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Journal of Applied Physiology... Jun 2023We sought to determine the effects of three treatments on hemoglobin (Hb) levels in patients with chronic mountain sickness (CMS): ) descent to lower altitude, )...
We sought to determine the effects of three treatments on hemoglobin (Hb) levels in patients with chronic mountain sickness (CMS): ) descent to lower altitude, ) nocturnal O supply, ) administration of acetazolamide. Nineteen patients with CMS living at an altitude of 3,940 ± 130 m participated in the study, which consisted of a 3-wk intervention phase and a 4-wk postintervention phase. Six patients spent 3 wk at an altitude of 1,050 m (low altitude group, LAG), six received supplemental oxygen for 12 h overnight (oxygen group, OXG), and seven received 250 mg of acetazolamide daily (acetazolamide group, ACZG). Hemoglobin mass (Hbmass) was determined using an adapted carbon monoxide (CO) rebreathing method before, weekly during, and 4 wk postintervention. Hbmass decreased by 245 ± 116 g ( < 0.01) in the LAG and by 100 ± 38 g in OXG, and 99 ± 64 g in ACZG ( < 0.05, each), respectively. In LAG, hemoglobin concentration ([Hb]) decreased by 2.1 ± 0.8 g/dL and hematocrit by 7.4 ± 2.9% (both < 0.01), whereas OXG and ACZG only trended toward lower values. Erythropoietin concentration ([EPO]) decreased between 81 ± 12% and 73 ± 21% in LAG at low altitude ( < 0.01) and increased by 161 ± 118% 5 days after return ( < 0.01). In OXG and ACZG, the [EPO] decrease was ∼75% and ∼50%, respectively, during the intervention ( < 0.01). Descent to low altitude (from 3,940 m to 1,050 m) is a fast-acting measure for the treatment of excessive erythrocytosis in patients with CMS, reducing Hbmass by 16% within 3 wk. Nighttime oxygen supplementation and daily acetazolamide administration are also effective, but reduce Hbmass by only 6%. To our knowledge, this is the first study examining the effect of three different treatments [descending to lower altitude (from 3,900 m to 1,050 m), nocturnal oxygen supply, and administration of acetazolamide] on changes in hemoglobin mass in patients experiencing chronic mountain sickness (CMS). We report that descent to low altitude is a fast-acting measure for the treatment of excessive erythrocytosis in patients with CMS, reducing Hbmass by 16% within 3 wk. Nighttime oxygen supplementation and daily acetazolamide administration are also effective, but reduce Hbmass by only 6%. In all three treatments, the underlying mechanism is a reduction in plasma erythropoietin concentration due to higher oxygen availability.
Topics: Humans; Altitude Sickness; Polycythemia; Altitude; Acetazolamide; Erythropoietin; Hemoglobins; Oxygen
PubMed: 37055035
DOI: 10.1152/japplphysiol.00076.2023 -
High Altitude Medicine & Biology Sep 2023Li Li, Lin Lin, Bo Wen, Peng-cheng Zhao, Da-sheng Liu, Guo-ming Pang, Zi-rong Wang, Yong Tan, and Cheng Lu. Promising natural medicines for the treatment of... (Review)
Review
Li Li, Lin Lin, Bo Wen, Peng-cheng Zhao, Da-sheng Liu, Guo-ming Pang, Zi-rong Wang, Yong Tan, and Cheng Lu. Promising natural medicines for the treatment of high-altitude illness. . 24:175-185, 2023.-High-altitude illness (HAI) is a dangerous disease characterized by oxidative stress, inflammatory damage and hemodynamic changes in the body that can lead to severe damage to the lungs, heart, and brain. Natural medicines are widely known for their multiple active ingredients and pharmacological effects, which may be important in the treatment of HAI. In this review, we outline the specific types of HAI and the underlying pathological mechanisms and summarize the currently documented natural medicines applied in the treatment of acute mountain sickness and high-altitude cerebral edema, high-altitude pulmonary edema, chronic mountain sickness, and high-altitude pulmonary hypertension. Their sources, types, and medicinal sites are summarized, and their active ingredients, pharmacological effects, related mechanisms, and potential toxicity are discussed. In conclusion, natural medicines, as an acceptable complementary and alternative strategy with fewer side effects and more long-term application, can provide a reference for developing more natural antialtitude sickness medicines in the future and have good application prospects in HAI treatment.
Topics: Humans; Altitude Sickness; Acetazolamide; Altitude; Acute Disease; Brain Edema
PubMed: 37504973
DOI: 10.1089/ham.2022.0139 -
Cardiology Research Apr 2024Acetazolamide and thiazide diuretics have been combined with loop diuretics to overcome diuretic resistance in heart failure patients. However, recent studies have... (Review)
Review
Acetazolamide and thiazide diuretics have been combined with loop diuretics to overcome diuretic resistance in heart failure patients. However, recent studies have assessed the upfront combination of acetazolamide and hydrochlorothiazide with loop diuretics in hospitalized patients with acute decompensated heart failure without loop diuretic resistance. We reviewed two recent randomized controlled trials on the upfront use of acetazolamide and thiazide diuretics in acute decompensated heart failure, respectively. When the two trials on acetazolamide are considered together, adding oral or intravenous acetazolamide to loop diuretics in decompensated heart failure patients resulted in increased diuresis and natriuresis. However, the effects were significantly higher in patients with serum bicarbonate ≥ 27 mmol/L and those with higher baseline glomerular filtration rate (GFR). Similarly, when the two trials on thiazide diuretics are considered together, adding hydrochlorothiazide to loop diuretics in decompensated heart failure patients resulted in increased diuresis and weight loss. However, it increases the risk of impaired renal function. When all the trials are considered together, the upfront use of acetazolamide may be helpful in carefully selected patients, including patients with underlying elevated bicarbonate levels (≥ 27 mmol/L) and those with good renal function (GFR > 50). Conversely, though the upfront use of thiazide diuretic added to intravenous furosemide improved diuretic response in acute decompensated heart failure, it causes an increased risk of worsening renal function and lack of clear evidence of reducing hospital length of stay.
PubMed: 38645830
DOI: 10.14740/cr1627 -
European Journal of Heart Failure Aug 2023Acetazolamide, an inhibitor of proximal tubular sodium reabsorption, leads to more effective decongestion in acute heart failure (AHF). It is unknown whether... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Acetazolamide, an inhibitor of proximal tubular sodium reabsorption, leads to more effective decongestion in acute heart failure (AHF). It is unknown whether acetazolamide alters serum sodium and potassium levels on top of loop diuretics and if baseline values modify the treatment effect of acetazolamide.
METHODS AND RESULTS
This is a pre-specified sub-analysis of the ADVOR trial that randomized 519 patients with AHF and volume overload in a 1:1 ratio to intravenous acetazolamide or matching placebo on top of standardized intravenous loop diuretics. Mean potassium and sodium levels at randomization were 4.2 ± 0.6 and 139 ± 4 mmol/L in the acetazolamide arm versus 4.2 ± 0.6 and 140 ± 4 mmol/L in the placebo arm. Hypokalaemia (<3.5 mmol/L) on admission was present in 44 (9%) patients and hyponatraemia (≤135 mmol/L) in 82 (16%) patients. After 3 days of treatment, 44 (17%) patients in the acetazolamide arm and 35 (14%) patients in the placebo arm developed hyponatraemia (p = 0.255). Patients randomized to acetazolamide demonstrated a slight decrease in mean potassium levels during decongestion, which was non-significant over time (p = 0.053) and had no significant impact on hypokalaemia incidence (p = 0.061). Severe hypokalaemia (<3.0 mmol/L) occurred in only 7 (1%) patients, similarly distributed between the two treatment arms (p = 0.676). Randomization towards acetazolamide improved decongestive response irrespective of baseline serum sodium and potassium levels.
CONCLUSIONS
Acetazolamide on top of standardized loop diuretic therapy does not lead to clinically important hypokalaemia or hyponatraemia and improves decongestion over the entire range of baseline serum potassium and sodium levels.
Topics: Humans; Acetazolamide; Heart Failure; Sodium; Sodium Potassium Chloride Symporter Inhibitors; Hyponatremia; Hypokalemia; Potassium; Diuretics
PubMed: 37062871
DOI: 10.1002/ejhf.2863 -
Nederlands Tijdschrift Voor Geneeskunde May 2023Loop diuretics are the cornerstone of the treatment of volume overload in decompensated heart failure. However, often complete decongestion cannot be achieved rapidly... (Randomized Controlled Trial)
Randomized Controlled Trial
Loop diuretics are the cornerstone of the treatment of volume overload in decompensated heart failure. However, often complete decongestion cannot be achieved rapidly with loop diuretics alone, partly due to compensatory upregulation of sodium resorption at other parts of the nephron. These compensatory mechanisms can be antagonized by using a combination of diuretics. In earlier research, a number of those combinations have been investigated, but no diuretic combination has been proven to be both efficient and safe yet. A recent multicenter, double-blind, randomized, placebo-controlled study - performed by Mullens et al. in 2022 - investigated adding acetazolamide (Diamox) to loop diuretics in patients with decompensated heart failure. They found that a higher rate of decongestion was achieved with the addition of acetazolamide without seemingly more side effects. The addition of acetazolamide can be considered in the treatment of decompensated heart failure.
Topics: Humans; Diuretics; Acetazolamide; Sodium Potassium Chloride Symporter Inhibitors; Heart Failure; Combined Modality Therapy
PubMed: 37257097
DOI: No ID Found -
Medicine Oct 2023Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology that primarily affects obese women of childbearing age. Symptoms include disabling... (Review)
Review
Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology that primarily affects obese women of childbearing age. Symptoms include disabling headaches, visual disturbances, and intracranial noises (pulsatile tinnitus). Currently, no standardized treatment guidelines are available and the current management focuses on weight loss and acetazolamide use. There is an increasing body of evidence suggesting that the initial use of topiramate may be considered in IIH treatment. Acetazolamide is the recommended initial treatment for IIH, with topiramate often used as a second-line agent. Topiramate has multiple benefits to indicate it would pose effective in IIH management. Through varying mechanisms, it leads to weight loss and improves migraine headache control, the most common headache phenotype in IIH. Topiramate also inhibits the carbonic anhydrase enzyme like acetazolamide to reduce intracranial pressure and treat papilledema. The safety profile of topiramate is comparable or superior to acetazolamide. To date, there are limited studies comparing topiramate to acetazolamide or other treatment modalities in IIH. Based on its varying mechanisms of action, topiramate is a strong potential treatment agent for IIH, yet acetazolamide is often chosen first-line. However, the data supporting use of acetazolamide or topiramate is inefficient to designate one agent preferred over the other. There is a need for further studies assessing topiramate use in the treatment of IIH, and comparing topiramate use to other treatment modalities.
Topics: Humans; Female; Pseudotumor Cerebri; Acetazolamide; Topiramate; Intracranial Pressure; Weight Loss; Headache; Intracranial Hypertension
PubMed: 37861536
DOI: 10.1097/MD.0000000000035545 -
Neurology. Clinical Practice Aug 2021To determine the efficacy and safety of the treatment with prolonged-release 4-aminopyridine (fampridine) and acetazolamide for patients with episodic ataxia type 2...
OBJECTIVE
To determine the efficacy and safety of the treatment with prolonged-release 4-aminopyridine (fampridine) and acetazolamide for patients with episodic ataxia type 2 (EA2), patients with EA2 were treated with a random sequence of fampridine, acetazolamide, and placebo in a 3-period crossover trial.
METHODS
A total of 30 patients with EA2 (8 female; aged 20-71 years; 18 genetically confirmed, 4 with a positive family history, 8 with the clinical diagnosis) were enrolled in this phase III, randomized, double-blind, placebo-controlled, 3-period crossover trial. Each period lasted 12 weeks with a 4-week washout period. Each patient received a random sequence of 20 mg/d fampridine, 750 mg/d acetazolamide, and placebo. The primary end point was the number of attacks during the last 30 days within the 12-week treatment period. Participants, caregivers, and those assessing the outcomes were blinded to the intervention.
RESULTS
Compared with placebo, fampridine reduced the number of attacks to 63% (95% CI 54%-74%) and acetazolamide to 52% (95% CI 46%-60%). A total of 39 (26.5%) adverse events were observed under treatment with fampridine (mostly tingling paresthesia and fatigue), 66 (44.9%) happened under acetazolamide (mostly taste disturbance and gastrointestinal complaints), and 42 (28.6%) under placebo (mostly gastrointestinal complaints).
CONCLUSION
Both fampridine and acetazolamide significantly reduce the number of attacks in patients with EA2 and related EA in comparison to placebo. Fampridine 10 mg twice daily had fewer side effects than acetazolamide 250 mg 3 times daily. The trial was registered with DRKS.de (DRKS00005258) and EudraCT (2013-000107-17). This study was supported by the Federal Ministry of Education and Research (BMBF) (grant number 01EO0901). Fampridine (study medication) was provided by Biogen Idec.
CLASSIFICATION OF EVIDENCE
Class II evidence.
PubMed: 34484942
DOI: 10.1212/CPJ.0000000000001017 -
Nuclear Medicine and Molecular Imaging Feb 2020Internal carotid artery (ICA) stenosis including Moyamoya disease needs revascularization when hemodynamic insufficiency is validated. Vascular reserve impairment was... (Review)
Review
Internal carotid artery (ICA) stenosis including Moyamoya disease needs revascularization when hemodynamic insufficiency is validated. Vascular reserve impairment was the key to find the indication for endarterectomy/bypass surgery in the atherosclerotic ICA stenosis and to determine the indication, treatment effect, and prognosis in Moyamoya diseases. Vascular reserve was quantitatively assessed by 1-day split-dose I-123 IMP basal/acetazolamide SPECT in Japan or by Tc-99m HMPAO SPECT in other countries using qualitative or semi-quantitative method. We summarized the development of 1-day basal/ acetazolamide brain perfusion SPECT for ICA stenosis, both quantitative and qualitative methods, and their methodological issues regarding (1) acquisition protocol; (2) qualitative assessment, either visual or deep learning-based; (3) clinical use for atherosclerotic ICA steno-occlusive diseases and mostly Moyamoya diseases; and (4) their impact on the choice of treatment options. Trials to use CT perfusion or perfusion MRI using contrast materials or arterial spin labeling were briefly discussed in their endeavor to use basal studies alone to replace acetazolamide-challenge SPECT. Theoretical and practical issues imply that basal perfusion evaluation, no matter how much sophisticated, will not disclose vascular reserve. Acetazolamide rarely causes serious adverse reactions but included fatality, and now, we need to monitor patients closely in acetazolamide-challenge studies.
PubMed: 32206127
DOI: 10.1007/s13139-019-00633-7 -
Journal of Applied Physiology... Jun 2022Acetazolamide prevents acute mountain sickness (AMS) by inhibition of carbonic anhydrase. Since it also reduces acute hypoxic pulmonary vasoconstriction (HPV), it may... (Randomized Controlled Trial)
Randomized Controlled Trial
Acetazolamide prevents acute mountain sickness (AMS) by inhibition of carbonic anhydrase. Since it also reduces acute hypoxic pulmonary vasoconstriction (HPV), it may also prevent high-altitude pulmonary edema (HAPE) by lowering pulmonary artery pressure. We tested this hypothesis in a randomized, placebo-controlled, double-blind study. Thirteen healthy, nonacclimatized lowlanders with a history of HAPE ascended (<22 h) from 1,130 to 4,559 m with one overnight stay at 3,611 m. Medications were started 48 h before ascent (acetazolamide: = 7, 250 mg 3 times/day; placebo: = 6, 3 times/day). HAPE was diagnosed by chest radiography and pulmonary artery pressure by measurement of right ventricular to atrial pressure gradient (RVPG) by transthoracic echocardiography. AMS was evaluated with the Lake Louise Score (LLS) and AMS-C score. The incidence of HAPE was 43% versus 67% (acetazolamide vs. placebo, = 0.39). Ascent to altitude increased RVPG from 20 ± 5 to 43 ± 10 mmHg ( < 0.001) without a group difference ( = 0.68). Arterial Po fell to 36 ± 9 mmHg ( < 0.001) and was 8.5 mmHg higher with acetazolamide at high altitude ( = 0.025). At high altitude, the LLS and AMS-C score remained lower in those taking acetazolamide (both < 0.05). Although acetazolamide reduced HAPE incidence by 35%, this effect was not statistically significant, and was considerably less than reductions of about 70%-100% with prophylactic dexamethasone, tadalafil, and nifedipine performed with the same ascent profile at the same location. We could not demonstrate a reduction in RVPG compared with placebo treatment despite reductions in AMS severity and better arterial oxygenation. Limited by small sample size, our data do not support recommending acetazolamide for the prevention of HAPE in mountaineers ascending rapidly to over 4,500 m. This randomized, placebo-controlled, double-blind study is the first to investigate whether acetazolamide, which reduces acute mountain sickness (AMS), inhibits short-term hypoxic pulmonary vasoconstriction, and also prevents high-altitude pulmonary edema (HAPE) in a fast-climbing ascent to 4,559 m. We found no statistically significant reduction in HAPE incidence or differences in hypoxic pulmonary artery pressures compared with placebo despite reductions in AMS and greater ventilation-induced arterial oxygenation. Our data do not support recommending acetazolamide for HAPE prevention.
Topics: Acetazolamide; Acute Disease; Altitude; Altitude Sickness; Humans; Hypertension, Pulmonary; Hypoxia; Pulmonary Artery; Pulmonary Edema
PubMed: 35511718
DOI: 10.1152/japplphysiol.00806.2021 -
International Journal of Molecular... Sep 2022This review paper considers the consequences of modulating tubular reabsorption proximal to the macula densa by sodium-glucose co-transporter 2 (SGLT2) inhibitors,... (Review)
Review
This review paper considers the consequences of modulating tubular reabsorption proximal to the macula densa by sodium-glucose co-transporter 2 (SGLT2) inhibitors, acetazolamide, and furosemide in states of glomerular hyperfiltration. SGLT2 inhibitors improve renal function in early and advanced diabetic nephropathy by decreasing the glomerular filtration rate (GFR), presumably by activating the tubuloglomerular feedback (TGF) mechanism. Central in this paper is that the renoprotective effects of SGLT2 inhibitors in diabetic nephropathy can only be partially explained by TGF activation, and there are alternative explanations. The sustained activation of TGF leans on two prerequisites: no or only partial adaptation should occur in reabsorption proximal to macula densa, and no or only partial adaptation should occur in the TGF response. The main proximal tubular and loop of Henle sodium transporters are sodium-hydrogen exchanger 3 (NHE3), SGLT2, and the Na-K-2Cl co-transporter (NKCC2). SGLT2 inhibitors, acetazolamide, and furosemide are the most important compounds; inhibiting these transporters would decrease sodium reabsorption upstream of the macula densa and increase TGF activity. This could directly or indirectly affect TGF responsiveness, which could oppose sustained TGF activation. Only SGLT2 inhibitors can sustainably activate the TGF as there is only partial compensation in tubular reabsorption and TGF response. SGLT2 inhibitors have been shown to preserve GFR in both early and advanced diabetic nephropathy. Other than for early diabetic nephropathy, a solid physiological basis for these effects in advanced nephropathy is lacking. In addition, TGF has hardly been studied in humans, and therefore this role of TGF remains elusive. This review also considers alternative explanations for the renoprotective effects of SGLT2 inhibitors in diabetic patients such as the enhancement of microvascular network function. Furthermore, combination use of SGLT2 inhibitors and angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs). in diabetes can decrease inflammatory pathways, improve renal oxygenation, and delay the progression of diabetic nephropathy.
Topics: Acetazolamide; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Diabetic Nephropathies; Furosemide; Glomerular Filtration Rate; Glucose; Humans; Sodium; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Sodium-Hydrogen Exchanger 3
PubMed: 36232506
DOI: 10.3390/ijms231911203