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American Journal of Physiology. Renal... Sep 2020Carbonic anhydrase (CAII) binds to the electrogenic basolateral Na-[Formula: see text] cotransporter (NBCe1) and facilitates [Formula: see text] reabsorption across the...
Carbonic anhydrase (CAII) binds to the electrogenic basolateral Na-[Formula: see text] cotransporter (NBCe1) and facilitates [Formula: see text] reabsorption across the proximal tubule. However, whether the inhibition of CAII with acetazolamide (ACTZ) alters NBCe1 activity and interferes with the ammoniagenesis pathway remains elusive. To address this issue, we compared the renal adaptation of rats treated with ACTZ to NHCl loading for up to 2 wk. The results indicated that ACTZ-treated rats exhibited a sustained metabolic acidosis for up to 2 wk, whereas in NHCl-loaded rats, metabolic acidosis was corrected within 2 wk of treatment. [Formula: see text] excretion increased by 10-fold in NHCl-loaded rats but only slightly (1.7-fold) in ACTZ-treated rats during the first week despite a similar degree of acidosis. Immunoblot experiments showed that the protein abundance of glutaminase (4-fold), glutamate dehydrogenase (6-fold), and SN1 (8-fold) increased significantly in NHCl-loaded rats but remained unchanged in ACTZ-treated rats. Na/H exchanger 3 and NBCe1 proteins were upregulated in response to NHCl loading but not ACTZ treatment and were rather sharply downregulated after 2 wk of ACTZ treatment. ACTZ causes renal [Formula: see text] wasting and induces metabolic acidosis but inhibits the upregulation of glutamine transporter and ammoniagenic enzymes and thus suppresses ammonia synthesis and secretion in the proximal tubule, which prevented the correction of acidosis. This effect is likely mediated through the inhibition of the CA-NBCe1 metabolon complex, which results in cell alkalinization. During chronic ACTZ treatment, the downregulation of both NBCe1 and Na/H exchanger 3, along with the inhibition of ammoniagenesis and [Formula: see text] generation, contributes to the maintenance of metabolic acidosis.
Topics: Acetazolamide; Acid-Base Equilibrium; Acidosis; Adaptation, Physiological; Amino Acid Transport Systems, Neutral; Ammonia; Animals; Bicarbonates; Chlorides; Diuretics; Electrolytes; Gene Expression Regulation; Half-Life; Kidney; Male; Rats; Rats, Sprague-Dawley; Urinalysis
PubMed: 32657159
DOI: 10.1152/ajprenal.00501.2019 -
BMJ Clinical Evidence Mar 2010Up to half of people who ascend to heights above 2500 m may develop acute mountain sickness, pulmonary oedema, or cerebral oedema, with the risk being greater at higher... (Review)
Review
INTRODUCTION
Up to half of people who ascend to heights above 2500 m may develop acute mountain sickness, pulmonary oedema, or cerebral oedema, with the risk being greater at higher altitudes, and with faster rates of ascent.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent, and to treat, acute mountain sickness? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 17 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acetazolamide, descent versus resting, dexamethasone, gingko biloba, and slow ascent.
Topics: Acetazolamide; Acute Disease; Altitude; Altitude Sickness; Ginkgo biloba; Humans; Pulmonary Edema
PubMed: 21718562
DOI: No ID Found -
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 -
Journal of Travel Medicine 2012
Topics: Acetazolamide; Altitude Sickness; Carbolines; Carbonic Anhydrase Inhibitors; Humans; Hypertension, Pulmonary; Male; Mountaineering; Tadalafil
PubMed: 22943266
DOI: 10.1111/j.1708-8305.2012.00646.x -
Journal of Applied Physiology... Sep 2018Acetazolamide, a carbonic anhydrase (CA) inhibitor used clinically and to prevent acute mountain sickness, worsens skeletal muscle fatigue in animals and humans. In... (Comparative Study)
Comparative Study Randomized Controlled Trial
Acetazolamide, a carbonic anhydrase (CA) inhibitor used clinically and to prevent acute mountain sickness, worsens skeletal muscle fatigue in animals and humans. In animals, methazolamide, a methylated analog of acetazolamide and an equally potent CA inhibitor, reportedly exacerbates fatigue less than acetazolamide. Accordingly, we sought to determine, in humans, if methazolamide would attenuate diaphragm and dorsiflexor fatigue compared with acetazolamide. Healthy men (dorsiflexor: n = 12; diaphragm: n = 7) performed fatiguing exercise on three occasions, after ingesting acetazolamide (250 mg three times a day) and then in random order, methazolamide (100 mg twice a day) or placebo for 48 h. For both muscles, subjects exercised at a fixed intensity until exhaustion on acetazolamide, with subsequent iso-time and -workload trials. Diaphragm exercise was performed using a threshold-loading device, while dorsiflexor exercise was isometric. Neuromuscular function was determined pre- and postexercise by potentiated transdiaphragmatic twitch pressure and dorsiflexor torque in response to stimulation of the phrenic and fibular nerve, respectively. Diaphragm contractility 3-10 min postexercise was impaired more for acetazolamide than methazolamide or placebo (82 ± 10, 87 ± 9, and 91 ± 8% of pre-exercise value; P < 0.05). Similarly, dorsiflexor fatigue was greater for acetazolamide than methazolamide (mean twitch torque of 61 ± 11 vs. 57 ± 13% of baseline, P < 0.05). In normoxia, methazolamide leads to less neuromuscular fatigue than acetazolamide, indicating a possible benefit for clinical use or in the prophylaxis of acute mountain sickness. NEW & NOTEWORTHY Acetazolamide, a carbonic anhydrase inhibitor, may worsen diaphragm and locomotor muscle fatigue after exercise; whereas, in animals, methazolamide does not impair diaphragm function. Compared with both methazolamide and the placebo, acetazolamide significantly compromised dorsiflexor function at rest and after exhaustive exercise. Similarly, diaphragm function was most compromised on acetazolamide followed by methazolamide and placebo. Methazolamide may be preferable over acetazolamide for clinical use and altitude illness prophylaxis to avoid skeletal muscle dysfunction.
Topics: Acetazolamide; Adult; Carbonic Anhydrase Inhibitors; Diaphragm; Electric Stimulation; Electromyography; Exercise; Healthy Volunteers; Humans; Male; Methazolamide; Muscle Contraction; Muscle Fatigue; Respiratory Muscles; Young Adult
PubMed: 29792554
DOI: 10.1152/japplphysiol.00256.2018 -
JSLS : Journal of the Society of... 2022To perform a systematic review and meta-analysis to evaluate the efficacy of perioperative acetazolamide (ACTZ) administration with laparoscopy for reducing... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
To perform a systematic review and meta-analysis to evaluate the efficacy of perioperative acetazolamide (ACTZ) administration with laparoscopy for reducing postoperative referred pain.
METHODS
The following databases were searched from inception to March 1, 2020: Cochrane, PubMed, PubMed Central, Ovid, and Embase. Electronic search used: Acetazolamide AND (laparoscopy OR laparoscopic OR Celioscopy OR Celioscopies OR Peritoneoscopy OR Peritoneoscopies). No limits or filters were used. We included only studies of patients who underwent abdominal laparoscopy (LSC), had a pain assessment at approximately 24 hours postoperatively, and included a treatment with ACTZ group and a no-treatment or minimal-treatment comparison group.
RESULTS
Five studies met inclusion criteria, with a combined total of 253 participants, 116 in the ACTZ group and 137 in the control group. A Bayesian hierarchical model was assumed for the study specific treatment effects. Posterior sampling was conducted via Markov Chain Monte Carlo methods, and posterior inference carried out on the hierarchical treatment effect. ACTZ significantly decreased average pain scores compared to control group by -0.726 points (95% confidence interval -1.175-0.264). The posterior probability that ACTZ decreases mean pain scores by ≥ 0.5 was 0.846.
CONCLUSION
Current available evidence demonstrates that perioperative ACTZ may provide a modest improvement in postoperative referred pain following LSC.
Topics: Acetazolamide; Bayes Theorem; Humans; Laparoscopy; Pain, Postoperative; Pain, Referred
PubMed: 36071992
DOI: 10.4293/JSLS.2022.00032 -
Frontiers in Endocrinology 2022Exposure to hypobaric hypoxia at high altitude puts mountaineers at risk of acute mountain sickness. The carbonic anhydrase inhibitor acetazolamide is used to accelerate...
Exposure to hypobaric hypoxia at high altitude puts mountaineers at risk of acute mountain sickness. The carbonic anhydrase inhibitor acetazolamide is used to accelerate acclimatization, when it is not feasible to make a controlled and slow ascend. Studies in rodents have suggested that exposure to hypobaric hypoxia deteriorates bone integrity and reduces bone strength. The study investigated the effect of treatment with acetazolamide and the bisphosphonate, zoledronate, on the skeletal effects of exposure to hypobaric hypoxia. Eighty 16-week-old female RjOrl : SWISS mice were divided into five groups: 1. Baseline; 2. Normobaric; 3. Hypobaric hypoxia; 4. Hypobaric hypoxia + acetazolamide, and 5. Hypobaric hypoxia + zoledronate. Acetazolamide was administered in the drinking water (62 mg/kg/day) for four weeks, and zoledronate (100 μg/kg) was administered as a single subcutaneous injection at study start. Exposure to hypobaric hypoxia significantly increased lung wet weight and decreased femoral cortical thickness. Trabecular bone was spared from the detrimental effects of hypobaric hypoxia, although a trend towards reduced bone volume fraction was found at the L4 vertebral body. Treatment with acetazolamide did not have any negative skeletal effects, but could not mitigate the altitude-induced bone loss. Zoledronate was able to prevent the altitude-induced reduction in cortical thickness. In conclusion, simulated high altitude affected primarily cortical bone, whereas trabecular bone was spared. Only treatment with zoledronate prevented the altitude-induced cortical bone loss. The study provides preclinical support for future studies of zoledronate as a potential pharmacological countermeasure for altitude-related bone loss.
Topics: Absorptiometry, Photon; Acetazolamide; Altitude; Altitude Sickness; Animals; Bone Density; Cancellous Bone; Cortical Bone; Female; Mice; Quadriceps Muscle; Zoledronic Acid
PubMed: 35222286
DOI: 10.3389/fendo.2022.831369 -
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 -
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 -
The European Respiratory Journal Dec 2012We tested the effect of acetazolamide on blood mechanical properties and pulmonary vascular resistance (PVR) during chronic hypoxia. Six groups of rats were either...
We tested the effect of acetazolamide on blood mechanical properties and pulmonary vascular resistance (PVR) during chronic hypoxia. Six groups of rats were either treated or not treated with acetazolamide (curative: treated after 10 days of hypoxic exposure; preventive: treated before hypoxic exposure with 40 mg · kg(-1) · day(-1)) and either exposed or not exposed to 3 weeks of hypoxia (at altitude >5,500 m). They were then used to assess the role of acetazolamide on pulmonary artery pressure, cardiac output, blood volume, haematological and haemorheological parameters. Chronic hypoxia increased haematocrit, blood viscosity and PVR, and decreased cardiac output. Acetazolamide treatment in hypoxic rats decreased haematocrit (curative by -10% and preventive by -11%), PVR (curative by -36% and preventive by -49%) and right ventricular hypertrophy (preventive -20%), and increased cardiac output (curative by +60% and preventive by +115%). Blood viscosity was significantly decreased after curative acetazolamide treatment (-16%) and was correlated with PVR (r=0.87, p<0.05), suggesting that blood viscosity could influence pulmonary haemodynamics. The fall in pulmonary vascular hindrance (curative by -27% and preventive by -45%) after treatment suggests that acetazolamide could decrease pulmonary vessels remodelling under chronic hypoxia. The effect of acetazolamide is multifactorial by acting on erythropoiesis, pulmonary circulation, haemorheological properties and cardiac output, and could represent a pertinent treatment of chronic mountain sickness.
Topics: Acetazolamide; Altitude Sickness; Animals; Blood Viscosity; Blood Volume; Carbonic Anhydrase Inhibitors; Chronic Disease; Heart; Hematocrit; Hemodynamics; Hemorheology; Hydrogen-Ion Concentration; Hypertension, Pulmonary; Hypoxia; Lung; Male; Pulmonary Circulation; Rats; Rats, Wistar; Stress, Mechanical
PubMed: 22523353
DOI: 10.1183/09031936.00216011