KLINICKÁ FARMAKOLOGIE A FARMACIE / Klin Farmakol Farm. 2026;40(1):47-55 / www.klinickafarmakologie.cz 54 PŘEHLEDOVÉ ČLÁNKY Interval QT, etiopatogeneze arytmie „torsade de pointes“ a riziková farmakoterapie rilátoru. U mladých nemocných lze zvážit jeho subkutánní variantu s tím, že se sníží budoucí riziko problémů s intravazálně zavedenými elektrodami (4). Rozhodování o léčbě těchto vrozených forem prodloužení QT patří do rukou odborníků na léčbu arytmií. V prevenci získaných forem syndromu dlouhého QT je vhodné pacienta poučit a nejlépe vybavit kartičkou, která upozorňuje na možná rizika (výše zmíněná stránka www.crediblemeds.org). Na této adrese je možné stáhnout i aplikaci, která vypočítává rizikové léky a kombinace. U vysoce rizikových pacientů je důležité vyšetřovat EKG před a po nasazení léčby. Je možné, že budou v budoucnu dostupná léčiva, která zvýší IKs proud a bude je tak možné použít při prevenci TdP u vysoce rizikových pacientů, tento koncept se ale zatím nepodařilo potvrdit na zvířecím modelu, další výzkum probíhá (98–100). Závěr Získané nebo vrozené prodloužení intervalu QT může vyústit v životu nebezpečnou komorovou tachykardii TdP a poté přejít k fibrilaci komor. Přestože je vztah mezi délkou intervalu QT a TdP velmi komplexní a frekvence TdP je velmi nízká, jde o potenciálně maligní arytmii. Proto je nutné mít o těchto vztazích povědomí a dobře zvažovat podání léčiv prodlužujících interval QT, zejména u pacientů s rizikovými faktory. LITERATURA 1. Lester RM, Paglialunga S, Johnson IA. QT Assessment in Early Drug Development: The Long and the Short of It. Int J Mol Sci. 2019;20(6):1324. 2. Yap YG, Camm AJ. Drug induced QT prolongation and torsades de pointes. Heart. 2003;89(11):1363-1372. 3. Isbister GK. Risk assessment of drug-induced QT prolongation. Aust Prescr. 2015;38(1):20-24. 4. Krahn AD, Laksman Z, Sy RW, et al. Congenital Long QT Syndrome. JACC Clin Electrophysiol. 2022;8(5):687-706. 5. Hondeghem LM, Carlsson L, Duker G. Instability and triangulation of the action potential predict serious proarrhythmia, but action potential duration prolongation is antiarrhythmic. Circulation. 2001;103(15):2004-2013. 6. Sanguinetti MC, Tristani-Firouzi M. hERG potassium channels and cardiac arrhythmia. Nature. 2006;440(7083):463-469. 7. Vandenberg JI, Perry MD, Perrin MJ, et al. hERG K(+) channels: structure, function, and clinical significance. Physiol Rev. 2012;92(3):1393-1478. 8. Hoffmann P, Warner B. Are hERG channel inhibition and QT interval prolongation all there is in drug-induced torsadogenesis? A review of emerging trends. J Pharmacol Toxicol Methods. 2006;53(2):87-105. 9. Nogawa H, Kawai T. hERG trafficking inhibition in drug- -induced lethal cardiac arrhythmia. Eur J Pharmacol. 2014;741:336-339. 10. van der Heyden MA, Smits ME, Vos MA. Drugs and trafficking of ion channels: a new pro-arrhythmic threat on the horizon? Br J Pharmacol. 2008;153(3):406-409. 11. Han S, Zhang Y, Chen Q, et al. Fluconazole inhibits hERG K(+) channel by direct block and disruption of protein trafficking. Eur J Pharmacol. 2011;650(1):138-144. 12. Mladěnka P, Applová L, Patočka J, et al. Comprehensive review of cardiovascular toxicity of drugs and related agents. Med Res Rev. 2018;38(4):1332-1403. 13. Shah RR. Drug-induced QT interval prolongation: regulatory perspectives and drug development. Ann Med. 2004;36(Suppl 1):47-52. 14. Milon D, Daubert JC, Saint-Marc C, et al. Torsade de pointes. Apropos of 54 cases. Ann Fr Anesth Reanim. 1982;1(5):513-520. 15. Hondeghem LM. Drug-Induced QT Prolongation and Torsades de Pointes: An All-Exclusive Relationship or Time for an Amicable Separation? Drug Saf. 2017. 16. Tsuji Y, Yamazaki M, Shimojo M, et al. Mechanisms of torsades de pointes: an update. Front Cardiovasc Med. 2024;11:1363848. 17. Thomas SH, Behr ER. Pharmacological treatment of acquired QT prolongation and torsades de pointes. Br J Clin Pharmacol. 2016;81(3):420-427. 18. Chan A, Isbister GK, Kirkpatrick CM, et al. Drug-induced QT prolongation and torsades de pointes: evaluation of a QT nomogram. QJM. 2007;100(10):609-615. 19. Cyr S, Abdelaziz L, Minichiello A, et al. Impact of antidepressant and antipsychotic use in the occurence of torsades de pointes arrhythmia: a case-control study. Gen Hosp Psychiatry. 2025;94:16-23. 20. Varro A, Baczko I. Cardiac ventricular repolarization reserve: a principle for understanding drug-related proarrhythmic risk. Br J Pharmacol. 2011;164(1):14-36. 21. Obreztchikova MN, Sosunov EA, Plotnikov A, et al. Developmental changes in IKr and IKs contribute to age-related expression of dofetilide effects on repolarization and proarrhythmia. Cardiovasc Res. 2003;59(2):339-350. 22. Yokohara S, Hashiguchi M, Shiga T. Psychotherapeutic drug-induced life-threatening arrhythmias: A retrospective analysis using the Japanese adverse drug event report database. J Arrhythm. 2023;39(6):928-936. 23. Choy AM, Lang CC, Chomsky DM, et al. Normalization of acquired QT prolongation in humans by intravenous potassium. Circulation. 1997;96(7):2149-2154. 24. Shaffer D, Singer S, Korvick J, et al. Concomitant risk factors in reports of torsades de pointes associated with macrolide use: review of the United States Food and Drug Administration Adverse Event Reporting System. Clin Infect Dis. 2002;35(2):197-200. 25. Orlandi C. A case of torsade de pointes caused by hypomagnesemia. G Ital Cardiol. 1986;16(12):1062-1065. 26. Pasławska U, Noszczyk-Nowak A, Kungl K, et al. Thyroid hormones concentrations and ECG picture in the dog. Pol J Vet Sci. 2006;9(4):253-257. 27. Corović N, Duraković Z, Misigoj-Duraković M. Dispersion of the corrected QT and JT interval in the electrocardiogram of alcoholic patients. Alcohol Clin Exp Res. 2006;30(1):150-154. 28. Cunha DF, Cunha SF, Ferreira TP, et al. Prolonged QTc intervals on the electrocardiograms of hospitalized malnourished adults. Nutrition. 2001;17(5):370-372. 29. Astrom-Lilja C, Odeberg JM, Ekman E, et al. Drug-induced torsades de pointes: a review of the Swedish pharmacovigilance database. Pharmacoepidemiol Drug Saf. 2008;17(6):587-592. 30. Darpö B. Spectrum of drugs prolonging QT interval and the incidence of torsade de pointes. Eur Heart J Suppl. 2001;3(Suppl K):K70-80. 31. Roden DM. Long QT syndrome: reduced repolarization reserve and the genetic link. J Intern Med. 2006;259(1):59-69. 32. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med. 2004;350(10):1013-1022. 33. Warner B, Hoffmann P. Investigation of the potential of clozapine to cause torsade de pointes. Adverse Drug React Toxicol Rev. 2002;21(4):189-203. 34. Liu Y, Xue Y, Wu S, et al. Effect of verapamil in the treatment of type 2 long QT syndrome is not a dose-dependent pattern: a study from bedside to bench, and back. Eur Heart J Suppl. 2016;18(suppl_A):A37-A46. 35. Milberg P, Reinsch N, Osada N, et al. Verapamil prevents torsade de pointes by reduction of transmural dispersion of repolarization and suppression of early afterdepolarizations in an intact heart model of LQT3. Basic Res Cardiol. 2005;100(4):365-371. 36. Taglialatela M, Castaldo P, Pannaccione A, et al. Cardiac ion channels and antihistamines: possible mechanisms of cardiotoxicity. Clin Exp Allergy. 1999;29(Suppl 3):182-189. 37. Olasinska-Wisniewska A, Olasinski J, Grajek S. Cardiovascular safety of antihistamines. Postepy Dermatol Alergol. 2014;31(3):182-186. 38. Hagiwara T, Satoh S, Kasai Y, et al. A comparative study of the fluoroquinolone antibacterial agents on the action potential duration in guinea pig ventricular myocardia. Jpn J Pharmacol. 2001;87(3):231-234. 39. Briasoulis A, Agarwal V, Pierce WJ. QT prolongation and torsade de pointes induced by fluoroquinolones: infrequent side effects from commonly used medications. Cardiology. 2011;120(2):103-110. 40. Abo-Salem E, Fowler JC, Attari M, et al. Antibiotic-induced cardiac arrhythmias. Cardiovasc Ther. 2014;32(1):19-25. 41. Brunetti L, Lee SM, Nahass RG, et al. The risk of cardiac events in patients who received concomitant levofloxacin and amiodarone. Int J Infect Dis. 2019;78:50-56. 42. Volberg WA, Koci BJ, Su W, et al. Blockade of human cardiac potassium channel human ether-a-go-go-related gene (HERG) by macrolide antibiotics. J Pharmacol Exp Ther. 2002;302(1):320-327. 43. Hancox JC, Hasnain M, Vieweg WV, et al. Azithromycin, cardiovascular risks, QTc interval prolongation, torsade de pointes, and regulatory issues: A narrative review based on the study of case reports. Ther Adv Infect Dis. 2013;1(5):155-165. 44. Albert RK, Schuller JL. Macrolide antibiotics and the risk of cardiac arrhythmias. Am J Respir Crit Care Med. 2014;189(10):1173-1180. 45. Gysel M, Vieweg WV, Hasnain M, et al. Torsades de pointes following clarithromycin treatment. Expert Rev Cardiovasc Ther. 2013;11(11):1485-1493. 46. Brown SM, Peltan I, Kumar N, et al. Hydroxychloroquine versus Azithromycin for Hospitalized Patients with COVID-19. Results of a Randomized, Active Comparator Trial. Ann Am Thorac Soc. 2021;18(4):590-597. 47. Farmakis IT, Minopoulou I, Giannakoulas G, et al. Cardiotoxicity of azithromycin in COVID-19: an overall proportion meta-analysis. Adv Respir Med. 2022;90(3). 48. Sung DJ, Kim JG, Won KJ, et al. Blockade of K+ and Ca2+ channels by azole antifungal agents in neonatal rat ventricular myocytes. Biol Pharm Bull. 2012;35(9):1469-1475. 49. von Heeren F, Tanner R, Theurillat R, et al. Determination of fluconazole in human plasma by micellar electrokinetic capillary chromatography with detection at 190 nm. Journal of Chromatography A. 1996;745(1):165-172. 50. Santos SR, Campos EV, Sanches C, et al. Fluconazole plasma concentration measurement by liquid chromatography for drug monitoring of burn patients. Clinics (Sao Paulo). 2010;65(2):237-243. 51. Salem M, Reichlin T, Fasel D, et al. Torsade de pointes and systemic azole antifungal agents: Analysis of global spontaneous safety reports. Glob Cardiol Sci Pract. 2017;2017(2):11. 52. Haeusler IL, Chan XHS, Guérin PJ, et al. The arrhythmogenic cardiotoxicity of the quinoline and structurally related antimalarial drugs: a systematic review. BMC Med. 2018;16(1):200. 53. Funck-Brentano C, Ouologuem N, Duparc S, et al. Evaluation of the effects on the QT-interval of 4 artemisinin-based
RkJQdWJsaXNoZXIy NDA4Mjc=