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Rapid Responses: Rapid Responses published:
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Diabetes insipidus induced by ofloxacin: search for the osmoles
- J F M Wetzels (7 September 2001)
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Ofloxacin and diabetes insipidus:mechanism known
- Andreas Schuld (9 September 2001)
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Diabetes insipidus induced by ofloxacin: water deprivation test
- Ajoy Sodani (9 September 2001)
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Re: Diabetes insipidus induced by ofloxacin: water deprivation test
- Rainer Kumm (22 October 2001)
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Inspidus or Insipidus
- Michael S Molloy, Zane Sherif (14 December 2003)
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Re: Inspidus or Insipidus
- Ed Cooper (14 December 2003)
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J F M Wetzels, Nephrologist Dept Nephrology University Medical Centre Nijmegen The Netherlands
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I have read with interest the case reported by drs Bharani and Kumar (BMJ 2001;323:547). The authors claim that their patient experienced diabetes insipidus and suggest that this was caused by the antibiotic ofloxacin. Interpretation of this case is difficult due to lack of hard data. I am especially puzzled by the urine osmolality (264 mOsmol/kg), which largely exceeds the values that are expected in patients with proven diabetes insipidus (urine osmolality < 100 mOsmol/kg). Either there has been made a typographical error, alternatively the polyuria was the result of a solute diuresis. Considering the total urine volume and urine osmolality the daily output exceeds 5000 osmoles! The question then must be resolved where did the osmoles come from? Other pertinent data could have helped in better defining the presumed disorder in water metabolism in this patient, e.g. changes in serum sodium level, in body weight, and a proper analysis of changes that occurred on rechallenge with the drug. |
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Andreas Schuld, Head, Parents of Fluoride Poisoned Children (PFPC) Vancouver, British Columbia, Canada
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LETTER TO THE EDITOR: In the September 8 issue of the BMJ Bharani and Kumar reported a case of diabetes insipidus induced by ofloxacin (1), stating that the mechanism of this interaction is not clear. Ofloxacin is a fluoroquinolone. Fluoroquinolones undergo de- fluorination in the human organism producing free fluoride, among other metabolites. Fluoride administration is known to cause polyuric "renal failure" resembling nephrogenic diabetes insipidus (2). The international literature reports on this numerous times, on occasion dubbing such conditions "fluorine diabetes" (3,4). Fluoride relase from anesthetic agents such as methoxyflurane have also shown to induce diabetes insipidus-like syndrome (2,5). In addition, the patient here had been given gentamicin prior to ofloxacin. That gentamicin combines with fluoride in inducing nephrotoxicity has been known since the 1970s (6,7). These effects are now established to be due to activation of heterotrimeric G proteins (8,9). Fluoride is firmly established to be the "universal" G protein activator. Current knowledge in biochemistry suggests that the activity observed by fluorides in inducing diabetes insipidus is related to activation of G/q11, involved in the mediation of vasopressin receptors (10,11,12). Regards, Andreas Schuld
1) Bharani A, Kumar H - "Drug points: Diabetes inspidus induced by ofloxacin" BMJ 323:547 (2001) 2) Rush GF, Willis LR - "Renal tubular effects of sodium fluoride" J Pharmacol Exp Ther 223(2):275-9 (1982) 3) Szymanska H, Mandat A, Bursiewicz H, Golebiowska I - "Glucose metabolism disorders in subjects exposed to fluorine compounds" Pol Arch Med Wewn 60(3):257-68 (1978) 4) Szymanska H, Gorzkowski E, Nieczajew A, Kedzierska D - "Disorders of carbohydrate metabolism during chronic exposure to fluorides--the fluorine diabetes" Pol Arch Med Wewn 51(1):57-65 (1974) 5) Bosch T - "Nephrotoxicity and fluoride from the viewpoint of the nephrologist" Anaesthesist 45 Suppl 1:S41-5 (1996) 6) Mazze RI, Cousins MJ - "Combined nephrotoxicity of gentamicin and methoxyflurane anaesthesia in man. A case report" Br J Anaesth 45(4):394-8 (1973) 7) Barr GA, Mazze RI, Cousins MJ, Kosek JC - "An animal model for combined methoxyflurane and gentamicin nephrotoxicity" Br J Anaesth 45(4):306-12 (1973) 8) Lee J, Yoo KS, Kang DG, Kim SW, Choi KC - "Gentamicin decreases the abundance of aquaporin water channels in rat kidney" Jpn J Pharmacol 85(4):391-8 (2001) 9) Decorti G, Malusa N, Furlan G, Candussio L, Klugmann FB - "Endocytosis of gentamicin in a proximal tubular renal cell line" Life Sci 65(11):1115-24 (1999) 10) Schoneberg T, Kostenis E, Liu J, Gudermann T, Wess J - "Molecular aspects of vasopressin receptor function" Adv Exp Med Biol 449:347-58 (1998) 11) Lynch CJ, Blackmore PF, Johnson EH, Wange RL, Krone PK, Exton JH - "Guanine nucleotide binding regulatory proteins and adenylate cyclase in livers of streptozotocin- and BB/Wor-diabetic rats.Immunodetection of Gs and Gi with antisera prepared against synthetic peptides" J Clin Invest 83(6):2050-62 (1989) 12) Hattori Y, Matsuda N, Sato A, Watanuki S, Tomioka H, Kawasaki H, Kanno M - "Predominant contribution of the G protein-mediated mechanism to NaF-induced vascular contractions in diabetic rats: association with an increased level of G(qalpha) expression" Pharmacol Exp Ther 292(2):761-8 (2000) |
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Ajoy Sodani, Consultant Neurophysician Indore
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I read the article by drs bharani and kumar with great interest. The response from dr Wetzels raises a pitfall in the diagnosis of diabetes insipidus(DI). One of diagnostic test for is water deprivation test and its response to anti diuretic hormone.The patient was on multiple drugs and undescribed drug interactions can not be ruled out. |
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Rainer Kumm, Locum Physician
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Sir, I wonder wether a complete review of the reported adverse events of Ofloxacine/Tarivid might be of interest to the readers of this journal and the general public. As a medical student I investigated the case of a patient who died of Thrombocytopenic Purpura secondary to an immunevasculitis (Moschkowitz). The patient received Ofloxacin for UTI several weeks before. Cases in which renal bleeds occured due to Ofloxacine (confirmed by re-exposure) have been reported. Prof. Schoenhoefer and Dr. Moebius, editors of the drug alert newsletter "Arzneitelegramm", Berlin ( http://www.arznei-telegramm.de ) wrote repeatedly about this (navigate to "Suche" (search) and type "Ofloxacin" , *floxacin). Pseudotumor cerebri and other neurologic complications are well documented as a class effect in Fluochinolones. Bearing in mind that Fluochinolones are being marketed as first line antibiotics in community aquired pneumonia and other infections I see a potential danger especially for elderly patients. They may be valuable antibiotics of second and third choice. |
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Michael S Molloy, Research St Vincents University Hospital, Zane Sherif
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Editor A slip of a digit and typing “Diabetes Inspidus” while doing an internet search resulted in GOOGLE recognising my mistake and offering me the correct spelling “Diabetes Insipidus”. However at first glance I was amazed at how many websites had been found using this search term. Three hundred and twenty three (323) sites were found with this misspelling. On examining a number I discovered the article responded to as published in the BMJ. Websites are not subject to the same peer review as medical journals and an error such as this should have been picked up at an earlier stage. Patients searching for information on the web may not have the same vocabulary as clinicians and may end up with poor results arising out of this[1]. Analysis of medical students usage of the web found that one of the commonest reasons for poor results while searching was misspelling[2]. Physicians themselves can also be the culprit in this regard and an Australian paper outlined some of the commoner errors made by physicians while referencing[3]. In publishing a peer reviewed paper one would hope that errors of whatever kind should be picked up at an early stage prior to publication to prevent embarrassment for all concerned. 1. Zeng, Q., et al., Patient and clinician vocabulary: how different are they? Medinfo, 2001. 10(Pt 1): p. 399-403. 2. Mitchell, J.A., et al., Medical students using Grateful Med: analysis of failed searches and a six-month follow-up study. Comput Biomed Res, 1992. 25(1): p. 43-55. 3. Mc, D.T.D., The appropriate use of references in a scientific research paper. Emerg Med (Fremantle), 2002. 14(2): p. 166-70. Competing interests: None declared |
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Ed Cooper, Locum Cons. Community Pediatrician Gt Ormond St, London WC1
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Molloy and Sherif's third reference in their letter admonishing us all to be careful with our accuracy is "Mc, D.T.D., The appropriate use of references in a scientific research paper. Emerg Med (Fremantle), 2002. 14(2): p. 166-70." The author is not Mc, D. T. D. but Taylor, D. McD. Pot, kettle, spot the deliberate mistake? So the lesson is perhaps about tolerance, understanding, making allowances as we struggle to communicate, in short supply in the BMJ rapid responses today. Isn't Google brilliant in picking up the inspidus? What a wonderful machine. Competing interests: None declared |
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