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Actions of glucose and potassium chloride on osmoreceptors slowing gastric emptying.

1. Five subjects were given 373 test meals of 750 ml. water containing a range of concentrations of glucose or potassium chloride.2. The greater the concentration of solute in the meals, the greater was the volume of the test meal recovered from the stomach after a fixed time.3. When the concentrations of the solutes were expressed as m-osmole/l. corrected by osmotic coefficients based on vapour pressures at 37 degrees C, glucose and potassium chloride were indistinguishable in slowing gastric emptying.4. These results are consistent with the regulation of gastric emptying by a duodenal receptor responding to osmotic pressure.5. Potassium chloride was more nauseating than glucose on an osmolar basis.

Duodenum↗

A comparative study of frusemide-amiloride and cyclopenthiazide-potassium chloride in the treatment of congestive cardiac failure in general practice.

Forty-seven patients entered this comparison of frusemide-amiloride and cyclopenthiazide-potassium chloride in the treatment of congestive cardiac failure in general practice. Frusemide-amiloride was 'very satisfactory' in 92% of the patients compared to only 55% who took cyclopenthiazide-potassium chloride. Significantly more patients were free of paroxysmal nocturnal dyspnoea and orthopnoea after taking frusemide-amiloride.

Amiloride↗

In vitro and in vivo evaluation of potassium chloride sustained release formulation prepared with saturated polyglycolyed glycerides matrices.

The aim of the present work was to evaluate the effect of sustained release of potassium chloride semi-solid matrices prepared with different kinds and added amounts of Gelucires by the in vitro dissolution test and in vivo oral absorption study, and compared with a commercial product (slow-K). The results indicating that the release rates of potassium from experimental formulations were dependent on the type of semi-solid matrices (Gelucires). The higher the melting point of the Gelucires was incorporated, the slower release rate of the active substance was observed. Moreover, the values of similarity factor of Formulae F05 and F09 versus the reference in three kinds of dissolution medium (f(2)) were higher than 50, indicating that these experimental formulations had similar sustained release effects to the reference (slow-K) in dissolution test. In vivo study, the cumulative amount (mEq) of potassium excreted curve and the excretion rate curve of F05 and F09 were found to be similar to that of slow-K, and there were no significant differences (P > 0.05) in the maximum excretion rate and the mean time to reach the maximum rate between formulations and slow-K, indicating that the potassium chloride sustained release dosage form could be prepared using the Gelucires as lipid excipients.

Animals↗

Bioavailability and pharmacokinetics of a new, slow-release potassium chloride capsule.

The bioavailability of a new, slow-release potassium chloride product consisting of coated beads in a hard gelatin capsule was compared with the bioavailability of two marketed products, an elixir and a slow-release tablet, by determining the urinary excretion of potassium. Twelve healthy male volunteers were dosed with a total of 80 mEq of potassium, in a single dose for the capsule and tablet and in three 26.6-mEq doses at 6-hr intervals for the elixir. Mean recoveries in 24-hr urine potassium levels from all three dosage forms after subtracting normal urine potassium excretion levels were 50.8% from the capsule, 53.9% from the elixir, and 63.1% from the tablet. Maximum excretion rates were reached at 2.0 hr for the elixir, 6.8 hr for the capsule, and 4.0 hr for the tablet. Fewer side effects were reported with the capsule than with the elixir and tablet.

Adult↗

Mucosal irritant potential of a potassium-sparing diuretic and of wax-matrix potassium chloride.

To measure their relative upper gastrointestinal irritant potential, either 5 mg amiloride and 50 mg hydrochlorothiazide (twice daily) or 24 mEq wax-matrix potassium chloride (three times a day) were given to 30 normal subjects with no prior endoscopic abnormalities in the esophagus, stomach, or duodenum. All subjects received glycopyrrolate, 2 mg (3 times a day) to slow gastric emptying. Repeat endoscopy after 7 days of treatment with wax-matrix potassium chloride revealed that 10 of 15 (67%) of the subjects developed one or more gradable upper gastrointestinal lesions (esophageal ulcer, gastric ulcer, eight cases of one or more mucosal erosions, and four cases of hyperemia or edema of the esophagus, stomach, or duodenum). Four subjects (27%) taking amiloride/hydrochlorothiazide developed either mild hyperemia or edema, but there were no erosions or ulcers in this group.

Amiloride↗

[Functional test with potassium chloride following long-term space mission].

To look into the potassiuretic function of kidneys in 11 cosmonauts on the second day post recovery after six-month MIR missions, functional testing with potassium chloride was performed. The following standard procedure was used before and after the missions: during morning hours fasting test-subjects consumed a 10% solution of potassium chloride in the amount of 0.55 ml/kg or 0.75 mmol of potassium per a kilogram of body mass with some additional liquid in the amount of 10 ml/kg of body mass. Later on, urine was collected for four hours. Administration of the potassium loading test after missions did not reveal any significant group-average changes in potassium excretion as compared with pre-flight levels; meanwhile, calcium excretion was increased. Reduced blood concentrations of potassium were determined in each of the cosmonauts immediately after landing. The main contributor to retaining of the renal potassiuretic function after prolonged missions appears to be the effective inflight physical countermeasures against the musculoskeletal deconditioning of the human body.

Adaptation, Physiological↗

Localization of the KCC4 potassium-chloride cotransporter in the nervous system.

Potassium-chloride cotransporters (KCCs) collectively play a crucial role in the function and development of both the peripheral and central nervous systems. KCC4 is perhaps the least abundant KCC in the adult mammalian brain, where its localization is unknown. In the embryonic brain, KCC4 mRNA is found in the periventricular zone, cranial nerves and choroid plexus [Eur J Neurosci 16 (2002) 2358]. To investigate the distribution of KCC4 protein in the nervous system we developed a rabbit polyclonal antibody directed against a short N-terminal peptide. Western blot analysis of brain microsomal protein using purified antibody revealed the presence of a band at approximately 145 kDa, consistent with the size of a glycosylated K-Cl cotransporter. Western blot analysis of brain, spinal cord and peripheral nerves revealed high expression levels in peripheral nerves and spinal cord, with low levels in whole brain. Within the brain, the cerebral cortex, hippocampus, and cerebellum revealed minimal KCC4 expression, whereas midbrain and brainstem demonstrated higher levels. In the adult mouse brain, KCC4 staining was observed on the apical membrane of choroid plexus epithelial cells as well as in cranial nerves. All other brain structures, e.g. cortex, hippocampus, cerebellum showed no KCC4 immunoreactivity, suggesting very low or absent expression of the cotransporter in these regions. Co-staining of KCC4 with anti-MAP2, GFAP and CNPase revealed that KCC4 is expressed in peripheral neurons. Thus, KCC4 is expressed on the apical membrane of the choroid plexus, where it likely participates to K(+) reabsorption. KCC4 is also expressed in peripheral neurons, where its function remains to be determined.

Animals↗

Bioavailability and pharmacokinetics of a new sustained-release potassium chloride tablet.

The bioavailability of a new sustained-release potassium chloride (KCl) tablet, designed for once-a-day dosing, was compared to a KCl elixir using urinary excretion data. The study utilized 25 male volunteers dosed in a crossover design in a dietary/activity-controlled environment. The regimens consisted of a total of 80 mEq of potassium in three equally divided doses of elixir every 6 hr and a single 80-mEq dose using four 20-mEq sustained-release (SR) tablets. The mean time to maximum rate of potassium urinary excretion was 2.2 hr for the first elixir dose and 5.5 hr after the SR tablet (P less than 0.01), thereby supporting the prolonged-release properties of this formulation. After correction for baseline urinary potassium excretion, the mean total 24-hr urinary potassium excretion was 42.18 mEq for the elixir and 40.41 mEq for the SR tablet. The results indicate that the absorption pattern from the SR tablet is equal to three doses of KCl elixir dosed 6 hr apart.

Adult↗

Constant potassium chloride release from microporous membrane-coated tablets prepared with aqueous colloidal polymer dispersions.

To achieve constant drug release and to avoid the use of organic solvents, potassium chloride tablets were coated with aqueous latexes containing dispersed pore-formers with pH-dependent solubility characteristics. The pore-forming agent, dibasic calcium phosphate, was insoluble in the latex but soluble at low pH. Upon contact with simulated gastric fluids, it leached out rapidly to form a rate-controlling, microporous membrane. The release of potassium chloride was linear with time up to 75-80% drug released. It increased with increasing level of pore-former and decreasing membrane thickness but was independent of the degree of agitation and the pH of the dissolution medium after leaching of the pigments. Upon storage at different relative humidities, moisture uptake of the film coat and variations in the release profiles over time were minimal.

Chemistry, Pharmaceutical↗

Upper gastrointestinal tract bleeding from oral potassium chloride. Comparative risk from microencapsulated vs wax-matrix formulations.

A retrospective cohort study was performed to assess the relative risk of upper gastrointestinal (UGI) tract bleeding from two formulations of potassium chloride. Relevant information was obtained from 1980 through 1984 Medicaid billing data from the states of Michigan, Minnesota, Florida, and Ohio. After patients with a history of UGI tract bleeding prior to their first prescription for either of the two potassium chloride preparations under study were excluded, data were analyzed for 28,790 patients (143,512 patient-months) dispensed a microencapsulated formulation exclusively and 76,118 patients (560,341 patient-months) dispensed a wax-matrix formulation exclusively. The risk of UGI tract bleeding within 30 days after each prescription for the drug of interest was examined. After sampling from the undiseased study subjects and adjusting for multiple potential confounding variables using logistic regression, an odds ratio (95% confidence interval) of 0.67 (0.52 to 0.85) was observed.

Administration, Oral↗

Amiloride, spironolactone, and potassium chloride in thiazide-treated hypertensive patients.

Dose-response curves for amiloride and spironolactone were defined in 15 hypertensive patients treated with bendroflumethiazide (bendrofluazide). The relative potency amiloride:spironolactone in correcting hypokalemia was 2.8:1, an estimate significantly lower than the 5:1 potency currently accepted. The relative potency for reduction of plasma sodium was 3.9:1 (amiloride:spironolactone). Amiloride was disproportionately potent in lowering serum bicarbonate, and the data do not suggest that these drugs elevate plasma potassium simply by correcting metabolic alkalosis. Changes in blood pressure were confounded by the presence of carryover effect between treatment phases. Both drugs increased plasma angiotension II and aldosterone, but the rise in aldosterone with spironolactone was smaller than expected from concurrent plasma angiotension II and potassium concentrations. This was consistent with a partial block of aldosterone biosynthesis by spironolactone. The activity of spironolactone did not require the presence of hyperaldosteronism. In a smaller study potassium chloride induced a significant log dose-response on plasma potassium, but the effect was small in absolute terms. At least 64 mmole potassium chloride was needed to match the effect of 20 mg amiloride or 56 mg spironolactone.

Adult↗

In vitro diagnosis of susceptibility to malignant hyperthermia: evaluation of tests with halothane-caffeine, potassium chloride, suxamethonium and caffeine-suxamethonium.

Susceptibility to MH was determined in 77 patients according to the protocol of the European MH Group. Additional muscle bundles were used for diagnostic in vitro tests with caffeine in the presence of 1% halothane, potassium chloride, suxamethonium, and caffeine-suxamethonium. Significant differences between MH-susceptible (MHS) and MH-negative (MHN) patients were obtained with the halothane-caffeine test and the potassium chloride test, whereas no differences were found with the suxamethonium test. In the test with caffeine-suxamethonium, a different response to caffeine but not to suxamethonium was obtained. In all tests there was an overlap in results between MHS and MHN groups, and the predictive values of the tests ranged between 63 and 95%. Prior small doses of caffeine followed by a 4 mmol/l dose of caffeine elicited significantly smaller contractures than 4 mmol/l given as the first dose of caffeine. This underlines the necessity of a common protocol for performance and interpretation of diagnostic tests for MH.

Caffeine↗

Application of potassium chloride to a Chernobyl-contaminated lake: modelling the dynamics of radiocaesium in an aquatic ecosystem and decontamination of fish.

This study tests a whole-lake experiment to reduce the bioaccumulation of radiocaesium (137Cs) in fish in lakes contaminated by the Chernobyl accident. In many lakes in the Chernobyl contaminated areas, radiocaesium activity concentrations in fish are still significantly higher (up to 100 times in some species) than acceptable limits for human consumption. Estimates of the long-term rate of decline of 137Cs in fish in these regions, in the absence of countermeasures, show that radioactivity in fish in some lakes may remain above acceptable consumption limits for a further 50-100 years from the present date. In February 1998 we applied 15 t of potassium chloride to Lake Svyatoe, Kostiukovichy. The addition of potassium chloride fertilizer to the lake resulted in a decrease in activity concentration of 137Cs to approximately 40% of pre-countermeasure values in a number of different fish species. In contrast to Lake Svyatoe, 137Cs activity concentrations in fish from four control lakes showed no systematic decrease over the study period. Simplified models for transfers of 137Cs in lakes successfully 'blind' predicted the changes in 137Cs in water and fish resulting from this major alteration of the potassium concentration of the lake. The experiment represents the first test of a predictive model for the dynamics of radiocaesium in response to a major perturbation in potassium (its major competitor ion) in a whole lake ecosystem.

Animals↗

The spasmogenic action of potassium chloride in guinea-pig trachealis.

Tissue bath experiments showed that potassium chloride (KC1) at 10-40 mmoll-1 evoked spasm of guinea-pig trachealis which was unaffected by atropine (1 mumoll-1), mepyramine (1 mumoll-1), tetrodotoxin (3 mumoll-1) or indomethacin (2.8 mumoll-1). Spasm evoked by KC1 was depressed in Ca2+-free Krebs solution or by exposure of tissues to LaCl3 (0.25-1 mmoll-1). Extracellular electrical recording showed that the spasm evoked by KCl 10 mmoll-1 was associated with promotion of electrical slow wave activity. Higher concentrations of KC1 abolished slow wave activity but caused further tension development. Intracellular recording confirmed the ability of KC1 10 mmoll-1 transiently to promote slow wave activity in individual trachealis cells. This action was associated with depolarization and tension development. Higher concentrations of KC1 evoked further tension development but slow waves were suppressed as the depolarization evoked by KC1 increased. KC1 (10-40 mmoll-1) increased the lanthanum-resistant calcium fraction of muscle-containing strips of trachea. It is concluded that KC1 acts directly on the smooth muscle of guinea-pig trachea. The spasmogenic action is associated with transient promotion of slow wave activity and a fall in resting membrane potential. The spasm involves the cellular influx of Ca2+ and is dependent on the presence of Ca2+ in the extracellular fluid.

Animals↗