Diuretic-induced hypokalaemia inducing torsades de pointes

Chvilicek, Jeffrey P.; Hurlbert, Barbara J.; Hill, Gary E.

doi:10.1007/bf03015102

Cited by 33 publications

(17 citation statements)

References 24 publications

(5 reference statements)

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“…Hypoglycaemia, moreover, has been repeatedly associated with a reduction in the serum K + concentration. Hypokalaemia lengthens the QT interval [73,74] and is also associated with an increase in rates of sudden death [75].…”

Section: The Two Proarrhythmic Mechanisms and Their Relevance To Hypomentioning

confidence: 99%

The case for hypoglycaemia as a proarrhythmic event: basic and clinical evidence

Nordin

2010

Diabetologia

132

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Recent clinical studies show that hypoglycaemia is associated with increased risk of death, especially in patients with coronary artery disease or acute myocardial infarction. This paper reviews data from cellular and clinical research supporting the hypothesis that acute hypoglycaemia increases the risk of malignant ventricular arrhythmias and death in patients with diabetes by generating the two classic abnormalities responsible for the proarrhythmic effect of medications, i.e. QT prolongation and Ca 2+ overload. Acute hypoglycaemia causes QT prolongation and the risk of ventricular tachycardia by directly suppressing K + currents activated during repolarisation, a proarrhythmic effect of many medications. Since diabetes itself, myocardial infarction, hypertrophy, autonomic neuropathy and congestive heart failure also cause QT prolongation, the arrhythmogenic effect of hypoglycaemia is likely to be greatest in patients with pre-existent cardiac disease and diabetes. Furthermore, the catecholamine surge during hypoglycaemia raises intracellular Ca 2+ , thereby increasing the risk of ventricular tachycardia and fibrillation by the same mechanism as that activated by sympathomimetic inotropic agents and digoxin. Diabetes itself may sensitise myocardium to the arrhythmogenic effect of Ca 2+ overload. In humans, noradrenaline (norepinephrine) also lengthens action potential duration and causes further QT prolongation. Finally, both hypoglycaemia and the catecholamine response acutely lower serum K + , which leads to QT prolongation and Ca 2+ loading. Thus, hypoglycaemia and the subsequent catecholamine surge provoke multiple, interactive, synergistic responses that are known to be proarrhythmic when associated with medications and other electrolyte abnormalities. Patients with diabetes and pre-existing cardiac disease may therefore have increased risk of ventricular tachycardia and fibrillation during hypoglycaemic episodes.

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Section: The Two Proarrhythmic Mechanisms and Their Relevance To Hypomentioning

confidence: 99%

The case for hypoglycaemia as a proarrhythmic event: basic and clinical evidence

Nordin

2010

Diabetologia

132

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“…Female patients are especially at high risk for proarrhythmia from methadone [16] due to the greater QT prolongation noted in women off medications [17, 18]. Additionally, hypokalemic [19] patients, patients with cardiac channel congenital abnormalities [20] as well as individuals with low magnesium [21] are at increased risk of serious arrhythmias due to an enhanced risk of torsade de pointes ventricular tachycardia. Given the potential for lethal arrhythmias, reducing the QT-prolonging effects of methadone would increase the safety of this therapy.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Chiral Isolates of Methadone on the Cardiac Potassium Channel IKr

et al. 2008

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Objectives: Methadone is a synthetic opioid, an analgesic and an antiaddictive. QT prolongation as well as torsade de pointes ventricular tachycardia and death have been reported with methadone. Methadone’s proarrhythmic toxicity is related to the inhibition of cardiac IKr channel and prolongation of the action potential. We hypothesized that the 2 isomers of methadone may have different effects on the IKr channel. Methods: The effects of the isomers on IKr were evaluated by using an oocytes system with heterogeneously expressed human ether-a-go-go-related gene (HERG) using the 2 electrode voltage clamp technique. r- and s-methadone were obtained by employing chiral high-performance liquid chromatography, separating methadone into 2 isolates, with optical rotations of –141 and +143 degrees. Results: At concentrations of 0.01, 0.03, 0.1, 1 and 3 mM, r/s-methadone produced a dose-dependent inhibition of HERG by 17 ± 5, 23 ± 4, 40 ± 4, 57 ± 3, 69 ± 3 and 80 ± 1%, respectively. The IC₅₀ of r/s-methadone was 0.21 ± 0.02 mM. At 0.1, 0.3 and 1 mM, s-methadone reduced HERG current by 50 ± 4, 76 ± 5 and 87 ± 5%, respectively, while r-methadone reduced HERG current by 26 ± 4, 53 ± 3 and 77 ± 3%, respectively. Conclusions: There was a significant difference (p < 0.01) in the percentage of current inhibition between r- and s-methadone, at 0.1 and 0.3 mM (52% reduction). Thus, r-methadone may be a safer agent due to less QT effect.

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“…34,35) Particularly in the diseased heart, hypokalemia might be a risk factor for secondary prolongation of QT interval and consequent life-threatening cardiac arrhythmia. [36][37][38] Considered together, these findings may offer a warning that the use of furosemide in patients with hyponatremia resulting from persistently high AVP levels theoretically seems inappropriate.…”

Section: Discussionmentioning

confidence: 97%

A Novel Vasopressin Dual V1A/V2 Receptor Antagonist, Conivaptan Hydrochloride, Improves Hyponatremia in Rats with Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH)

Wada

Matsukawa

Fujimori

et al. 2007

Biological & Pharmaceutical Bulletin

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The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a clinical state in which the secretion of antidiuretic hormone (ADH), also called arginine vasopressin (AVP), is not suppressed appropriately when plasma osmolality falls below the osmotic threshold and may lead to impaired renal water excretion, increased total body water, and hyponatremia. 1) SIADH is associated with a number of underlying clinical conditions, such as malignancy, lung disease, and central nervous system and hormonal disorders. 2)AVP is a peptide hormone that is released from the posterior pituitary gland in response to an increase in plasma osmolality and volume depletion. Three classes of specific receptor have been identified in the periphery. The vasopressin V 1A receptor, which has been identified in vascular smooth muscle cells, hepatocytes and platelets, and the vasopressin V 1B receptor, which is found predominantly in the anterior pituitary, are coupled to the phosphoinositide pathway and elevation of intracellular Ca 2ϩ . The vasopressin V 2 receptor, which is located in the kidney and the vascular endothelium, is coupled to the adenylate cyclase pathway, causing an increase in c-AMP.3) AVP elicits a potent water reabsorption effect in the collecting ducts of the kidney via the vasopressin V 2 receptors, as well as systemic vasoconstriction via the vasopressin V 1A receptors. [4][5][6] The facilitation of renal water reabsorption via the vasopressin V 2 receptor results in an increase in total body water, which in turn causes a decrease in blood sodium concentration and plasma osmolality. The increased total body water causes inhibition of sodium reabsorption in the proximal tubule via inhibition of the renin-angiotensin-aldosterone system, as well as elevation of glomerular filtration rate and facilitation of the secretion of atrial natriuretic peptide (ANP) from the atrium.7) These stimuli produce sustained urinary sodium excretion, and result in hyponatremia, the most common electrolyte disorder associated with SIADH. Clinical manifestations of hyponatremia range from mild symptoms, such as headache, nausea, and vomiting, to severe symptoms, such as disorientation, disturbed consciousness and seizures. 8) Although the treatment of hyponatremia should be directed at the primary underlying etiology of disorder, this is not always entirely possible. Thus, the general approach to the management of hyponatremia is normalization of blood sodium concentration by the prevention of water retention in the body. 9)One treatment used for acute severe hyponatremia is the intravenous administration of furosemide concomitantly with hypertonic saline. Diuretics are used in the treatment of chronic hyponatremia, however, resistance to loop diuretics such as furosemide is a common problem in hyponatremia patients.10) Further, loop diuretics may worsen hyponatremia and induce hypokalemia, a potentially serious electrolyte disorder that can result in the prolongation of QT interval and the subsequent risk of ventricular arrhyt...

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Diuretic-induced hypokalaemia inducing torsades de pointes

Cited by 33 publications

References 24 publications

The case for hypoglycaemia as a proarrhythmic event: basic and clinical evidence

The case for hypoglycaemia as a proarrhythmic event: basic and clinical evidence

The Effects of Chiral Isolates of Methadone on the Cardiac Potassium Channel IKr

A Novel Vasopressin Dual V1A/V2 Receptor Antagonist, Conivaptan Hydrochloride, Improves Hyponatremia in Rats with Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH)

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