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At least 19 recordsLinked to original sources

PubMed1977

Potentiation by the injection vehicle of the teratological action of acetazolamide in rats.

The high alkalinity of the injection vehicle of certain parenteral solutions of acetazolamide produces necrosis of the skin upon sc injection. The possible modification of this effect on the teratogenicity of acetazolamide was examined. Acetazolamide in a vehicle of pH 10.5 produced 36.6% fetal malformations, in a vehicle of pH 8.7, 6.1%, and in neutral suspension, 11.8%. Adrenal medullectomy or phentolamine plus the high pH acetazolamide reduced the frequency to 23.2 and 24.4%, respectively. The teratogenicity of the low pH acetazolamide was increased by epinephrine to 64.2%. The frequency of hemimelia and micromelia, and of bilateral involvement, was greater in litters exposed to the high pH acetazolamide or the epinephrine-acetazolamide combinations, and was reduced by phentolamine or adrenal medullectomy. Neither the high pH vehicle nor epinephrine produced fetal defects in the absence of acetazolamide. The biological disposition of acetazolamide was not altered by any of the treatments. Reduction of uterine blood flow may be responsible for the potentiation of teratogenicity by the high pH vehicle.

Abnormalities, Drug-Induced↗

PubMed1978

Effects of acetazolamide on myotonia.

Myotonia can occur in the periodic paralyses, particularly the hyperkalemic form. The beneficial response to acetazolamide in hypokalemic and hyperkalemic periodic paralysis has led us to study the effect of acetazolamide in 9 patients with disorders having myotonia as the major problem, 7 with myotonia congenita and 2 with paramyotonia congenita. Patients were studied before acetazolamide administration with glucose and potassium loading tests. All patients had an increase in myotonia with potassium, but no weakness occurred with either test. Acetazolamide treatment decreased myotonia in all patients and in 3 proved the most satisfactory therapy. Side-effects during acetazolamide therapy included paresthesias in 5 patients and renal calculus in 1. Flaccid weakness occurred in a patient with paramyotonia congenita. Acetazolamide treatment was associated in all patients with partially compensated metabolic acidosis and lowering of serum potassium within the normal range. Kaliuresis was also noted during introduction of therapy. Acetazolamide appears to be an acceptable treatment for occasional patients with myotonia who are unresponsive to or intolerant of other therapies.

Acetazolamide↗

PubMed2026

Acetazolamide to prevent ventilatory drive withdrawal in REM sleep apnoea: a randomised controlled trial.

BACKGROUND: Obstructive sleep apnoea (OSA) pathogenesis during rapid-eye movement (REM) sleep has been linked to dips in ventilatory drive and downstream genioglossus hypotonia. The carbonic anhydrase inhibitor acetazolamide is known to increase ventilatory drive and improve OSA severity. Therefore, we tested the effect of acetazolamide on REM-predominant OSA severity (apnoea hypopnoea index (AHI) and hypoxic burden, co-primary outcomes) and underlying physiological mechanisms (ventilatory drive, ventilation and pharyngeal muscle activity). METHODS: 11 participants with REM-predominant OSA per baseline polysomnography (REM AHI/non-REM AHI≥2) were allocated to receiving acetazolamide 500 mg for three nights (first night at half dose) or placebo according to a randomised, crossover, double-blind design. Detailed physiological polysomnography with recording of diaphragm and genioglossus electromyography was conducted after each intervention, with a 1-week washout in between. RESULTS: As hypothesised, acetazolamide reduced AHI by 35.5% (95% CI 23.1% to 46.3%) and hypoxic burden by 35.9% (95% CI 21.1% to 48.4%) vs placebo (p<0.001), meeting the primary endpoint. Mechanistic analysis in REM revealed that, unexpectedly, acetazolamide did not mitigate dips in ventilatory drive versus placebo (first decile (+0.1 (-1.0 to 1.3) L/min, p=0.8). Rather, acetazolamide reduced collapsibility (increased ventilation at eupneic drive: +1.4 (1.2 to 1.8) L/min) and raised muscle responsiveness (ventilation vs drive slope: +32 (25 to 41) %ventilation/drive, p<0.001; genioglossus versus drive slope: +0.33 (0.13 to 0.54) %max/(L/min), p=0.001). CONCLUSIONS: Acetazolamide modestly improved REM OSA, with meaningful improvements in upper airway physiology, but failed to mitigate the dips in ventilatory drive responsible for REM OSA. TRIAL REGISTRATION NUMBER: NCT05589792.

Humans↗

PubMed1977

Effect of acetazolamide and parathyroid hormone on HCO3 and PO4 excretion.

It has been recently demonstrated that parathyroid hormone (PTH) inhibits renal cortical carbonic anhydrase. Based on this in vitro study, it was suggested that PTH depresses proximal reabsorption of phosphate and bicarbonate reabsorption in vivo by inhibiting carbonic anhydrase. To test this hypothesis, we measured bicarbonate and phosphate excretion in four groups of dogs. Group I received PTH for 2 hours; group II received acetazolamide for 2 hours; group III received PTH for 2 hours and acetazolamide in the 2nd hour; and in group IV, acetazolamide was given for 2 hours with PTH ADDED IN THE 2ND HOUR. Acetazolamide administration resulted in maximal bicarbonate excretion in the 1st hour and maximal phosphate excretion in the 2nd hour. Addition of acetazolamide to animals receiving PTH or addition of PTH to animals receiving acetazolamide resulted in additional increases in bicarbonate and phosphate excretion. These data demonstrate that PTH induces bicarbonate and phosphate excretion regardless of whether carbonic anhydrase is intact or nearly 100% inhibited by acetazolamide. These data do not support the hypothesis that PTH inhibits bicarbonate and phosphate reabsorption by inhibiting carbonic anhydrase.

Acetazolamide↗

PubMed1975

Effect of acetazolamide on sodium and chloride transport by in vitro rabbit ileum.

Acetazolamide (8 mM) aboishes active Cl absorption and inhibits but does not abolish active Na absorption by stripped, short-circuited rabbit ileum. These effects are not accompanied by significant changes in the transmural electrical potential difference or short-circuit current. Studies of the undirectional influxes of Na andCl indicate that acetazolamide inhibits the neutral, coupled NaCl influx process at the mucosal membranes. This action appears to explain the observed effect of acetazolamide on active, transepithelial Na and Cl transport. Acetazolamide did not significantly inhibit either spontaneous or theophylline-induced Cl secretion by this preparation, suggesting that the theophylline-induced secretion may not simply be due tothe unmasking of a preexisting efflux process when the neutral influx mechanism is inhibited by theophylline. Finally, inhibition of the neutral NaCl influx process by acetazolamide does not appear to be attributable to an inhibition of endogenous HCO3production or an elevation in intracellular cyclic-AMP levels. Instead, it appearstheat the effect of acetazolamide is due to a direct interaction with a membrane component involved in the coupled influx process.

Acetazolamide↗

PubMed1979

Acidosis inhibits the hypocalcemic effect of acetazolamide.

The effect of acetazolamide on calcium metabolism was examined using sham-operated, ureter-ligated and nephrectomized rats. Acetazolamide doses from 10 to 500 mg/kg produced significant hypocalcemic effects in ureter-ligated and nephrectomized rats. However, doses of acetazolamide up to 1000 mg/kg were devoid of hypocalcemic activity when administered to sham-operated rats. Sham-operated rats exhibited an acidotic response to acetazolamide while ureter-ligated rats did not. Attenuation of this drug-induced acidotic response with i.p. injections of tris(hydroxymethyl)amino-methane uncovered a hypocalcemic effect of acetazolamide in sham-operated rats. Also, the hypocalcemia associated with acetazolamide treatment of ureter-ligated rats was negated when an acidosis was induced by prior injection of NH4Cl. These data indicate that the administration of inhibitors of carbonic anhydrase produces a hypocalcemia when a metabolic acidosis is not present.

Acetazolamide↗

PubMed1977

Comparison of ocular hypotensive effects of acetazolamide and atenolol.

The ocular hypotensive effect of single oral doses of (a) atenolol (50 mg), (b) acetazolamide (500 mg), (c) atenolol (50 mg) and acetazolamide (500 mg) in combination, and (d) vehicle (inert tablets) were compared in 8 patients with glaucoma. In this single-dose, double-masked trial the combination was observed as most effective in reducing ocular tension. Both the combination and atenolol performed markedly better than vehicle. That acetazolamide did not reduce ocular tension significantly more than vehicle is probably explained by relatively low initial ocular tensions. There was no evidence of interaction between atenolol and acetazolamide in this study. Acetazolamide probably remains the first-choice oral medication for glaucoma. It is cautiously suggested that beta-blocking drugs may have a future therapeutic role, but longer-term studies on larger numbers will be required to establish this.

Acetazolamide↗

PubMed1977

Ouabain, acetazolamide, and Cl-flux in isolated frog skin: evidence for two distinct active Cl-transport mechanisms.

Two distinctly different mechanisms for active Cl- transport in epithelia may exist: one, ouabain-sensitive and cation-dependent, and the other, acetazolamide-sensitive and cation-independent. As a test of this hypothesis the three active Cl- transport systems in isolated short-circuited skin of Rana pipiens were examined. Sensitivity to ouabain (10(-4) M) and acetazolamide (5 X 10(-3) M) and dependence on Na+ and K+ in the medium were ascertained. The first system, net chloride influx in ordinary Ringer, exhibited specific ouabain sensitivity and acetazolamide insensitivity. As we have previously shown this system to be clearly dependent on Na+ on the cis and K+ on the trans side, cation dependence was not re-studied. The second system, isoproterenol-stimulated net Cl- outflux, was also ouabain-sensitive and acetazolamide-insensitive. It was dependent on the presence of Na+ on the cis side, but the K+ dependence was less clear. In contrast to the first two, the third system (net influx in low Cl- medium sulfate Ringer containing 2.4 mM Cl-) was largely ouabain-insensitive, completely acetazolamide-sensitive and independent of both Na+ and K+. Thus, the hypothesis of two distinct mechanisms seems to hold for the three active Cl- transport systems in frog skin. Data from various other Cl- transporting epithelia are examined, and the general applicability of such a scheme of categorization for active Cl- transport mechanisms is discussed.

Acetazolamide↗

PubMed1978

Slow postcapillary changes in blood pH in vivo: titration with acetazolamide.

A stopped-flow pH electrode apparatus was used to investigate the mechanisms underlying slow changes in plasma pH (pHO) after blood leaves the pulmonary capillaries in carbonic anhydrase-inhibited animals. After acetazolamide was administered to an anesthetized dog or cat, arterial blood was withdrawn through the electrode apparatus into a syringe. Syringe movement was then suddenly stopped. Temperature and pHO of the blood in the electrode chamber were monitored both before and after blood withdrawal ceased. After stopping flow, pHO of the blood in the electrode chamber a) rose 0.02 after a dose of about 1 mg/kg acetazolamide; b) did not change after a dose of about 2 mg/kg acetazolamide; and c) fell 0.10 after a dose greater than about 5 mg/kg acetazolamide. With reasonable red cell and plasma carbonic anhydrase activities assumed for each dose level of acetazolamide, a computer model of the reaction and transport processes occurring in blood after gas exchange in the lung yielded predicted time courses of pHo that were in good agreement with the experimental results. The observed slow pHo changes are largely a result of disequilibrium of [H+] between red blood cells and plasma as blood leaves the pulmonary capillaries.

Acetazolamide↗

PubMed1977

Effects of acetazolamide on proximal tubule C1, Na, and HCO3 transport in normal and acidotic dogs during distal blockade.

It has been suggested that the establishment of a tubular fluid to plasma chloride gradient in the late proximal tubule by the reabsorption of bicarbonate (and other anions) in the early proximal tubule is responsible for a significant part of sodium chloride and water reabsorption in the proximal tubule. In the present study the effects of acetazolamide on proximal tubule water and electrolyte excretion were examined in 6 normal dogs and 10 chronic ammonium chloride-loaded dogs during distal blockade produced by ethacrynic acid and chlorothiazide administration. During distal blockade control urine/plasma osmolality and urine/plasma sodium were close to unity in all experiments. Urine/plasma chloride and urine/plasma bicarbonate were 1.21+/-0.02 and 0.75+/-0.07 in normal and 1.24+/-0.01 and 0.04+/-0.01 in acidotic dogs, respectively. After the administration of acetazolamide (20 mg/kg i.v.), there was a significant increase in urine flow, absolute and fractional excretion of sodium, bicarbonate, and chloride in all animals. Associated with these effects, urine/plasma osmolality and urine/plasma sodium remained unchanged but urine/plasma chloride decreased significantly to 1.15+/-0.01 in normal and to 1.19+/-0.01 in acidotic dogs. In acidotic dogs there was a significant correlation between the increase in bicarbonate, sodium, or chloride excretion after acetazolamide and the plasma bicarbonate level (range 6.8-12.5 meq/liter). These data demonstrate a significant effect of acetazolamide on bicarbonate, sodium, and chloride reabsorption in the proximal tubule even in the face of severe acidosis. Moreover, the data suggest that the decrease in chloride reabsorption (and accompanying sodium) after acetazolamide is related to the decrease in bicarbonate reabsorption and the associated decrease in the transtubular chloride gradient.

Acetazolamide↗

PubMed1977

Therapeutic testing by acetazolamide in the differentiation of a benign from a malignant niche.

Recognising the inhibitory activity of acetazolamide upon acid gastric secretion and its favorable effects in the treatment of gastric ulcer which we have described (see reference) - we applied the therapeutical testing by acetazolamide in the differentiation of benign from malignant niches of the stomach. Acetazolamide was administered orally at doses of 25-30 mg per kilogram body weight in a long term trial, together with 3 gr sodium bicarbonate, 1 gr potassium bicarbonate, 1.5 gr magnesium oxide per day and an increased quantity of liquids, to 741 patients with radiologically demonstrated ulcer craters. The fundamental criterion was the size of the niche as established by radiologic examination. In all gastric ulcers the size of the niche was considerably reduced after 7-9 days of treatment with acetazolamide; the niche disappeared in 2-3 weeks. This favorable result was obtained without diet and rest. In 38 cases in which there was no significant radiologic change of the niche after 7-9 days of treatment with acetazolamide - the malignancy of the niche was confirmed. The simplicity and the effectiveness of this rapid therapeutic test, makes it useful in the differentiation of benign from a malignant ulcer craters.

Acetazolamide↗

PubMed1978

Gastrointestinal therapeutic system for acetazolamide. Efficacy and side effects.

Acetazolamide has been formulated in a new gastrointestinal therapeutic system that delivers the drug at an essentially constant rate of 15 mg/hr (GITS 15/125). We compared the therapeutic effect, magnitude of plasma concentration fluctuations, and incidence of side effects produced by the GITS 15/125 with conventional 250-mg acetazolamide tablets on eight glaucomatous patients randomly assigned to a different regimen each week. One or two GITS 15/125 twice a day (bid) were found as effective in reducing intraocular pressure as one 250-mg acetazolamide tablet. Plasma concentration fluctuations with the GITS 15/125 were decreased, compared with acetazolamide tablets, and, as a result, the incidence of drowsiness, tingling feet, tingling hands, and confusion was substantially reduced.

Acetazolamide↗

PubMed1975

Binding-site interaction of chlorthalidone and acetazolamide, two drugs transported by red blood cells.

When 14C-chlorthalidone was administered orally to 2 healthy volunteers, the total recovery of radioactivity in urine (about 75 percent) and feces was close to 100 percent. Most of the label recovered in the blood was bound to the blood cells. When the procedure was repeated while the 2 subjects were receiving acetazolamide, the excretion of labeled material in urine and feces was essentially unchanged, but the blood cells contained less and the plasma more of the blood radioactivity. The half-life of the radioactivity in plasma and blood cells had decreased by about 65 percent. Intravenous administration of acetazolamide (single dose) to 2 other subjects who had received 14C-chlorthalidone orally resulted in a marked drop in the blood cell radioactivity, whereas that in plasma increased. The affinity of chlorthalidone for red blood cells was further evidenced on incubation of 14C-chlorthalidone with human blood. Of the incubated radioactivity, 94 percent to 99 percent was recovered in the erythrocytes. Preincubation of the blood samples with acetazolamide prior to the addition of 14C-chlorthalidone, as well as incubation of acetozolamide in blood samples previously incubated with 14C-chlorthalidone, demonstrated that acetazolamide is able to inhibit and to displace chlorthalidone from blood cells. There are several lines of evidence indicating that chlorthalidone is transported attached to the erythrocyte carbonic anhydrase.

Acetazolamide↗

PubMed1976

Effect of parathyroid hormone on phosphate reabsorption in the presence of acetazolamide.

The hypothesis that parathyroid hormone and carbonic anhydrase inhibitors have a common mechanism or site of action on phosphate reabsorption by the renal tubule was tested by administration of parathyroid hormone in the absence and presence of acetazolamide in thyroparathyroidectomized dogs. Re-collection micropuncture and electron probe microanalysis methodologies were utilized. In the absence of acetazolamide, parathyroid hormone increased fractional delivery of phosphate (and volume) from the proximal tubule from 25 +/- 2 to 38 +/- 3%, P less than 0.025, and increased fractional phosphate excretion from 3.8 +/- 1.2 to 19.9 +/- 3.7%, P less than 0.005 (eight dogs). In the presence of acetazolamide, parathyroid hormone increased fractional delivery of phosphate (but not volume) from the proximal tubule from 50 +/- 4 to 58 +/- 5%, P less than 0.025, and increased fractional excretion of phosphate from 8.7 +/- 2.2 to 31.0 +/- 4.3%, P less than 0.001 (12 dogs). Thus, the effects of parathyroid hormone were additive to the effects of maximal inhibition of carbonic anhydrase indicating that parathyroid hormone and carbonic anhydrase inhibitors have different mechanisms of action on phosphate reabsorption by the renal tubule. In addition, phosphate reabsorption beyond the point of micropuncture in the late proximal tubule was much more markedly inhibited by parathyroid hormone than by acetazolamide.

Acetazolamide↗

PubMed1979

Effects of acetazolamide and changes of acid-base balance on the content of cyclic nucleotides in the rat kidney.

Changes in tissue levels of cyclic adenosine 3':5'-monophosphate (cAMP) and cyclic guanosine 3':5'-monophosphate (cGMP) in the rat kidney in response to acid-base changes and administration of acetazolamide were measured. cAMP was determined according to the method described by Gilman and cGMP by radioimmunoassay. 1 mg/kg acetazolamide increased bicarbonate excretion 100-fold over the control values to 2.52 +/- 0.5 mEq/min (mean +/- SEM; n = 6), but did not influence cGMP and cAMP tissue content. 10 and 100 mg/kg acetazolamide increased cGMP tissue levels to 0.277 +/- 0.048 and 0.482 +/- 0.07 pmol/mg dry weight in comparison to 0.192 +/- 0.04 in the controls, whereas no changes in cAMP levels occurred. Chronic as well as acute metabolic alkalosis induced an increase of cGMP levels (0.26 +/- 0.03 and 0.29 +/- 0.06 pmol/mg), whereas chronic metabolic and acute respiratory acidosis lowered cGMP levels to 0.14 +/- 0.02 and 0.13 +/- 0.02 pmol/mg. cAMP tissue levels were not affected by changes in acid-base balance. The data could suggest that cGMP participates in the regulation of acid-base balance and renal effects of acetazolamide.

Acetazolamide↗

PubMed1977

Acetazolamide-induced weakness in paramyotonia congenita.

Acetazolamide has been shown to be effective prophylaxis for both hypokalemic and hyperkalemic paralysis. A patient with paramyotonia congenita, a related disorder with myotonia and episodic weakness, was studied during treatment with acetazolamide. Athough the patient's myotonia was virtually abolished, severe quadriparesis was produced during each trial of acetazolamide. This response distinguished this patient's condition from other forms of familial periodic paralysis and suggests that acetazolamide may be deleterious to some patients with periodic paralysis.

Acetazolamide↗

PubMedDate not supplied

Effect of acetazolamide on insulin sensitivity in dogs with alloxan diabetes.

The effect of acetazolamide on the sensitivity to exogenous insulin in the alloxanised diabetic dogs was studied. The administration of acetazolamide caused acidosis and insulin resistance. The liver insulinase activity of diabetic dogs after acetazolamide administration was also studied to evaluate the role of this enzyme for the destruction of exogenous insulin. It was observed that insulinase did not play role for the development of insulin resistance after acetazolamide administration.

Acetazolamide↗

PubMed1977

Effects and interactions of furosemide and acetazolamide on tubular function in rat kidney.

Furosemide and acetazolamide effects on tubular function in rat kidney have been studied by micropuncture. Furosemide produced a marked rise in fractional proximal fluid reabsorption when urine loss was not replaced, and sodium excretion rose significantly indicating a distal effect. If urinary losses were replaced proximal fractional reabsorption was depressed and fractional sodium excretion increased more than 60%. After replacing urinary losses, acetazolamide had a greater depressive effect on proximal tubular fluid reabsorption than furosemide but sodium excretion values were about 1/3 of those obtained with furosemide. Superimposition of one drug during the action of the other resulted in potentiation of proximal inhibition, suggesting a different mechanism of action. The changes observed in potassium excretion are of great interest. Separately, furosemide or acetazolamide produced kaliuresis. When furosemide was administered during acetazolamide diuresis, however, potassium excretion was reduced despite the sharp rise in sodium excretion.

Acetazolamide↗