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Effects of acetazolamide on metabolic and respiratory responses to exercise at maximal O2 uptake.

Changes in blood gases, ions, lactate, pH, hemoglobin, blood temperature, total body metabolism, and muscle metabolites were measured before and during exercise (except muscle), at fatigue, and during recovery in normal and acetazolamide-treated horses to test the hypothesis that an acetazolamide-induced acidosis would compromise the metabolism of the horse exercising at maximal O2 uptake. Acetazolamide-treated horses had a 13-mmol/l base deficit at rest, higher arterial Po2 at rest and during exercise, higher arterial and mixed venous Pco2 during exercise, and a 48-s reduction in run time. Arterial pH was lower during exercise but not in recovery after acetazolamide. Blood temperature responses were unaffected by acetazolamide administration. O2 uptake was similar during exercise and recovery after acetazolamide treatment, whereas CO2 production was lower during exercise. Muscle [glycogen] and pH were lower at rest, whereas heart rate, muscle pH and [lactate], and plasma [lactate] and [K+] were lower and plasma [Cl-] higher following exercise after acetazolamide treatment. These data demonstrate that acetazolamide treatment aggravates the CO2 retention and acidosis occurring in the horse during heavy exercise. This could negatively affect muscle metabolism and exercise capacity.

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Mechanism of acetazolamide-induced rise in renal vascular resistance assessed in the dog whole kidney.

The reduction in renal blood flow (RBF) and glomerular filtration rate (GFR) observed after the administration of the carbonic anhydrase inhibitors acetazolamide and benzolamide had been explained as due to activation of the tubuloglomerular feedback mechanism. If correct, pharmacologic blockade of this pathway should prevent the development of renal vasoconstriction with the carbonic anhydrase inhibitors. Thus, the current study evaluates in the dog whole kidney the effect of acetazolamide (20 mg/kg body weight) in the presence or absence of furosemide (5 mg/kg body weight), a drug which blocks the tubuloglomerular feedback. Acetazolamide resulted in a large increase in urinary bicarbonate excretion accompanied by a significant reduction in GFR (16%) and RBF (18%). By contrast with the effects of acetazolamide, furosemide did not alter GFR and increased RBF. In addition, the loop diuretic induced a large chloruresis without changes in urinary bicarbonate excretion. The infusion of acetazolamide in furosemide-treated dogs resulted in a significant increment in renal bicarbonate excretion and in a significant reduction in the levels of both GFR (28%) and RBF (13%). Therefore, furosemide pretreatment did not block the effects of acetazolamide on renal hemodynamic parameters. Consequently, the acetazolamide-induced reduction in both GFR and RBF cannot be accounted for by changes in chloride levels in the juxtaglomerular region due to enhanced salt transport in the macula densa/distal nephron. The increased renal vascular resistance observed with acetazolamide might occur by either a direct effect of this agent on the renal circulation or as a result of changes in intrarenal pressure secondary to the inhibition of proximal fluid reabsorption.

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Effect of acetazolamide on cerebral blood flow velocity and CO2 elimination in normotensive and hypotensive newborn piglets.

The objectives of this study were to measure the effect of acetazolamide on cerebral circulation, pulmonary elimination of CO2, and cerebrovascular response to hypotension in newborn piglets. Eighteen anaesthetized newborn piglets were studied. A fontanelle was surgically created and the cerebral blood flow velocity (CBFV) in an intracranial artery measured by a computerized Doppler system. In 8 piglets, 30 ml/kg of blood was removed to produce hypotension before the administration of acetazolamide. Acetazolamide (50 mg/kg i.v.) given to normotensive piglets consistently produced a large increase in CBFV (median 45% by 5 min) with no change in mean arterial blood pressure or heart rate. The rise in CBFV was negatively correlated with the starting partial pressure of CO2 in arterial blood. Within 1 min of administration of acetazolamide, the end-expiratory CO2 pressure started to fall (mean fall 1.4 kPa), and the partial pressure of CO2 in the arterial blood started to rise (mean rise 2.0 kPa), despite the controlled ventilation being unchanged. Acetazolamide had no effect on CBFV in the hypotensive piglet. It seems likely that acetazolamide produces cerebral vasodilatation by inhibiting the elimination of CO2. In hypotension, there is maximal cerebral vasodilatation, and acetazolamide cannot increase CBFV further. The interference of acetazolamide with CO2 elimination could seriously limit its use in the treatment of hydrocephalus in preterm infants.

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Acetazolamide: a treatment for chronic mountain sickness.

RATIONALE: Chronic mountain sickness or Monge's disease is characterized by an excessive polycythemia in high-altitude dwellers, with a prevalence of 5 to 18% above 3,200 m. To date, no pharmacologic treatment is available. OBJECTIVES: We evaluated the efficacy of acetazolamide in the treatment of chronic mountain sickness and the importance of nocturnal hypoxemia in its pathophysiology. METHODS: A double-blind placebo-controlled study was performed in three groups of patients from Cerro de Pasco, Peru (4,300 m), treated orally for 3 weeks with placebo (n = 10), 250 mg of acetazolamide (n = 10), or 500 mg of acetazolamide (n = 10), daily. RESULTS: Acetazolamide decreased hematocrit by 7.1% (p < 0.001) and 6.7% (p < 0.001), serum erythropoietin by 67% (p < 0.01) and 50% (p < 0.001), and serum soluble transferrin receptors by 11.1% (p < 0.05) and 3.4% (p < 0.001), and increased serum ferritin by 540% (p < 0.001) and 134% (p < 0.001), for groups treated with 250 and 500 mg of acetazolamide, respectively. Acetazolamide (250 mg) increased nocturnal arterial O(2) saturation by 5% (p < 0.01) and decreased mean nocturnal heart rate by 11% (p < 0.05) and the number of apnea-hypopnea episodes during sleep by 74% (p < 0.05). The decrease in erythropoietin was attributed mainly to the acetazolamide-induced increase in ventilation and arterial O(2) saturation. CONCLUSIONS: Acetazolamide, the first efficient pharmacologic treatment of chronic mountain sickness without adverse effects, reduces hypoventilation, which may be accentuated during sleep, and blunts erythropoiesis. Its low cost may allow wide development with a considerable positive impact on public health in high-altitude regions.

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Regional cerebral blood flow after acetazolamide challenge in patients with dural arteriovenous fistula: simple way to evaluate intracranial venous hypertension.

BACKGROUND AND PURPOSE: Because venous hypertension determines the clinical severity of dural arteriovenous fistulas (DAVFs), evaluation of intracranial venous pressure is important in making decisions concerning treatment. We determined whether intracranial venous hypertension could be quantified by using an acetazolamide test in a manner that indicates whether treatment of the DAVF is necessary. METHODS: We enrolled 21 untreated patients: 11 with a sigmoid and/or transverse DAVF, six with a cavernous DAVF, two with an anterior cranial fossa DAVF, and two with a superior sagittal sinus DAVF. Cerebral hemodynamics were studied with stable-xenon CT. Patients were angiographically classified into three groups, and regional cerebral blood flow (rCBF) after acetazolamide challenge was compared between angiographic groups, between patients with and those without symptoms attributable to intracranial venous hypertension, and between preembolization and postembolization examinations. RESULTS: A high angiographic grade was associated with decreased resting rCBF and a blunted response to acetazolamide. Response to acetazolamide was more sensitive to venous hypertension, as angiographically assessed, than decreased resting rCBF. Resting rCBF and the increase in rCBF associated with acetazolamide were significantly lower in the symptomatic group than in the asymptomatic group. Treatment of the DAVF significantly enhanced the increased rCBF due to the acetazolamide challenge. CONCLUSION: Cerebral venous hypertension in DAVF reduced the response to acetazolamide, as shown on stable-Xe CT. Therefore, a patient with DAVF and a reduced rCBF response to acetazolamide requires treatment irrespective of his or her symptoms.

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Vascular effects of acetazolamide on the choroid plexus.

Decreases in production of cerebrospinal fluid (CSF) after administration of acetazolamide have been attributed in part to constriction of blood vessels of the choroid plexus. The first goal of the present study was to examine effects of acetazolamide on blood flow to the choroid plexus. We measured blood flow (microspheres) and the production of CSF (ventriculo-cisternal perfusion) in anesthetized rabbits. Under control conditions, blood flow to the choroid plexus was 466 +/- 34 (mean +/- S.E.) ml min-1 100 g-1 and CSF production was 9.4 +/- 0.9 microliters min-1. Acetazolamide (25 mg kg-1 i.v.) decreased production of CSF by 55 +/- 5% despite a 2-fold increase in blood flow to the choroid plexus. The second goal of this study was to examine the role of hypercapnia, which occurs after administration of acetazolamide, in producing increases in blood flow. In animals in which hypercapnia was prevented by increases in ventilation, acetazolamide produced a similar increase in blood flow to the choroid plexus. We conclude that acetazolamide decreases the production of CSF but, in contrast to predictions based on studies in vitro, acetazolamide produces a marked increase in blood flow to the choroid plexus. Thus, changes in blood flow to the choroid plexus and production of CSF are uncoupled after administration of acetazolamide.

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Gastric mucosal protection by acetazolamide in rats. Roles of prostaglandins, sulfhydryls, and gastric motility.

The aim of this study was to test the hypothesis that protective effect of subcutaneous acetazolamide, a carbonic anhydrase inhibitor, against ethanol-induced gastric mucosal damage is dependent on indomethacin- or iodoacetamide-sensitive mechanisms. In addition we studied the effects of acetazolamide on gastric motility and the influence of indomethacin and iodoacetamide on this parameter. Indomethacin (30 mg/kg) or iodoacetamide (100 ag/kg) was administered subcutaneously in doses that previously had been demonstrated to inhibit endogenous prostaglandins synthesis and gastric mucosal sulfhydryls respectively. At 30 min after these or control subcutaneous pretreatment, the rats were given subcutaneous acetazolamide or vehicle. Thirty min later 96% ethanol was administered orally and the rats were sacrificed 60 min after ethanol administration. The lesions of the gastric glandular mucosa were measured in length and width and expressed in square millimeters. Gastric motility was recorded by a balloon method. The results showed that neither indomethacin nor iodoacetamide aggravated ethanol-induced gastric mucosal damage. The protective effect of subcutaneous acetazolamide was suppressed by pretreatment with indomethacin but not with that of iodoacetamide. Acetazolamide inhibited gastric motility in a dose-dependent fashion. The inhibited gastric motility induced by acetazolamide was reversed by indomethacin but not by iodoacetamide. A highly significant relationship was found between the inhibitory effect of acetazolamide on the motor activity and the mucosal lesions (r +/- 0.8777, P < 0.01). We conclude that the mechanism mediating subcutaneous acetazolamide protection against 96% ethanolinduced gastric mucosal lesions is dependent on indomethacin- and independent of iodoacetamide sensitive mechanisms.

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Cyclodextrins in acetazolamide eye drop formulations.

The interaction of acetazolamide with beta-cyclodextrin, (beta-CD), dimethyl-beta-cyclodextrin (DM-beta-CD) and trimethyl-beta-cyclodextrin (TM-beta-CD) was monitored spectrophotometrically. The results revealed formation of equimolar complexes. The apparent solubility of acetazolamide in water was found to increase linearly with increasing CD concentration. The effect of CDs on the permeation of acetazolamide through semi-permeable membranes and the topical delivery of acetazolamide was investigated. Maximum acetazolamide penetration was obtained when just enough CD was used to keep all acetazolamide in solution. For an acetazolamide concentration of 10 mg/ml, the optimum CD concentration appeared to be 3.5 mmol/l for beta-CD, 2.8 mmol/l for TM-beta-CD and 6.0 mmol/l for DM-beta-CD. The effect of CDs on the bioavailability of acetazolamide was assessed by measuring the intraocular pressure in rabbits. The results indicated that CDs have a significant influence on the biological performance of the drug leading to augmentation in its intensity of action and bioavailability as well as prolongation in its duration of action.

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Ginkgo biloba and acetazolamide prophylaxis for acute mountain sickness: a randomized, placebo-controlled trial.

BACKGROUND: Acute mountain sickness (AMS) commonly occurs when unacclimatized individuals ascend to altitudes above 2000 m. Acetazolamide and Ginkgo biloba have both been recommended for AMS prophylaxis; however, there is conflicting evidence regarding the efficacy of Ginkgo biloba use. We performed a randomized, placebo-controlled trial of acetazolamide vs Ginkgo biloba for AMS prophylaxis. METHODS: We randomized unacclimatized adults to receive acetazolamide, Ginkgo biloba, or placebo in double-blind fashion and took them to an elevation of 3800 m for 24 hours. We graded AMS symptoms using the Lake Louise Acute Mountain Sickness Scoring System (LLS) and compared the incidence of AMS (defined as LLS score > or =3 and headache). RESULTS: Fifty-seven subjects completed the trial (20 received acetazolamide; 17, Ginkgo biloba, and 20, placebo). The LLS scores were significantly different between groups; the median score of the acetazolamide group was significantly lower than that of the placebo group (P=.01; effect size, 2; and 95% confidence interval [CI], 0 to 3), unlike that of the Ginkgo biloba group (P=.89; effect size, 0; and 95% CI, -2 to 2). Acute mountain sickness occurred less frequently in the acetazolamide group than in the placebo group (effect size, 30%; 95% CI, 61% to -15%), and the frequency of occurrence was similar between the Ginkgo biloba group and the placebo group (effect size, -5%; 95% CI, -37% to 28%). CONCLUSIONS: In this study, prophylactic acetazolamide therapy decreased the symptoms of AMS and trended toward reducing its incidence. We found no evidence of similar efficacy for Ginkgo biloba.

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Topical 2.0% dorzolamide vs oral acetazolamide for prevention of intraocular pressure rise after neodymium:YAG laser posterior capsulotomy.

OBJECTIVE: To compare the efficacy and safety of topical 2.0% dorzolamide hydrochloride with oral acetazolamide in preventing intraocular pressure (IOP) rise following neodymium:YAG (Nd:YAG) laser posterior capsulotomy. DESIGN: A prospective, randomized, double-masked, placebo-controlled study. PATIENTS: Two hundred ten patients undergoing Nd:YAG laser posterior capsulotomy. INTERVENTION: Pretreatment with dorzolamide, acetazolamide, or placebo. Dorzolamide administration as a single drop (1 drop approximately 20 microL) 1 hour before capsulotomy. Acetazolamide administration as a single dose of 125 mg orally 1 hour before capsulotomy. RESULTS: At first and third hour postoperatively, IOPs and IOP changes from baseline were significantly (P<.001) higher in the placebo group than in the dorzolamide or acetazolamide group. At the same time, IOPs and IOP changes from baseline were similar (P>.50) in the dorzolamide and acetazolamide groups. No patient treated with dorzolamide or acetazolamide experienced an IOP higher than 30 mm Hg after capsulotomy, but 15.7% of patients receiving placebo had an IOP above this level (P<.001). Of patients receiving placebo, 5.7% experienced IOP higher than 35 mm Hg. No serious side effects were recorded in any of the studied patients. CONCLUSION: Topical 2.0% dorzolamide and oral acetazolamide, given prophylactically as a single administration 1 hour before Nd:YAG laser posterior capsulotomy, have comparable high efficacy and safety in preventing IOP elevation following this procedure.

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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.

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Interaction of dietary zinc, genetic strain, and acetazolamide in teratogenesis in mice.

The effect of dietary zinc and genetic strain on acetazolamide-induced malformations was assessed. CBA (sensitive) and SWV (resistant) mice were fed purified diets containing five different levels of zinc throughout gestation and were given acetazolamide orally for a limited period during organogenesis. Controls received either no treatment or the drug vehicle. Litters were assessed for resorptions and malformations at term. The significance for influencing litter outcome was tested for the three main treatments: strain, dietary zinc level, and acetazolamide dose, plus their interactions. The magnitude of the litter response was strongly influenced by strain. The incidence of forelimb ectrodactyly, a characteristic malformation caused by acetazolamide, was much greater in CBA than in SWV fetuses. SWV fetuses had no ectrodactyly when dams were fed at least 9 micrograms/g zinc, but 5-8% showed ectrodactyly when dams received a zinc-deficient (0.4 or 4.5 micrograms/g) diet. The incidence of ectrodactyly in the CBA strain decreased as dietary zinc increased, but was still present when dams were fed a high (1,000 micrograms/g) zinc diet. The incidence of resorptions and total abnormal sites from litters of dams receiving acetazolamide decreased as dietary zinc increased, with the magnitude of the response being influenced by the strain. A significant (dietary zinc X acetazolamide) and (strain X acetazolamide) interaction was found for the ectrodactyly response. The results demonstrate the importance of considering interactions among genetic strain, diet, and drugs, as well as single factors as determinants of fetal risk.

Abnormalities, Drug-Induced↗

Estimating intracellular pH in developing rodent embryos using a computer imaging technique: changes in embryonic pH and proliferation rates following maternal treatment with acetazolamide.

Using the transplacental distribution of the weak acid 5,5-dimethyloxazolidine-2,4-dione (DMO), a computer assisted imaging technique has been developed to permit the estimation of intracellular pH (pHi) in very specific areas of the developing rodent embryo. The study reported here demonstrates the heterogeneity of radiolabeled DMO distribution in the developing mouse forelimb. The pattern of pHi distribution shifts from one of high pHi values in the proximal core of the mesoderm on day 10 of gestation to one of higher pHi values in the mesoderm just underlying the ectoderm on day 11. Studies [Scott et al. (1990) Toxicol. Appl. Pharmacol. 103:238-254] in which DMO concentration was monitored following treatment with acetazolamide or acetazolamide plus amiloride were done in whole embryo homogenates or pooled limb samples which allow for the calculation of an average pHi but may not reflect the pHi in very specific locations of the limb. Two hours after acetazolamide administration, the pHi pattern was not significantly changed from control. Intracellular pH was raised above control levels but was not significant statistically except in the peripheral mesoderm in the ventral third of the forelimb. Fifteen hours after acetazolamide treatment, there was a significant decrease in pHi values with no change in pattern. However, treatment with acetazolamide plus amiloride for 15 hr produced a marked reduction of pHi values throughout the forelimb bud. Changes in bromodeoxyuridine labeling index (an indication of proliferative activity) following treatment with acetazolamide or acetazolamide plus amiloride are reported. The combination treatment reduced the labeling index by approximately 15% below that of control embryos in the limb region where absence of digit(s) will occur. However, we found no overall correlation of proliferative rate and pHi of limb bud mesoderm in treated embryos. Consequently, we were unable to causally associate reduced pHi with decreased proliferative rate.

Abnormalities, Drug-Induced↗

Effect of systemic acetazolamide on the fluid movement across the aqueous-vitreous interface.

In an attempt to study the effect of systemic acetazolamide on the fluid flow between the aqueous and vitreous in normal eyes, 50 mg kg(-1) acetazolamide was given intravenously every hour for 3 hr and the time change of the aqueous flow rate was calculated in two groups of rabbits, applying one of the following two different methods to each: the fluorescein method II of Jones and Maurice, a classical fluorometric method, or the more recently developed Johnson-Maurice method which entails intravitreal injection of FITC-dextran and measurements of its concentration in the anterior chamber many days after the injection. The flow rate after acetazolamide calculated by the fluorescein method II of Jones and Maurice in one group of rabbits was reduced to 55 +/- 5% (mean +/- S.E. n = 9) of the control on the average. When calculated by the Johnson-Maurice method in another group of rabbits, the reduction was to 80 +/- 4% (n = 11) of the control rate. The difference between the above figures was significant (P less than 0.005). Furthermore, the effect of acetazolamide calculated by the first procedure was significantly greater than that calculated by the second at 1 and 2.33 hr and at later times after the acetazolamide injection (P less than 0.05-0.01). On the other hand, the outflow pressure was reduced by 53-60% in both groups. The difference between the flow rates after acetazolamide determined by the above two methods was best explained by assuming that the FITC-dextran movement from the vitreous into the aqueous was reduced by about 25% after acetazolamide administration.(ABSTRACT TRUNCATED AT 250 WORDS)

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Lactic acid production in mouse calvaria in vitro with and without parathyroid hormone stimulation: lack of acetazolamide effects.

The effect of acetazolamide on lactic acid production in mouse calvaria explants was examined in an attempt to explain in vivo inhibition of Ca mobilization from bone by sulfonamide inhibitors of carbonic anhydrase. Lactic acid production was evaluated in 8-10-week-old CD-1 mouse calvaria over a time period consistent with acetazolamide inhibition of both PTH-stimulated and nonstimulated Ca mobilization from bone in vivo. Labeled lactate, derived from [3,4-14C]glucose, and total lactate production were determined at 2-h intervals for up to 8 h. Simultaneous assessment of 14CO2 production and [14C]pyruvate levels established that acetazolamide produced no other related metabolic effects and that the drug did not block PTH stimulation of CO2 production. Acetazolamide (4.5 X 10(-4) M) was found to have no effect on labeled or total lactate production in mouse calvaria for up to 8 h of treatment. In addition, acetazolamide did not block PTH (10(-7) M) stimulation of lactate production. However, Cl 13,850 (10(-4) M), a structural analog of acetazolamide devoid of inhibitory activity on carbonic anhydrase or Ca mobilization from bone, was shown to significantly reduce lactate production from mouse calvaria. These results, therefore, suggest that acetazolamide does not inhibit Ca mobilization from bone through inhibition of lactic acid production and fail to support a mechanistic relationship between lactic acid production and Ca mobilization from bone.

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Acetazolamide inhibits osmotic water permeability by interaction with aquaporin-1.

Water channel proteins, known as aquaporins, are transmembrane proteins that mediate osmotic water permeability. In a previous study, we found that acetazolamide could inhibit osmotic water transportation across Xenopus oocytes by blocking the function of aquaporin-1 (AQP1). The purpose of the current study was to confirm the effect of acetazolamide on water osmotic permeability using the human embryonic kidney 293 (HEK293) cells transfected with pEGFP/AQP1 and to investigate the interaction between acetazolamide and AQP1. The fluorescence intensity of HEK293 cells transfected with pEGFP/AQP1, which corresponds to the cell volume when the cells swell in a hyposmotic solution, was recorded under confocal laser fluorescence microscopy. The osmotic water permeability was assessed by the change in the ratio of cell fluorescence to certain cell area. Acetazolamide, at concentrations of 1 and 10muM, inhibited the osmotic water permeability in HEK293 cells transfected with pEGFP/AQP1. The direct binding between acetazolamide and AQP1 was detected by surface plasmon resonance. AQP1 was prepared from rat red blood cells and immobilized on a CM5 chip. The binding assay showed that acetazolamide could directly interact with AQP1. This study demonstrated that acetazolamide inhibited osmotic water permeability through interaction with AQP1.

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Presumed "sulfa allergy" in patients with intracranial hypertension treated with acetazolamide or furosemide: cross-reactivity, myth or reality?

PURPOSE: To determine whether acetazolamide or furosemide produce allergic cross-reactions in patients with self-reported "sulfa allergy." DESIGN: Retrospective case series. METHODS: A retrospective review included patients with intracranial hypertension and a self-reported sulfa allergy treated with either acetazolamide or furosemide seen at the University of Iowa Hospitals and Clinics from 1972 to 2003. All presumed medication-related side effects were collected, including both predictable adverse effects (for example, paresthesias, fatigue) and unpredictable adverse reactions (for example, cutaneous fixed eruptions, urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, anaphylaxis). RESULTS: We reviewed 363 charts. Of these, 329 patients (91%) were excluded. Of the remaining 34 cases that did report a so-called sulfa allergy, 13 (38%) received acetazolamide alone, 7 (21%) received furosemide alone, and 14 (41%) received both acetazolamide and furosemide. Of the 27 patients who received acetazolamide, 10 (37%) had no documented allergic cross-reaction to sulfa, and 2 (7%) cases had urticaria. The remaining 15 (56%) of acetazolamide-treated patients experienced predictable adverse reactions for this drug (for example, paresthesias). No patient experienced a severe allergic cross-reaction to sulfa. Of 21 patients who received furosemide, no unpredictable adverse reactions or allergic cross-reactions to sulfa were noted. CONCLUSIONS: We find little clinical or pharmacological evidence to suggest that a self-reported sulfa allergy is likely to produce a life-threatening cross-reaction with acetazolamide or furosemide. These medications should be considered for intracranial hypertension if the risk-to-benefit ratio warrants their use.

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Nitric oxide modulates cerebral blood flow stimulation by acetazolamide in the rat cortex: a laser Doppler scanning study.

The involvement of nitric oxide (NO) in cerebral blood flow (CBF) stimulation by acetazolamide was studied in anaesthetised, mechanically ventilated Wistar rats. CBF was monitored by laser Doppler scanning. Acetazolamide induced a long-lasting significant rCBF-increase. Application of NG-Nitro-L-arginine (L-NNA), an inhibitor of all NO synthetases (NOS), prevented CBF stimulation by acetazolamide. Continuous infusion of the exogenous NO donor SIN-1 (3-morpholinosydnonimine) suppressed L-NNA induced increases of mean arterial blood pressure without effect on rCBF in comparison to baseline. Additional acetazolamide injection then again caused a significant increase of rCBF in spite of NOS-inhibition. We thus conclude that NO is involved in acetazolamide-induced CBF stimulation. The mere continuous presence of NO is sufficient to re-establish the acetazolamide-response in spite of NOS-inhibition. These data suggest that NO acts rather as a modulator than as a mediator of the acetazolamide-induced CBF response.

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