Slow delayed rectifier potassium current blockade contributes importantly to drug-induced long QT syndrome

Circulation: Arrhythmia and Electrophysiology

Volumn 6, Issue 5, 2013, Pages 1002-1009

  Veerman, Christiaan C ^a   Verkerk, Arie O ^b   Blom, Marieke T ^a   Klemens, Christine A ^a   Langendijk, Pim N J ^d,e   Van Ginneken, Antoni C G ^b   Wilders, Ronald ^b   Tan, Hanno L ^a,c  

^a ACADEMIC MEDICAL CENTER   (Netherlands)

^b Department of Anatomy Embryology and Physiology   (Netherlands)

^c Department of Cardiology ^*  (Netherlands)

^d UNIVERSITY OF AMSTERDAM   (Netherlands)

^e REINIER DE GRAAF HOSPITAL   (Netherlands)

Author keywords

Drug induced long QT syndrome; Fluoxetine; Long QT syndrome; Potassium channels; Torsade de pointes

Indexed keywords

CODEINE; DELAYED RECTIFIER POTASSIUM CHANNEL; FLUOXETINE; NORFLUOXETINE; POTASSIUM CHANNEL KCNE1; POTASSIUM CHANNEL KCNQ1; TRAMADOL; KCNE1 PROTEIN, HUMAN; SEROTONIN UPTAKE INHIBITOR; VOLTAGE GATED POTASSIUM CHANNEL; POTASSIUM CHANNEL;

ADULT; ARTICLE; CASE REPORT; CELL STRAIN HEK293; CHANNEL GATING; COMPUTER SIMULATION; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG INDUCED LONG QT SYNDROME; DRUG POTENCY; DRUG SAFETY; DRUG WITHDRAWAL; ELECTROCARDIOGRAM; FAINTNESS; FEMALE; GENE MUTATION; HEART LEFT VENTRICLE HYPERTROPHY; HEART MUSCLE FIBER MEMBRANE POTENTIAL; HEART REPOLARIZATION; HEART VENTRICLE FIBRILLATION; HETEROLOGOUS EXPRESSION; HETEROZYGOTE; HUMAN; HUMAN CELL; LONG QT SYNDROME; MIDDLE AGED; PATCH CLAMP TECHNIQUE; POTASSIUM CURRENT; PRIORITY JOURNAL; QT PROLONGATION; TORSADE DES POINTES; ACTION POTENTIAL; CELL CULTURE; CHEMICALLY INDUCED; ECHOCARDIOGRAPHY; ELECTROCARDIOGRAPHY; EXERCISE TEST; GENETICS; MUTAGENESIS; MUTATION; PEDIGREE; RISK FACTOR; CHEMICALLY INDUCED DISORDER; DRUG-INDUCED LONG QT SYNDROME;

ACTION POTENTIALS; CELLS, CULTURED; COMPUTER SIMULATION; ECHOCARDIOGRAPHY; ELECTROCARDIOGRAPHY; EXERCISE TEST; FEMALE; FLUOXETINE; HUMANS; KCNQ1 POTASSIUM CHANNEL; LONG QT SYNDROME; MIDDLE AGED; MUTAGENESIS; MUTATION; PATCH-CLAMP TECHNIQUES; PEDIGREE; POTASSIUM CHANNELS, VOLTAGE-GATED; RISK FACTORS; SEROTONIN UPTAKE INHIBITORS;

DRUG-INDUCED LONG QT SYNDROME; FLUOXETINE; LONG QT SYNDROME; POTASSIUM CHANNELS; TORSADE DE POINTES;

EID: 84891527042     PISSN: 19413149     EISSN: 19413084     Source Type: Journal    
DOI: 10.1161/CIRCEP.113.000239     Document Type: Article

References (35)

1. Darpo B, Nebout T, Sager PT. Clinical evaluation of QT/QTc prolongation and proarrhythmic potential for nonantiarrhythmic drugs: the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use E14 guideline. J Clin Pharmacol. 2006;46:498-507.
2. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med. 2004;350:1013-1022.
3. Zareba W, Cygankiewicz I. Long QT syndrome and short QT syndrome. Prog Cardiovasc Dis. 2008;51:264-278.
4. De Ponti F, Poluzzi E, Cavalli A, Recanatini M, Montanaro N. Safety of non-antiarrhythmic drugs that prolong the QT interval or induce torsade de pointes: an overview. Drug Saf. 2002;25:263-286.
5. Mitcheson JS, Chen J, Lin M, Culberson C, Sanguinetti MC. A structural basis for drug-induced long QT syndrome. Proc Natl Acad Sci U S A. 2000;97:12329-12333.
6. Lindgren S, Bass AS, Briscoe R, Bruse K, Friedrichs GS, Kallman MJ, Markgraf C, Patmore L, Pugsley MK. Benchmarking safety pharmacology regulatory packages and best practice. J Pharmacol Toxicol Methods. 2008;58:99-109.
7. Letsas KP, Alexanian IP, Pappas LK, Kounas SP, Efremidis M, Sideris A, Kardaras F. QT interval prolongation and torsade de pointes associated with indapamide. Int J Cardiol. 2006;112:373-374.
8. Camm AJ, Savelieva I. New antiarrhythmic drugs for atrial fibrillation: focus on dronedarone and vernakalant. J Interv Card Electrophysiol. 2008;23:7-14.
9. Rajamani S, Eckhardt LL, Valdivia CR, Klemens CA, Gillman BM, Anderson CL, Holzem KM, Delisle BP, Anson BD, Makielski JC, January CT. Drug-induced long QT syndrome: hERG K+ channel block and disruption of protein trafficking by fluoxetine and norfluoxetine. Br J Pharmacol. 2006;149:481-489.
10. Varriale P. Fluoxetine (Prozac) as a cause of QT prolongation. Arch Intern Med. 2001;161:612.
11. Nykamp DL, Blackmon CL, Schmidt PE, Roberson AG. QTc prolongation associated with combination therapy of levofloxacin, imipramine, and fluoxetine. Ann Pharmacother. 2005;39:543-546.
12. Itoh H, Shimizu W, Hayashi K, Yamagata K, Sakaguchi T, Ohno S, Makiyama T, Akao M, Ai T, Noda T, Miyazaki A, Miyamoto Y, Yamagishi M, Kamakura S, Horie M. Long QT syndrome with compound mutations is associated with a more severe phenotype: a Japanese multicenter study. Heart Rhythm. 2010;7:1411-1418.
13. ten Tusscher KH, Noble D, Noble PJ, Panfilov AV. A model for human ventricular tissue. Am J Physiol Heart Circ Physiol. 2004;286:H1573-H1589.
14. ten Tusscher KH, Panfilov AV. Alternans and spiral breakup in a human ventricular tissue model. Am J Physiol Heart Circ Physiol. 2006;291:H1088-H1100.
15. Magyar J, Szentandrássy N, Bányász T, Kecskeméti V, Nánási PP. Effects of norfluoxetine on the action potential and transmembrane ion currents in canine ventricular cardiomyocytes. Naunyn Schmiedebergs Arch Pharmacol. 2004;370:203-210.
16. Orsulak PJ, Kenney JT, Debus JR, Crowley G, Wittman PD. Determination of the antidepressant fluoxetine and its metabolite norfluoxetine in serum by reversed-phase HPLC with ultraviolet detection. Clin Chem. 1988;34:1875-1878.
17. Vree TB, Verwey-van Wissen CP. Pharmacokinetics and metabolism of codeine in humans. Biopharm Drug Dispos. 1992;13:445-460.
18. Hiemke C, Härtter S. Pharmacokinetics of selective serotonin reuptake inhibitors. Pharmacol Ther. 2000;85:11-28.
19. Fanoe S, Jensen GB, Sjøgren P, Korsgaard MP, Grunnet M. Oxycodone is associated with dose-dependent QTc prolongation in patients and low-affinity inhibiting of hERG activity in vitro. Br J Clin Pharmacol. 2009;67:172-179.
20. Deisemann H, Ahrens N, Schlobohm I, Kirchhoff C, Netzer R, Möller C. Effects of common antitussive drugs on the hERG potassium channel current. J Cardiovasc Pharmacol. 2008;52:494-499.
21. Makita N, Horie M, Nakamura T, Ai T, Sasaki K, Yokoi H, Sakurai M, Sakuma I, Otani H, Sawa H, Kitabatake A. Drug-induced long-QT syndrome associated with a subclinical SCN5A mutation. Circulation. 2002;106:1269-1274.
22. Itoh H, Sakaguchi T, Ding WG, Watanabe E, Watanabe I, Nishio Y, Makiyama T, Ohno S, Akao M, Higashi Y, Zenda N, Kubota T, Mori C, Okajima K, Haruna T, Miyamoto A, Kawamura M, Ishida K, Nagaoka I, Oka Y, Nakazawa Y, Yao T, Jo H, Sugimoto Y, Ashihara T, Hayashi H, Ito M, Imoto K, Matsuura H, Horie M. Latent genetic backgrounds and molecular pathogenesis in drug-induced long-QT syndrome. Circ Arrhythm Electrophysiol. 2009;2:511-523.
23. Mangoni AA, Kinirons MT, Swift CG, Jackson SH. Impact of age on QT interval and QT dispersion in healthy subjects: a regression analysis. Age Ageing. 2003;32:326-331.
24. Stengl M, Volders PG, Thomsen MB, Spätjens RL, Sipido KR, Vos MA. Accumulation of slowly activating delayed rectifier potassium current (IKs) in canine ventricular myocytes. J Physiol. 2003;551(Pt 3):777-786.
25. Roden DM, Yang T. Protecting the heart against arrhythmias: potassium current physiology and repolarization reserve. Circulation. 2005;112:1376-1378.
26. Jost N, Virág L, Bitay M, Takács J, Lengyel C, Biliczki P, Nagy Z, Bogáts G, Lathrop DA, Papp JG, Varró A. Restricting excessive cardiac action potential and QT prolongation: a vital role for IKs in human ventricular muscle. Circulation. 2005;112:1392-1399.
27. Varro A, Baláti B, Iost N, Takács J, Virág L, Lathrop DA, Csaba L, Tálosi L, Papp JG. The role of the delayed rectifier component IKs in dog ventricular muscle and Purkinje fibre repolarization. J Physiol. 2000;523(Pt 1):67-81.
28. Towart R, Linders JT, Hermans AN, Rohrbacher J, van der Linde HJ, Ercken M, Cik M, Roevens P, Teisman A, Gallacher DJ. Blockade of the I (Ks) potassium channel: an overlooked cardiovascular liability in drug safety screening? J Pharmacol Toxicol Methods. 2009;60:1-10.
29. Varró A, Baczkó I. Cardiac ventricular repolarization reserve: a principle for understanding drug-related proarrhythmic risk. Br J Pharmacol. 2011;164:14-36.
30. Park KS, Kong ID, Park KC, Lee JW. Fluoxetine inhibits L-type Ca2+ and transient outward K+ currents in rat ventricular myocytes. Yonsei Med J. 1999;40:144-151.
31. Pacher P, Magyar J, Szigligeti P, Bányász T, Pankucsi C, Korom Z, Ungvári Z, Kecskeméti V, Nánási PP. Electrophysiological effects of fluoxetine in mammalian cardiac tissues. Naunyn Schmiedebergs Arch Pharmacol. 2000;361:67-73.
32. Magyar J, Rusznák Z, Harasztosi C, Körtvély A, Pacher P, Bányász T, Pankucsi C, Kovács L, Szûcs G, Nánási PP, Kecskeméti V. Differential effects of fluoxetine enantiomers in mammalian neural and cardiac tissues. Int J Mol Med. 2003;11:535-542.
33. O'Hara T, Rudy Y. Quantitative comparison of cardiac ventricular myocyte electrophysiology and response to drugs in human and nonhuman species. Am J Physiol Heart Circ Physiol. 2012;302:H1023-H1030.
34. Guo B, Li C, Wang G, Chen L. Rapid and direct measurement of free concentrations of highly protein-bound fluoxetine and its metabolite norfluoxetine in plasma. Rapid Commun Mass Spectrom. 2006;20:39-47.
35. Johnson RD, Lewis RJ, Angier MK. The distribution of fluoxetine in human fluids and tissues. J Anal Toxicol. 2007;31:409-414.