Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ACETAZOLAMIDE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources
PubMed1995

Evaluation of the acetazolamide test. Vasoreactivity and cerebral blood volume.

BACKGROUND AND PURPOSE: We evaluated the potential usefulness of the acetazolamide test by investigating whether acetazolamide vasoreactivity reflected the change in resting cerebral blood volume caused by compensatory vasodilation due to a decline in cerebral perfusion pressure. METHODS: We measured resting and acetazolamide-activated cerebral blood flow with a stable xenon-enhanced CT system and resting cerebral blood volume with the subtraction technique using contrast-enhanced CT in 30 patients with various diseases. These parameters were measured in the anterior, middle, and posterior cerebral arterial territories of both hemispheres separately. We evaluated the statistical relationships between resting cerebral blood volume and vasoreactivity in these three territories, and the significance of the correlations was tested by ANOVA/ANCOVA to adjust for the double entries. RESULTS: Significant negative linear relationships were demonstrated between the resting cerebral blood volume and the change in cerebral blood flow, expressed as a percentage induced by acetazolamide activation, for the anterior (r = -.607, P = .0004), middle (r = -.551, P = .0015), and posterior (r = -.523, P = .0078) cerebral arterial territories and between the resting cerebral blood volume and the increase in cerebral blood flow (absolute values) for the anterior (r = -.512, P = .0164) and middle (r = -.523, P = .0001) but not the posterior (r = -.571, P = .0563) cerebral arterial territories. CONCLUSIONS: The acetazolamide test appears to be useful for the investigation of compensatory vasodilation: the vasoreactivity can be calculated as the increased cerebral blood flow expressed as a percentage or an absolute value, which both reflect cerebral blood volume directly.

Acetazolamide↗
PubMed1996

Sex-related differences in acetazolamide-induced cerebral vasomotor reactivity.

BACKGROUND AND PURPOSE: Cerebral vasomotor reactivity can easily be assessed reliably by measuring vasodilatory response to acetazolamide by transcranial Doppler sonography. The aim of this study was to confirm the hypothesis that female sex is associated with an increased cerebrovascular flow reserve. METHODS: Blood flow velocity of the middle cerebral artery was measured by transcranial Doppler sonography in 36 healthy sex- and age-matched subjects. After the initial blood flow velocities were recorded, the subjects received 14.3 mg/kg body wt acetazolamide, ie, 1 g/70 kg, intravenously. The measurements were repeatedly performed at 5-minute intervals starting 10 minutes after injection and lasting for 30 minutes. The highest measured flow velocities were used for further analysis. RESULTS: In both groups mean blood flow velocity increased significantly after acetazolamide (women, from 60.2 +/- 12.5 to 89.9 +/- 14.4 cm/s, P < .006; men, from 54.5 +/- 18.8 to 75.7 +/- 24.5 cm/s, P < .02). The difference in mean blood flow velocity after acetazolamide between groups of women and men was statistically significant (P < .02). CONCLUSIONS: Female subjects show an increased vasodilatory response to the acetazolamide test compared with men.

Acceleration↗
PubMed1996

Relationships between cerebral regional blood flow velocities and volumetric blood flows and their respective reactivities to acetazolamide.

BACKGROUND AND PURPOSE: The technique of transcranial Doppler ultrasonography (TCD) is widely used for assessment of cerebral blood flow velocity. Whether measurement of changes in TCD velocity can be used for studying volumetric cerebral blood flow variations remains a matter of debate. We therefore investigated the relationship between flow velocity and volumetric cerebral blood flow before and during acetazolamide-induced vasodilation. METHODS: The middle cerebral artery mean blood flow velocity (MV) measured by TCD and the corresponding regional and hemispheric cerebral blood flows assessed with 133Xe single-photon emission CT were measured in 52 unselected patients. Absolute values of flow and velocity before and after stimulation and their reactivity to acetazolamide were compared. When the correlation was statistically significant, the linearity of the relationship was tested. RESULTS: Absolute values of hemispheric cerebral blood flow were correlated with MV both before (r = .315, P = .02) and after acetazolamide (r = .436, P = .001), whereas regional cerebral blood flow was correlated with MV only after acetazolamide (before, r = .262, P = .06; after, r = .446, P = .001). All these relationships fitted a linear model. In contrast, there was no correlation between acetazolamide-induced relative increments of flow and velocity. CONCLUSIONS: Our results support a linear model describing the relationship between absolute values of flow and velocity when arterial section is the slope and anastomotic blood flow is the intercept. In contrast, relative increments in volumetric flow and velocity may be proportional only if anastomotic flow is negligible, ie, in subjects without cerebrovascular disease. We conclude that, for patients with cerebrovascular disease, TCD does not satisfactorily model cerebral vasoreactivity in terms of volumetric cerebral blood flow.

Acetazolamide↗
PubMed1987

Respiratory stimulants and sleep periodic breathing at high altitude. Almitrine versus acetazolamide.

We studied the effects of almitrine, acetazolamide, and placebo on the hypoxic ventilatory response (HVR), sleep periodic breathing, and arterial oxygen saturation (SaO2) in 4 healthy climbers. In a laboratory on Denali (Mt. McKinley) at 4,400 m (PB = 440 mm Hg), we used a double-blind, randomized, three-way crossover design. The HVR was measured during the waking state. Periodic breathing and SAO2% were measured during 3-h sleep studies. Almitrine and acetazolamide both increased SaO2% during sleep, although almitrine increased periodic breathing, whereas acetazolamide decreased periodic breathing. The HVR (delta VE/delta SaO2%) was doubled with almitrine (p less than 0.05), but unchanged with acetazolamide. The HVR was positively related to periodic breathing (p less than 0.05). We conclude that periodic breathing during sleep at high altitude is related to the hypoxic ventilatory response, and that acetazolamide is a superior agent to almitrine for ameliorating periodic breathing.

Acetazolamide↗
PubMed2004

Experimental retinal vein occlusion: effect of acetazolamide and carbogen (95% O2/5% CO2) on preretinal PO2.

PURPOSE: To evaluate the variations of preretinal oxygen partial pressure (Po(2)) in normal and in ischemic postexperimental branch retinal vein occlusion (BRVO) areas, during normoxia, hyperoxia (100% O(2)), and carbogen (95% O(2), 5% CO(2)) breathing before and after intravenous injection of acetazolamide. METHODS: Preretinal Po(2) measurements were obtained in intervascular retinal areas, distant from the retinal vessels of 13 anesthetized mini-pigs with oxygen-sensitive microelectrodes (10 microm tip diameter) introduced through the vitreous cavity by a micromanipulator. The microelectrode tip was placed <50 microm from the vitreoretinal interface in the preretinal vitreous. Po(2) was measured continuously for 10 minutes under systemic normoxia, hyperoxia, and carbogen breathing. A BRVO was induced with an argon green laser, and oxygen measurements were repeated under normoxia, hyperoxia, and carbogen breathing, before and after intravenous injection of acetazolamide (500 mg bolus). RESULTS: In hyperoxia, a moderate nonsignificant preretinal Po(2) increase in both normal (DeltaPo(2) = 2.20 +/- 4.16 mm Hg; n = 25) and ischemic retinas (DeltaPo(2) = 4.30 +/- 3.57 mm Hg; n = 16) was measured in spite of a substantial increase in systemic Pao(2). Carbogen breathing induced a significant increase in systemic Paco(2) and a higher systemic Pao(2) than hyperoxia. Furthermore, it significantly increased the preretinal Po(2) in normal areas (DeltaPo(2) = 19.37 +/- 16.41 mm Hg; n = 26), and in ischemic areas (DeltaPo(2) = 14.94 +/- 8.53 mm Hg; n = 14). Intravenous acetazolamide did not affect the preretinal Po(2). Acetazolamide induced an increase of the preretinal Po(2) to a greater extent when it was associated with carbogen breathing (DeltaPo(2) = 15.15 +/- 9.15 mm Hg; n = 7) than when it was combined with hyperoxia (DeltaPo(2) = 6.96 +/- 4.49 mm Hg; n = 7). CONCLUSIONS: Carbogen breathing significantly increased preretinal Po(2) in normal and in ischemic postexperimental BRVO areas of mini-pigs. The concomitant use of acetazolamide injection and carbogen breathing or hyperoxia could restore an appropriate oxygenation of BRVO areas.

Acetazolamide↗
PubMed2005

Effect of carbogen breathing and acetazolamide on optic disc PO2.

PURPOSE: Acetazolamide was previously shown to increase optic disc partial pressure of oxygen (PO(2)). The study was conducted to evaluate optic disc PO(2) variations during normoxia, hyperoxia (100% O(2)), and carbogen breathing (95% O(2), 5% CO(2)), before and after intravenous administration of acetazolamide. METHODS: PO(2) measurements were obtained at intervascular areas of the optic disc in nine anesthetized minipigs using oxygen-sensitive microelectrodes (10-microm tip diameter) placed at <50 microm from the optic disc. PO(2) was measured continuously during 10 minutes under normoxia, hyperoxia, or carbogen breathing. Oxygen measurements were repeated under these conditions after intravenous injection of acetazolamide (500-mg bolus). RESULTS: In hyperoxia, optic disc PO(2) increased moderately (DeltaPO(2) = 4.81 +/- 1.16 mm Hg (mean +/- SD; 24%; P < 0.001) after a much larger increase in systemic PaO(2). Carbogen breathing induced a significant increase in both systemic PaO(2) and PaCO(2), which resulted in a large increase in optic disc PO(2) (DeltaPO(2) = 13.17 +/- 2.18 mm Hg; 67%; P < 0.001). Acetazolamide induced a slow and progressive increase in both systemic PaCO(2) and optic disc PO(2) (30 minutes DeltaPO(2) = 4.24 +/- 2.45 mm Hg; 24%; P < 0.04). However, it was when carbogen was simultaneously administered that optic disc PO(2) increased most substantially (DeltaPO(2) = 18.91 +/- 5.23 mm Hg; 90%; P < 0.002). CONCLUSIONS: Carbogen breathing increases optic disc Po(2) significantly in minipigs, more than hyperoxia. The association of acetazolamide injection with carbogen breathing could induce an additional increase in optic disc PO(2) through the effect of higher systemic PaCO(2).

Acetazolamide↗
PubMed1974

Effects of acetazolamide on the urinary excretion of cyclic AMP and on the activity of renal adenyl cyclase.

Acetazolamide, an inhibitor of the enzyme carbonic anhydrase, increased the urinary excretion of cyclic AMP in normal and parathyroidectomized rats. The increase was greater in rats with intact parathyroid glands than in parathyroidectomized rats. This rise in the urinary excretion of cyclic AMP was not due to an increase in urine flow or a change in urine pH. Furosemide caused an increase in urine flow, but did not affect the excretion of cyclic AMP or phosphate. Alkalinization of the urine with bicarbonate did not increase the urinary excretion of phosphate or cyclic AMP. Acetazolamide increased the productionof cyclic AMP by rat renal cortical slices in vitro. This effect was dose-dependent. Acetazolamide also stimulated the activity of renal cortical adenyl cyclase in a dose-dependent manner but had no effect on the activity of cyclic nucleotide phosphodiesterase. The pattern of urinary excretion of cyclic AMP and phosphate after administration of acetazolamide was similar to that observed in rats given parathyroid hormone. It is suggested that acetazolamide stimulates the renal production of cyclic AMP by activating adenyl cyclase and that this may be the mechanism by which this inhibitor of carbonic anhydrase produces phosphaturia.

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↗
PubMed1984

Effect of acetazolamide on cerebral blood flow and cerebral metabolic rate for oxygen.

The aim of this study was to evaluate the effect of acetazolamide on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2). CBF, arterial and jugular venous partial O2 pressure, partial CO2 pressure, pH, and O2 saturation percentage were measured in six patients before and 3 and 20 minutes after intravenous administration of 1 g of acetazolamide. CBF was measured by the intracarotid 133xenon injection technique. In addition, changes in CBF were estimated from the arteriovenous oxygen content difference. CBF increased in all patients after acetazolamide, by approximately 55 and 70% after 3 and 20 min, respectively. The CBF changes were of the same order whether calculated from the 133Xe clearance or from the arteriovenous oxygen differences (A-V)O2. CMRO2, calculated from (A-V)O2 differences and CBF, remained constant. Except for an increase in the venous oxygen saturation, the blood gases remained constant. Acetazolamide, in a dose sufficient to inhibit the erythrocyte carbonic anhydrase (EC 4.2.1.1), thus induced a rapid and marked increase in CBF, leaving CMRO2 unchanged. This effect of acetazolamide on CBF is probably explained by a decrease in brain pH rather than by brain tissue hypoxia due to inhibition of oxygen unloading in the brain capillaries.

Acetazolamide↗
PubMed1986

Acetazolamide in prevention of acute mountain sickness.

A controlled comparative between-group study of 48 climbers ascending Kilimanjaro (5895m) was designed as an extension to our previous double-blind cross-over trial on the same peak in 1980, using acetazolamide to decrease the incidence and effects of Acute Mountain Sickness. A group taking acetazolamide 500 mg each morning for one day before reaching 3000m were compared with 3 control groups of Caucasian subjects and lowland and highland Africans. Efficacy was assessed on climbing performance and scores derived from symptoms recorded daily by subjects. Those taking acetazolamide reached higher altitudes and had lower symptom scores than those in control groups. The results support the use of acetazolamide as an effective prophylactic for Acute Mountain Sickness, for most people in a dose of 500 mg in the morning starting one day before ascent above 3000m. The optimal dose of prophylactic acetazolamide is not established, nor is the most appropriate time for medication prior to ascent.

Acetazolamide↗
PubMed2006

Acetazolamide-mediated decrease in strong ion difference accounts for the correction of metabolic alkalosis in critically ill patients.

INTRODUCTION: Metabolic alkalosis is a commonly encountered acid-base derangement in the intensive care unit. Treatment with the carbonic anhydrase inhibitor acetazolamide is indicated in selected cases. According to the quantitative approach described by Stewart, correction of serum pH due to carbonic anhydrase inhibition in the proximal tubule cannot be explained by excretion of bicarbonate. Using the Stewart approach, we studied the mechanism of action of acetazolamide in critically ill patients with a metabolic alkalosis. METHODS: Fifteen consecutive intensive care unit patients with metabolic alkalosis (pH > or = 7.48 and HCO3- > or = 28 mmol/l) were treated with a single administration of 500 mg acetazolamide intravenously. Serum levels of strong ions, creatinine, lactate, weak acids, pH and partial carbon dioxide tension were measured at 0, 12, 24, 48 and 72 hours. The main strong ions in urine and pH were measured at 0, 3, 6, 12, 24, 48 and 72 hours. Strong ion difference (SID), strong ion gap, sodium-chloride effect, and the urinary SID were calculated. Data (mean +/- standard error were analyzed by comparing baseline variables and time dependent changes by one way analysis of variance for repeated measures. RESULTS: After a single administration of acetazolamide, correction of serum pH (from 7.49 +/- 0.01 to 7.46 +/- 0.01; P = 0.001) was maximal at 24 hours and sustained during the period of observation. The parallel decrease in partial carbon dioxide tension was not significant (from 5.7 +/- 0.2 to 5.3 +/- 0.2 kPa; P = 0.08) and there was no significant change in total concentration of weak acids. Serum SID decreased significantly (from 41.5 +/- 1.3 to 38.0 +/- 1.0 mEq/l; P = 0.03) due to an increase in serum chloride (from 105 +/- 1.2 to 110 +/- 1.2 mmol/l; P < 0.0001). The decrease in serum SID was explained by a significant increase in the urinary excretion of sodium without chloride during the first 24 hours (increase in urinary SID: from 48.4 +/- 15.1 to 85.3 +/- 7.7; P = 0.02). CONCLUSION: A single dose of acetazolamide effectively corrects metabolic alkalosis in critically ill patients by decreasing the serum SID. This effect is completely explained by the increased renal excretion ratio of sodium to chloride, resulting in an increase in serum chloride.

Acetazolamide↗
PubMed1985

Positive renal response to intravenous acetazolamide in patients with carbonic anhydrase II deficiency.

Carbonic anhydrase II (CA II) is the only soluble isozyme of CA which is known to be expressed in kidney. We recently identified a deficiency of this enzyme as the basis for the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. In order to explore the physiological importance of CA II in the kidney, we studied the renal response to intravenously infused acetazolamide in two CA II-deficient patients and two control subjects. Following acetazolamide infusion, the CA II-deficient patients exhibited a prompt rise in urinary pH and HCO3- excretion similar to the response seen in control subjects. These findings indicate that CA II-deficient patients, who lack detectable CA II in their erythrocytes, still expressed an acetazolamide-inhibitable CA activity in their kidneys. These results can be explained in three ways: 1) the CA II deficiency which is profound in the erythrocytes of these patients may not be expressed in their kidney. 2) An acetazolamide-sensitive CA other than CA II, such as CA I and CA III, which is not normally expressed in kidney, is expressed in kidneys of CA II-deficient patients. 3) The CA II deficiency is expressed in kidney in these patients but the acetazolamide response is due to inhibition of the luminal, membrane-bound CA which is the product of a different gene and unaffected by the CA II deficiency mutation. We favor the third possibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗
PubMed1992

The effects of acetazolamide on the ventilatory response to high altitude hypoxia.

Acetazolamide treatment ameliorates the symptoms of AMS; however, the mechanism by which this occurs is unclear. To examine the effects of acetazolamide on oxygenation, CO2 responsiveness and ventilatory pattern during acute exposure to HA, we studied two groups of subjects at SL and following rapid (less than 8 h) transport to HA. Acetazolamide or placebo tablets were given to groups 1 and 2, respectively, in a double-blind manner after baseline SL measurements; treatment was continued during HA exposure. There was no difference in the ventilatory pattern at HA, between the two groups. While the Ve achieved in response to CO2 at HA vs SL was much greater in each group the percent change from baseline at HA versus that at SL was not significantly different. The beneficial effects of acetazolamide in AMS are associated with a higher level of ventilation at HA and better oxygenation: CO2 chemosensitivity is not affected by acetazolamide at HA.

Acetazolamide↗
PubMed2006

Prevention of acute mountain sickness by acetazolamide in Nepali porters: a double-blind controlled trial.

OBJECTIVE: This study aimed to determine the efficacy, tolerability, and practicality of acetazolamide for the prevention of acute mountain sickness (AMS) in Nepali trekking porters early in the trekking season. METHODS: This study was a randomized, double-blind controlled trial with 400 male Nepali porters in the Mount Everest region of Nepal, trekking from Namche Bazaar (3440 m) to Lobuche (4930 m), the study endpoint. Participants were randomized to receive 250 mg acetazolamide daily or placebo, and AMS symptom scores (Lake Louise) were compared in highlanders vs lowlanders. RESULTS: Only 109 (27.2%) of the 400 porters completed the trial (28 highlanders, 81 lowlanders). The rest either dropped out (275/400 porters, 68.8%) or were excluded (16/400 porters, 4%). Acute mountain sickness occurred in 13 (11.9%) of 109 porters; all were lowlanders; 7 were taking acetazolamide, 6 taking placebo. Birthplace, acclimatization in the week before the trial, ascent rate, and rest days were the most important variables affecting the incidence of AMS. No highlanders, but 13 (16.1%) of 81 lowlanders had AMS (P = .016). Acclimatization in the pretrial week reduced AMS incidence (P = .013), as did a slower ascent rate (P = .0126), but rest days were the most potent prophylactic variable (P = .0001). Side effects were more frequent in porters taking acetazolamide than in the placebo group (P = .0001), but there were no serious side effects. CONCLUSIONS: Acetazolamide was tolerable, but impractical for the routine prevention of AMS in Nepali porters. A good trekking schedule and adequate acclimatization remain the most effective preventive measures. This study identified lowland porters as a high-risk group for developing AMS.

Acetazolamide↗
PubMed1997

Brain pH responses to acetazolamide and hypercapnia in cats.

The involvement of increased brain tissue CO2 tension in acetazolamide-induced brain acidosis was investigated by comparing the brain pH response to acetazolamide with that to hypercapnia. CO2 and pH sensors were placed bilaterally into cerebral white matter to 15 mm depth in cats. Group 1 cats (n = 9) breathed spontaneously, and in situ brain tissue PCO2, and pH (PbCO2 and pHb) were measured after intravenous acetazolamide administration (20 mg/kg). Group 2 cats (n = 9) were paralyzed and ventilated mechanically, and the changes of pHb were investigated by adjusting the ventilation to maintain the same Pbco2 values as in the acetazolamide-treated group. PbCO2 changes were not significantly different between the two groups. However, pHb responses were quite different: the fall in pHb was progressive in Group 1 but transient in Group 2. Brain acidosis after acetazolamide administration is not due to the rise in brain tissue CO2 tension.

Acetazolamide↗
PubMed1998

Cerebral blood flow and the response to acetazolamide during the acute, subacute, and chronic stages of aneurysmal subarachnoid hemorrhage.

Cerebral blood flow (CBF) and response to acetazolamide were measured during the acute, subacute, and chronic stages after aneurysmal subarachnoid hemorrhage and correlated with symptomatic vasospasm and clinical outcome in 45 patients who underwent early clipping of ruptured cerebral aneurysms, of whom 18 had symptomatic vasospasm and 27 did not. Xenon-enhanced computed tomography was used to measure CBF in both groups during the acute, subacute, and chronic stages, defined as days 0-4, 5-20, and > or = 21, respectively. Vasoresponse was assessed by the CBF increase in response to 1 g of acetazolamide administered after the baseline CBF study, except in the subacute stage of patients with symptomatic vasospasm. Outcome was scored based on activities of daily living 2-3 months after subarachnoid hemorrhage. CBF values and the response to acetazolamide were preserved during the acute stage but CBF values fell considerably below control values during the subacute stage in patients with vasospasm. The regions with flow values below 15 ml/100 g/min subsequently converted to infarction and the regions with those above 19 ml/100 g/min remained intact without infarction. During the chronic stage, low CBF persisted, but the response to acetazolamide was higher than that of the control group. Outcome scores were good and fair. CBF values were normal during all stages in patients without vasospasm. The response to acetazolamide fell transiently during the subacute stage. All outcome scores were excellent. In conclusion, the CBF informations soon after the onset of symptomatic vasospasm are useful to predict a reversibility of ischemic brain tissue and a final outcome. We suggest that vasospasm may cause a pathological or ischemic insult to brain tissue during the subacute stage, and the brain may remain metabolically depressed thereafter, leading to a poor outcome. Even clinically asymptomatic patients may suffer mildly vasospastic or ischemic conditions during the subacute stage.

Acetazolamide↗
PubMed2002

Pathogenic mechanism, prophylaxis, and therapy of symptomatic acidosis induced by acetazolamide.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 cycle damage. We demonstrate that the dramatic disappearance of metabolic acidosis and normalizing metabolism after blood transfusion were due to the citrate contained in the packed red blood cell bag. This hypothesis was confirmed by animal experimentation. We argue that the metabolic disorder and bone marrow suppression may be related. CONCLUSION: We demonstrate how acetazolamide can lead to symptomatic metabolic acidosis and probably to bone marrow suppression. We suggest citrate as a possible prophylaxis and treatment for these adverse reactions.

Acetazolamide↗
PubMedDate not supplied

Chronic acetazolamide intoxication.

Severe acidosis associated with acetazolamide therapy is rare. We report the first case in which plasma and whole blood acetazolamide concentrations were measured. A 61 year-old patient receiving oral acetazolamide for treatment of glaucoma presented with a 7 day history of declining mental status. The patient was lethargic and oriented only to name. The respiratory rate was 36 per minute in a Kussmaul pattern with arterial blood gases revealing a pH of 7.23, pO2 68 mmHg, paCO2 14 mmHg and bicarbonate 6 mEq/L. Serum creatinine was 3.1 mg%, Cl 126 mEq/L, and anion gap 15. Urine pH was 6.0. Infection and other causes of acidosis and bicarbonate loss were excluded, and he was discharged with normal mental status and improving acid-base balance 18 days after admission. Acetazolamide concentrations four days after the last dose were 26.38 mcg/ml and 38.84 mcg/ml in serum and whole blood, respectively. The serum half-life was 34 hours, compared to a range of 1.5 to 6 hours in subjects with normal renal function. Monitoring acetazolamide concentrations may be useful in adjusting dosage and preventing toxicity in patients with decreased renal function.

Acetazolamide↗