Diuretic-induced hypokalaemia: an updated review

Lin, Ziying; Wong, LC; Cheung, Bernard M Y

doi:10.1136/postgradmedj-2020-139701

Cited by 15 publications

(10 citation statements)

References 82 publications

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“…Alkalosis and hypokalemia also increased occurrences of EAD and long‐QT syndrome, which may be supported by following clinic reports. Diuretic‐induced hypokalemia was a common and potentially life‐threatening adverse drug reaction in clinical practice 54 . It was reported that among 31 patients suffering from heart disease with documented TdP due to quinidine, serum potassium concentrations were measured in 21 patients.…”

Section: Discussionmentioning

confidence: 99%

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Assessment of Quinidine‐Induced Torsades de Pointes Risks Using a Whole‐Body Physiologically Based Pharmacokinetic Model Linked to Cardiac Ionic Current Inhibition

Zhang,

Zhou,

Yang

et al. 2024

Clin Pharma and Therapeutics

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The lethality of torsades de pointes (TdP) by drugs is one of main reasons that some drugs were withdrawn from the market. In order to assess drug‐induced TdP risks, a model of cardiac ionic current suppression in human ventricular myocytes (Tor‐ORd model), combined with the maximum effective free therapeutic plasma concentration or the maximum effective free therapeutic myocyte concentration was often used, with the latter proved to be more relevant and more accurate. We aimed to develop a whole‐body physiologically based pharmacokinetic (PBPK) model, incorporated with a human cardiomyocyte pharmacodynamic (PD) model, to provide a comprehensive assessment of drug‐induced TdP risks in normal and specific scenarios. Quinidine served as an example to validate the PBPK‐PD model via predicting plasma quinidine concentrations and quinidine‐induced changes in QT interval(ΔQTc). The predicted plasma quinidine concentrations and ΔQTc values following oral administration or intravenous administration of quinidine were comparable to clinic observations. Visual predictive checks showed that the most of the observed plasma concentrations and ΔQTc values fell within 5th and 95th percentiles of simulations. The validated PBPK‐PD model was further applied to assess the TdP risks using frequencies of early afterdepolarization and long‐QT syndrome occurrence in 4 scenarios such as therapeutic dose, supra‐therapeutic dose, alkalosis and hyperkalemia in a 200 human subjects. In conclusion, the developed PBPK‐PD model may be applied to predict the quinidine pharmacokinetics and quinidine‐induced TdP risks in healthy subjects, but also simulate quinidine‐induced TdP risks under disease conditions such as hypokalemia and alkalosis.

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Section: Discussionmentioning

confidence: 99%

“…Diuretic-induced hypokalemia was a common and potentially life-threatening adverse drug reaction in clinical practice. 54 It was reported that among 31 patients suffering from heart disease with documented TdP due to quinidine, serum potassium concentrations were measured in 21 patients. Five (24%) of 21 patients showed hypokalemia.…”

Section: Articlementioning

confidence: 99%

Assessment of Quinidine‐Induced Torsades de Pointes Risks Using a Whole‐Body Physiologically Based Pharmacokinetic Model Linked to Cardiac Ionic Current Inhibition

Zhang,

Zhou,

Yang

et al. 2024

Clin Pharma and Therapeutics

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“…These results suggest that there may be a relation between potassium and phosphate, potentially mediated by FGF23. It has been shown that thiazide diuretics induce more hypokalemia than loop diuretics, despite the direct action of loop diuretics in Henle’s loop [ 37 ]. In the RS, thiazide diuretic users had lower serum potassium than nonusers.…”

Section: Discussionmentioning

confidence: 99%

Diuretic Use and Serum Phosphate: Rotterdam Study and UK Biobank

Bosman,

Campos-Obando,

de Keyser

et al. 2024

Journal of the Endocrine Society

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Purpose Hypophosphatemia (serum phosphate < 0.80 mmol/L) leads to musculoskeletal complaints. The most common drugs linked to hypophosphatemia are thiazide and loop diuretics but studies in the general population are lacking. Our aim was to study associations between diuretic use and serum phosphate in the Rotterdam study (RS), a population based cohort study, with replication in UK Biobank (UKBB). Methods Associations between thiazide and loop diuretic and serum phosphate and odds of hypophosphatemia were analyzed with cross-sectional multivariate linear and logistic regression in participants without chronic kidney disease in RS and UKBB. Analyses were adjusted for age, sex and BMI, and pooled in three RS cohorts with further adjustment for cohort and serum potassium, which was not available in UKBB. Results Thiazide diuretics were associated with lower serum phosphate in both sexes. This association lost significance in RS females after adjustment for BMI and in males after adjustment for serum potassium. Thiazide use increased odds of hypophosphatemia in females in both cohorts and in males in UKBB only. Loop diuretics were associated with lower serum phosphate in females but not males. Adjustment for BMI attenuated these associations. Associations between loop diuretics and increased odds of hypophosphatemia in females lost significance after BMI adjustment. Conclusions Thiazides, but not loop diuretics, and increased BMI and decreased serum potassium should be considered as contributing factors in subjects with hypophosphatemia. Further studies are needed to replicate the findings and elucidate the potential role of hypokalemia as a mediator of this effect.

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“…16 Thiazide diuretic and loop diuretics are well-known causes of hypokalemia. 17 Hypomagnesemia is an important cause of hypokalemia. 18 Hypokalemia associated with magnesium deficiency is often refractory to treatment with potassium.…”

Section: Discussionmentioning

confidence: 99%

“…Both contain licorice and are known to cause hypokalemia attributable to pseudoaldosteronism 16 . Thiazide diuretic and loop diuretics are well‐known causes of hypokalemia 17 …”

Section: Discussionmentioning

confidence: 99%

Severe hypokalemia in the emergency department: A retrospective, single‐center study

Makinouchi

Machida

Matsui

et al. 2022

Health Science Reports

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Background and Aims: Hypokalemia is one of the most common problems in the emergency department (ED). Severe hypokalemia, defined as a serum potassium level ≤2.5 mEq/L, is a relatively uncommon electrolyte disorder, and few studies have reported its prevalence, etiology, symptoms, and management in the ED.Therefore, we aimed to investigate them in this study.Methods: This retrospective single-center study included adult patients whose serum potassium levels were measured in the ED between 2012 and 2019. Data including age, sex, serum potassium levels, and serum creatinine levels were collected from the electronic medical records. Results:The serum potassium levels of 21,616 adult patients were measured. The median age of these patients was 73 years (range: 57-83 years), and 38% were men.The prevalence of severe hypokalemia was 0.4%. The most common symptom of symptomatic severe hypokalemia was weakness (p = 0.001). Malnutrition, use of Japanese herbal medicine, and use of diuretics were the main causes of severe hypokalemia. Sixty-one patients (70%) underwent electrocardiography. Fifty-nine patients (68%) received treatment for severe hypokalemia within one day of the visit. Conclusion:The management of severe hypokalemia in the ED may be suboptimal.Emergency physicians should be vigilant to avoid missing hypokalemia.

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Diuretic-induced hypokalaemia: an updated review

Cited by 15 publications

References 82 publications

Assessment of Quinidine‐Induced Torsades de Pointes Risks Using a Whole‐Body Physiologically Based Pharmacokinetic Model Linked to Cardiac Ionic Current Inhibition

Assessment of Quinidine‐Induced Torsades de Pointes Risks Using a Whole‐Body Physiologically Based Pharmacokinetic Model Linked to Cardiac Ionic Current Inhibition

Diuretic Use and Serum Phosphate: Rotterdam Study and UK Biobank

Severe hypokalemia in the emergency department: A retrospective, single‐center study

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