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PHARMACOTHERAPYOF TORSADEPOINTES
 Torsade de pointes or torsades is a Frenchterm that literally means "twisting of thepoints" is a ventricular tachycardia...
Mechanism of Torsades de Pointes Early after depolarizations Transmural reentry
Ventricular ActionPotentialNa+IKrCa++IKs
Afterdepolarization
Reentry Triggered
Mechanisms Of Drug - InducedQT Prolongation and Tdp Block of repolarizing K+ currents Stimulation of ICa-l Stimulation ...
HERG Channel
 GENE: human ether a go- go related gene. CODES FOR: Ikr MUTATION: STUCTURE:
RISK FACTORS Hypokalemia Severe hypomagnesium Female gender CHF Baseline QT prolongation Congenital long QT syndrome...
Causes of Torsades de Pointes Congenital LQTSJervell Lange Nielsen SyndromeRomano Waed Syndrome Acquired LQTS
 Electrolye Imbalance: Low Magnesium Low Potassium Low Calcium Organic heart disease: CHF,IHD,Congenital long QT syn...
 ANTIARRYTHMIC DRUG:QuinidineProcainamideDisopyramideEncainideFlecainide PSYCHIATRIC DRUG: ChlorpromazineHaloperidol,Dro...
 ANTIHISTAMINICS:Terfinadine,Astemazole,Diphenhydramine,Hydroxyzine,Estimazole,Loratidine. ANTIMICROBIALS:Erythromycin,C...
 ANTIDIURETICHORMONE:Vasopressin CCBs: Nicardipine, Isradipine. DIURETICS:Indapamide. OTHERS:Adenosine,Orgaanophosphat...
Drugs Withdrawn for TdPDrug ClassTerfenadine AntihistamineSertindole AntipsychoticAstemizole AntihistamineGrepafloxacin An...
CLINICAL FEATURES Symtoms : syncopepalpitationssudden death ECG signs:Long QT intervalWide QRSContinuously changingQRS m...
Diagnosis First measure the QT interval Secondly, correct it for the heart rate, if heartrate is above 60. Determine if...
QT Interval• Measure frombeginning of q waveto where the t wavereturns to baseline.• “Rule of thumb” is itShould be less t...
 LAB STUDIES: CARDIAC ENZYMES: IMAGING STUDIES:
MANAGEMENT ACUTE CASES:Remove the offending drugCorrect K,Mg levelsMg: doc-in suspected EADsdose:1-2g initially given in ...
 MEXILITINE: ISOPROTERENOL:MOA:Indication:C/I: TEMPORARY TRANSVENOUS PACING:Atrial pacing preferredPacing at 90-110bpm ...
 LONG TERM MANAGEMENT:Beta blockers: PropranololEsmolol,NadololLimitations:SCD can occurLong term complianceS/E:IMPLANTAB...
 Management of congenital long QTsyndrome:Beta blockers:ICDs: Prevention of drug induced Tdps:
 RECENT ADVANCES:Genetic testing for carriers of long QT syndrome:FAMILION LQTS TEST:USES: NOVELTHERAPY: Sodium channel ...
Drug Induced QT ProlongationPreclinical Screeing In vitro APD effectsIsolated myocytes(dog,rabbit,g. pig)Purkinje fibers ...
Torsades de-pointes
Torsades de-pointes
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Torsades de-pointes

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Torsades de-pointes

  1. 1. PHARMACOTHERAPYOF TORSADEPOINTES
  2. 2.  Torsade de pointes or torsades is a Frenchterm that literally means "twisting of thepoints" is a ventricular tachycardia associatedwith a long QT time on the resting ECG. During Torsade de pointes the ventriclesdepolarize in a circular fashion resulting inQRS complexes with a continuously turningheart axis around the baseline (hence thename Torsade de Pointes). It was first described by Dessertenne in 1966 .
  3. 3. Mechanism of Torsades de Pointes Early after depolarizations Transmural reentry
  4. 4. Ventricular ActionPotentialNa+IKrCa++IKs
  5. 5. Afterdepolarization
  6. 6. Reentry Triggered
  7. 7. Mechanisms Of Drug - InducedQT Prolongation and Tdp Block of repolarizing K+ currents Stimulation of ICa-l Stimulation of INa
  8. 8. HERG Channel
  9. 9.  GENE: human ether a go- go related gene. CODES FOR: Ikr MUTATION: STUCTURE:
  10. 10. RISK FACTORS Hypokalemia Severe hypomagnesium Female gender CHF Baseline QT prolongation Congenital long QT syndrome Ventricular arrhythmia Concurrent use of drugs that causes QTprolongation.
  11. 11. Causes of Torsades de Pointes Congenital LQTSJervell Lange Nielsen SyndromeRomano Waed Syndrome Acquired LQTS
  12. 12.  Electrolye Imbalance: Low Magnesium Low Potassium Low Calcium Organic heart disease: CHF,IHD,Congenital long QT syn.Dilated,Hypertrophic cardiomyopathy,Myocarditis,Kawasaki diseases. Eatingdisorders: Bulimia Anorexia
  13. 13.  ANTIARRYTHMIC DRUG:QuinidineProcainamideDisopyramideEncainideFlecainide PSYCHIATRIC DRUG: ChlorpromazineHaloperidol,Droperidol,Amitryptylline,NortryptyllineDoxepin,quitapiene. ANTICONVULSANTS:Fosphenytoin. MUSCLE RELAXANT:Tizanidine RESPIRATORY:Salmetrol.
  14. 14.  ANTIHISTAMINICS:Terfinadine,Astemazole,Diphenhydramine,Hydroxyzine,Estimazole,Loratidine. ANTIMICROBIALS:Erythromycin,ClarithromycinKetoconazole,Quinine,Cloroquine,Halofantrine,Sparfloxocin. SEROTONINAGONISTS/ANTAGONISTS:Ketanserin,Cisapride. IMMUNOSUPRESSANTS:Tacrolimus
  15. 15.  ANTIDIURETICHORMONE:Vasopressin CCBs: Nicardipine, Isradipine. DIURETICS:Indapamide. OTHERS:Adenosine,Orgaanophosphates,Cocaine,Papaverine.
  16. 16. Drugs Withdrawn for TdPDrug ClassTerfenadine AntihistamineSertindole AntipsychoticAstemizole AntihistamineGrepafloxacin AntibioticCisapride GI Prokinetic
  17. 17. CLINICAL FEATURES Symtoms : syncopepalpitationssudden death ECG signs:Long QT intervalWide QRSContinuously changingQRS morphology
  18. 18. Diagnosis First measure the QT interval Secondly, correct it for the heart rate, if heartrate is above 60. Determine if it is greater than 0.5 seconds (500msec) in duration. Lastly, compare QTc to previous QTc’s todetermine if it is lengthening. QTc for man:440ms and females:460ms.
  19. 19. QT Interval• Measure frombeginning of q waveto where the t wavereturns to baseline.• “Rule of thumb” is itShould be less than50% of R-R interval.•If =/> 500 msec 0.50seconds) or > 50% ofR-R interval: risk forTorsades de Pointes!
  20. 20.  LAB STUDIES: CARDIAC ENZYMES: IMAGING STUDIES:
  21. 21. MANAGEMENT ACUTE CASES:Remove the offending drugCorrect K,Mg levelsMg: doc-in suspected EADsdose:1-2g initially given in 30-60secsrepeat every 5-15min alternativelyMOA:K: MOA: rapid repolarisation.LIDOCAINE:
  22. 22.  MEXILITINE: ISOPROTERENOL:MOA:Indication:C/I: TEMPORARY TRANSVENOUS PACING:Atrial pacing preferredPacing at 90-110bpm until QT is normal. IF Tdp does not terminate spontaneously:
  23. 23.  LONG TERM MANAGEMENT:Beta blockers: PropranololEsmolol,NadololLimitations:SCD can occurLong term complianceS/E:IMPLANTABLE CARDIOVERTERDEFIBRILLATOR:Indications: Patients with VT,VF,abortedcardiac arrest.used with beta blockers.
  24. 24.  Management of congenital long QTsyndrome:Beta blockers:ICDs: Prevention of drug induced Tdps:
  25. 25.  RECENT ADVANCES:Genetic testing for carriers of long QT syndrome:FAMILION LQTS TEST:USES: NOVELTHERAPY: Sodium channel blockersCCBsAtropineProtien kinase inhibitorsAlpha blockersPotassium chanl.openers
  26. 26. Drug Induced QT ProlongationPreclinical Screeing In vitro APD effectsIsolated myocytes(dog,rabbit,g. pig)Purkinje fibers (dog,rabbit)Papillary muscle (guinea pig) In vivo modelsConscious rabbitConcious HypokalemicdogsCanine models with

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