The Use of Diamox, a Carbonic Anhydrase Inhibitor, as an Oral Diuretic in Patients with Congestive Heart Failure

Friedberg, Charles K.; Taymor, Robert C.; Minor, James B.; Halpern, Mark

doi:10.1056/nejm195305212482102

Cited by 61 publications

(11 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Normal subjects sometimes develop drowsiness and paresthesias after receiving doses of the drug exceeding 1 g (47)(48)(49), and such a response was observed to begin about 2 hours after infusion in one of our controls. This response, whose mechanism is unknown, was qualitatively entirely different from the increased confusion and mental obtundity found in the cirrhotics, and the time -delay was also dissimilar to the cirrhotics' immediate worsening.…”

Section: Normal Valuesmentioning

confidence: 71%

The Toxic Effects of Carbon Dioxide and Acetazolamide in Hepatic Encephalopathy *

Posner¹,

Plum²

1960

J. Clin. Invest.

173

View full text Add to dashboard Cite

Section: Normal Valuesmentioning

confidence: 71%

The Toxic Effects of Carbon Dioxide and Acetazolamide in Hepatic Encephalopathy *

Posner¹,

Plum²

1960

J. Clin. Invest.

173

View full text Add to dashboard Cite

“…We conclude that carbonic anhydrase is a novel candidate for anti‐hypertrophic therapy. As the carbonic anhydrase inhibitors acetazolamide (Diamox), methazolamide (Neptazane) and ETZ (Cardrase) have been used as diuretics and anti‐glaucoma drugs since the 1950s (Friedberg et al 1953; Moyer & Ford, 1958; Becker, 1960), anti‐CAII therapy might be readily adopted in treatment of CH.…”

Section: Discussionmentioning

confidence: 99%

Carbonic anhydrase inhibition prevents and reverts cardiomyocyte hypertrophy

Álvarez¹,

Johnson²,

Sowah³

et al. 2007

The Journal of Physiology

View full text Add to dashboard Cite

Hypertrophic cardiomyocyte growth contributes substantially to the progression of heart failure. Activation of the plasma membrane Na + -H + exchanger (NHE1) and Cl − -HCO 3 − exchanger (AE3) has emerged as a central point in the hypertrophic cascade. Both NHE1 and AE3 bind carbonic anhydrase (CA), which activates their transport flux, by providing H + and HCO 3 − , their respective transport substrates. We examined the contribution of CA activity to the hypertrophic response of cultured neonatal and adult rodent cardiomyocytes. Phenylephrine (PE) increased cell size by 37 ± 2% and increased expression of the hypertrophic marker, atrial natriuretic factor mRNA, twofold in cultured neonatal rat cardiomyocytes. Cell size was also increased in adult cardiomyocytes subjected to angiotensin II or PE treatment. These effects were associated with increased expression of cytosolic CAII protein and the membrane-anchored isoform, CAIV. The membrane-permeant CA inhibitor, 6-ethoxyzolamide (ETZ), both prevented and reversed PE-induced hypertrophy in a concentration-dependent manner in neonate cardiomyocytes (IC 50 = 18 µM). ETZ and the related CA inhibitor methazolamide prevented hypertrophy in adult cardiomyocytes. In addition, ETZ inhibited transport activity of NHE1 and the AE isoform, AE3, with respective EC 50 values of 1.2 ± 0.3 µM and 2.7 ± 0.3 µM. PE significantly increased neonatal cardiomyocyte Ca 2+ transient frequency from 0.33 ± 0.4 Hz to 0.77 ± 0.04 Hz following 24 h treatment; these Ca 2+ -handling abnormalities were completely prevented by ETZ (0.28 ± 0.07 Hz). Our study demonstrates a novel role for CA in mediating the hypertrophic response of cardiac myocytes to PE and suggests that CA inhibition represents an effective therapeutic approach towards mitigation of the hypertrophic phenotype.

show abstract

“…In the course of reducing proximal reabsorption, CAI also activate TGF, which causes GFR and renal blood flow to decline [15] . This negative impact of CAI on glomerular filtration, and therefore in diuretic activity, may explain why CAI never became first-line therapy for edematous conditions, notwithstanding initial enthusiasm in the 1950s [16] .…”

Section: Introductionmentioning

confidence: 99%

Combined Effects of Carbonic Anhydrase Inhibitor and Adenosine A1 Receptor Antagonist on Hemodynamic and Tubular Function in the Kidney

Miracle

Rieg²,

Blantz³

et al. 2007

Kidney Blood Press Res

View full text Add to dashboard Cite

Background: Carbonic anhydrase inhibitors (CAI) reduce proximal reabsorption, activating tubuloglomerular feedback (TGF) and reducing glomerular filtration rate (GFR). Adenosine A1 receptors (A1R) mediate the TGF response and stimulate proximal reabsorption. Methods: Clearance and micropuncture studies were performed in Wistar rats to determine whether blockade of A1R (KW3902 0.3 mg/kg i.v.) would prevent CAI (benzolamide 5 mg/kg i.v.) from lowering GFR, whether CAI and KW3902 exert additive effects on sodium excretion, and to what extent such interactions depend on events in the glomerulus, proximal tubule, or distal nephron. Results: KW3902 raised GFR and prevented CAI from lowering GFR. KW3902 and CAI caused additive diuresis and natriuresis. KW3902 and CAI increased lithium clearance, but their effects were redundant. CAI increased the dependence of proximal reabsorption on active chloride transport. KW3902, alone, did likewise, but to a lesser extent than CAI. Adding KW3902 to CAI lessened the shift toward active chloride transport. Conclusions: The data reveal that A1R mediate glomerular vascular resistance whether or not TGF is activated, that additive effects of CAI and KW3902 on salt excretion occur, in part, because KW3902 inhibits reabsorption downstream from the macula densa, and that KW3902 likely inhibits proximal reabsorption by interfering with apical sodium-hydrogen exchange.

show abstract

The Use of Diamox, a Carbonic Anhydrase Inhibitor, as an Oral Diuretic in Patients with Congestive Heart Failure

Cited by 61 publications

References 18 publications

The Toxic Effects of Carbon Dioxide and Acetazolamide in Hepatic Encephalopathy *

The Toxic Effects of Carbon Dioxide and Acetazolamide in Hepatic Encephalopathy *

Carbonic anhydrase inhibition prevents and reverts cardiomyocyte hypertrophy

Combined Effects of Carbonic Anhydrase Inhibitor and Adenosine A<sub>1</sub> Receptor Antagonist on Hemodynamic and Tubular Function in the Kidney

Contact Info

Product

Resources

About