Posts Tagged ‘trimetazidine’

A drug with a peculiar mode of action is recently making waves across the globe (At least some parts of it !) Basically , when the world was looking for an  anti anginal drug without much hemodynamic effects Trimetazidine fitted this slot .While it’s popularity soared  in Europe and Japan , the Americans thought there was a  need for a similar drug but supposedly  different mechanism of action . Thus  Ranalozine was born.It is a piperazine derivative.

How does Ranalozine act ?

There are three important actions for Ranlozine  (  4th one a real surprise !)

  • Antianginal
  • Anti arrhythmic
  • Possible lusiotropic effect
  • Anti diabetic*

*It is  surprising to note Ranalozine was  reducing Hb A1 c . This is incidental or a simple statistical fairy tale we do not know !

Anti anginal

  • It acts on the late Na ion channel  in phase  2 of action potenial .
  • This facilitates  excess Ca  to be removed from the cells by the NA/Ca exchanger
  • Calcium exit improves  ischemic  myocyte’s   metabolic performance as  cell injury is prevented .

This makes this drug an effective anti anginal.

The MERLIN TIMI 36 in NSTEMI  population became a  big dampener against the enthusiasm for this drug.But it did not affect much the sale of the drug !


A drug , which acts on phase  2  Na channel , it is not at all a  surprise to have anti  arrhythmic properties .

It can reduce phase 2 reentry like EADS

pro-arrhythmic action

Paradoxically  by blocking Na channels it stretches  the phase 2 and hence  QT interval is prolonged

Lusiotropic action

By preventing  the calcium from accumulating  from the cytosol it has a  theoretical ! lusiotropic action.

It is funny , even  theoretical action  is  enough ,  for  many drugs  to enter  the standard cardiology literature !

What is major advantage of  Ranalozine  over other drugs ?

It virtually has no hemodyanmic effects .

Unlike other anti-arrhythmic drugs it acts , only  if the late Na channels are abnormally active .

(Which is a case during episodes of ischemia .)  This prevents  QT interval to prolong in normal persons

In spite of all these meaningful actions and less side effects , FDA approval why cardiologists in the back of the  mind think this drug is not  based on strong scientific principles , and it could  simply  represent  an industry sponsored  placebo ?

I do not know the  answer  to this question ,  but I do share the same feeling.

Will it succeed the test of time ?

In this context , I recall a famous statement   by my professor “A drug , which has least side effects , is very unlikely to have any desired effect also”

But  with  world  ,  taking a commercial avatar  a success of a  drug  lies ,  not in  having a desired action but in  how many million packs are ultimately   sold  in the market. It is akin to a bad movie succeeding  phenomenally  in box office while  a good one lying silently   unnoticed

Read Full Post »

During acute  ischemia the most immediate requirement for the heart is




D.High energy ATPs

E.Free fatty acid

Answer : A  will be considered  by most , as  correct answer .  A can provide B to E . But it is also a fact heart can survive without  A.  

Myocardium requires energy first  ! it does not in fact bother about from where it is coming at the time of crises.It may be right if you restore the coronary blood flow all other components (B-E) are made available to the heart .

The heart can survive off  the coronary circulation with only chemical support during cardiac surgery and also a during  heart transplantation  explanted  donor heart survives on a ice box during transit and till it is transplanted into the recipient heart

But ironically we spend much of our energy and efforts in restoring blood flow.One need to spare a thought about the quality of blood also . This is especially important  in the setting of ischmia  where a  metabolic centric approach will add further benefit.

Energy based approach to ischemia : Is it relevent ?

Heart is a fascinating  mechano biological organ  pumping   millions of  gallons of blood  .Fuel for this is self generated  on a continuous basis  from the circulation blood .So  the key to human survival is the coronary blood flow that supplies the fuel and nutrients to the heart. When this key supply line is under threat  during  acute coronary syndrome cardiologist have  the only option of restoring the compromised blood supply by any means . But during chronic ischemia there is  no  urgency. There has always been an option of enriching the  blood with energisers like ATPs,  glucose,  hemoglobin etc .Providing energy support to the failing heart has never captured the imagination of cardiac physicians until recently.Still most are skeptical about  the concept of biochemical ischemia.

Click to download full PPT presentation

Metabolic manipulation of  CAD( Will be available shortly)

Read Full Post »