zithromax and Hypokalemia

Most patients with end-stage renal disease depend on intermittent hemodialysis to maintain levels of serum potassium and other electrolytes within a normal range. However, one of the challenges has been the safety of using a low-potassium dialysate to achieve that goal, given the concern about the effects that rapid and/or large changes in serum potassium concentrations may have on cardiac electrophysiology and arrhythmia. Additionally, in this patient population, there is a high prevalence of structural cardiac changes and ischemic heart disease, making them even more susceptible to acute arrhythmogenic triggers. This concern is highlighted by the knowledge that about two-thirds of all cardiac deaths in dialysis are due to sudden cardiac death and that sudden cardiac death accounts for 25% of the overall death for end-stage renal disease. Developing new approaches and practice standards for potassium removal during dialysis, as well as understanding other modifiable triggers of sudden cardiac death, such as other electrolyte components of the dialysate (magnesium and calcium), rapid ultrafiltration rates, and safety of a number of medications (ie, drugs that prolong the QT interval or use of digoxin), are critical in order to decrease the unacceptably high cardiac mortality experienced by hemodialysis-dependent patients.

Topics: Aged; Arrhythmias, Cardiac; Azithromycin; Bicarbonates; Black or African American; Calcium; Coronary Circulation; Death, Sudden, Cardiac; Drug Interactions; Fatal Outcome; Hemodialysis Solutions; Humans; Hypertension; Hypokalemia; Kidney Failure, Chronic; Long QT Syndrome; Magnesium; Male; Omeprazole; Potassium; Proton Pump Inhibitors; Renal Dialysis; Time Factors; Ultrafiltration

Hydroxychloroquine, chloroquine and azithromycin are three drugs that were proposed to treat coronavirus disease 2019 (COVID-19). While concern already existed around their proarrhythmic potential, there are little data regarding how altered physiological states encountered in patients such as febrile state, electrolyte imbalances or acidosis might change their risk profiles.. Potency of human ether-à-go-go related gene (hERG) block was measured using high-throughput electrophysiology in the presence of variable environmental factors. These potencies informed simulations to predict population risk profiles. Effects on cardiac repolarisation were verified in human induced pluripotent stem cell-derived cardiomyocytes from multiple individuals.. Chloroquine and hydroxychloroquine blocked hERG with IC. Our study demonstrates how proarrhythmic risk can be exacerbated by metabolic changes and pre-existing disease. More broadly, the study acts as a blueprint for how high-throughput in vitro screening, combined with in silico simulations, can help guide both preclinical screening and clinical management of patients in relation to drugs with potential to prolong repolarisation.

Topics: Acidosis; Azithromycin; Chloroquine; COVID-19 Drug Treatment; Female; Humans; Hydroxychloroquine; Hypokalemia; Induced Pluripotent Stem Cells; SARS-CoV-2

Topics: Anti-Bacterial Agents; Antimalarials; Antiviral Agents; Azithromycin; Clinical Trials as Topic; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Drug Interactions; Drug Repositioning; Drug Synergism; Electrocardiography; Humans; Hydroxychloroquine; Hyperkalemia; Hypokalemia; Long QT Syndrome; SARS-CoV-2

Topics: Anti-Bacterial Agents; Antimalarials; Antiviral Agents; Azithromycin; Clinical Trials as Topic; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Drug Interactions; Drug Repositioning; Drug Synergism; Electrocardiography; Humans; Hydroxychloroquine; Hyperkalemia; Hypokalemia; Long QT Syndrome; Magnesium; Patient Safety; RNA, Viral; SARS-CoV-2; Treatment Outcome