenem can be used at higher doses than imipenem/cilastatin. Since the neurotoxicity of beta-lactam antibacterials seems to be caused by an interaction with gamma-aminobutyric acid (GABA) receptors, other drugs with a similar mechanism of action, such as fluoroquinolone antibacterials, should be used with caution when combined with carbapenemsThe neurotoxic potencies are considerably different among various beta-lactam antibiotics. Some carbapenem antibiotics, a new class beta-lactam antibiotic, also induce convulsion in human and laboratory animals. As for the neurotoxicity of carbapenem antibiotics, the presence of amino group in the C-2 side chain is an important factor in inducing convulsion and the strength of basicity of the amino group is correlated with the convulsant activity. The beta-lactam ring of carbapenem is not necessary to evoke convulsions. The neurotoxicity of carbapenem antibiotics is related to only a part of the structure, including the C-2 side chain, but not to the carbapenem skeleton itself. In comparison with other beta-lactam antibiotics, it has been found that the structure responsible for the convulsive action of carbapenems is significantly different from penicillins and cephalosporins in which the beta-lactam ring is essential to evoke convulsion. The induction of convulsions by carbapenem antibiotics is predominantly caused through the inhibition of gamma aminobutyric acid receptor in a similar manner as with penicillins and cephalosporins. However, the detail mechanism may be different not only among carbapenems, cephalosporins, and penicillins but among carbapenem compounds themselves. It is important to know the neurotoxic potential of a compound by investigating the effect of direct administration into the central nervous system such as intraventricular administration, since the penetration through blood-brain barrier or the pharmacokinetic property is varied in seriously ill patients. Possible drug interactions regarding neurotoxicity are also discussed. We hope these findings described here will be helpful in developing more efficient and safer beta-lactam antibiotics of a new generation.It seems clear that the high degree of neurotoxity of imipenemcilastatin and ritipenem is not a class phenomenon for carbapenems and penems but that, as discussed here, there are carbapenems that have a lower degree of neurotoxicity and therefore can be given at high doses and are useful in the treatment of infections in the central nervous system (CNS). The time to onset of epileptogenic activity ranges from 12 hours to 9 days after -lactam antibiotic therapy is initiated.11-13 Treatment of penicillin- and carbapenem-induced seizures remains controversial.9 Cessation of seizure activity has been reported 12 to 72 hours after therapy is discontinued.11-13Clinical and experimental data suggest that benzodiazepines and barbiturates may be more efficacious than other anticonvulsants such as phenytoin.2,3 Benzodiazepines and barbiturates are positive modulators of GABAa receptors. Their efficacy is based on the hypothetical mechanism by which -lactams induce seizures.2