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1、Acquired Long QT Syndrome by Antiarrhythmic DrugsChen Liying MD Cardiology Department An Zhen Hospital Beijing CHINA. NASPE-Heart Rhythm Association International fellow. Bologna 2004.Franco Naccarella MD Cardiology Department Azienda USL Citt di Bologna ITALYStefano Sdringola Maranga MD Cardiology
2、Division Hermann Memorial Hospital Houston TX USA CHINA 1-16/11/2005 CARDIOSTIM 2004 June 16-19 Nice, FranceGENETIC FACTORCONGENITAL ACQUIRED LONG QT SYNDROMELONG QT SYNDROME (“ FORME FRUSTE “) - IT SHOULD BE REMEMBERED THE LOW PENETRANCE OF GENETIC DISORDERS - BETWEEN ENVIRONMENTAL FACTORS THE MOST
3、 IMPORTANT SEEMS TO BE THE CONCOMITANT HYPOKALEMIAFIGURE 1 - SCHEMATIC REPRESENTATION OF DIFFERENT FACTORS BEING INVOLVED IN TDP INDUCTIONTRIGGER (DRUGS)ENVIRONMENTAL FACTORSGenetic characterization of congenital LQT syndromeMechanims of Drug-induced QT Prolongation and TdP 1lThe blockade of Ikr cur
4、rent by antiarrhythmic drugs that are capable of prolonging the action potential duration is at least in part responsible for their proarrhythmic effect. lIt is interesting to note that many other drugs that cause the development of early afterdepolarizations and TdP block the Ikr channel. lThe inci
5、dence of TdP remain low, however, and not all drugs that block Ikr have the same arrhythmogenic potential. The precise reason for the different effects of Ikr blocker is unknown.Mechanims of Drug-induced QT Prolongation and TdP 2lThus, in an ordinary situation, the administration of an Ikr blocker m
6、ight not prolong the QT interval.lHowever in the presence of an otherwise subclinical lesion in the repolarization mechanisms (i.e. reduced repolarization reserve), the same Ikr blocker may precipitate marked QT prolongation and TdP.Mechanims of Drug-induced QT Prolongation and TdP 3lThe causes for
7、these lesions may be acquired (e.g. myocardial infarction, congestive heart failre, ischemia, etc.) or congenital (formes frustes of congenital long QT syndrome). lThe extent of QT prolongation and risk of TdP associated with a given drug may not be linearly related to the dose of plasma level of th
8、e drug, because patient and metabolic factors are also important (e.g. gender, electrolyte levels, etc) lThere is not a simple relationship of drug-induced QT prolongation and the likelihood of the development of TdP which can sometimes occur without any noticeable prolongation of the QT interval.To
9、rsades de PointesFactors Modulate the Effects of Drugs That Block IKrHypokalemia and hypomagnesemia Hypertrophy and heart failure Gender Metabolic factors Sympathetic activity Multiple actions of drugs that block IKr “Forme fruste” of the congenital long QT syndromePart 1: Cardiac Drugs able to indu
10、ce QT Prolongation and TdPClass AntiarrhythmicsQuinidine l Blocks the delayed rectifier Ikr as well as IKs l Quinidine Syncope l Causes QT prolongation early during therapy , usually within 1 week l QT prolongation 1.5% l TdP 1% 8.8%, especially when QT interval 520ms, hypokalemia and bradycardiaLi
11、Li KuiKui: rude and rush by nature. : rude and rush by nature. QuinidineQuinidineClass III Antiarrhythmic Drugs 1d, l Sotalol Blocks the delayed rectifier Ikr potassium current No effect on the slow component Iks current Additional -blocking effect Incidence of TdP increases with dose and the baseli
12、ne values of the QT interval. TdP occurred early even with low doses of oral d,l -sotalol, especially in patients with congestive heart failure and low ejection fraction. BaoBao ZhengZheng: a clean political career and a : a clean political career and a man of justice. man of justice. SotalolSotalol
13、Drug induced TDP: comparison between Quinidine and SotalolClass III Antiarrhythmic Drugs 2Amiodarone lUnique drug which possesses pharmacological properties from all four antiarrhythmic classes lHas the same potent effects on QT prolongation as other Class III agents, but the associated incidence of
14、 TdP is very low. lTdP usually occurs during concomitant therapy with other QT prolonging drugs or in the context of severe electrolyte disturbance. lIntravenous amiodarone is also safe and effective for the treatment of ventricular tachyarrhythmias.MengMeng LiangLiang: a good general. : a good gene
15、ral. AmiodaronAmiodarond- Sotalol Ibutilide Azimilide Tedisamil Ersentilide Dofetilide Dronedarone AlmokalantNew Class III drugsPart 2: Acquired Long QT Syndrome by Non- Antiarrhythmic DrugsPart 3 Drug Drug InteractionCytochrome P450(CYP) enzymes are divided into two classes on the basis of the fund
16、amental characteristics of their substratesl Those primarily involved in the metabolism of drugs and other xenobiotics l Those involved in the biosynthesis and metabolism of steroid hormones and other endobioticsMetabolic factorsPart 4 How to Avoid Drug- Induced Torsades de PointesFlow chart for Sotalol administration
