Abstract
Acetazolamide, a noncompetitive carbonic anhydrase inhibitor, can produce symptomatic acidosis and bone marrow suppression by a mechanism that is still unknown. This presentation occurs in the elderly, patients with renal or liver failure, people with diabetes, and newborns. The objective of this study was to understand the pathogenic mechanism of these adverse effects and to propose a possible prophylaxis and therapy. Four human clinical cases were studied, and one animal experiment was performed. Four preterm newborns with posthemorrhagic ventricular dilation developed severe metabolic acidosis after treatment with acetazolamide. The acidosis suddenly disappeared after a packed red blood cell transfusion. Metabolic studies were performed in one patient and in newborn guinea pigs treated with 200 mg/kg acetazolamide. Acetazolamide can produce severe lactic acidosis with an increased lactate-to-pyruvate ratio, ketosis with a low beta-hydroxybutyrate-to-acetoacetate ratio, and a urinary organic acid profile typical of pyruvate carboxylase deficiency. The acquired enzymatic injury resulting from the inhibition of mitochondrial carbonic anhydrase V that provides bicarbonate to pyruvate carboxylase can produce tricarboxylic acid cy...Continue Reading
References
Dec 1, 1979·The Journal of Pediatrics·H A PearsonJ C Marsh
Jan 1, 1979·Current Medical Research and Opinion·P Siklos, R G Henderson
Nov 1, 1976·Acta paediatrica Scandinavica·J M SaudubrayJ P Leroux
Nov 1, 1990·The Journal of Clinical Investigation·A RötigJ M Saudubray
Dec 1, 1990·Journal of Internal Medicine·M KeisuO Mortimer
Apr 1, 1989·Journal of Clinical Pharmacology·D J ChapronK R Sweeney
Oct 1, 1986·Biochemical Pharmacology·D HäussingerW Gerok
Nov 15, 1986·Archives of Biochemistry and Biophysics·S J Dodgson, R E Forster
Jan 1, 1970·The Biochemical Journal·B H Robinson, M L Halperin
Oct 1, 1980·Biochemical Genetics·S JefferyN Carter
Dec 1, 1994·Acta Paediatrica·E MercuriL Dubowitz
Mar 1, 1994·Journal of Leukocyte Biology·A R CampbellE R Swenson
Mar 19, 1993·Neuroscience Letters·A NógrádiN D Carter
Dec 1, 1995·AIDS·M de MartinoA Vierucci
Jan 1, 1997·Developmental Neuroscience·S A HazenC J Lynch
Nov 20, 1998·Lancet·P Raupp
Apr 20, 1999·Pediatric Neurology·M H LibensonH E Gilmore
Citations
Apr 17, 2013·Proceedings of the National Academy of Sciences of the United States of America·Gul N ShahWilliam S Sly
Apr 20, 2004·The British Journal of Ophthalmology·F H Zaidi, P E Kinnear
Jul 4, 2007·Journal of Perinatal Medicine·David M CarrollBabyn S Paul
Jun 18, 2010·The Journal of Pediatrics·Luca FilippiRenzo Guerrini
Sep 28, 2005·Diabetes Care·Patricia L Brubaker
Feb 26, 2005·American Journal of Nephrology·Fang Qiang Zhou
Feb 27, 2016·F1000Research·Amy Quynh Trang PhamOrson W Moe
Oct 6, 2010·Advances in Health Sciences Education : Theory and Practice·Aliki ThomasW Dale Dauphinee
Oct 20, 2018·Chinese Medical Journal·Li-Jun SuXue-Wu Liu
Nov 28, 2019·Journal of Neonatal-perinatal Medicine·A Ibrahim, N Hussain