1. PHARMACOTHERAPY
OF TORSADEPOINTES

2.  Torsade de pointes or torsades is a French
term that literally means "twisting of the
points" is a ventricular tachycardia associated
with a long QT time on the resting ECG.
 During Torsade de pointes the ventricles
depolarize in a circular fashion resulting in
QRS complexes with a continuously turning
heart axis around the baseline (hence the
name Torsade de Pointes).
 It was first described by Dessertenne in 1966 .

3. Mechanism of Torsades de Pointes
 Early after depolarizations
 Transmural reentry

4. Ventricular Action
Potential
Na+
IKr
Ca++
IKs

5. Afterdepolarization

6. Reentry Triggered

7. Mechanisms Of Drug - Induced
QT Prolongation and Tdp
 Block of repolarizing K+ currents
 Stimulation of ICa-l
 Stimulation of INa

8. HERG Channel

9.  GENE: human ether a go- go related gene.
 CODES FOR: Ikr
 MUTATION:
 STUCTURE:

10. RISK FACTORS
 Hypokalemia
 Severe hypomagnesium
 Female gender
 CHF
 Baseline QT prolongation
 Congenital long QT syndrome
 Ventricular arrhythmia
 Concurrent use of drugs that causes QT
prolongation.

11. Causes of Torsades de Pointes
 Congenital LQTS
Jervell Lange Nielsen Syndrome
Romano Waed Syndrome
 Acquired LQTS

13.  Electrolye Imbalance:
 Low Magnesium
 Low Potassium
 Low Calcium
 Organic heart disease:
 CHF,IHD,
Congenital long QT syn.
Dilated,Hypertrophic cardiomyopathy,Myoc
arditis,Kawasaki diseases.
 Eating
disorders:
 Bulimia
 Anorexia

14.  ANTIARRYTHMIC DRUG:Quinidine
Procainamide
Disopyramide
Encainide
Flecainide
 PSYCHIATRIC DRUG: Chlorpromazine
Haloperidol,Droperidol,
Amitryptylline,Nortryptylline
Doxepin,quitapiene.
 ANTICONVULSANTS:Fosphenytoin.
 MUSCLE RELAXANT:Tizanidine
 RESPIRATORY:Salmetrol.

15.  ANTIHISTAMINICS:Terfinadine,Astemazole,
Diphenhydramine,Hydroxyzine,Estimazole,Loratidine.
 ANTIMICROBIALS:Erythromycin,Clarithromycin
Ketoconazole,Quinine,Cloroquine,Halofantrine,Sparfloxo
cin.
 SEROTONIN
AGONISTS/ANTAGONISTS:Ketanserin,Cisapride.
 IMMUNOSUPRESSANTS:Tacrolimus

16.  ANTIDIURETIC
HORMONE:Vasopressin
 CCBs: Nicardipine, Isradipine.
 DIURETICS:Indapamide.
 OTHERS:Adenosine,Orgaanophosphates,
Cocaine,Papaverine.

17. Drugs Withdrawn for TdP
Drug Class
Terfenadine Antihistamine
Sertindole Antipsychotic
Astemizole Antihistamine
Grepafloxacin Antibiotic
Cisapride GI Prokinetic

18. CLINICAL FEATURES
 Symtoms : syncope
palpitations
sudden death
 ECG signs:
Long QT interval
Wide QRS
Continuously changing
QRS morphology

19. Diagnosis
 First measure the QT interval
 Secondly, correct it for the heart rate, if heart
rate is above 60.
 Determine if it is greater than 0.5 seconds (500
msec) in duration.
 Lastly, compare QTc to previous QTc’s to
determine if it is lengthening.
 QTc for man:440ms and females:460ms.

20. QT Interval
• Measure from
beginning of q wave
to where the t wave
returns to baseline.
• “Rule of thumb” is it
Should be less than
50% of R-R interval.
•If =/> 500 msec 0.50
seconds) or > 50% of
R-R interval: risk for
Torsades de Pointes!

21.  LAB STUDIES:
 CARDIAC ENZYMES:
 IMAGING STUDIES:

22. MANAGEMENT
 ACUTE CASES:
Remove the offending drug
Correct K,Mg levels
Mg: doc-in suspected EADs
dose:1-2g initially given in 30-60secs
repeat every 5-15min alternatively
MOA:
K: MOA: rapid repolarisation.
LIDOCAINE:

23.  MEXILITINE:
 ISOPROTERENOL:
MOA:
Indication:
C/I:
 TEMPORARY TRANSVENOUS PACING:
Atrial pacing preferred
Pacing at 90-110bpm until QT is normal.
 IF Tdp does not terminate spontaneously:

24.  LONG TERM MANAGEMENT:
Beta blockers: Propranolol
Esmolol,Nadolol
Limitations:SCD can occur
Long term compliance
S/E:
IMPLANTABLE CARDIOVERTER
DEFIBRILLATOR:
Indications: Patients with VT,VF,aborted
cardiac arrest.
used with beta blockers.

25.  Management of congenital long QT
syndrome:
Beta blockers:
ICDs:
 Prevention of drug induced Tdps:

26.  RECENT ADVANCES:
Genetic testing for carriers of long QT syndrome:
FAMILION LQTS TEST:
USES:
 NOVELTHERAPY: Sodium channel blockers
CCBs
Atropine
Protien kinase inhibitors
Alpha blockers
Potassium chanl.openers

27. Drug Induced QT Prolongation
Preclinical Screeing
 In vitro APD effects
Isolated myocytes
(dog,rabbit,g. pig)
Purkinje fibers (dog,rabbit)
Papillary muscle (guinea pig)
 In vivo models
Conscious rabbit
Concious Hypokalemic
dogs
Canine models with