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Comparative acute ototoxicity of loop diuretic compounds

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Summary

A microelectrode was used to measure endocochlear potentials (EP) in adult chinchillas and to study the effects of a series of loop diuretics. EP was measured before, during and for several hours after the intravenous injection of the following loop diuretics: furosemide, piretanide, bumetanide, ethacrynic acid, indacrinone stereoisomers and ozolinone. The first four loop diuretics caused a substantial dose-related reduction of EP. The (−) isomer of indacrinone was found to cause a dose-related reduction of EP to a moderate degree. The (+) isomer of indacrinone and ozolinone caused very little change of EP, even in very high doses. Findings are consistent with data on the mechanism of action of these agents in the kidney.

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References

  1. Anniko M, Sobin A (1987) Ethacrynic acid effects on the isolated inner ear: evaluation of the ototoxic potential in an organ culture system. An J Otolaryngol 8:48–62

    Google Scholar 

  2. Asakuma S, Snow JB Jr (1980) Effects of furosemide and ethacrynic acid on the endocochlear direct current potential in normal and kanamycin sulfate-treated guinea pigs. Otolaryngol Head Neck Surg 88:188–193

    Google Scholar 

  3. Bagger-Sjoback D, Filipek CS, Schacht J (1980) Characteristics and drug responses of cochlear and vestibular adenylate cyclase. Arch Otorhinolaryngol 228:217–222

    Google Scholar 

  4. Blaine EH, Fanelli GM Jr, Irvin JD, Tolbert JA, Davies RO (1982) Enantiomers of indacrinone: a new approach to producing an isouricemic diuretic. Clin Exp Hypertens [A] 4:161–176

    Google Scholar 

  5. Bosher SK (1980) The nature of the ototoxic effects of ethacrynic acid upon the mammalian endolymph system. I Functional aspects. Acta Otolaryngol (Stockh) 89:407–418

    Google Scholar 

  6. Bosher SK, Smith C, Warren RL (1973) The effects of ethacrynic acid upon the cochlear endolymph and stria vascularis. Acta Otolaryngol(Stockh) 75:184–191

    Google Scholar 

  7. Brooks BA, Lant AF, McNabb WR, Noormohamed FH (1984) Stereo-specificity of diuretic receptors in the nephron: a study of the enantiomers of indacrinone (MK-196) in man. Renal Physiol 7:304–310

    Google Scholar 

  8. Brummett R, Smith CA, Ueno Y, Cameron S, Richter R (1977) The delayed effects of ethacrynic acid on the stria vascularis of the guinea pig. Acta Otolaryngol (Stockh) 83:98–112

    Google Scholar 

  9. Chemtob S, Kaplan BS, Sherbotie JR, Aranda JV (1989) Pharmacology of diuretics in the newborn. Pediatr Clin North Am 36:1231–1250

    Google Scholar 

  10. Cooperman LB, Rubin IL (1973) Toxicity of ethacrynic acid and furosemide. Am Heart J 85:831–834

    Google Scholar 

  11. Comis SD, Osborne MP, Jeffries D Jr (1990) The effect of furosemide upon the morphology of hair bundles in the guinea pig cochlear hair cells. Acta Otolaryngol (Stockh) 109:49–56

    Google Scholar 

  12. Cragoe EJ Jr (ed) (1983) Diuretics: chemistry, pharmacology and medicine. Wiley, New York, pp 201–266

    Google Scholar 

  13. Field MJ, Fowler N, Giebisch GH (1984) Effects of enantiomers of indacrinone (MK-196) on cation transport by the loop of Henle and distal tubule studies by microperfusion in vivo. J Pharmacol Exp Ther 230:62–68

    Google Scholar 

  14. Forbush B, Palfrey HC (1983) [3H] bumetanide binding to membranes isolated from dog kidney outer medulla. J Biol Chem 258:11787–11792

    Google Scholar 

  15. Forge A, Brown AM (1982) Ultra-structural and electrophysiological studies of acute ototoxic effects of furosemide. Br J Audiol 16:109–116

    Google Scholar 

  16. Gallagher KL, Jones JK (1979) Furosemide-induced ototoxicity. Ann Intern Med 91:744–745

    Google Scholar 

  17. Garvin JL, Spring KR, Santi PA (1988) Secretion of endolymph by semicircular canals of the shark. Am J Physiol 255 F711-F719

    Google Scholar 

  18. Giesen-Crouse EM, Welsch C, Imbs JL, Schmidt M, Schwartz J (1985) Characterization of a high affinity piretanide receptor on kidney membranes. Eur J Pharmacol 114:23–31

    Google Scholar 

  19. Giesen-Crouse E, Fandeleur P, Welsch D, Englert M, Lang HJ, Schmidt M, Imbs JL (1988) Binding of loop diuretics to their renal receptors: use as an screening model for potential diuretic activity. Fundam Clin Pharmacol 2:145–147

    Google Scholar 

  20. Göttl KH, Roesch A, Klinke R (1985) Quantitative evaluation of ototoxic side effects of furosemide, piretanide, bumetanide, azosemide and ozolinone in the cat — a new approach to the problem of ototoxicity. Naunyn Schmiedeberg's Arch Pharmacol 331:275–282

    Google Scholar 

  21. Green TP, Mirkin BL (1982) Determinants of diuretic response to furosemide in infants with congestive heart failure. Pediatr Cardiol 3:47–51

    Google Scholar 

  22. Green TP, Johnson DE, Buss JL, Landrum BG, Ferrara TB, Thompson PR (1988) Prophylactic furosemide in severe respiratory distress syndrome: blinded prospective study. J Pediatr 112:605–612

    Google Scholar 

  23. Greger R (1985) Ion transport mechanisms in thick ascending limb of Henle's loop of mammalian nephron. Physiol Rev 65 760–797

    CAS  PubMed  Google Scholar 

  24. Greger R (1988) Chloride transport in thick ascending limb, distal convolution and collecting duct. Annu Rev Physiol 50: 111–122

    Google Scholar 

  25. Greger R, Wangemann P (1987) Loop diuretics. Renal Physiol 10:174–183

    Google Scholar 

  26. Greven J (1987) The pharmacological basis of the action of loop diuretics. In: Puschett JB, Greenberg A (eds) Diuretics II: chemistry, pharmacology and clinical applications. Elsevier, Amsterdam, pp 173–181

    Google Scholar 

  27. Haas M (1989) Properties and diversity of (Na-K-Cl) cotransporters. Annu Rev Physiol 51: 443–452

    Google Scholar 

  28. Heidland A, Wigand ME (1970) Einfluss hoher Furosemiddosen auf Gehörfunktion bei Urämie. Klin Wochenschr 48:1052–1056

    Google Scholar 

  29. Hirashima N (1978) Blocking effect of radio-contrast media on cochlear depression. Ann Otol Rhinol Laryngol 87:32–36

    Google Scholar 

  30. Hommerich CP (1990) Ototoxicity of loop diuretics, morphological and electrophysiological examinations in animal experiments. In: Pfaltz CR (ed) New aspects of cochlear mechanics and inner ear pathophysiology. Adv Otorhinolaryngol (Basel) 44:92–164

  31. Ikeda K, Morizono T (1989) Electrochemical profiles for monovalent ions in the stria vascularis: cellular model of ion transport mechanisms. Hear Res 39:279–286

    Google Scholar 

  32. Imbs JL, Schmidt M, Giesen-Crouse E (1987) Pharmacology of the loop diuretics: state of the art. Adv Nephrol 16: 137–158

    Google Scholar 

  33. Kemp DT (1979) Evidence of mechanical nonlinearity and frequency selective amplification in the cochlea. Arch Otorhinolaryngol 224:37–45

    Google Scholar 

  34. Kim KE, Onesti G, Moyer JH, Schwartz C (1971) Ethacrynic acid and furosemide. Diuretic and hemodynamic effects and clinical uses. Am J Cardiol 27:407–415

    Google Scholar 

  35. Kleinknecht D, Ganeval D, Gonzalez-Duque LA, Fermanian J (1976) Furosemide in acute oliguric renal failure — a controlled trial. Nephron 17:51–58

    Google Scholar 

  36. Komune A, Morimitsu T (1985) Dissociation of the cochlear microphonics and endocochlear potential after ethacrynic acid injection. Arch Otorhinolaryngol 241:149–156

    Google Scholar 

  37. Kusakari J, Ise I, Comegys TN, Thalmann I, Thalmann R (1978) Effect of ethacrynic acid, furosemide and ouabain upon the endolymphatic potential and upon high energy phosphates of the stria vascularis. Laryngoscope 88:12–37

    Google Scholar 

  38. Kusakari J, Kambayashi J, Ise I, Kawamoto K (1978) Reduction of the endocochlear potential by the new ‘loop’ diuretic, bumetanide. Acta Otolaryngol (Stockh) 86:336–341

    Google Scholar 

  39. Lukeman DS, Fanestil DO (1987) Interactions of diuretics with the peripheral-type benzodiazepine receptor in rat kidney. J Pharmacol Exp Ther 241:950–955

    Google Scholar 

  40. Marcus DC, Marcus NY, Greger R (1987) Sidedness of action of loop diuretics and ouabain on nonsensory cells of the utricle: a micro-Ussing chamber for inner ear tissues. Hear Res 30:55–64

    Google Scholar 

  41. Marks SC, Schacht J (1981) Effects of ototoxic diuretics on cochlear Na+ K+-ATPase and adenylate cyclase. Scand Audiol [Suppl] 14:131–137

    Google Scholar 

  42. Reference deleted

  43. Matz GJ (1976) The ototoxic effects of ethacrynic acid in man and animals. Laryngoscope 86:1065–1086

    Google Scholar 

  44. McCann EM, Lewis K, Deming DD, Donovan MJ, Brady JP (1985) Controlled trial of furosemide therapy in infants with chronic lung disease. J Pediatr 106:957–962

    Google Scholar 

  45. Morizono T, Rybak LP, Asp S (1980) Endocochlear potential and potassium concentration in endolymph and perilymph of the chinchilla. Arch Otorhinolaryngol 229:149–153

    Google Scholar 

  46. Mroczek WJ, Davidov M, Finnerty FA (1974) Large dose furosemide therapy for hypertension. Long term use in 22 patients. Am J Cardiol 33:546–549

    Google Scholar 

  47. Paloheimo S, Thalmann R (1977) Influence of “loop” diuretics upon Na+ and K+-ATPase and adenylate cyclase of the stria vascularis. Arch Otorhinolaryngol 217:347–359

    Google Scholar 

  48. Rugg EL, Simmon NL, Tivey DR (1986) An investigation of [3H]-bumetanide uptake in a cultured renal cell line (MDCK). Q J Exp Physiol 71:165–182

    Google Scholar 

  49. Rybak LP (1982) Pathophysiology of furosemide ototoxicity. J Otolaryngol 11:127–133

    Google Scholar 

  50. Rybak LP (1985) Furosemide ototoxicity: clinical and experimental aspects. Laryngoscope 95: [Suppl 38]:1–14

    Google Scholar 

  51. Rybak LP (1986) Drug ototoxicity. Annu Rev Pharmacol Toxicol 26:79–99

    Google Scholar 

  52. Rybak LP (1988) Ototoxicity of ethacrynic acid (a persistent clinical problem). J Laryngol Otol 102:518–520

    Google Scholar 

  53. Rybak LP, Whitworth C (1986) Comparative ototoxicity of furosemide and piretanide. Acta Otolaryngol (Stockh) 101: 59–65

    Google Scholar 

  54. Rybak LP, Whitworth C (1987) Some organic acids attenuate the effects of furosemide on the endocochlear potential. Hear Res 26:89–93

    Google Scholar 

  55. Rybak LP, Whitworth C (1987) Ototoxicity of indacrinone is stereospecific. Hear Res 31:169–174

    Google Scholar 

  56. Rybak LP, Green TP, Juhn SK, Morizono T, Mirkin BL (1979) Elimination kinetics of furosemide in perilymph and serum of the chinchilla: neuropharmacologic correlates. Acta Otolaryngol(Stockh) 88:382–387

    Google Scholar 

  57. Rybak LP, Green TP, Juhn SK, Morizono T (1984) Probenecid reduces cochlear effects and perilymph penetration of furosemide in chinchilla. J Pharmacol Exp Ther 230:706–709

    Google Scholar 

  58. Rybak LP, Santiago W, Whitworth C (1986) An experimental study using sodium salicylate to reduce cochlear changes induced by furosemide. Arch Otorhinolaryngol 243:180–182

    Google Scholar 

  59. Rybak LP, Whitworth C, Scott V (1990) Organic acids do not alter the cochlear effects of ethacrynic acid. Hear Res 46:95–100

    Google Scholar 

  60. Schlatter E, Greger R, Weidtke C (1983) Effects of ‘high ceiling’ diuretics on active salt transport in the cortical thick ascending limb of Henle's loop in the rabbit kidney. Correlation of chemical structure and inhibitory potency. Pfügers Arch 396:210–217

    Google Scholar 

  61. Thalmann I, Kobayaski T, Thalmann R (1982) Arguments against a mediating role of the adenylate cyclase-cyclic AMP system in the ototoxic action of loop diuretics. Laryngoscope 92:589–593

    Google Scholar 

  62. Tuzel IH (1981) Comparison of adverse reactions to bumetanide and furosemide. J Clin Pharmacol 21:615–619

    Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Southern Illinois University School of Medicine, 62794-9230, Springfield, IL, USA

    L. P. Rybak, C. Whitworth & V. Scott

  2. Department of Pharmacology, Southern Illinois University School of Medicine, 62794-9230, Springfield, IL, USA

    L. P. Rybak

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  1. L. P. Rybak
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  2. C. Whitworth
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Rybak, L.P., Whitworth, C. & Scott, V. Comparative acute ototoxicity of loop diuretic compounds. Eur Arch Otorhinolaryngol 248, 353–357 (1991). https://doi.org/10.1007/BF00169028

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  • DOI: https://doi.org/10.1007/BF00169028

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