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      Indian Journal of Pharmacology
      Medknow Publications & Media Pvt Ltd

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          Abstract

          Sir, We thank the authors for their valuable comments in the case reported by us.[1] The patient had developed hypersensitivity reaction (itching and burning sensation all over the body relieved by tablet cetirizine) 6 hrs after the 1st dose of metronidazole. He experienced similar itching and burning sensation, followed by dizziness, confusion, convulsion, and transient loss of consciousness for a period of 15-20 min, 2 hours after the second dose of metronidazole. Subsequently, he suffered from shivering and palpitations and had developed pain in both feet during walking, redness of face and neck, itching and erosion over the scrotal skin, and later had developed other suggestive manifestations of Stevens Johnson syndrome (SJS). The adverse effects of central nervous system like aseptic meningitis, convulsion, cerebellar toxicity, mental illness are known to appear after large doses or long duration of treatment with metronidazole.[2] The median duration following metronidazole use in patients who developed encephalopathy is reported to be 54 days although 26% patients had taken it less than a week and 11% had taken it for less than 72 hours.[3] Two patients reported with encephalopathy with a total dose of metronidazole 41.25 g in patient-1 and 24 g in patient-2.[4] Our patient had a rapid development of cutaneous hypersensitivity reaction about 6 hours after first dose of metronidazole which was relieved by antihistamine. Two hours after the second dose, the itching and burning sensation reappeared all over the body, followed by nervous system manifestations. Later he had developed SJS. Amount of drug in first and second dose was 400 mg each. Neither dose was high, nor was the metronidazole used for prolonged duration. Sequential rapid development of cutaneous reaction, neurological symptoms, and SJS with usual therapeutic dose (400 mg, only two doses taken by the patient) was suggestive of a common pathophysiological sequence (immunological) for all symptoms. It is difficult to explain hypersensitivity and neurotoxicity occurring in this patient as separate adverse events. In our opinion, neither the time relation nor the dose or duration of treatment support this possibility.

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          Metronidazole-induced central nervous system toxicity: a systematic review.

          To assess patient and medication factors that contribute to metronidazole toxicity. We searched PUBMED from 1965 through April 7, 2011, and performed a hand search of bibliographies. Case reports or case series reporting metronidazole-induced central nervous toxicity. Two authors independently abstracted demographics, metronidazole indication, dose and duration, neurological manifestations, and outcomes as well as brain imaging findings. Among 64 patients, 48 (77%) had cerebellar dysfunction, 21 (33%) had altered mental status, and 8 (15%) had seizures. Patients' ages averaged 53.3 years (range, 12-87 years), and 64% were male. The median duration of metronidazole was 54 days, although 26% had taken it less than a week and 11% had taken it less than 72 hours. Among cases with outcome data, most patients either improved (n = 18 [29%]) or had complete resolution of their symptoms with discontinuation of metronidazole (n = 41 [65%]). There was no difference in resolution of symptom by age (P = 0.71) or sex (P = 0.34). The patients with cerebellar dysfunction were less likely to experience complete resolution than those with mental status changes or seizures (relative risk, 0.67; 95% confidence interval (CI), 0.49-0.92). Nearly all patients (n = 55 [86%]) underwent imaging of the brain: 44 (69%) underwent magnetic resonance imaging (MRI) and 12 (19%) underwent computed tomographic studies. All patients with cerebellar dysfunction had abnormalities on imaging: 93% (n = 39) had a cerebellar lesion, although numerous areas in the brain were affected. On follow-up MRIs, 25 patients (83%) had complete resolution of abnormalities. Metronidazole can rarely cause central nervous system toxicity; it does not seem to be a dose- or duration-related phenomenon. Most patients will have MRI abnormalities. Prognosis is excellent with metronidazole cessation.
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            Reversible magnetic resonance imaging findings in metronidazole-induced encephalopathy.

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              Stevens-Johnson syndrome following use of metronidazole in a dental patient

              Metronidazole alone rarely causes Stevens-Johnson syndrome (SJS). We present a case of an elderly male patient who, following metronidazole use, developed neurological symptoms followed by pain and blisters on both soles, erythema of face and neck, scrotal itching and erosion, and hemorrhagic encrustation around the lips and oral mucous membrane. Initial neurological symptoms followed by mucocutaneous manifestation of SJS following metronidazole use is probably a new presentation of this case.
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                Author and article information

                Journal
                Indian J Pharmacol
                Indian J Pharmacol
                IJPharm
                Indian Journal of Pharmacology
                Medknow Publications & Media Pvt Ltd (India )
                0253-7613
                1998-3751
                Sep-Oct 2014
                : 46
                : 5
                : 565-566
                Affiliations
                [1]Department of Pharmacology, Burdwan Medical College, Burdwan, West Bengal, India. E-mail: goutameswar09@ 123456gmail.com
                Article
                IJPharm-46-565b
                10.4103/0253-7613.140603
                4175904
                92bea7ee-9641-4d67-b73d-c594d125e99c
                Copyright: © Indian Journal of Pharmacology

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Pharmacology & Pharmaceutical medicine
                Pharmacology & Pharmaceutical medicine

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