长QT综合征的抗心律失常药物-ppt课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,Fare clic per modificare lo stile del titolo,*,Fare clic per modificare gli stili del testo dello schema,Secondo livello,Terzo livello,Quarto livello,Quinto livello,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,长QT综合征的抗心律失常药物-ppt课件,1,长QT综合征的抗心律失常药物-ppt课件,2,长QT综合征的抗心律失常药物-ppt课件,3,长QT综合征的抗心律失常药物-ppt课件,4,GENETIC FACTOR,CONGENITAL ACQUIRED,LONG QT SYNDROMELONG QT SYNDROME,( FORME FRUSTE ),- IT SHOULD BE REMEMBERED THE LOW PENETRANCE OF GENETIC DISORDERS,- BETWEEN ENVIRONMENTAL FACTORS THE MOST IMPORTANT SEEMS TO BE THE CONCOMITANT HYPOKALEMIA,FIGURE 1 - SCHEMATIC REPRESENTATION OF DIFFERENT FACTORS BEING INVOLVED IN TDP INDUCTION,TRIGGER (DRUGS),ENVIRONMENTAL FACTORS,GENETIC FACTORFIGURE 1 - SCHEM,Genetic characterization of congenital LQT syndrome,Genetic characterization of co,6,Mechanims of Drug-induced QT Prolongation and TdP 1,The blockade of,I,kr,current by antiarrhythmic drugs that are capable of prolonging the action potential duration is at least in part responsible for their proarrhythmic effect.,It is interesting to note that many other drugs that cause the development of early afterdepolarizations and TdP block the,I,kr,channel.,The incidence of TdP remain low, however, and not all drugs that block,I,kr,have the same arrhythmogenic potential. The precise reason for the different effects of,I,kr,blocker is unknown.,Mechanims of Drug-induced QT P,7,Mechanims of Drug-induced QT Prolongation and TdP 2,Thus, in an ordinary situation, the administration of an,I,kr,blocker might not prolong the QT interval.,However in the presence of an otherwise subclinical lesion in the repolarization mechanisms (i.e.,reduced repolarization reserve,), the same,I,kr,blocker may precipitate marked QT prolongation and TdP.,Mechanims of Drug-induced QT P,8,Mechanims of Drug-induced QT Prolongation and TdP 3,The causes for these lesions may be acquired (e.g. myocardial infarction, congestive heart failre, ischemia, etc.) or congenital (formes frustes of congenital long QT syndrome).,The 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 the drug, because patient and metabolic factors are also important (e.g. gender, electrolyte levels, etc),There 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.,Mechanims of Drug-induced QT P,9,Torsades de Pointes,Torsades de Pointes,10,Factors Modulate the Effects of Drugs That Block I,Kr,Hypokalemia and hypomagnesemia,Hypertrophy and heart failure,Gender,Metabolic factors,Sympathetic activity,Multiple actions of drugs that block I,Kr,“Forme fruste” of the congenital long QT syndrome,Factors Modulate the Effects,11,Part 1: Cardiac Drugs able to induce QT Prolongation and TdP,Part 1: Cardiac Drugs able to,12,Class, Antiarrhythmics,Quinidine,Blocks the delayed rectifier,I,kr,as well as,I,Ks,Quinidine Syncope,Causes QT prolongation early during therapy , usually within,1,week,QT prolongation 1.5%,TdP 1% 8.8%, especially when QT interval 520ms, hypokalemia and bradycardia,Class Antiarrhythmics Qui,13,Li Kui: rude and rush by nature. Quinidine,Li Kui: rude and rush by natur,14,Class III,Antiarrhythmic Drugs 1,d, l Sotalol,Blocks the delayed rectifier I,kr,potassium current,No effect on the slow component I,ks,current,Additional,-blocking effect,Incidence of TdP increases with dose and the baseline 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.,Class III Antiarrhythmic Drugs,15,Bao Zheng: a clean political career and a man of justice. Sotalol,Bao Zheng: a clean political c,16,Drug induced TDP: comparison between Quinidine and Sotalol,Drug induced TDP: comparison b,17,Class III,Antiarrhythmic Drugs 2,Amiodarone,Unique,drug which possesses pharmacological properties from all four antiarrhythmic classes,Has the same potent effects on QT prolongation as other Class III agents, but the associated incidence of TdP is very low.,TdP usually occurs during concomitant therapy with other QT prolonging drugs or in the context of severe electrolyte disturbance.,Intravenous amiodarone is also safe and effective for the treatment of ventricular tachyarrhythmias.,Class III Antiarrhythmic Drugs,18,Meng Liang: a good general. Amiodaron,Meng Liang: a good general. Am,19,d- Sotalol,Ibutilide,Azimilide,Tedisamil,Ersentilide,Dofetilide,Dronedarone,Almokalant,New Class,III drugs,d- SotalolNew Class III drugs,20,长QT综合征的抗心律失常药物-ppt课件,21,长QT综合征的抗心律失常药物-ppt课件,22,长QT综合征的抗心律失常药物-ppt课件,23,长QT综合征的抗心律失常药物-ppt课件,24,长QT综合征的抗心律失常药物-ppt课件,25,Part 2: Acquired Long QT Syndrome by Non- Antiarrhythmic Drugs,Part 2: Acquired Long QT Syndr,26,长QT综合征的抗心律失常药物-ppt课件,27,Part 3 Drug Drug Interaction,Part 3 Drug Drug Interacti,28,Cytochrome P450(CYP) enzymes are divided into two classes on the basis of the fundamental characteristics of their substrates,Those primarily involved in the metabolism of drugs and other xenobiotics,Those involved in the biosynthesis and metabolism of steroid hormones and other endobiotics,Metabolic factors,Cytochrome P450(CYP) enzymes a,29,长QT综合征的抗心律失常药物-ppt课件,30,Part 4 How to Avoid Drug-Induced Torsades de Pointes,Part 4 How to Avoid Drug-Indu,31,长QT综合征的抗心律失常药物-ppt课件,32,长QT综合征的抗心律失常药物-ppt课件,33,长QT综合征的抗心律失常药物-ppt课件,34,长QT综合征的抗心律失常药物-ppt课件,35,Flow chart for Sotalol administration,Flow chart for Sotalol adminis,36,Conclusions 1,The discordance between QT prolongation and the incidence of TDP among antiarrhythmic drugs that prolong ventricular refractoriness has stimulated immense interest in separating the salutary terapeutic effects from the adverse proarrhythmic action of antiarrhytmic drugs.,Rapidly expanding knowledge of ion channel kinetics and structure, will aid the development of new drugs with specific profiles of channel blocking properties which have an effective antiarrhythmic action with minimal proarrhythmic potential.,Conclusions 1The discordance b,37,Conclusions 2,For non antiarrhythmic drugs wich prolongs QT interval, dose, duration of treatment, route of administration and magnitude of liver and kidney clearances will affect the intensity and duration of the exposure to the drug.,The most suitable raccomandation for a prescribing physician for both antiarrhythmic and non cardiac drugs is to consult the drug information sheets, the reference books, national formularies, and other drug compendia, to avoid unwanted drug interactions and additive effects on,I,kr,channels.,Conclusions 2For non antiarrhy,38,Conclusions 3,The overall incidence of TdP in patients who use drugs that block,I,kr,is low (3%), and not all drugs that block,I,kr,have the same arrhythmogenic potential. The extact reasons for this are unknown but,there are many factors which physicians must know and monitor when using drugs that block,I,kr,Hypokalemia and hypomagnesemia,Hypertrophy and heart failure,Female gender,Metabolic factors and drug interactions,Symphatethic activity and,-,stimulation,Multiple actions of drugs thab block,I,kr,(the low incidence of TdP due to Amiodarone may be due to its blocking effects of calcium and sodium currents, thus suppressing the development of early afterdepolarizations, and preventing reentry.,Formes frustes of the congenital long QT syndrome.,Conclusions 3The overall incid,39,THANK YOU,THANK YOU,40,长QT综合征的抗心律失常药物-ppt课件,41,长QT综合征的抗心律失常药物-ppt课件,42,长QT综合征的抗心律失常药物-ppt课件,43,