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European Heart Journal Aug 2023
Topics: Humans; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Metolazone; Heart Failure
PubMed: 37572039
DOI: 10.1093/eurheartj/ehad463 -
Pharmacology & Therapeutics Jan 2020Epilepsies represent one of the most common neurological diseases worldwide. They are characterized by recurrent spontaneous seizures with severe impact on a patient's... (Review)
Review
Epilepsies represent one of the most common neurological diseases worldwide. They are characterized by recurrent spontaneous seizures with severe impact on a patient's life. An imbalance in excitatory and inhibitory signalling is considered the main underlying pathophysiological mechanism. Therefore, GABA-mimetic drugs, strengthening the main inhibitory signalling system in the CNS, are frequently used as antiepileptic or anticonvulsant drugs. However, the therapeutic effect of such treatment depends on the chloride gradient along the plasma membrane. Impairment of chloride homeostasis, caused by alterations in the functional balance of chloride transporters, was implicated in the pathophysiology of epilepsy and numerous other diseases. Breakdown or even inversion of the chloride gradient may result in ineffective or in worst cases proconvulsant effects of GABA-mimetics. Unfortunately, such situations are reported in considerable number. Consequently, bumetanide, an inhibitor of Na-K-Cl cotransporters gained interest as potential add-on therapy re-establishing the chloride gradient and thereby the hyperpolarizing effects of GABA-mimetic drugs. Indeed, preclinical studies yielded encouraging results, especially when applied in combination with GABA-mimetics in epilepsy models. However, bumetanide induces a strong diuretic effect and displays poor penetration across the blood-brain barrier, two adverse features for chronic antiepileptic treatment. Therefore, new compounds overcoming these limitations are under development. This review focuses on alterations in chloride homeostasis and its underlying molecular mechanisms in epilepsy, on the potential impact of impaired chloride homeostasis on the treatment of epilepsy and on concepts to overcome this problem including recent development of bumetanide derivatives with improved pharmacological profile.
Topics: Animals; Anticonvulsants; Blood-Brain Barrier; Bumetanide; Chlorides; Diuretics; Drug Development; Epilepsy; Humans; Sodium Potassium Chloride Symporter Inhibitors; Tissue Distribution
PubMed: 31626872
DOI: 10.1016/j.pharmthera.2019.107422 -
Current Rheumatology Reviews Apr 2024Osteoarthritis (OA) is becoming a major medical burden worldwide due to changing lifestyles and aging populations. Osteoarthritis is a disease characterized by a variety...
BACKGROUND
Osteoarthritis (OA) is becoming a major medical burden worldwide due to changing lifestyles and aging populations. Osteoarthritis is a disease characterized by a variety of anatomic and physiological changes to joints, including cartilage degradation, bone remodeling, and the formation of osteophytes. These changes cause pain, stiffness, swelling, and limitations in joint function. Glucosamine serves as a fundamental constituent for cartilage, the resilient connective tissue responsible for cushioning joints. Glucosamine Sulphate Potassium Chloride (GSPC) supplementation is widely employed to mitigate symptoms linked to osteoarthritis, a degenerative joint disorder hallmarked by cartilage degradation.
AIM
Palliative care aims at minimizing pain and disability and improving function, performance, and quality of life. In this study, the emulgel formulation of GSPC was developed and checked for its potential.
OBJECTIVE
Currently, OA does not have a definitive treatment. Since conventional dosage forms cannot deliver the active drug content at a predefined target site in a predictable manner throughout the treatment period, a new carrier system is always required. Considering their reduced size, targeting potential, and site specificity, nanocarrier-based approaches could hold an answer to shortcomings associated with conventional routes. Thus, the objective of the current study was to formulate and characterize glucosamine sulphate potassium chloride-loaded emulgel for the treatment of osteoarthritis.
METHODS
Microemulsion of glucosamine sulphate potassium chloride was formulated using a spontaneous emulsification method comprising of oleic acid (oil phase), Tween 80, Tween 20 (surfactant) and PEG 400, Span 80 (co-surfactant), and distilled water (aqueous phase). The microemulsions were evaluated for surface morphology, globule size, poly-dispersibility index (PDI), zeta potential, and viscosity, and the final batch of microemulsions was selected.
RESULT
The optimized microemulsion contained 35% co-surfactant (propylene glycol), 20% surfactant (Tween 20), and 15% oil (oleic acid) and glucosamine sulphate potassium chloride in a dose of 60 mg, which has sufficient drug loading capacity with a droplet size of 182 nm for optimized formulation. The optimized microemulsion formulation was added to gel prepared by Carbopol 934 in a 1:1 (w/w) ratio, leading to the formulation of glucosamine sulphate potassium chloride- containing emulgel. The prepared emulgel was further evaluated for viscosity, drug content, pH, and in-vitro drug release. Emulgel formulation (F6) showed 88% drug release after 6 hours, and it followed the Higuchi model.
CONCLUSION
Glucosamine Sulphate Potassium Chloride (GSPC) is used in the treatment of OA by increasing the production of proteoglycans, which can cause the cartilage to break down. Emulgel formulation (F3) showed 75.41% drug release, and formulation (F6) showed 88% drug release after 6 h. Therefore, it may be concluded that an emulgel of GSPC can be used as a controlled-release dosage form of the drug for local application in OA.
PubMed: 38584559
DOI: 10.2174/0115733971291114240326042453 -
British Journal of Clinical Pharmacology Apr 2021To determine whether oral potassium chloride (KCI) therapy with concomitant anticholinergic exposure among hospitalized patients is associated with an excess risk for...
AIM
To determine whether oral potassium chloride (KCI) therapy with concomitant anticholinergic exposure among hospitalized patients is associated with an excess risk for upper gastrointestinal bleeding (UGIB).
METHODS
A retrospective controlled study among hospitalized patients between January 2007 and April 2019 who were treated with oral KCI. Patients were divided into two groups: with or without concomitant exposure to agents with anticholinergic activity. Outcome was defined as any UGIB.
RESULTS
The final sample included 13 728 subjects who received oral KCI treatment, of them 3542 (25.8%) had at least one documented overlap with an anticholinergic agent. Mean age was 67.6 (±17.2) and 6893 (50.2%) were females. Median KCI dose was 2.4 g (interquartile range [IQR] 1.2-5.4, n = 9416) with the majority (90.4%) being treated with the wax-matrix form (Slow-K). Twenty-six (0.2%) patients experienced an UGIB event. Univariate analysis demonstrated a significantly higher rate of UGIB among patients concomitantly treated with oral KCI and anticholinergics (0.3%) compared to those without anticholinergic exposure (0.1%, P = 0.018), with median 7 days (IQR 3-16.8) from first KCI dose to bleeding event. Multivariate analysis demonstrated that concomitant anticholinergic exposure (Odds Ratio 2.48, 95% Confidence Interval 1.11-6.51, P = 0.022) and anticoagulation treatment among patients with hemato-oncologic disease (OR 6.61, 95% CI 1.96-22.25, P = 0.002) were significantly associated with UGIB.
CONCLUSION
Hospitalized patients treated concomitantly with oral KCI and anticholinergic agents have significantly increased risk for UGIB.
Topics: Aged; Cholinergic Antagonists; Cohort Studies; Female; Gastrointestinal Hemorrhage; Humans; Potassium Chloride; Retrospective Studies
PubMed: 33068044
DOI: 10.1111/bcp.14616 -
Clinical Therapeutics Nov 2023Omadacycline is a broad-spectrum intravenous and oral tetracycline antibiotic approved for the treatment of community-acquired bacterial pneumonia and acute bacterial...
PURPOSE
Omadacycline is a broad-spectrum intravenous and oral tetracycline antibiotic approved for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. Available information on the compatibility of intravenous omadacycline is limited to sterile water, 0.9% sodium chloride, and 5% dextrose via a dedicated line. The objective of this work was to determine the intravenous compatibility of omadacycline with commonly used intravenous fluids and medications using simulated Y-site administration.
METHODS
Omadacycline was prepared at concentrations consistent with a maintenance dose (1 mg/mL) and a loading dose (2 mg/mL) with 0.9% sodium chloride according to the prescribing information. Compatibility via simulated Y-site administration was assessed with selected crystalloids (lactated Ringer's solution, magnesium sulfate, and normal saline with potassium chloride) and intravenous medications (bumetanide, furosemide, heparin, and insulin). Y-site administration was simulated by mixing 5 mL of omadacycline with 5 mL of each parenteral product prepared at standard concentrations for infusion. Compatibility was assessed by using visual, Tyndall beam, microscopy, and spectrophotometry methods at 0, 30, and 60 minutes.
FINDINGS
Omadacycline appeared physically compatible with lactated Ringer's solution, magnesium sulfate, normal saline with potassium chloride, bumetanide, heparin, and insulin at standard infusion concentrations. However, although the lower concentrations of omadacycline 1 mg/mL and furosemide 2 mg/mL showed compatibility, higher concentrations of either agent in combination resulted in incompatibility.
IMPLICATIONS
Omadacycline appeared physically compatible with all products tested and incompatible with furosemide. Simultaneous administration of omadacycline with tested intravenous medications, except furosemide, is suggested to be safe.
Topics: Humans; Sodium Chloride; Ringer's Lactate; Infusions, Intravenous; Saline Solution; Bumetanide; Furosemide; Magnesium Sulfate; Potassium Chloride; Tetracyclines; Glucose; Heparin; Insulins
PubMed: 37777376
DOI: 10.1016/j.clinthera.2023.09.004 -
Meat Science Jul 2020The objectives of this study were to evaluate the effects of power ultrasound (nominal intensity 600 W·cm for 10 min) and the addition of potassium chloride (KCl) on...
The objectives of this study were to evaluate the effects of power ultrasound (nominal intensity 600 W·cm for 10 min) and the addition of potassium chloride (KCl) on the physicochemical properties and sensorial acceptance of low sodium restructured cooked ham. Four treatments of low sodium restructured cooked ham (mean of 324.52 mg Na/100 g) were prepared: CT - Control Treatment; UsT - Ultrasound Treatment; KT - addition of 0.5% KCl; UsKT - Ultrasound Treatment and addition of 0.5% KCl. Ultrasound application reduced the total fluid released and improved the sensory acceptance for salty taste and flavor compared to CT. The addition of KCl showed the lowest values for total fluid release, the highest scores for all parameters of sensory acceptance, improved hardness and chewiness, which results were not statistically different from the results obtained by combining ultrasound and KCl. Therefore, the use of KCl was considered a technological and sensorial viable alternative to produce low sodium restructured cooked ham. CHEMICAL COMPOUNDS USED IN THIS RESEARCH: Methanol (PubChem CID: 887); Chloroform (PubChem CID: 6212); Sodium Carbonate (PubChem CID: 10340); Sodium hydroxide (PubChem CID: 14798); Boric acid (PubChem CID: 7628).
Topics: Animals; Color; Consumer Behavior; Humans; Meat Products; Potassium Chloride; Sodium Chloride, Dietary; Swine; Taste; Ultrasonic Waves
PubMed: 32224414
DOI: 10.1016/j.meatsci.2020.108130 -
Clinical Pharmacology in Drug... Mar 2023Potassium (K ) is an endogenous substance that is an essential dietary component. However, the interaction between dietary arrangements and specific effects of dietary K... (Randomized Controlled Trial)
Randomized Controlled Trial
Potassium (K ) is an endogenous substance that is an essential dietary component. However, the interaction between dietary arrangements and specific effects of dietary K intake in bioequivalence studies remains unclear. To investigate the influence of dietary arrangement on the bioequivalence of potassium chloride (KCl) sustained-release tablets in healthy Chinese volunteers, the pharmacokinetics of KCl were compared in two open-label, single-center, randomized, two-period crossover studies with different dietary conditions. All volunteers received an oral dose of 6 g of KCl sustained-release tablets under fasting conditions, with different dietary arrangements. Urine samples were collected on baseline days and 48 hours after tablet consumption. Inductively coupled plasma-optical emission spectrometry was used to measure the concentration of K in the urine samples. Pharmacokinetic parameters were analyzed using Phoenix WinNonlin software in a noncompartmental model. In either clinical trial, no significant differences were observed in the maximal rate of urinary excretion and cumulative urinary excretion from 0 to 24 hours of K between the reference and test drugs. The bioequivalence studies of both KCl sustained-release tablet formulations were successfully conducted under different dietary conditions.
Topics: Humans; Delayed-Action Preparations; East Asian People; Potassium Chloride; Tablets; Therapeutic Equivalency; Cross-Over Studies
PubMed: 36321352
DOI: 10.1002/cpdd.1180 -
Biomaterials Science Jan 2022Electrodynamic therapy (EDT) has recently emerged as an alternative approach for tumor therapy the generation of ROS by platinum (Pt) nanoparticles under electric...
Electrodynamic therapy (EDT) has recently emerged as an alternative approach for tumor therapy the generation of ROS by platinum (Pt) nanoparticles under electric field. An interesting phenomenon observed during EDT is that the increased on-site concentration of chloride ions is highly beneficial for ROS generation and inhibition efficacy. Here, in this study, nanoclusters (KCC), consisting of potassium chloride (KCl) nanocrystals and amorphous calcium carbonate (CaCO), were synthesized and integrated with platinum nanoparticles (KCCP). In this system, KCC can dissolve and release calcium and chloride ions within tumor cells. The intracellular chloride ions considerably facilitated ROS generation by Pt nanoparticles under an electric field. More importantly, the excessive calcium ions and ROS formed a cycle of mutual promotion and self-amplification in cells, leading to agitated tumor inhibition, both and .
Topics: Calcium Carbonate; Humans; Metal Nanoparticles; Nanoparticles; Neoplasms; Platinum; Potassium Chloride
PubMed: 34928270
DOI: 10.1039/d1bm01464a -
Pesticide Biochemistry and Physiology May 2023The K/Cl cotransporter (KCC) is the primary mechanism by which mature neurons maintain low intracellular chloride (Cl) concentration and has been shown to be...
The K/Cl cotransporter (KCC) is the primary mechanism by which mature neurons maintain low intracellular chloride (Cl) concentration and has been shown to be functionally coupled to the GABA-gated chloride channels (GGCC) in Drosophila central neurons. Further, pharmacological inhibition of KCC has been shown to lead to acute toxicity of mosquitoes that highlights the toxicological relevance of insect KCC. Yet, gaps in knowledge remain regarding physiological drivers of KCC function and interactions of ion flux mechanisms upstream of GGCC in insects. Considering this, we employed electrophysiological and fluorescent microscopy techniques to further characterize KCC in the insect nervous system. Fluorescent microscopy indicated insect KCC2 is expressed in rdl neurons, which is the neuron type responsible for GABA-mediated neurotransmission, and are coexpressed with inward rectifier potassium (Kir) 2 channels. Coexpression of Kir2 and KCC2 suggested the possibility of functional coupling between these two K flux pathways. Indeed, extracellular recordings of Drosophila CNS showed pre-block of Kir channels prior to block of KCC led to a significant (P < 0.001) increase in CNS firing rates over baseline that when taken together, supports functional coupling of Kir to KCC function. Additionally, we documented a synergistic increase to toxicity of VU0463271, an established KCC inhibitor, above the expected additive toxicity after co-treatment with the Kir inhibitor, VU041. These data expand current knowledge regarding the physiological roles of KCC and Kir channels in the insect nervous system by defining additional pathways that facilitate inhibitory neurotransmission through GGCC.
Topics: Animals; Potassium; Chlorides; Potassium Chloride; Central Nervous System; Drosophila; Symporters; gamma-Aminobutyric Acid
PubMed: 37105628
DOI: 10.1016/j.pestbp.2023.105389 -
Archives of Gynecology and Obstetrics Mar 2023This study sought to compare the efficacy and outcomes of fetal intracardiac intraventricular and interventricular septal potassium chloride (KCl) injections during the... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study sought to compare the efficacy and outcomes of fetal intracardiac intraventricular and interventricular septal potassium chloride (KCl) injections during the induced fetal demise process in a cohort of pregnant women with severe fetal abnormality who opted for late termination of pregnancy (TOP).
MATERIALS AND METHODS
This study consisted of 158 pregnant women who requested late TOP for severe fetal abnormality between 22 and 36 weeks of pregnancy. Participants were randomly assigned with the simple randomization procedure to one of two feticide procedure groups: the intraventricular KCl injection group and the interventricular septal KCl administration group. We studied the clinical outcomes of both the feticide procedures.
RESULTS
The median total dose of strong KCl was significantly lower in the interventricular septal KCl administration group (3 mL) than in the intraventricular KCl injection group (5 mL, p < 0.001). The median time to reach asystole and the median total duration of the procedure was significantly shorter in the interventricular septal KCl administration group (42 s and 85 s, respectively) than in the intraventricular KCl injection group (115 s and 150 s, respectively, p < 0.001). We detected a statistically significant correlation between the gestational week at feticide and the total dose of KCl (r = 0.705, p < 0.001), time to reach asystole (r = 0.653, p < 0.001), and total duration of the procedure (r = 0.683, p < 0.001).
CONCLUSION
KCl administered directly into the interventricular septum induces immediate and permanent fetal cardiac asystole with a 100% of success rate without comprising maternal safety. We did not observe any maternal complications related to the procedure in our cases. Since the consequences of failed feticide procedure are challenging for both parents and healthcare providers, and providers are also concerned about potential legal implications regarding an unintended live birth, it is crucial to guide a strict protocol to confirm permanent fetal cardiac asystole.
Topics: Pregnancy; Female; Humans; Potassium Chloride; Pregnancy Trimester, Second; Fetal Heart; Pregnancy, Multiple; Heart Arrest
PubMed: 36271257
DOI: 10.1007/s00404-022-06795-8