Fabrication of acetazolamide loaded leciplex for intraocular delivery: Optimization by 32 full factorial design, in vitro, ex vivo and in vivo pharmacodynamics.

The complex structure of the eye poses challenges in delivering drugs effectively, which can be circumvented by employing nanotechnologies. The present study aimed to prepareacetazolamide-loadedleciplex (ACZ - LP) using a simple one-step fabrication approach followed byoptimization employing a 32 Full Factorial Design. The ACZ - LP demonstrated high entrapment efficiency (93.25 ± 2.32 %), average diameter was recorded around 171.03 ± 3.32 with monodisperse size distribution and zeta potential of 41.33 ± 2.10 mV. Invitro release and ex vivo permeation studies of prepared formulation demonstrated an initial burst release in 1 h followed by sustained release pattern as compared to plain acetazolamide solution. Moreover, an ex vivo corneal drug retention (27.05 ± 1.20 %) and in vitro mucoadhesive studies with different concentration of mucin indicated strong electrostatic bonding confirming the mucoadhesive characteristics of the formulation. Additionally, the histopathological studies ensured that the formulation was non-irritant and nontoxic while and HET-CAM ensured substantial tolerability of the formulation. The in vivo pharmacodynamic investigation carried out on a rabbit model demonstrated that treatment with ACZ - LP resulted in a significant and prolonged reduction in intraocular pressure as compared to plain acetazolamide solution, acetazolamide oral tablet, and Brinzox®. In summary, the ACZ - LP is anefficient and versatile drug delivery approach which demonstrates significant potential in controlling glaucoma.

Using modified Fenn diagrams to assess ventilatory acclimatization during ascent to high altitude: Effect of acetazolamide.

High altitude (HA) ascent imposes systemic hypoxia and associated risk of acute mountain sickness. Acute hypoxia elicits a hypoxic ventilatory response (HVR), which is augmented with chronic HA exposure (i.e., ventilatory acclimatization; VA). However, laboratory-based HVR tests lack portability and feasibility in field studies. As an alternative, we aimed to characterize area under the curve (AUC) calculations on Fenn diagrams, modified by plotting portable measurements of end-tidal carbon dioxide ( P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) against peripheral oxygen saturation ( S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) to characterize and quantify VA during incremental ascent to HA (n = 46). Secondarily, these participants were compared with a separate group following the identical ascent profile whilst self-administering a prophylactic oral dose of acetazolamide (Az; 125 mg BID; n = 20) during ascent. First, morning P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ and S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ measurements were collected on 46 acetazolamide-free (NAz) lowland participants during an incremental ascent over 10 days to 5160 m in the Nepal Himalaya. AUC was calculated from individually constructed Fenn diagrams, with a trichotomized split on ranked values characterizing the smallest, medium, and largest magnitudes of AUC, representing high (n = 15), moderate (n = 16), and low (n = 15) degrees of acclimatization. After characterizing the range of response magnitudes, we further demonstrated that AUC magnitudes were significantly smaller in the Az group compared to the NAz group (P = 0.0021), suggesting improved VA. These results suggest that calculating AUC on modified Fenn diagrams has utility in assessing VA in large groups of trekkers during incremental ascent to HA, due to the associated portability and congruency with known physiology, although this novel analytical method requires further validation in controlled experiments. HIGHLIGHTS: What is the central question of this study? What are the characteristics of a novel methodological approach to assess ventilatory acclimatization (VA) with incremental ascent to high altitude (HA)? What is the main finding and its importance? Area under the curve (AUC) magnitudes calculated from modified Fenn diagrams were significantly smaller in trekkers taking an oral prophylactic dose of acetazolamide compared to an acetazolamide-free group, suggesting improved VA. During incremental HA ascent, quantifying AUC using modified Fenn diagrams is feasible to assess VA in large groups of trekkers with ascent, although this novel analytical method requires further validation in controlled experiments.

The Rise in Tubular pH during Hypercalciuria Exacerbates Calcium Stone Formation.

In calcium nephrolithiasis (CaNL), most calcium kidney stones are identified as calcium oxalate (CaOx) with variable amounts of calcium phosphate (CaP), where CaP is found as the core component. The nucleation of CaP could be the first step of CaP+CaOx (mixed) stone formation. High urinary supersaturation of CaP due to hypercalciuria and an elevated urine pH have been described as the two main factors in the nucleation of CaP crystals. Our previous in vivo findings (in mice) show that transient receptor potential canonical type 3 (TRPC3)-mediated Ca2+ entry triggers a transepithelial Ca2+ flux to regulate proximal tubular (PT) luminal [Ca2+], and TRPC3-knockout (KO; -/-) mice exhibited moderate hypercalciuria and microcrystal formation at the loop of Henle (LOH). Therefore, we utilized TRPC3 KO mice and exposed them to both hypercalciuric [2% calcium gluconate (CaG) treatment] and alkalineuric conditions [0.08% acetazolamide (ACZ) treatment] to generate a CaNL phenotype. Our results revealed a significant CaP and mixed crystal formation in those treated KO mice (KOT) compared to their WT counterparts (WTT). Importantly, prolonged exposure to CaG and ACZ resulted in a further increase in crystal size for both treated groups (WTT and KOT), but the KOT mice crystal sizes were markedly larger. Moreover, kidney tissue sections of the KOT mice displayed a greater CaP and mixed microcrystal formation than the kidney sections of the WTT group, specifically in the outer and inner medullary and calyceal region; thus, a higher degree of calcifications and mixed calcium lithiasis in the kidneys of the KOT group was displayed. In our effort to find the Ca2+ signaling pathophysiology of PT cells, we found that PT cells from both treated groups (WTT and KOT) elicited a larger Ca2+ entry compared to the WT counterparts because of significant inhibition by the store-operated Ca2+ entry (SOCE) inhibitor, Pyr6. In the presence of both SOCE (Pyr6) and ROCE (receptor-operated Ca2+ entry) inhibitors (Pyr10), Ca2+ entry by WTT cells was moderately inhibited, suggesting that the Ca2+ and pH levels exerted sensitivity changes in response to ROCE and SOCE. An assessment of the gene expression profiles in the PT cells of WTT and KOT mice revealed a safeguarding effect of TRPC3 against detrimental processes (calcification, fibrosis, inflammation, and apoptosis) in the presence of higher pH and hypercalciuric conditions in mice. Together, these findings show that compromise in both the ROCE and SOCE mechanisms in the absence of TRPC3 under hypercalciuric plus higher tubular pH conditions results in higher CaP and mixed crystal formation and that TRPC3 is protective against those adverse effects.

Exposure to topiramate and acetazolamide causes endocrine disrupting effects in female rats during estrus.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a disease characterized by elevated intracranial pressure (ICP) and is a disease of young females. The first line pharmacological treatments include acetazolamide and topiramate and given the nature of IIH patients and the dosing regimen of these drugs, their effect on the endocrine system is important to evaluate. We aimed to assess the effects of acetazolamide and topiramate on steroid profiles in relevant endocrine tissues. METHODS: Female Sprague Dawley rats received chronic clinically equivalent doses of acetazolamide or topiramate by oral gavage and were sacrificed in estrus. Tissue specific steroid profiles of lateral ventricle CP, 4th ventricle CP, CSF, serum, uterine horn and fundus, ovaries, adrenal glands and pituitary glands were assessed by quantitative targeted LC-MS/MS. We determined luteinizing hormone (LH) and follicle stimulating hormones (FSH) levels in paired serum by ELISA. RESULTS: Topiramate increased the concentration of estradiol and decreased the concentration of DHEA in lateral choroid plexus. Moreover, it decreased the concentration of androstenediol in the pituitary gland. Topiramate increased serum LH. Acetazolamide decreased progesterone levels in serum and uterine fundus and increased corticosteroid levels in the adrenal glands. CONCLUSION: These results demonstrate that both acetazolamide and topiramate have endocrine disrupting effects in rats. Topiramate primarily targeted the choroid plexus and the pituitary gland while acetazolamide had broader systemic effects. Furthermore, topiramate predominantly targeted sex hormones, whereas acetazolamide widely affected all classes of hormones. A similar effect in humans has not yet been documented but these concerning findings warrants further investigations.

A mathematical model for temporal cerebral blood flow response to acetazolamide evaluated in patients with Moyamoya disease.

BACKGROUND: Paired cerebral blood flow (CBF) measurement is usually acquired before and after vasoactive stimulus to estimate cerebrovascular reserve (CVR). However, CVR may be confounded because of variations in time-to-maximum CBF response (tmax) following acetazolamide injection. With a mathematical model, CVR can be calculated insensitive to variations in tmax, and a model offers the possibility to calculate additional model-derived parameters. A model that describes the temporal CBF response following a vasodilating acetazolamide injection is proposed and evaluated. METHODS: A bi-exponential model was adopted and fitted to four CBF measurements acquired using arterial spin labelling before and initialised at 5, 15 and 25 min after acetazolamide injection in a total of fifteen patients with Moyamoya disease. Curve fitting was performed using a non-linear least squares method with a priori constraints based on simulations. RESULTS: Goodness of fit (mean absolute error) varied between 0.30 and 0.62 ml·100 g-1·min-1. Model-derived CVR was significantly higher compared to static CVR measures. Maximum CBF increase occurred earlier in healthy- compared to diseased vascular regions. CONCLUSIONS: The proposed mathematical model offers the possibility to calculate CVR insensitive to variations in time to maximum CBF response which gives a more detailed characterisation of CVR compared to static CVR measures. Although the mathematical model adapts generally well to this dataset of patients with MMD it should be considered as experimental; hence, further studies in healthy populations and other patient cohorts are warranted.

Acetazolamide Challenge Changes Outer Retina Bioenergy-Linked and Anatomical OCT Biomarkers Depending on Mouse Strain.

Purpose: The purpose of this study was to test the hypothesis that optical coherence tomography (OCT) bioenergy-linked and anatomical biomarkers are responsive to an acetazolamide (ACZ) provocation. Methods: C57BL/6J mice (B6J, a strain with relatively inefficient mitochondria) and 129S6/ev mice (S6, a strain with relatively efficient mitochondria) were given a single IP injection of ACZ (carbonic anhydrase inhibitor) or vehicle. In each mouse, the Mitochondrial Configuration within Photoreceptors based on the profile shape Aspect Ratio (MCP/AR) index was determined from the hyper-reflective band immediately posterior to the external limiting membrane (ELM). In addition, we tested for ACZ-induced acidification by measuring contraction of the external limiting membrane-retinal pigment epithelium (ELM-RPE) thickness; the hyporeflective band (HB) signal intensity at the photoreceptor tips was also examined. Finally, the nuclear layer thickness was measured. Results: In response to ACZ, MCP/AR was greater-than-vehicle in B6J mice and lower-than-vehicle in S6 mice. ACZ-treated B6J and S6 mice both showed ELM-RPE contraction compared to vehicle-treated mice, consistent with dehydration in response to subretinal space acidification. The HB intensity at the photoreceptor tips and the outer nuclear layer thickness (B6J and S6), as well as the inner nuclear layer thickness of B6J mice, were all lower than vehicle following ACZ. Conclusions: Photoreceptor respiratory efficacy can be evaluated in vivo based on distinct rod mitochondria responses to subretinal space acidification measured with OCT biomarkers and an ACZ challenge, supporting and extending our previous findings measured with light-dark conditions.

Effects of furosemide, acetazolamide and amiloride on renal cortical and medullary tissue oxygenation in non-anaesthetised healthy sheep.

It has been proposed that diuretics can improve renal tissue oxygenation through inhibition of tubular sodium reabsorption and reduced metabolic demand. However, the impact of clinically used diuretic drugs on the renal cortical and medullary microcirculation is unclear. Therefore, we examined the effects of three commonly used diuretics, at clinically relevant doses, on renal cortical and medullary perfusion and oxygenation in non-anaesthetised healthy sheep. Merino ewes received acetazolamide (250 mg; n = 9), furosemide (20 mg; n = 10) or amiloride (10 mg; n = 7) intravenously. Systemic and renal haemodynamics, renal cortical and medullary tissue perfusion and P O 2 ${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$ , and renal function were then monitored for up to 8 h post-treatment. The peak diuretic response occurred 2 h (99.4 ± 14.8 mL/h) after acetazolamide, at which stage cortical and medullary tissue perfusion and P O 2 ${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$ were not significantly different from their baseline levels. The peak diuretic response to furosemide occurred at 1 h (196.5 ± 12.3 mL/h) post-treatment but there were no significant changes in cortical and medullary tissue oxygenation during this period. However, cortical tissue P O 2 ${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$ fell from 40.1 ± 3.8 mmHg at baseline to 17.2 ± 4.4 mmHg at 3 h and to 20.5 ± 5.3 mmHg at 6 h after furosemide administration. Amiloride did not produce a diuretic response and was not associated with significant changes in cortical or medullary tissue oxygenation. In conclusion, clinically relevant doses of diuretic agents did not improve regional renal tissue oxygenation in healthy animals during the 8 h experimentation period. On the contrary, rebound renal cortical hypoxia may develop after dissipation of furosemide-induced diuresis.

An asiatic acid derived trisulfamate acts as a nanomolar inhibitor of human carbonic anhydrase VA.

This investigation delves into the inhibitory capabilities of a specific set of triterpenoic acids on diverse isoforms of human carbonic anhydrase (hCA). Oleanolic acid (1), maslinic acid (2), betulinic acid (3), platanic acid (4), and asiatic acid (5) were chosen as representative triterpenoids for evaluation. The synthesis involved acetylation of parent triterpenoic acids 1-5, followed by sequential reactions with oxalyl chloride and benzylamine, de-acetylation of the amides, and subsequent treatment with sodium hydride and sulfamoyl chloride, leading to the formation of final compounds 21-25. Inhibition assays against hCAs I, II, VA, and IX demonstrated noteworthy outcomes. A derivative of betulinic acid, compound 23, exhibited a Ki value of 88.1 nM for hCA VA, and a derivative of asiatic acid, compound 25, displayed an even lower Ki value of 36.2 nM for the same isoform. Notably, the latter compound displayed enhanced inhibitory activity against hCA VA when compared to the benchmark compound acetazolamide (AAZ), which had a Ki value of 63.0 nM. Thus, this compound surpasses the inhibitory potency and isoform selectivity of the standard compound acetazolamide (AAZ). In conclusion, the research offers insights into the inhibitory potential of selected triterpenoic acids across diverse hCA isoforms, emphasizing the pivotal role of structural attributes in determining isoform-specific inhibitory activity. The identification of compound 25 as a robust and selective hCA VA inhibitor prompts further exploration of its therapeutic applications.

Acetazolamide and topiramate lower intracranial pressure through differential mechanisms: The effect of acute and chronic administration.

BACKGROUND AND PURPOSE: Diseases of raised intracranial pressure (ICP) cause severe morbidity and mortality. Multiple drugs are utilised to lower ICP including acetazolamide and topiramate. However, the evidence for their use is unclear. We aimed to assess the ICP modulatory effects and molecular effects at the choroid plexus (CP) of acetazolamide and topiramate. EXPERIMENTAL APPROACH: Female rats were implanted with telemetric ICP probes for physiological, freely moving 24/7 ICP recordings. Randomised cross-over studies were performed, where rats received acute (24 h) high doses of acetazolamide and topiramate, and chronic (10 days) clinically equivalent doses of acetazolamide and topiramate, all via oral gavage. Cerebrospinal fluid (CSF) secretion assays, and RT-qPCR and western blots on in vitro and in vivo CP, were used to investigate drug actions. KEY RESULTS: We demonstrate that acetazolamide and topiramate achieved maximal ICP reduction within 120 min of administration, and in combination doubled the ICP reduction over a 24-h period. Chronic administration of acetazolamide or topiramate lowered ICP by 25%. Topiramate decreased CSF secretion by 40%. Chronic topiramate increased the gene expression of Slc12a2 and Slc4a10 and protein expression of the sodium-dependent chloride/bicarbonate exchanger (NCBE), whereas chronic acetazolamide did not affect the expression of assessed genes. CONCLUSIONS AND IMPLICATIONS: Acetazolamide and topiramate are effective at lowering ICP at therapeutic levels. We provide the first evidence that topiramate lowers CSF secretion and that acetazolamide and topiramate may lower ICP via distinct molecular mechanisms. Thus, the combination of acetazolamide and topiramate may have utility for treating raised ICP.

Acetazolamide and human carbonic anhydrases: retrospect, review and discussion of an intimate relationship.

Acetazolamide (AZM) is a strong pharmacological sulphonamide-type (R-SO2-NH2, pKa 7.2) inhibitor of the activity of several carbonic anhydrase (CA) isoforms, notably of renal CA II (Ki, 12 nM) and CA IV (Ki, 74 nM). AZM is clinically used for about eighty years in various diseases including epilepsy and glaucoma. Pharmacological AZM increases temporarily the urinary excretion of bicarbonate (HCO3-) and sodium ions (Na+) and sustainably the urinary pH. AZM is excreted almost unchanged over several hours at high rates in the urine. Closely parallel concentrations of circulating and excretory AZM are observed upon administration of therapeutical doses of AZM. In a proof-of-principle study, we investigated the effects of the ingestion of a 250-mg AZM-containing tablet by a healthy volunteer on the urinary excretion of organic and inorganic substances over 5 h (range, 0, 0.5, 1, 1.5, 2, 3, 4, 5 h). Measured analytes included: AZM, amino acids and their metabolites such as guanidinoacetate, i.e. the precursor of creatine, of asymmetrically (ADMA) and symmetrically (SDMA) dimethylated arginine, nitrite (O = N-O-, pKa 3.4) and nitrate (O2N-O-, pKa -1.37), the major metabolites of nitric oxide (NO), the C-H acidic malondialdehyde (MDA; (CHO)2CH2, pKa 4.5), and creatinine for correction of analytes excretion. All analytes were measured by validated isotopologues using gas chromatography-mass spectrometry (GC-MS) methods. AZM excretion in the urine reached its maximum value after 2 h and was fairly stable for the next 3 h. Time series analysis by the ARIMA method was performed. AZM ingestion increased temporarily the urinary excretion of the amino acids Leu + Ile, nitrite and nitrate, decreased temporarily the urinary excretion of other amino acids. AZM decreased sustainably the urinary excretion of MDA, a biomarker of oxidative stress (i.e. lipid peroxidation). Whether this decrease is due to inhibition of the excretion of MDA or attenuation of oxidative stress by AZM is unknown. The acute and chronic effects of AZM on the urinary excretion of electrolytes and physiological substances reported in the literature are discussed in depth in the light of its extraordinary pharmacokinetics and pharmacodynamics. Tolerance development/drug resistance to AZM in chronic use and potential mechanisms are also addressed.

Prospecção de atividade inibitória da pasta de hidróxido de cálcio e acetazolamida sobre Enterococcus faecalis e Candida albicans / Antimicrobial effect of calcium hydroxide paste and acetazolamide against the Enterococcus faecalis and Candida albicans

Introdução: A medicação intracanal é fundamental para o tratamento de um dente avulsionado, sendo a pasta de hidróxido de cálcio comumente indicada. A acetazolamida é uma substância inibidora da anidrase carbônica e da reabsorção óssea, podendo ser sugerida como medicação intracanal em dentes avulsionados. Contudo, para que uma substância seja sugerida, estudos devem comprovar sua eficácia tanto in vitro como in vivo. Objetivo: Avaliar in vitro a ação antimicrobiana da pasta de hidróxido de cálcio e da acetazolamida, associadas a diferentes veículos, contra os micro-organismos Enterococcus faecalis e Candida albicans. Materiais e métodos: As formulações selecionadas foram: acetazolamida (pó) com soro fisiológico; acetazolamida (pó) com glicerina; acetazolamida e hidróxido de cálcio (pó) em porções iguais com soro fisiológico; acetazolamida e hidróxido de cálcio (pó) em porções iguais adicionando-se glicerina; acetazolamida (líquido) e hidróxido de cálcio (pó) com soro fisiológico. Como controle positivo foram utilizadas concentrações de clorexidina de 20%, 10%, 5%, 2,5%, 1,25% e 0,65% e como controle negativo a glicerina. O experimento foi realizado por teste de difusão em ágar. Resultados: Não houve inibição do crescimento das bactérias com os medicamentos utilizados, apenas com o controle positivo.Conclusão: As formulações de hidróxido de cálcio e acetazolamida não apresentaram atividade inibitóriacontra o E. faecalis e C. albicans.

Introduction: The intracanal medication is essential for the treatment of avulsed tooth, being the calcium hydroxide paste usually indicated. The acetazolamide is an inhibiting substance of carbonic anhydrase and the bone resorption, being suggested as intracanal medication in avulsed teeth. However, for this substance became an alternative as intracanal therapeutic agent, it must be tested in vitro and in vivo. Objective: To evaluate, in vitro, the antimicrobial action of calcium hydroxide paste and acetazolamide associated with different vehicles, against the Enterococcus faecalis and Candida albicans. Materials and methods: The experimental groups were: acetazolamide (powder) with physiological serum; acetazolamide (powder) with glycerin; acetazolamide and calcium hydroxide (powder) in equal portions with physiological serum; acetazolamide and calcium hydroxide (powder) in equal portions added with glycerin; acetazolamide (liquid) and calcium hydroxide (powder) with physiological serum. Clorexidine was used for positive control in concentrations of 20%, 10%, 5%, 2.5%, 1.25% and 0.65% and glycerin was used as negative control. The study was carried through by test of diffusion in agar. Results: No experimental groups showed inhibition of the bacterial growth, only inhibited by the positive control. Conclusion: The groups with calcium hydroxide and acetazolamide did not show antimicrobial activity against the E. faecalis and C. albicans.

Chachacoma ¿un tratamiento alternativo para la prevención del mal agudo de montaña? / Chachacoma, an alternative treatment to prevention od acute mountain sickness?

Chachacoma is an herbal folk remedy used by natives and tourists to avoid high altitude sickness (AMS) when mountain climbing. Chachacoma has been described as a hypotensor. Acetazolamide is presently the best treatment for prevention of AMS and it's function is diuretic. The objectives of the present study was to make a comparative analysis of the efficacy of these two treatments for AMS. A group of 22 healthy subjects (22+- 1 years) with no high altitude experience were divided into two group of 11, one of which received a cup of Chachacoma infusion and a second group of 11 received 250mg of acetazolamide the morning prior to making an ascent (2000 m+). The day prior to the ascent the following parameters were measured on all subjects: heart rate (HR), respiratory rate (RR), systolic and diastolic pressure (SAP,DAP) and oxigen saturation (SatO2). In the following days in Colchane the measurements were repeated and the Lake Louise Test was used to determine AMS symptoms. Values were expressed +- 1 std. deviation and differences were evaluated with a student test ( vs Chachacoma, p>0.05). The incidence of AMS in the Chachacoma group was 55 percent, compared to 36 percent in the acetazolamide group (p<0.05). No significant differences were observed in arterial pressure between groups. However, the point score for AMS for the acetazolamide group was lower than that for the Chachacoma group. It was concluded that acetazolamide was more effient in preventing the symptoms of AMS than Chachacoma.

Chachacoma es un tratamiento etnomedicinal para el MAM en nativos y turistas que ascienden a grandes alturas. Chachacoma es descrita como hipotensor. Acetazolamida actualmente es el mejor tratamiento para prevenir MAM, su función es de diurético. Nuestro objetivo fue comparar su eficiencia en la prevención del MAM. Un estudio fue aplicado a 22 sujetos (22+- 1 años), sanos, sin experiencia a grandes alturas (>2000 m). Un grupo (n=11) con Chachacoma (1 taza con infusión dada en la mañana del ascenso), otro grupo (n=11) con Acetazolamida (250 mg en la mañana del ascenso), El día previo al ascenso se determinaron: frecuencia cardíaca (FC) y respiratoria (FR), presiones sistólicas y diastólicas (PAS,PAD) y saturación de oxigeno (Sat=2). En los siguientes días en Colchane las mediciones fueron repetidas y se usó un test de Lake-Louise para determinar síntomas de MAM. Los valores se expresaron en promedios +- DS, la diferencia fue medida con test de Student (vs Chachacoma, p<0,05). La incidencia de MAM en el grupo de Chachacoma fue 55 por ciento, contra el 36 por ciento del grupo de Acetazolamida )p<0.05). No se observaron cambios en presión arterial en ambos grupos. Sin embargo, el puntaje de MAM para el grupo de Acetazolamida fue menor que el de Chachacoma. En conclusión, Acetazolamida es más eficiente previniendo síntomas de MAM.

Luminal acid in water-inmersion stress and the antiulcer effect of axetazolamide in the rat gastric mucosa

En ratas con píloro ligado, la secreción ácida gástrica (volumen y débito) de los animales en estrés por 10 h (inmovilización e inmersión en agua (21 grados celsius) fue significativamente menor que la de las ratas sin estrés. Acetazolomida, un potente inhibidor de la anhidrasa carbónica, administrada por vía intraperitoneal cada 5 h por un total de dos veces, dosis dependientemente (100, 50, 25 mg/kg) inhibió la secreción ácida y la formación de lesiones mucosas gástricas inducidas por el estrés (dosis antisecretoras). La acetazolamida (5 mg/kg) no tuvo efecto sobre dos parámetros (dosis noantisecretora). El incremento de las lesiones mucosas gástricas inducidas por la instilación intragástrica de 150 mM HCL (0.5 ml/h) durante el estrés, no fueinhibido por dosis antisecretoras de acetazolamida. Se concluye que: (1) la exposición de ratas por 10 h de estrés (inmovilización e inmersión en agua) disminuye la secreción ácida gástrica (2) la acetazolamida, inhibiendo la secreción ácida gástrica protégé a la mucosa de las lesiones inducidas por el estrés y (3) una mínima cantidad de ácido en el lumen gástrico es suficiente para desarrollar las lesiones inducidas por este tipo de estrés.

Análise dos efeitos colaterais provocados pelo uso da acetazolamida via oral nos primeiros 5 dias de tratamento com relaçäo aos níveis séricos de potássio / Side effects of acetazolamide per os during the first five days of treatment and relationship with seric potassium level

Os autores realizaram um estudo duplo-cego para determinar uma possível entre potássio sérico e efeitos colaterais, que aparecem nos primeiros 5 dias de tratamento com acetazolamida 500 mg, via oral. Em todos aqueles que usaram a droga produziu-se efeitos colaterais, sendo o mais comum parestesias. Näo houve diferença significativa entre os níveis de postássio sérico antes e após o tratamento

Efecto de la acetazolamida en pacientes portadores de bronquitis crónica obstructiva y alcalosis metabólica / Acetazolamide effect in patients with obstructive chronic bronchitis and metabolic alkalosis

Nueve pacientes portadores de bronquitis crónica obstructiva hipercápnica y alcalosis metabólica recibieron oralmente una dosis inicial de 500 mg de acetazolamida seguida durante 6 días de una dosis diaria de 250 mg; la serie control estuvo constituída por 7 pacientes de características similares. El grupo tratado mostró una disminución de la PaCO2 desde 59 a 45 mmHg (p<0.001) y del bicarbonato real (de 36 a 26 mEq/L;p<0.0025), con ascenso no significativo de la PaCO2 pero sí de la relación PaCO2/FiO2, que aumentó en promedio desde 212 a 266 mmHg (p<0.01). El grupo control también disminuyó significativamente la PaCO2 y el bicarbonato aunque en un nivel menor; no se modificó la PaO2 pero si aumentó la PaO2/FiO2, aunque también en nivel menor, siendo significativa sólo la diferencia de PaCO2 y relación PaO2/FiO2 entre ambos grupos desde el primer día de tratamento. Ni la ventilación minuto ni el PH se modificaron significativamente en ninguno de los grupos. Se concluye que: 1o. La acetazolamida mejora la PaO2 y PaCO2 mas rapidamente que lo que ocurre en los pacientes no tratados, 2o. No hay peligro de acidosis metabólica severa con el esquema utilizado y 3o. La dosis inicial tiene un efecto rápido apreciable en forma significativa dentro de las primeras 24 horas

Hipercapnea inducida por acetazolamida, su efecto en la circulación pulmonar: estudio experimental / Acetazolamide induced hipercapnea, its effect on the pulmonary circulation: experimental study

Se diseño un modelo de hipercapnea, sin hipoxemia ni acidosis y se evaluaron los efectos del CO2 en la circulación arterial pulmonar. Se estudiaron 6 perros a los que se administró dosis única de acetazolamida (120mg/Kg) para inhibir la acción de la anhidrasa carbónica. Con esta dosis se logró aumentar la PaCO2 de 27.mmHg a 41.mmHg y la PvCO2 de 31.mmHg a 46.mmHg (p<0.01). A lo largo de tres horas la PaCO2 y la PvO2 permanecieron estables y no ocurrió hipoxemia. El pH arterial y el venoso se mantuvieron en promedio en 7.35 ñ 02 y 7.32 ñ.03 respectivamente. Hemodinâmicamente hubo aumento de las resistencias pulmonares totales de 312 ñ 156 a 435 ñ 173 d.s.cm >- (p<0.01) y la presión media de la arteria pulmonar no se modificó. Estos hallazgos aunados a la disminución del índice latido de 20.7 ñ 8.3 a 13.2 ñ 4.8 ml/lat. (p<0.5), sin haber ocurrido cambios en la presión capilar pulmonar, ni en la presión diastólica final del ventrículo derecho nos sugieren posible vasoconstricción pulmonar, la que se atribuye a incremento de la PaCO2 y la PvCO2, en ausencia de otros factores vasoactivos o pasivos

Efectos oculares y sistémicos de la administración preoperatoria de acetézolamida en la cirugía de la catarata senil / Ocular and systemic effects preoperative administration of acetozolamide in surgery of senile cataract

Se analizam los efectos de la administración preoperatoria de acetazolamida, tanto en forma fraccionada como em dosis única, sobre la presión intraocular preoperatoria, la presión vítrea intraoperatoria, el equilibrio ácido-base y los electrolitos plasmáticos en 99 casos de catarata senil pura operados por el autor en el Servicio de Oftalmología del Hospital José Joaquím Aguirre entre los años 1980 y 1982, divididos al azar en tres grupos de estudio, a saber: grupo I, 33 pacientes que recibieron acetazolamida en dosis de 250 mgr por vía oral 18, 10 y 2 horas antes de la operación; grupo II, 33 pacientes que recibieron acetazolamida en dosis única de 500 mgr por vía oral 2 horas antes de la operación; y grupo III, 33 pacientes que no recibieron premedicación (grupo control). La disminución de la presión intraocular observada con ambos tipos de premedicación fue leve (aproximadamente 7%) y estadísticamente no significativa. La premedicación fraccionada provocó mayores alteraciones sistémicas que la premedicación en dosis única, caracterizadas por una acidosis metabólica moderada, compensada con hiperventilación. Los electrolitos plasmáticos no experimentaron modificaciones significativas. No se apreció relación entre la acidosis metabólica inducida por la droga y la cuantía del efecto hipotensor ocular, ni se evidenció una mayor efectividad de la acetazolamida en el control de la presión vítrea durante la extracción de la catarata en comparación con el grupo de pacientes que no recibió premedicación

Acetazolamida e manitol: estudo comparativo do efeito hipotensor ocular / Acetalozamide and mannitol: comparative study of ocular hypotensive effect

Estuda-se a participaçäo dos hipotensores oculares, Acetazolamida (500 mg) e o Manitol endovenoso (2 g/Kg), no pré-operatório das cirurgias oculares, para que se busque o "ótimo" de hipotensäo ocular durante o ato cirúrgico. Estudam-se 50 pacientes normotensos selecionados. Após comentários sobre o mecanismo de açäo das duas drogas hipotensoras, conclui-se que: 1 - Com Diamox em dose única (500 mg), via oral: - a queda máxima da Po obtida foi em torno de 8.50 mmHg, após 120'; - o retorno ao nível inicial (12.00 mmHg) de morou 330'. 2 - Com Manitol endovenoso a 20% (2 g/Kg de peso aproximadamente): - a queda máxima da Po obtida foi em torno de 7.60 mmHg, após 90'; - o retorno ao nível inicial (12.00 mmHg) demorou 450'. 3 - Com a associaçäo Diamox + Manitol, nas mesmas doses: - a queda máxima da Po obtida foi em torno de 7.10 mmHg, após 90'; - o retorno ao nível inicial (12.00 mmHg) demorou 450'. 4 - Os resultados favoreceram ligeiramente a associaçäo, porém sem interesse clínico: O Manitol isoladamente lhe corresponde. 5 - O início da cirurgia näo deve ser precipitado, lembrando-nos de que 90 - 120' constitui o interregno para se atingir o declínio tensional máximo