Document Detail

Acetazolamide and breathing. Does a clinical dose alter peripheral and central CO(2) sensitivity?
MedLine Citation:
PMID:  10556126     Owner:  NLM     Status:  MEDLINE    
Improvement of blood gases with the carbonic anhydrase inhibitor acetazolamide in some patients with chronic obstructive pulmonary disease (COPD) is believed to result from an effect on the ventilatory control system. Carbonic anhydrase is ubiquitously present within the body, particularly in tissues involved in the control of breathing. Because low inhibitor concentrations are sufficient to block the enzyme in many tissues, it is of interest to document the effect of clinical doses of acetazolamide on the CO(2) sensitivities of the peripheral and central chemoreflex loops. In this study we measured the effect of chronic acetazolamide (250 mg by way of mouth, every 8 h during 3 days) on the dynamic ventilatory response to step changes in end-tidal PCO(2) in nine healthy volunteers. Data were analyzed using a two-compartment model comprising a fast peripheral and slow central compartment, enabling us to separate drug effects on the peripheral and central chemoreflex loops, respectively. Compared with placebo, acetazolamide did not change the CO(2) sensitivities and time constants of both chemoreflex loops. However, mean (+/- SD) resting ventilation increased from 12.22 +/- 2.41 to 14.01 +/- 1.85 L. min(-1), resulting in a decrease in end-tidal PCO(2) from 40.0 +/- 4.7 to 33.3 +/- 3.5 mm Hg. Base excess decreased from -0.08 +/- 1.20 to -7.48 +/- 2.07 mmol. L(-1), indicating metabolic acidosis and explaining a leftward shift of the CO(2) response curve by 7.3 mm Hg. Possible clinical implications of these results are discussed.
L J Teppema; A Dahan
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  160     ISSN:  1073-449X     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  1999 Nov 
Date Detail:
Created Date:  1999-12-21     Completed Date:  1999-12-21     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1592-7     Citation Subset:  AIM; IM    
Department of Physiology, Leiden University Medical Center, Leiden, The Netherlands.
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MeSH Terms
Acetazolamide / administration & dosage*,  pharmacology
Carbon Dioxide / blood,  physiology*
Carbonic Anhydrase Inhibitors / administration & dosage*,  pharmacology
Chemoreceptor Cells / drug effects,  physiology
Double-Blind Method
Pulmonary Ventilation / drug effects*
Reflex / drug effects*
Respiratory Center / physiology
Reg. No./Substance:
0/Carbonic Anhydrase Inhibitors; 124-38-9/Carbon Dioxide; 59-66-5/Acetazolamide

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