Changes In Serum Electrolytes Research Articles

Short-term effects of the DASH diet in adults with moderate chronic kidney disease: a pilot feeding study

BackgroundAlthough the Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure (BP) for adults with normal kidney function, evidence is lacking regarding its safety and efficacy in chronic kidney disease (CKD). We aimed to test the effects of the DASH diet on serum electrolytes and BP in adults with moderate CKD.MethodsIn a prospective before–after feeding study, 11 adults with an estimated glomerular filtration rate of 30–59 mL/min/1.73 m2 and medication-treated hypertension were provided a reduced-sodium, run-in diet for 1 week followed by a reduced-sodium, DASH diet for 2 weeks. Changes in serum electrolytes and BP were compared pre–post DASH.ResultsEleven participants underwent feeding; 1 completed 1 week and 10 completed 2 weeks of DASH. Compared with baseline, DASH modestly increased serum potassium at 1 week (mean ± standard deviation, +0.28 ± 0.4 mg/dL; P = 0.043) but had no significant effect on potassium at 2 weeks (+0.15 ± 0.28 mg/dL; P = 0.13). Serum bicarbonate was reduced (−2.5 ± 3.0 mg/dL; P = 0.03) at 2 weeks. Neither incident hyperkalemia nor new onset metabolic acidosis was observed. Clinic BP and mean 24-h ambulatory BP was unchanged. DASH significantly reduced mean nighttime BP (−5.3 ± 5.8 mmHg; P = 0.018), and enhanced percent declines in both nocturnal systolic BP (−2.1% to −5.1%; P = 0.004) and diastolic BP (−3.7% to −10.0%; P = 0.008).ConclusionsThese pilot data suggest that a reduced-sodium DASH dietary pattern does not cause acute metabolic events in adults with moderate CKD and may improve nocturnal BP. Definitive studies are needed to determine long-term effects of DASH in CKD.

Slipping up on the sliding scale: fluid and electrolyte management in variable rate intravenous insulin infusions

AbstractThis study aimed to analyse variations in intravenous fluid therapy and electrolyte management with variable rate intravenous insulin infusions (VRIIIs); and to quantify serum electrolyte changes pre‐ versus post‐VRIII and variations therein depending on supplemented fluid electrolyte compositions.A retrospective study was undertaken involving 174 VRIIIs prescribed over a 10‐week period at a tertiary teaching hospital. Each VRIII had their associated fluid prescription and serum electrolytes analysed.The results showed that 5% dextrose (46%) and 0.9% NaCl (34%) were the most commonly prescribed fluids; 64% of fluids did not have the recommended potassium supplementation. Administration of a VRIII resulted in a significant drop in serum potassium levels (p < 0.0001) for those who did not receive supplementation. There was no drop in serum potassium for those patients who did receive supplemental potassium. Eleven patients (6.4%) developed new‐onset hypokalaemia (K ≤3.5 mmol/L) after implementation of a VRIII.Our study supports the hypothesis that VRIIIs cause hypokalaemia and that this can be averted by supplemental potassium, thus preventing potentially avoidable hypokalaemic complications. A large variation exists in prescribing fluids with VRIIIs. Introduction of the national surgical and medical VRIII guidelines, together with improved availability to recommended fluids, and a quality improvement project, are our next steps to improve patient outcomes. Copyright © 2016 John Wiley & Sons.

Animal toxins and renal ion transport: Another dimension in tropical nephrology.

Renal vascular and tubular ion channels and transporters involved in toxin injury are reviewed. Vascular ion channels modulated by animal toxins, which result in haemodynamic alterations and changes in blood pressure, include ENaC/Degenerin/ASIC, ATP sensitive K channels (KATP ), Ca activated K channels (Kca) and voltage gated Ca channels, mostly L-type. Renal tubular Na channels and K channels are also targeted by animal toxins. NHE3 and ENaC are two important targets. NCC and NKCC may be involved indirectly by vasoactive mediators induced by inflammation. Most renal tubular K channels including voltage gated K channels (Kv1), KATP , ROMK1, BK and SK are blocked by scorpion toxins. Few are inhibited by bee, wasp and spider venoms. Due to small envenoming, incomplete block and several compensatory mechanisms in renal tubules, serum electrolyte charges are not apparent. Changes in serum electrolytes are observed in injury by large amount of venom when several channels or transporters are targeted. Envenomings by scorpions and bees are examples of toxins targeting multiple ion channels and transporters.

Early onset of hypertension and serum electrolyte changes as potential predictive factors of activity in advanced HCC patients treated with sorafenib: results from a retrospective analysis of the HCC-AVR group.

Hypertension (HTN) is frequently associated with the use of angiogenesis inhibitors targeting the vascular endothelial growth factor pathway and appears to be a generalized effect of this class of agent. We investigated the phenomenon in 61 patients with advanced hepatocellular carcinoma (HCC) receiving sorafenib. Blood pressure and plasma electrolytes were measured on days 1 and 15 of the treatment. Patients with sorafenib-induced HTN had a better outcome than those without HTN (disease control rate: 63.4% vs. 17.2% (p=0.001); progression-free survival 6.0 months (95% CI 3.2-10.1) vs. 2.5 months (95% CI 1.9-2.6) (p<0.001) and overall survival 14.6 months (95% CI9.7-19.0) vs. 3.9 months (95% CI 3.1-8.7) (p=0.003). Sodium levels were generally higher on day 15 than at baseline (+2.38, p<0.0001) in the group of responders (+4.95, p <0.0001) compared to patients who progressed (PD) (+0.28, p=0.607). In contrast, potassium was lower on day 14 (−0.30, p=0.0008) in the responder group (−0.58, p=0.003) than in those with progressive disease (−0.06, p=0.500). The early onset of hypertension is associated with improved clinical outcome in HCC patients treated with sorafenib. Our data are suggestive of an activation of the renin-angiotensin system in patients with advanced disease who developed HTN during sorafenib treatment.

The peripartum period influenced the serum macromineral profile in mares

Abstract. Changes in metabolic requirements during pregnancy may produce nutritional imbalances predisposing mares to pathological conditions. Therefore, we aimed to examine changes in serum macrominerals during the peripartum period in mares. Fifteen pregnant mares (Group A) were monitored starting at the 263rd day of pregnancy until the 21st day after foaling. Seven non-pregnant and non-lactating mares were used as a control group (Group B). Group A was subjected to blood sampling within 24 ± 12 h after parturition (P) and then 7, 14 and 21 days after foaling (+1, +2, +3 weeks, respectively). Group B was subjected to regular sampling throughout the study to ensure that seasonal changes had no significant effect on studied parameters. Serum samples were analysed for serum electrolytes including sodium (Na+), potassium (K+), calcium (Ca+ + ), phosphorus (P+), chloride (Cl−) and magnesium (Mg+ + ). Two-way repeated measures of analysis of variance (ANOVA) was applied to evaluate significant effects of peripartum on electrolyte concentrations. Group A showed a decrease in Cl− concentrations (P = 0.011) after foaling and lower P+ concentrations (P = 0.015) compared to Group B throughout the study. The linear regression model showed an increase in Na+ concentrations (P = 0.002) and a gradual decrease in serum Ca+ + (P = 0.001) during pregnancy. Because the most significant changes in serum electrolytes occurred within 2 weeks before and 2 weeks after foaling, monitoring serum electrolyte concentrations would indicate whether the mare needs further mineral supplementation at this stage. The significant changes in a mare's macromineral profile that we observed over the peripartum provide enhanced knowledge about mineral interrelations and their modifications during specific physiological conditions such as late pregnancy and early postpartum.

Serum electrolyte changes in senile cataract patients at tertiary care teaching hospital in Marathwada region, Maharashtra, India

Background: Cataract is one of the leading causes of blindness in developing countries. The most common type of cataract is senile cataract. The exact pathogenesis of cataract is not known, but it is believed that age, sex, radiation and serum electrolyte changes are important responsible risk factor. Rise in serum sodium level is responsible for formation of cataract. Potassium and chloride are not responsible factor for formation of cataract as that of serum sodium level. The purpose of this study is to estimate serum sodium and potassium in senile cataract patients, as compared to those without cataract. Methods: This study consists of 100 senile cataract patients and age matched 100 normal healthy individuals without cataract, serum electrolyte is measured by using an electrolyte analyzer. Results: In our study there is significant rise in serum sodium and chloride levels in cases compare to control group which is statistically significant. Serum potassium levels are in significant. Conclusion: We have concluded that serum sodium and chloride are important markers of senile cataract formation. Restrictions of salt in the diet delay the process of cataract formation.

Electrolyte Level Changes in Acute Myocardial Infarction Patients as Compared to Healthy Individuals in Khan Younis Governorate, Gaza Strip

Acute myocardial infarction (AMI) is one of the leading causes of morbidity and mortality across the world. Serum electrolytes changes in AMI have not been studied in Khan Younis Governorate-Palestine. Hence, this study was undertaken to investigate any changes in the serum electrolytes with special attention to serum sodium, potassium, calcium, magnesium and chloride in cases of AMI. Aim: To determine the pattern of changes of serum electrolytes AMI patients and then compare with non AMI (i.e. healthy persons). Materials and Method: The study consisted of a hundred people divided equally into study group and control group. Samples were taken from the Central Heart Unit in Nasser Hospital - Khan Younis. The study group comprised cases of confirmed diagnosis of recent onset of AMI. Clinical data was collected using interviewing questionnaires. The first paragraph of the questionnaire was for personal data which included age, sex and education level. The blood samples of both groups were automatically analyzed for serum electrolytes (Na+, K+, Cl-, Ca+ and Mg+) where the latter was analyzed manually. The cases were taken from AMI patients within 48 hours of admission. Results: The mean of age of controls was 47.18±64 while that of cases was 56.34±12.84. Significant low level of calcium was found in AMI patients while the level observed for magnesium was high. The levels of potassium and magnesium in AMI patients with hypertension was observed to be low with p-value < 0.05. Moreover, potassium levels were also low in AMI patients with diabetes with p-value <0.05. The changesin electrolytes werenot statistically significant in association with smoking. Conclusion: The decrease in sodium level was observed only in patients with AMI compared with healthy persons.

Kidney function predictors and associated serum electrolytes changes in HIV out patients attending Jaramogi Oginga Odinga teaching and referral hospital, Kisumu county, Kenya

Background: Kidney disease has been recognised as one of the health challenges complicating HIV infection, prognosis and management. Early recognition, diagnosis and treatment are therefore key to ameliorating the deleterious impacts of kidney disease in HIV infected patients. Objectives: To assess serum kidney function markers in order to highlight the state of kidney health and the impact of its functional impairment on other serum electrolytes and body fluids parameters Design: A case-control study. Setting: At Jaramogi Oginga Odinga Teaching and Referral Hospital’s Patient support centre. Subjects: Eight Hundred HIV positive and 406 HIV negative participants above 18 years of age. Results: Mean serum creatinine and urea levels was significantly elevated in HIV – infected individuals than the healthy control group (95.2μmol/l v/s 86.2μmol/l, p<0.0001 and 4.6mmol/l v/s 4.1mmol/l, p<0.0001 respectively). The prevalence of pathological levels of serum creatinine, urea and sodium was higher in HIV-infected patients than HIV-negative participants (26.1% v/s 11.8%, p<0.0001; 4.4% v/s 0.5%, P<0.0001and 26.1% v/s 10.6%, p=0.001 respectively). Females experienced more serum creatinine disorders than their male counterparts (31.8% v/s 18.1%, p<0.0001). Age and antiretroviral treatment were not predictors of aberrations in levels of kidney function markers in HIV infected patients. AIDS defining CD4 depletion was associated with enhanced deterioration of kidney function. However, kidney function anomalies were not sufficient explanation for co-existing electrolyte anomalies as clinically altered creatinine states only correlated and co-varied with urea states (r =0.715) while sodium states co-varied with chloride levels (r = 0.296). Conclusion: Kidney function disorders are not infrequent in HIV infected individuals. Serum sodium aberration is observed more frequently in seropositive than in seronegative individuals. Routine review of kidney health status in local HIV infected individuals ought to be adopted for comprehensive management of HIV patients, more so among the female gender.

An Investigator-Blinded Randomized Controlled Prospective Study Comparing Efficacy, Tolerability, and Safety of Two Bowel Preparations in the Community Setting: Miralax Versus PEG Electrolyte Lavage Solution (PEG-ELS)

Introduction: Although not FDA approved, Miralax (PEG 3350) mixed with Gatorade is a frequently used colonoscopy bowel preparation. There is conflicting data regarding its efficacy and tolerability, and limited data on its safety. We aimed to compare the efficacy, tolerability and safety of Miralax with Gatorade and PEG-ELS (polyethylene glycol electrolyte lavage solution) in the community setting. Methods: Patients undergoing elective screening colonoscopy were randomized to receive either splitdosed Miralax or PEG-ELS. Serum electrolytes, calcium, and phosphorus were determined before and after the preparation. Patients completed a Likert scaled questionnaire (1 = strongly agree; 5 = strongly disagree) evaluating their experience with the preparation just before colonoscopy. Quality of preparation was scored by blinded endoscopists using the Boston Bowel Preparation Scale (BBPS). Results: Sixty seven patients received either Miralax (N=38) or PEG-ELS (N=29). The groups were comparable regarding age, sex, and race.There was no significant difference in efficacy between the Miralax and PEG-ELS groups, with mean total BBPS scores of 7.34 and 7.82, respectively (p=.153). There was no significant difference in the ability to complete at least 75% of the preparation between the groups, but more patients were willing to retake (29.1 vs 40.4; p=.008) and/or recommend (28.5 vs 41.1; p=.003) their Miralax preparation in the future. The Miralax group also found the amount of preparation (27.9 vs 41.9, p=.001) and its taste (26.3 vs 44, p < .001) more acceptable and their preparation to be more tolerable (27.4 vs 42.6, p < .001). The Miralax group experienced less headache than the PEG-ELS group (29.2 vs 40.1, p=.003) but there was otherwise no significant difference in side effects. Finally, there was no significant difference in serum electrolytes before and after taking the preparations in either group. Conclusion: Both split-dosed preparations are effective at colon cleansing without adverse changes in serum electrolytes. However, patients in the Miralax group found their preparation to be more tolerable than those in the PEG-ELS group. Additionally, more patients were in favor of using or recommending Miralax again in the future. This study adds to the growing body of data regarding bowel preparation regimens and supports the effectiveness and safety of Miralax in preparing the bowel for colonoscopy with improved patient acceptance and tolerability.

RETRACTED ARTICLE: Serotonin 5-HT7 receptor agonist, LP-211, exacerbates Na+, K+-ATPase/Mg2+-ATPase imbalances in spinal cord-injured male rats

BackgroundThe observed controversy that N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (LP-211), a selective serotonin (5-HT7) receptor agonist, may either modify or exacerbate imbalances in serum electrolyte concentrations and renal tissue of spinal cord trauma cases has not been reported yet. The aim of this study was to better understand the effects of a new 5-HT7 receptor agonist, LP-211, on serum electrolyte changes in spinal cord injured- (SCI) rats.MethodsSixty male rats were assigned to the following groups: A) Intact (saline as vehicle, 1 ml/kg, i.p.), B) Intact [LP-211, (0.003–0.3 mg/kg, i.p.)], C) Sham-operated [laminectomy + vehicle (1 ml/kg, i.p.)], D) Sham-operated [laminectomy + LP-211 (0.003–0.3 mg/kg, i.p.)], E) Treatment [laminectomy + spinal trauma (SCI) + vehicle (1 ml/kg, i.p.)], F) Treatment [laminectomy + spinal trauma + LP-211 (0.003–0.3 mg/kg, i.p.)]. SCI was performed by placing an aneurysm clip, extradurally at the level of T10. After two weeks, LP-211 was administered cumulatively and each dose was injected (i.p.) with 20 min interval. At the end of the experiment, blood samples were collected for biochemical evaluations of the electrolytes employing standard commercial kits.ResultsThe present results indicate elevated serum levels of Na+, K+, and Mg2+ in SCI rats and significant differences demonstrated between the groups [P < 0.001, F(5, 35) = 23.92], [P < 0.001, F(5, 35) = 67.63], [P < 0.001, F(5, 35) = 71.144], respectively. So that, in groups B, D and F, there was a significant increase in K+ and Mg2+ serum levels compared to the groups A, C, and E (P < 0.001). Furthermore, Na+ serum levels in SCI (LP-211), laminectomy (LP-211), and intact (LP-211) groups tended to be statistically lower than SCI (saline), laminectomy (saline) and intact (saline) groups. Infact, hyponatremia, hyperkalemia and hypermagnesemia was obtained in group F. Nevertheless, in the remaining measured serum electrolytes such as calcium (Ca2+), iron (Fe2+) and phosphorus (P3−), chlorine (Cl−), copper (Cu+), and zinc (Zu+), no significant changes were observed.ConclusionIt was shown that acute additive LP-211 treatments in the SCI group led to hyponatremia, hyperkalemia and hypermagnesemia, it may be stated that LP-211 treatment as a promising candidate for treating SCI complications in some systems especially urinary tract might take into consideration and further studies would be needed to clarify its benefits or drawbacks. The observed discrepancies, nevertheless; will also pose new questions. Altogether, this will ultimately contribute to further understanding the pathophysiological role regarding 5-HT7 receptor activation.

The short-term and long-term effects of tolvaptan in patients with heart failure: a meta-analysis of randomized controlled trials.

A comprehensive evaluation of the benefits of tolvaptan for the management of heart failure (HF) is lacking. The objective of this meta-analysis was to assess the short-term and long-term effects of tolvaptan in patients with HF. Articles were searched from PubMed, MEDLINE and Cochrane Library before March 31, 2015. Randomized controlled trials enrolling adult HF patients and reporting the all-cause mortality, cardiac events, body weight change or changes of serum electrolytes including sodium, potassium and creatinine were included in our meta-analysis. Ten studies covering 5574 patients met the inclusion criteria. Based on the data of meta-analysis, tolvaptan had no impact on the all-cause mortality [relative risk (RR) 0.96; 95 % confidence interval (CI) 0.87-1.06; P = 0.40] and incidence of cardiac events (RR 1.03; 95 % CI 0.96-1.11; P = 0.40) of HF patients. Furthermore, in comparison with control treatments, tolvaptan significantly decreased the body weight [weight mean difference (WMD), -0.87; 95 % CI -1.03 to -0.71; P < 0.001] and statistically increased serum sodium (WMD, 2.58; 95 % CI -1.83 to 3.33; P < 0.001) without any change in serum potassium (WMD, 0.01; 95 % CI -0.03 to 0.05; P = 0.577). However, serum creatinine may be increased slightly by tolvaptan (WMD, 0.05; 95 % CI 0.03-0.07; P < 0.001). This meta-analysis suggests that in HF patients, tolvaptan may not bring long-term benefits, but it effectively improves the volume overload and hyponatremia without obvious increases in serum potassium and creatinine. Hence, tolvaptan is likely to be a promising diuretic for the treatment of HF.

A Case of Severe Hypercalcemia and Hyperphosphatemia Concomitant to Hyperthyroidism

Changes of serum electrolytes in patients with hyperthyroidism are often disregarded. Hypercalcemia has been reported in 17% to 50% of patients with hyperthyroidism. However, severe and symptomatic hypercalcemia is rare among patients with hyperthyroidism. We report a rare case of symptomatic hypercalcemia and hyperphosphatemia in a 31-year-old male patient who was diagnosed with hyperthyroidism. He visited our hospital with nausea, vomiting, and tremor. Thyroid function test showed severe thyrotoxicosis and serum calcium and phosphorus were elevated but parathyroid hormone was low, excluding primary hyperparathyroidism as the cause of hypercalcemia. Saline hydration with diuretics to lower serum calcium and antithyroid medication with lugol solution were administered for six days. But symptoms persisted and he was treated with intravenous pamidronate. Symptoms were relieved after resolution of hypercalcemia and hyperphosphatemia. The case suggests that severe and symptomatic hypercalcemia and hyperphosphatemia can complicate hyperthyroidism and early correction of hypercalcemia can relieve symptoms.

Evaluation of Changes in Serum Concentration of Sodium in a Transurethral Resection of the Prostate/ Евалуација На Промените Во Серумската Концентрација На Натриум При Трансуретралнa Ресекција На Простатa

Abstract Introduction and objectives: The purpose of this study was to evaluate changes in serum electrolytes during Transurethral resection of the prostate (TURP) and to evaluate the degree of correlation of hyponatremia and the factors that affect the incidence of TURP syndrome and to show the impact of the duration of the procedure on the severity of hyponatremia due to absorption of irrigation fluid in the systemic circulation. Materials and Methods: This study examined 60 male patients planned for elective TURP. The level of serum electrolytes are determined by taking venous blood samples preoperatively and Postoperatively and when the duration of the operation was longer than 60 minutes, the level of serum electrolytes was determined intraoperative. The amount of used irrigation fluid, the weight of resection prostate, and duration of surgery, were also followed. Patients were divided in two groups according to the length of the surgical procedure: Group 1 (30- 60 min) and Group 2 (&gt; 60 min). Results: Statistically significant reduction of serum sodium and the elevation of the potassium level in serum observed postoperatively and was directly proportional to the volume of of the used irrigation fluid, the duration of the procedure and volume of the resected prostate. Conclusions: To evaluate changes in serum electrolyte during TURP is simple and economical method for the indirect estimation of irrigation fluid absorption into the systemic circulation during TURP and opportunity for early identification of TURP syndrome

Normal saline versus balanced-salt solution as intravenous fluid therapy during neurosurgery: effects on acid-base balance and electrolytes.

This prospective, randomized controlled study compared the changes in acid-base balance and serum electrolytes with the use of intravenous balanced and non-balanced crystalloid solutions intraoperatively during elective neurosurgery. Thirty consented adult patients who underwent craniotomy were randomly allocated into two groups of 15 patients each. The non-balanced group received 0.9% normal saline while the balanced group received Sterofundin®ISO as the intraoperative fluid for maintenance. Biochemical indices for acid-base balance and serum electrolytes were analyzed periodically. In the non-balanced group, significant changes were noted in the pH, base excess and bicarbonate values over time compared to its respective baseline values (P<0.01). Four patients (27.7%) also developed a pH<7.35 and 5 patients (33.3%) developed marked acidosis with base excess <-4.0 at the end of surgery. Both mean sodium and chloride levels were also significantly higher compared to its baseline values respectively (142.6±2.4 versus 138±2.7 mmol/L, P<0.01 and 105.7±4.1 versus 113.2±3.0 mmol/L (P<0.01). A balanced solution (Sterofundin®ISO) provided significantly better control over acid-base balance, sodium and chloride levels when used as intraoperative fluid maintenance and replacement during elective neurosurgery.

The Effects of Aldosterone Antagonists in Patients With Resistant Hypertension: A Meta-Analysis of Randomized and Nonrandomized Studies.

A few studies have shown aldosterone antagonists (AA) to be effective therapy in patients with resistant hypertension (RH). We performed a meta-analysis of randomized and nonrandomized studies of AA in patients with RH. We searched PUBMED, EMBASE, and CENTRAL for studies on the use of AA in patients with RH. Meta-analysis was performed using random-effects model. The change in office and ambulatory blood pressures (BP), effects on biochemical profile, change in the number of antihypertensive agents, and adverse events were main outcomes. We included 15 studies (3 randomized controlled trials, 1 nonrandomized comparative study, and 11 single-arm studies) with 1,204 total patients in the meta-analysis. In comparative studies, AA reduced systolic BP (SBP) by 24.26 mm Hg (95% CI: 8.65-39.87, P = 0.002) and diastolic BP (DBP) by 7.79 mm Hg (3.79-11.79, P = 0.0001). Similarly, AA reduced SBP by 22.74 mm Hg (18.21-27.27, P < 0.00001) and DBP by 10.49 mm Hg (8.85-12.13, P < 0.00001) in single-arm studies. AA resulted in significant change in serum electrolytes in single-arm studies but not in comparative studies. Significantly more adverse events were noted in single-arm studies but not in comparative studies. On the basis of the current meta-analysis, we conclude that AA is safe and effective therapy in patients with RH.

Changes of Serum Electrolytes and hematological Profiles in Yorkshire at a High ambient Temperature

Changes of Serum Electrolytes and hematological Profiles in Yorkshire at a High ambient Temperature

Comparison of routes for achieving parenteral access with a focus on the management of patients with Ebola virus disease.

Comparison of routes for achieving parenteral access with a focus on the management of patients with Ebola virus disease.

An experimental study on the effect of felodipine on serum electrolytes and lithium concentration in albino rabbits

Objectives: To study the effect of felodipine, a calcium channel blocker, on concurrent administration with lithium carbonate on serum electrolytes and lithium in Albino rabbits. Material and Methods: Albino rabbits weighing 2.5 – 3 kg were divided in three group of ten each and were administered lithium carbonate and/or felodipine in suspension made of gum tragacanth daily for eight days. Blood was drawn from marginal ear vein after 24 hours of first dose and then at 28th day of drug/s administration for acute and chronic effects respectively. Serum was separated out and supernatant was decanted after centrifugation at 3000 rpm. Serum sodium, potassium and/or lithium were estimated using flame photometry. Heart rate was measured by heart transducer and polygraph. Mortality was observed till a week after last dose administration in this study. Results: Acute effects of co-administration of felodipine and lithium resulted in highly significant decrease in heat rate but no fall in serum potassium and insignificant increase in sodium levels from the baseline values. On chronic co-administration, significant decrease in heat rate was maintained without any significant change in serum electrolytes and lithium levels from base line. No mortality was observed in the group treated with felodipine and lithium simultaneously. Conclusions: Felodipine with lithium co-administration minimally affect the serum electrolytes and lithium concentration and thus appears relatively safe for co-administration.Key words: Bipolar-disorder, Felodipine, Hypertension, Lithium

Effect of canagliflozin on serum electrolytes in patients with type 2 diabetes in relation to estimated glomerular filtration rate (eGFR)

Objective:Effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on serum electrolytes were evaluated using pooled data from studies of patients with type 2 diabetes mellitus (T2DM).Research design and methods:Analyses were performed using two datasets, each including four placebo-controlled studies: Population 1 (N = 2215), patients with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (mean = 89.6 mL/min/1.73 m2) and Population 2 (N = 721), patients with baseline eGFR ≥45 and <60 mL/min/1.73 m2 (mean = 53.3 mL/min/1.73 m2).Clinical trial registration:ClinicalTrials.gov identifier: NCT01081834.ClinicalTrials.gov identifier: NCT01106625.ClinicalTrials.gov identifier: NCT01106677.ClinicalTrials.gov identifier: NCT01106690.ClinicalTrials.gov identifier: NCT01032629.ClinicalTrials.gov identifier: NCT01064414.ClinicalTrials.gov identifier: NCT01106651.Main outcome measures:Mean percent changes from baseline in serum electrolytes (potassium, sodium, magnesium, bicarbonate, phosphate, calcium) and outlier analyses were assessed in patients receiving canagliflozin 100 and 300 mg or placebo. Potassium changes were further evaluated based on baseline therapy with anti-hypertensive agents that interfere with potassium excretion (renin-angiotensin aldosterone system-acting agents and/or potassium-sparing diuretics).Results:Mean percent changes from baseline in potassium with canagliflozin 100 and 300 mg and placebo were 0.6%, 1.0%, and 0.5%, respectively (Week 26; Population 1); and 1.7%, 2.8%, and 0.7%, respectively (Week 18/26; Population 2). The proportion of patients who had potassium elevations meeting pre-defined outlier criteria (>5.4 mmol/L [5.4 mEq/L] and >15% increase from baseline) with canagliflozin 100 and 300 mg and placebo was 4.5%, 6.8%, and 4.7% (Population 1); and 5.2%, 9.1%, and 5.5% (Population 2). In both populations, potassium elevations were usually <6.5 mmol/L for patients treated with canagliflozin or placebo; elevations ≥6.5 mmol/L were rare but more frequent in patients taking anti-hypertensive agents that affect potassium excretion in both the canagliflozin and placebo groups. Small mean percent changes in sodium, bicarbonate, and calcium were seen across groups in both populations; small mean percent increases in magnesium and phosphate were seen with canagliflozin vs placebo, but without an increase in patients meeting outlier criteria. Adverse events related to changes in electrolytes were low across groups.Conclusions:In patients with T2DM, canagliflozin was generally associated with small mean percent changes in serum electrolytes. Infrequent episodes of potassium elevation occurred with canagliflozin 300 mg, but occurred more often in patients with reduced eGFR.

Effects of Hydrochlorothiazide on the Pharmacokinetics, Pharmacodynamics, and Tolerability of Canagliflozin, a Sodium Glucose Co-transporter 2 Inhibitor, in Healthy Participants

BackgroundMany patients with type 2 diabetes mellitus (T2DM) also have hypertension, which is commonly treated with thiazide diuretics, including hydrochlorothiazide (HCTZ). Canagliflozin, a sodium glucose cotransporter 2 inhibitor developed for the treatment of T2DM, lowers plasma glucose by inhibiting renal glucose reabsorption, thereby increasing urinary glucose excretion and mild osmotic diuresis. Because patients with T2DM are likely to receive concurrent canagliflozin and HCTZ, potential interactions were evaluated. ObjectiveThis study evaluated the effects of HCTZ on the pharmacokinetic and pharmacodynamic properties and tolerability of canagliflozin in healthy participants. MethodsThis Phase I, single-center, open-label, fixed-sequence, 2-period study was conducted in healthy participants. During period 1, participants received canagliflozin 300 mg once daily for 7 days, followed by a 14-day washout period. During period 2, participants received HCTZ 25 mg once daily for 28 days, followed by canagliflozin 300 mg + HCTZ 25 mg once daily for 7 days. Blood samples were taken before and several times after administration on day 7 of period 1 and on days 28 and 35 of period 2 for canagliflozin and HCTZ pharmacokinetic analyses using LC-MS/MS. Blood and urine samples were collected for up to 24 hours after canagliflozin administration on day 1 of period 1 and day 35 of period 2 for pharmacodynamic glucose assessment. Tolerability was also evaluated. ResultsThirty participants were enrolled (16 men, 14 women; all white; mean age, 43.7 years). Canagliflozin AUC during a dosing interval (T) at steady state (AUCτ,ss) and Cmax at steady state (Cmax,ss) were increased when canagliflozin was coadministered with HCTZ, with geometric mean ratios (90% CI) of 1.12 (1.08–1.17) and 1.15 (1.06–1.25), respectively. AUCτ,ss and Cmax,ss for HCTZ were similar with and without canagliflozin coadministration. The 24-hour mean renal threshold for glucose and mean plasma glucose were comparable for canagliflozin alone and coadministered with HCTZ. The change in 24-hour urine volume from baseline was −0.1 L with canagliflozin alone and 0.4 L with HCTZ alone and with canagliflozin + HCTZ. The overall incidence of adverse events (AEs) was higher with canagliflozin + HCTZ (69%) than with canagliflozin (47%) or HCTZ (50%) alone; most AEs were of mild severity. Overall, minimal changes in serum electrolytes (eg, sodium, potassium) were observed after coadministration of canagliflozin + HCTZ compared with individual treatments. ConclusionsAdding canagliflozin treatment to healthy participants on HCTZ treatment had no notable pharmacokinetic or pharmacodynamic effects; canagliflozin coadministered with HCTZ was generally well tolerated, with no unexpected tolerability concerns. ClinicalTrials.gov identifier: NCT01294631.