Disease relevance of Diacarb

• Effect of acetazolamide on hypoxemia during sleep at high altitude [1].
• Letter: Anticonvulsants, acetazolamide and osteomalacia [2].
• Acute mountain sickness and acetazolamide. Clinical efficacy and effect on ventilation [3].
• Acute metabolic alkalosis perpetuating hypercarbia. A role for acetazolamide in chronic obstructive pulmonary disease [4].
• On the summit AMS was less common in climbers receiving acetazolamide, and they experienced less headache, nausea, drowsiness, shortness of breath, and dizziness and a greater sense of satisfaction and psychological well-being [3].

Psychiatry related information on Diacarb

• Responses to hypercarbia induced by acetazolamide in panic disorder patients [5].
• METHODS: We used the MRI bolus tracking method in 15 symptomatic patients with CADASIL (5 with dementia) and 10 age-matched control subjects before and 20 minutes after the intravenous injection of acetazolamide (ACZ, 17 mg/kg) [6].
• Two elderly patients, who were chronically receiving aspirin, developed lethargy, incontinence, and confusion after dosing with acetazolamide [7].
• Acetazolamide significantly reduced tremor severity, but there was no statistically significant change in patient self-assessment of function or motor task rating [8].
• Resting and acetazolamide-challenged technetium-99m-ECD SPECT in transient global amnesia [9].

High impact information on Diacarb

• Sixty-four climbers participated in a randomized clinical trial of acetazolamide prophylaxis for acute mountain sickness (AMS) during rapid, active ascent of MT Rainier [3].
• Expired vital capacity was also greater on the summit in the acetazolamide group (6.9 +/- 0.4 L compared with 5.8 +/- 0.4 L) [3].
• Sacrococcygeal teratoma in a neonate. Association with maternal use of acetazolamide [10].
• V408A/+ mice showed stress-induced loss of motor coordination that was ameliorated by acetazolamide, a carbonic anhydrase inhibitor that minimizes EA1 symptoms in human patients [11].
• Instead, luminal AVP appeared to modulate an acetazolamide-sensitive electrogenic ion transport because 200 microM basolateral acetazolamide suppressed the luminal AVP-induced hyperpolarization (percentage of Vt from -50.4 +/- 10.8 to -5.1 +/- 1.4; P less than 0.005) [12].

Chemical compound and disease context of Diacarb

• Intravenous infusion of NaHCO3 (0.5 M) also significantly prevented the lesion with a concomitant suppression of the PD reduction in response to hemorrhagic shock, but these effects were significantly reversed by pretreatment of the animals with acetazolamide (50 mg/kg) [13].
• A report by Mathew et al. showed, however, that administration of the carbonic anhydrase inhibitor acetazolamide, which is believed to increase brain CO2 level, did not cause panic in panic disorder patients [14].
• This study demonstrates that prophylaxis with dexamethasone can reduce the symptoms associated with acute mountain sickness during active ascent and that acetazolamide can cause side effects that may limit its effectiveness as prophylaxis against the disease [15].
• METHODS: Cerebral vasomotor reactivity was assessed using transcranial Doppler ultrasonology and the Diamox test (intravenous administration of 1.0 g acetazolamide) in 44 asymptomatic patients with severe (> 70%) internal carotid artery stenosis [16].
• Eight normal male volunteers (not suffering from migraine) received 0.5 mg ergotamine and 1 mg dihydroergotamine i.v. Cerebral blood flow was measured by the xenon-133 inhalation method and single-photon-emission computerized tomography before and after intravenous acetazolamide administration (1 g) [17].

Biological context of Diacarb

• CONCLUSION: In established cases of acute mountain sickness, treatment with acetazolamide relieves symptoms, improves arterial oxygenation, and prevents further impairment of pulmonary gas exchange [18].
• Mapping the gene for acetazolamide responsive hereditary paryoxysmal cerebellar ataxia to chromosome 19p [19].
• The concentrations of acetazolamide needed to enhance the KCa2+ current by 50% in vitro were 6.17 and 4.01x10(-6) M at -60 and +30 mV of membrane potentials, respectively [20].
• Prolongation of the beta-phase half-time was associated with oral acetazolamide medication and with increased intracranial pressure, indicating that inhibition of CSF production slows MTX clearance [21].
• The evidence therefore indicates that the position of the acetazolamide moiety in the active site is independent of both pH and the presence of the covalent bond to histidine-64 [22].

Anatomical context of Diacarb

• 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 [23].
• 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 [23].
• Absolute reabsorption of bicarbonate was also significantly higher in superficial than in juxtamedullary nephrons after administration of acetazolamide (727 +/- 82 vs. 346 +/- 126 pmol/min; P less than 0.05) [24].
• Bicarbonate reabsorption that was insensitive to acetazolamide occurred in the superficial and deep loop of Henle and between the distal tubule and base collecting duct [25].
• Blocking the carbonic anhydrase with acetazolamide (100 mg/kg) completely prevented the protective effect of a 1 M HCO3- infusion, and 6 out of 8 stomachs ulcerated [26].

Associations of Diacarb with other chemical compounds

• Thus, acetazolamide caused either inhibition or stimulation of Na+ uptake depending on the conditions with respect to pH and HCO3- gradients [27].
• Furthermore, an outwardly directed bicarbonate concentration gradient from the deep loop of Henle to vasa recta was demonstrated during acetazolamide (delta tCO2 = 20.9 +/- 3.3 mM), but was abolished during combined mannitol and acetazolamide administration (delta tCO2 = 3.5 +/- 0.9 mM) [25].
• In addition, acetazolamide may potentiate the phosphaturic effect of parathyroid hormone by promoting accumulation of cyclic AMP in tissue [28].
• Addition of forskolin stimulated an increase in short-circuit current that was likely a result of bicarbonate secretion because it was inhibited by a HCO3(-)-free solution, by addition of the carbonic anhydrase inhibitor, acetazolamide, or by mucosal addition of the anion channel blocker, diphenylamine 2-carboxylate [29].
• The reaction depends upon the trapping of OH ions produced during gastric stimulation and is blocked by the benzimidazole, Hassle 149/94, which inhibits the K+ + H+-ATPase and by acetazolamide, an inhibitor of carbonic anhydrase activity [30].

Gene context of Diacarb

• Some remarkable clinical features were observed in a large hypoPP family carrying an SCN4A mutation: a complete penetrance in men and women, an early age at onset, postcritic myalgias and an increased number and severity of attacks induced by acetazolamide [31].
• Similar to CA VA, CA VB is a "low activity" enzyme with a sensitivity to acetazolamide [32].
• The valproyl derivative of acetazolamide (5-valproylamido-1,3,4-thiadiazole-2-sulfonamide, 6M) was one of the best hCA I and hCA II inhibitor in the series and exhibited very strong anticonvulsant properties in an MES test in mice [33].
• The isoenzyme CA III, which is resistant to inhibition by sulfonamides, did not appear to be present in these ocular tissues, since the histochemical staining of enzyme activity was completely abolished by 10(-6) M acetazolamide [34].
• Cerebral perfusion reserve was obtained from 6 patients (3 MELAS, 1 MERRF, 1 KSS, 1 CCOD) for a comparative analysis using the split-dose 123I-IMP SPECT method before and after the injection of acetazolamide [35].

Analytical, diagnostic and therapeutic context of Diacarb

• In this "symmetrical" perfusion situation, acetazolamide blockade prevented tCO2 entry [36].
• Acetazolamide increased VA/Q mismatch and reduced arterial PO2 measured at equilibrium but these did not occur in the control group [37].
• Simultaneous renal clearance studies and free-flow micropuncture studies of the superficial proximal tubule were performed on plasma-repleted Sprague-Dawley rats treated with acetazolamide, 50 mg/kg body weight [38].
• Acetazolamide, compared in a double-blind study with a placebo and also compared with no tablets at all, reduced both the incidence and the severity of A.M.S. in those who flew to 2800 m but not in those who hiked up to that altitude [39].
• Furosemide but not acetazolamide (n = 6 each) increased medullary oxygenation (delta R2* = 7.62 Hz; P < .01), consistent with the separate sites of action of these diuretics in the nephron and with previous direct measurements of their effects in anesthetized rats with oxygen microelectrodes [40].

References