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Treatment of "permanent" muscle weakness in familial Hypokalemic Periodic Paralysis.

Three patients with Hypokalemic Periodic Paralysis (HOPP)-associated progressive interattack muscle weakness, who became unresponsive or worsened by acetazolamide, responded favorably to dichlorophenamide, a more potent carbonic anhydrase inhibitor. Dichlorophenamide in single-blind placebo-controlled trials, considerably improved functional strength in two of the patients and had a moderate but definite effect in the third. Muscle groups graded 4/5 (MRC scale)returned to normal; very weak (0-3/5) atrophic muscles, improved to a minor degree. In one patient with acetazolamide-resistant paralytic attacks, dichlorophenamide also diminished the frequency and severity of the acute attacks. Dichlorophenamide had, in the present study, less effect than acetazolamide in reducing serum HCO3(-) and elevating Cl-. Its effectiveness may be related to the degree of sensitivity of certain HOPP patients to alterations of Cl- and/or HCO3(-) serum levels or to a different action of the drug unrelated to carbonic anhydrase inhibition or acidosis. Dichlorophenamide should be considered as an alternate to acetazolamide in the treatment of patients with HOPP-associated interattack muscle weakness who have become unresponsive or worsened by acetazolamide.

Adult↗

The effect of carbonic anhydrase inhibitors on secretion by the parotid and mandibular glands of red kangaroos Macropus rufus.

The effects of carbonic anhydrase inhibitors on secretion by macropodine parotid and mandibular glands were investigated using anaesthetized red kangaroos. In the parotid gland, acetazolamide (500 mumol.l-1) reduced a stable acetylcholine-evoked, half-maximal flow rate of 2.02 +/- 0.034 to 0.27 +/- 0.023 ml.min-1 (87% reduction). Concurrently, salivary bicarbonate concentration and secretion fell (129.4 +/- 1.46 to 80.9 +/- 1.63 mmol.l-1 and 264.8 +/- 7.96 to 22.3 +/- 2.30 mumol.min-1, respectively), phosphate and chloride concentrations rose (14.0 +/- 0.79 to 27.6 +/- 0.85 mmol.l-1 and 5.6 +/- 0.25 to 27.5 +/- 1.32 mmol.l-1, respectively), sodium concentration and osmolality were unaltered, and potassium concentration fell (8.8 +/- 0.33 to 6.4 +/- 0.29 mmol.l-1). High-rate cholinergic stimulation during acetazolamide blockade was unable to increase salivary flow beyond 11 +/- 0.9% of that for equivalent unblocked control stimulation. However, superimposition of isoprenaline infusion on the acetylcholine stimulation caused a three-fold increase in the blocked flow rate. These treatments were accompanied by small increases in salivary phosphate and chloride concentrations but not bicarbonate concentration. Methazolamide infusion caused similar changes in parotid secretion. In the mandibular gland, acetazolamide infusion had no effect on salivary flow rate during either low- or high-level acetylcholine stimulation. Acetazolamide caused no alterations in salivary electrolyte secretion at low flow rates, but curtailed the rise in bicarbonate concentration associated with high-level acetylcholine stimulation. Acetazolamide administration did not affect the increase in salivary flow rate associated with isoprenaline infusion, but did block the concomitant increase in bicarbonate concentration and secretion substantially.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Psychophysical and neurobiological evidence that the oral sensation elicited by carbonated water is of chemogenic origin.

The sensation produced by carbonated beverages has been attributed to chemical excitation of nociceptors in the oral cavity via the conversion of CO(2) to carbonic acid in a reaction catalyzed by carbonic anhydrase. In separate studies, we tested if the carbonic anyhdrase blocker, acetazolamide, reduced either the intensity of sensation in humans or c-fos expression by trigeminal neurons in rats, evoked by application of carbonated water to the tongue. In the psychophysical experiment, one-half of the dorsal tongue was pretreated with acetazolamide (1 or 2%), after which the tongue was exposed bilaterally to carbonated water. In a two-alternative forced-choice paradigm, subjects chose which side of the tongue yielded a stronger sensation and additionally rated the magnitude of sensation on each side. Pretreatment with acetazolamide reduced the magnitude of sensation elicited by carbonated water in a concentration-dependent manner, since a significant majority of subjects chose the untreated side of the tongue as having a stronger sensation and assigned significantly higher intensity ratings to that side. Acetazolamide did not affect the irritant sensation from citric acid, while capsaicin pretreatment reduced both the sensation elicited by carbonated water and the irritation induced by citric acid application. In a separate experiment using rats, delivery of carbonated water to the tongue significantly increased the number of cells expressing c-fos-like immunoreactivity in the dorsomedial trigeminal nucleus caudalis (versus saline controls); this was significantly reduced by pretreatment with acetazolamide. Our results support the hypothesis that carbonated water activates lingual nociceptors via conversion of CO(2) to carbonic acid; the nociceptors in turn excite trigeminal neurons involved in signaling oral irritation.

Administration, Oral↗

The Role of External Carbonic Anhydrase in Inorganic Carbon Acquisition by Chlamydomonas reinhardii at Alkaline pH.

The role of external carbonic anhydrase in inorganic carbon acquisition and photosynthesis by Chlamydomonas reinhardii at alkaline pH (8.0) was studied. Acetazolamide (50 micromolar) completely inhibited external carbonic anhydrase (CA) activity as determined from isotopic disequilibrium experiments. Under these conditions, photosynthetic rates at low dissolved inorganic carbon (DIC) were far greater than could be maintained by CO(2) supplied from the spontaneous dehydration of HCO(3) (-) thereby showing that C. reinhardii has the ability to utilize exogenous HCO(3) (-). Acetazolamide increased the concentration of DIC required to half-saturate photosynthesis from 38 to 80 micromolar, while it did not affect the maximum photosynthetic rate. External CA activity was also removed from the cell-wall-less mutant (CW-15) by washing. This had no effect on the photosynthetic kinetics of the algae while the addition of acetazolamide to washed cells (CW-15) increased the K((1/2)) (DIC) from 38 to 80 micromolar. Acetazolamide also caused a buildup of the inorganic carbon pool upon NaHCO(3) addition, indicating that this compound partially inhibited internal CA activity. The effects of acetazolamide on the photosynthetic kinetics of C. reinhardii are likely due to the inhibition of internal rather than a consequence of the inhibition of external CA. Further analysis of the isotopic disequilibrium experiments at saturating concentration of DIC provided evidence consistent with active CO(2) transport by C. reinhardii. The observation that C. reinhardii has the ability to take up both CO(2) and bicarbonate throws into question the role of external CA in the accumulation of DIC in this alga.

Journal Article↗

Glaucoma treatment with timolol.

Thirty-two eyes from 19 patients with either capsular glaucoma, pigmentary glaucoma or primary open angle glaucoma were given topical timolol and followed through a 3--6 months period. Twelve eyes were previously out of control on full medication including pilocarpine, epinephrine and acetazolamide. Eight of these eyes could be adequately controlled throughout the follow-up period on topical timolol or a combination of timolol and pilocarpine, but without resorting to acetazolamide. One eye needed acetazolamide in combination with timolol, and three eyes had to be referred to surgery. Twelve eyes were adequately controlled either on pilocarpine or full medication, but could be equally well controlled on timolol alone, or timolol and pilocarpine in combination. Acetazolamide could be withheld from all of the six patients who used this drug. Eight eyes were previously untreated. They could all be adequately controlled either on timolol (5 eyes) or timolol and pilocarpine (3 eyes). The study indicates that the effect of timolol 0.5% X 2 may be stronger than the combined effect of epinephrine 1% X 2 and acetazolamide 500 mg a day. Topical timolol was well tolerated. No side reactions occurred and the pupillary size and reactions were not influenced by the timolol treatment.

Administration, Topical↗

[General anesthesia vs. retrobulbar anesthesia in cataract surgery. A randomized comparison of patients at risk].

Several studies comparing retrobulbar block (RB) and general anaesthesia (GA) for cataract surgery in the elderly have been published. Most of them were retrospective. Our prospective study was designed in order to determine the benefits or disadvantages using RB or GA. Arterial blood gases (ABG) and cardiovascular stability were explored in high-risk patients undergoing elective unilateral cataract extraction. METHODS. Forty patients over 65 years of age and with other co-existing diseases (ASA III-IV) were allocated randomly to receive either GA or RB. No premedication was given to either group of patients. On arrival in the anaesthetic room, a radial artery was cannulated for collection of blood samples and direct monitoring of the blood pressure. Pulse oximetry and ECG were continuously monitored in all patients, the end-expiratory CO2 (F(eexCO2)) only in the GA group. GA was induced with vecuronium 0.1 mg/kg and thiopentone 5 mg/kg; the lungs were ventilated with 100% oxygen. After intubation of the trachea controlled mechanical ventilation was continued with N2O/O2 (55:45) and enflurane 1%-2%. Only enflurane concentrations were varied to correct changes in mean arterial pressure (MAP) if these exceeded +/- 20%. Respiratory frequency and tidal volume were kept constant until completion of surgery. The patients were extubated when they were able to ventilate more than 5 1/min (pressure support 10 cmH2O; PEEP 5 cmH2O). After extubation no O2 was given. In the RB group neural block was undertaken with prilocaine 2% (3 ml) as a retrobulbar injection and prilocaine 1% (5 ml) to block the facial innervation of the orbicularis muscle (Van Lint, O'Brien). Oxygen 3 1/min was administered by nasal tube during the operation. Nine arterial samples for blood gas analysis were collected: (1) control; (2) before operation; (3) 5 min after beginning the operation; (4) 15 min after beginning the operation and before i.v. administration of 500 mg acetazolamide over 5 min; (5) after acetazolamide; (6 and 7) 10 and 20 min after acetazolamide; and (8 and 9) 15 and 30 min after operation (RB) or extubation (GA). RESULTS. The patient demography, including duration of anaesthesia and operation, was similar in both groups (Table 1). Four patients in the GA group (2 needed O2 after extubation because of hypoxaemia) and 2 in the RB group were excluded. No significant differences were seen in base excess (BE) and standard bicarbonate (SHCO3). Arterial O2 tension, arterial O2 saturation, and pulse-oximetric O2 saturation were higher in the RB group intra- and postoperatively (Figs. 1, 3, 4). Arterial CO2 tension (PaCO2) was significantly higher in the GA group during the pre- and postoperative period (Fig. 2), but not during the operation. The PaCO2- F(eexCO2) gradient ranged between 5 and 9 mmHg. Administration of acetazolamide did not influence this gradient by regressive analysis. The postoperative outcome of the patients was comparable in both groups. Nausea or vomiting did not occur. MAP was significantly higher in the RB group during the operation. No significant differences were seen in the pre- and postoperative period. Heart rate in the GA group was higher only after extubation, but was within physiological limits. DISCUSSION. Despite the differing results between the two groups, our study showed no important advantage related to either RB or GA. Changes in ABG, MAP, and heart rate during the investigation period were within physiological limits in elderly patients. Intravenous acetazolamide did not influence ABG in a significant manner. With regard to the preference of each patient, we recommend both RB and GA for cataract surgery in high-risk patients on the assumption of sufficient preoperative treatment of co-existing diseases. In conclusion, cardiovascular and ABG stability were maintained during both anaesthetic techniques.

Aged↗

Carbonic anhydrase inhibitors for hypercapnic ventilatory failure in chronic obstructive pulmonary disease.

BACKGROUND: Carbonic anhydrase inhibitors such as acetazolamide cause a mild metabolic acidosis and may stimulate breathing. Some patients with severe chronic obstructive pulmonary disease (COPD) develop chronic hypercapnic ventilatory failure. In theory, they may benefit from use of these drugs with a fall in arterial carbon dioxide level (PCO2) and a rise in arterial oxygen (PO2). OBJECTIVES: To determine the effectiveness and safety of acetazolamide in the treatment of hypercapnic ventilatory failure due to COPD SEARCH STRATEGY: The Cochrane Register of Controlled Clinical Trials was searched along with Medline, Embase, Central and CINAHL for relevant randomised control trials. SELECTION CRITERIA: Trials were included in the review provided they were placebo controlled, carried out in patients with stable chronic ventilatory failure due to COPD. DATA COLLECTION AND ANALYSIS: Data were extracted and analysed by two reviewers (PJ and MG) and agreement was reached by consensus. Where data could be aggregated they were analysed using a fixed efefcts model and reported as a weighted mean difference (WMD) and its associated 95% confidence interval (95% CI). MAIN RESULTS: Four trials were included in the review. Of these, two were randomised parallel studies, one was a crossover study and the other had a sequential design. A total of 84 patients were involved. Study quality was mixed and the studies were short (typically two weeks). All studies showed a similar direction and size of effect. In the randomised parallel studies, acetazolamide caused a metabolic acidosis and produced a non-significant fall in PCO2 (WMD -0.41 kPa; 95% CI -0.91, 0.09; N=2) and a significant rise in PO2 (WMD 1.54 kPa; 95% CI 0.97, 2.11; N=2). One study reported an improvement in sleep but there were no data concerning outcomes such as health status, symptoms, exacerbation rate, hospital admissions or deaths. Side effects were reported infrequently. REVIEWER'S CONCLUSIONS: Acetazolamide can produce a small increase in arterial PO2 and fall in PCO2. These conclusions are drawn from a few small short studies that were not all of high quality. It is not known whether this physiological improvement is associated with clinical benefit.

Acetazolamide↗

Comparative effects of intraocular pressure between systemic and topical carbonic anhydrase inhibitors: a clinical masked, cross-over study.

The aims of the following study were to compare the efficacy of Dorzolamide 1% eye drops with systemic Acetazolamide on the ocular pressure diurnal curve in patients with maximal medical therapy. Three ocular pressure curve were performed in glaucomatous patients, already receiving maximal medical therapy. After a baseline curve, patients were pretreated either with Dorzolamide 1% eye drops or 250 mg Acetazolamide tablets in a double-blind cross-over study. Dorzolamide 1% eye drops and 250 mg Acetazolamide tablets significantly reduced intraocular pressure (IOP) at 2 and 4 h after pretreatment. Both treatments caused a significantly additional decrease of IOP despite maximal medical therapy. Dorzolamide 1% eye drops is as effective as Acetazolamide tablets in reducing the IOP curve. Topical carbonic anhydrase inhibitors may represent an additional and safer treatment for those patients with uncontrolled medical glaucoma.

Acetazolamide↗

Respiratory function and carbonic anhydrase inhibition.

Acetazolamide (Diamox) induced carbonic anhydrase inhibition is an efficient means of eliminating surplus water and bicarbonate in the overhydrated and alkalotic patient. Previous studies have demonstrated an unexpected and unexplained increase in arterial and venous oxygenation during acute carbonic anhydrase inhibition. In the present investigation we assessed the effect of acetazolamide 15 mg kg-1 on pulmonary gas exchange in 10 critically ill, mechanically ventilated patients. Median arterial oxygen tension increased by 0.9 kPa and central venous oxygen tension and content by 16-18% and 6-8% respectively. The improved oxygenation could, however, not be attributed to an improved pulmonary oxygen exchange as both pulmonary venous admixture (Qs Qt-1) and physiological dead space ventilation (VD VT-1) increased. The increase in arterial oxygen tension can be explained by a rightward shift of the oxyhemoglobin dissociation curve due to the increased acidity of the blood during carbonic anhydrase inhibition (Bohr effect). Acetazolamide does not depress oxygen consumption, so the increase in central venous oxygen content probably reflects an improved cardiac performance. This could conceivably be mediated via sympathetic activation in response to acetazolamide induced carbon dioxide retention.

Acetazolamide↗

Phosphate transfer and tubular pH during renal stopped flow microperfusion experiments in the rat.

The loss of 32P-phosphate salts by the luminal compartment of cortical tubules was studied in control and in acetazolamide-infused rats, during stopped-flow microperfusion with 100 mM phosphate-raffinose solutions. When the initial pH of the perfusion solution was low (5.5), phosphate was lost more rapidly from proximal tubules than at high initial pH (8.2). The average half-time of phosphate loss was 31.9 s during acid, and 66.0 s during alkaline perfusion in proximal tubules of control rats; in acetazolamide-infused rats half-times were 77.0 and 86.6 s for acid and alkaline perfusions. Thus acetazolamide infusion slows the rate of phosphate loss by proximal tubules, when the perfusion solution is acid, but has no significant effect if its pH is alkaline. These half-times compare to proximal acidification rates of 7.23 s in control and 13.2 s in acetazolamide-infused rats. In distal tubules of control rats no significant loss of phosphate was observed during the period of perfusion. It is concluded that the loss of phosphate, in proximal tubules, is markedly slower than the changes in tubular pH and so its effect on tubular acidification must be of minor importance. In distal tubules changes in pH are not due to transepithelial phosphate movement.

Acetazolamide↗

Sequential change of hemodynamic reserve in patients with major cerebral artery occlusion or severe stenosis.

To identify regional vasodilatory capacity and its sequential change, we evaluated prospectively a total of 78 acetazolamide tests in 51 patients with occlusion or greater than 75% stenosis of the carotid or middle cerebral arteries. The relative distribution of cerebral blood flow was determined by single photon emission computed tomography using N-isopropyl-p-[123I]-iodoamphetamine before and after intravenous injection of acetazolamide. Reduced vasodilatory capacity was demonstrated in 20 patients (38%), including 5 patients with hemodynamic transient ischemic attacks or infarction. Follow-up acetazolamide tests revealed asymptomatic progression of the arterial lesion (from stenosis to occlusion) in 1 patient and almost complete improvement of vasodilatory capacity in 5 patients, including 3 without surgical intervention. During an average follow-up period of 18.5 months, 4 patients died from cardiac causes or neoplasm; no neurovascular events occurred. Much larger numbers of patients with longer observation periods will be necessary to clarify the contribution of chronic hemodynamic failure to subsequent stroke. However, the present data indicate that the acetazolamide test is useful for assessing the course of high grade stenosis or occlusion of major cerebral arteries.

Acetazolamide↗

Diastolic blood pressure influences cerebrovascular reactivity measured by means of 123I-iodoamphetamine brain single photon emission computed tomography in medically treated patients with occlusive carotid or middle cerebral artery disease.

OBJECTIVE: Impaired cerebrovascular reactivity (CVR) to vasodilating agents is a predictor of the onset and prognosis of ischemic stroke. It is realized that the CVR improves or worsens when measured periodically during the clinical course in medically treated patients with occlusive cerebrovascular disease. In these patients, we investigated the possible relationship between the interval change in CVR and that in systemic blood pressure (BP). METHODS: Forty-two patients (14 females and 28 males, mean age +/- SD: 65.3 +/- 8.8 years) with severe stenosis or occlusion of the common carotid, internal carotid, or middle cerebral arteries repeatedly underwent single photon emission computed tomography (SPECT) studies using 123I-iodoamphetamine to measure cerebral blood flow (CBF) distribution and CVR at a more-than-6-month interval (mean +/- SD: 18.5 +/- 8.8 months). The CVR was separately estimated in cerebral hemispheres ipsilateral and contralateral to the most severe vascular lesion as the % increase in CBF after acetazolamide loading to CBF at rest. Systemic BP was measured four times at enrollment and the follow-up SPECT studies during resting and acetazolamide loading. Average BP at each SPECT study was an average of BP measurements during resting and acetazolamide loading. Interval changes in CVR were correlated with those in average systolic BP, average diastolic BP, and average mean arterial BP. RESULTS: The interval changes in CVR were significantly correlated with those in average diastolic BP in the ipsilateral hemisphere (y = 0.71x + 1.43, r2 = 0.11, p < 0.05) and in the contralateral hemisphere (y = 0.88x - 0.46, r2 = 0.16, p < 0.05) but not with those in average systolic BP or average mean arterial BP. CONCLUSIONS: In medically treated patients with steno-occlusive carotid artery or middle cerebral artery lesions, the interval change in CVR to acetazolamide by means of 123I-IMP SPECT was influenced by the diastolic BP at the SPECT studies. Monitoring diastolic BP is important to evaluate interval change in CVR.

Acetazolamide↗

Intraocular pressure effects of carbonic anhydrase inhibitors in primary open-angle glaucoma.

We tested the effect on intraocular pressure of three commonly used oral carbonic anhydrase inhibitor preparations in a controlled, randomized, comparative study on patients with primary open-angle glaucoma. Preparations tested included acetazolamide tablets, acetazolamide Sequels, and methazolamide tablets. The effect of the three carbonic anhydrase inhibitors was assessed by using a statistical modeling approach as well as by evaluating the average maximum reduction in intraocular pressure for each preparation. Dosage and time effects were also determined. As expected, each drug preparation was more effective in reducing intraocular pressure when administered to a patient who had already been treated with the carbonic anhydrase inhibitor preparation. The amount of intraocular pressure lowering was directly related to dose for both acetazolamide preparations. Of particular interest was the finding that maximal rapid reduction of intraocular pressure was obtained with a 500-mg dosage of acetazolamide tablets.

Acetazolamide↗

Liver carbonic anhydrase and urea synthesis. The effect of diuretics.

In isolated perfused rat liver, urea synthesis is rapid and reversibly inhibited not only by the well-known carbonic anhydrase inhibitors acetazolamide, methazolamide and ethoxzolamide, but also by diuretics, like xipamide, mefruside, chlortalidone, and chlorothiazide. Furosemide was without effect. Similar to findings with isolated perfused rat liver, acetazolamide inhibits urea synthesis from ammonium ions in normal and cirrhotic human liver slices. Inhibition of urea synthesis by xipamide and acetazolamide is accompanied by a 70% decrease of the cellular citrulline content and the tissue levels of 2-oxoglutarate and citrate, suggesting a block of urea synthesis at a step prior to citrulline formation. At a constant extracellular pH (7.4), inhibition of urea synthesis by xipamide, mefruside and acetazolamide was overcome by increasing the extracellular concentrations of HCO3- and CO2 to above twice the normal values. This shows that inhibition of urea synthesis by these diuretics is not due to an unspecific inhibition of one of the urea cycle enzymes but is due to an inhibition of mitochondrial carbonic anhydrase and therefore due to an impaired HCO3- provision for mitochondrial carbamoylphosphate synthesis. It is concluded that the activity of mitochondrial carbonic anhydrase is required for urea synthesis also in human liver and that several diuretics impair urea synthesis by inhibition of mitochondrial carbonic anhydrase. The pathophysiological significance of these data is discussed with respect to the development of diuretics-induced hyperammonemia and alkalosis in liver disease.

Acetazolamide↗

Water uptake by Rana temporaria: effects of diuretics and the renin--angiotensin system, and nephrectomy.

Adult Rana temporaria, acclimated to tap water or hyperosmotic (0.9% NaCl saline) media, were injected with Acetazolamide, Frusemide, or Captopril, or were nephrectomized and injected with captopril. Saline-injected animals served as controls. Total water flux and drinking rates were determined by body weight changes and by the rate of accumulation of an environmental marker (phenol red) in the gut, respectively. Changes in plasma corticosteroids and ion concentrations were also assessed. Acetazolamide and frusemide produced hyponatraemia in tap water-acclimated animals, but induced increased aldosterone levels in frogs in both environments. Captopril reduced body weight and aldosterone levels of tap water frogs, but had no effect on plasma ion composition. Animals treated with captopril on immersion in saline had plasma hypoosmotic to their environment. Saline-acclimated frogs drank less environmental water than did those in tap water. Captopril, acetazolamide, and frusemide all stimulated drinking rates of saline-acclimated frogs; captopril, however, had no effect on the drinking rates of nephrectomized animals, indicating that the dipsogenic actions of this drug are probably reflected by inhibition of the renin-angiotensin system. In tap water animals, acetazolamide stimulated drinking, while frusemide stimulated integumental water uptake. No correlation was apparent between plasma aldosterone and corticosterone concentrations, or between changes in body weight and drinking rates. This suggests that there are independent mechanisms controlling aldosterone and corticosterone secretion, as well as integumentary and buccal uptake of water in R. temporaria.

Acetazolamide↗

The CSF HCO3 increase in hypercapnia relationshp to HCO3, glutamate, glutamine and NH3 in brain.

To study the role of carbonic anhydrase in the CSF [HCO3] increase in respiratory acidosis and its effect on brain ammonia, anesthetized rats were subjected to hypercapnia (7% CO2) for 2 hours. The animals received periodic intraventricular injections of either 'mock' CSF or 'mock' CSF and acetazolamide for 45 minutes prior and during hypercapnia when: (a) plasma [HCO3-] was allowed to increase normally and (2) plasma [HCO3] increase was prevented by i.v. HC1 infusion, CSF [HCO3] increased 8.5 mM/L after 2 hours of hypercapnia (delta PCO2 40) in the rats with intraventricular 'mock' CSF injections, and only 6 mM/L in the animals with acetazolamide injections. CSF [HCO3-] increased 7 mM/L during hypercapnia and HCl infusion with intraventricular 'mock' CSF injections, but only 2 mM/L with acetazolamide injections. Changes in total brain CO2 (increase) and brain glutamic acid (decrease) in hypercapnia were not affected by intraventricular acetazolamide and i.v. HCl. The increase of brain NH4+ and glutamine in hypercapnia was reduced in these conditions. It is concluded that there are at least two sources for the CSF [HCO3-] increase in hypercapnia; one formed in the CNS and dependent on carbonic anhydrase, and the other derived from plasma [HCO3-] increase.

Acetazolamide↗

Phenotype-dependent functional and pharmacological properties of BK channels in skeletal muscle: effects of microgravity.

We investigated the involvement of calcium-activated potassium channel (BK) in skeletal muscle phenotype determination and response to acetazolamide, a BK opener. The BKs of slow-twitching soleus (SOL) and fast-twitching flexor digitorum brevis (FDB) muscles of the rat were investigated by patch-clamp technique. The changes of BK properties following muscle disuse were investigated in the hindlimb-unloaded (HU) rat, an animal model of disuse/microgravity. Two functionally different BKs were found in skeletal muscle. The BK of FDB was sensitive to calcium and to acetazolamide, in contrast the BK of SOL was less sensitive to calcium and was resistant to acetazolamide. After 3-14 days HU, in parallel with the slow-to-fast phenotype transition of the fibers, the BK of SOL acquired properties similar to those of FDB. In skeletal muscle, the BK plays muscle-specific roles contributing to the calcium-dependent phenotype determination/adaptation to disuse. The phenotype specificity of acetazolamide has implications for drug-based therapy of neuromuscular disorders associated to disuse.

Acetazolamide↗

Sleep apnea and intracranial hypertension in men.

PURPOSE: To investigate sleep apnea as an associated finding in idiopathic intracranial hypertension (IIH) in men. DESIGN: Multicenter, retrospective, noncomparative interventional case series. METHODS: Retrospective review of all men with the diagnosis of IIH seen within the last 5 years at three tertiary care academic ophthalmologic institutions. Cases with sleep apnea (SA) and IIH were identified and reviewed. RESULTS: Thirty-two cases of IIH in men were reviewed. Six cases with SA met the modified Dandy criteria for the diagnosis of IIH. Of these six patients, one received acetazolamide alone, four received acetazolamide and continuous positive airway pressure (CPAP), and one was treated with CPAP alone. All patients had preserved central acuity (20/20 or better in both eyes), enlarged blind spots, and optic disc edema in both eyes. Five patients had normal visual fields after treatment, and one patient had residual visual field loss. Three patients had normal optic nerve examinations, with resolution of the optic disc edema at last follow-up. After resolution of the optic disc edema, these three patients were maintained on CPAP but discontinued acetazolamide. Two patients had persistent but improved papilledema and are under continued treatment with acetazolamide and CPAP. One patient had optic disc pallor in both eyes and is stable. CONCLUSIONS: SA was a common finding in men meeting the modified Dandy criteria for IIH in adults. Treatment of sleep apnea with nocturnal oxygenation may improve the signs and symptoms of IIH in affected men.

Acetazolamide↗