drug remodelling

Jim W wrote:
>James,
>At some point I would like to hear what you know about drug remodeling...

Hi Jim, I'm afraid I know very little,
and maybe I'm putting 2 and 2 together to make 5 but....

I've read on many occasions that medications used in AF often initially works quite well but after a period of months/years they lose their ability to keep AF at bay.

The question is whether this is due to changes the body makes in response to the medication or it's an unrelated change (like a worsening of the underlying AF).

As an example of drug remodelling
A recent New Scientist article 'What doesn't kill you'
(New Scientist vol 180 issue 2418 - 25 October 2003, page 38
or
[archive.newscientist.com]
if you have a subscription)

is an interesting article about why taking beta blockers is good for CHF patients. (when intuitively it's quite a bad idea).

'....If the patient takes a beta blocker, on the other hand, initially the drug will cause a decrease in heart rate, as expected [which is bad for someone with CHF and initially puts them in more danger]. But several months later, the drug has somehow forced the body to compensate, possibly by increasing the number of -adrenoceptors....'

I'm not at all sure anyone knows why certain medication lose their efficacy but I suspect at least in some cases it will be directly due to a response to the medication rather than a degeneration of the underlying ailment. (since the mechanism of action for many drugs is unknown it's hardly surprising that the body's long term response to such drugs might involve some re-modelling to try to accommodate them)

Hope this helps - and if anyone can shed any more light on the issue I'm all ears - or should that be eyes
--
James D

Hi James,

Thanks. My cardiologist believes that AF is degenerative in nature and that it usually ends up being chronic. Whether he is right or wrong, I am not sure; but if he is correct, then when one is taking antiarrythmics successfully-over time the atrium continues to remodel(?), degenerate, or whatever until the drug is finally no longer effective. This would explain why one would start having breakthroughs on the drug at lower doses, but working at higher doses until finally the drug becomes totally useless reguardless of the doseage.

Thanks again,

Jim W.

Hi Jim,
I think many doctors consider AF to be one disorder (and often a disorder of the elderly!). I've always seen AF as a symptom with potentially many causes. I would not be surprised if both myself and your doctor were correct

I'm sure PubMed will turn something up if we go searching.

There is plenty of evidence that AF doesn't get worse in everyone and there's also evidence that some people (a minority) recover. Either the people who have managed to cure themselves are sustaining the correct balance to avoid AF in a still susceptible heart or they've undergone some re-modelling so that AF is no longer likely. I hope they've managed the latter (but suspect it's a bit of both!)


All the best
--
James D (34)
a believer in NSR begets NSR

I don't think AF can get worse without breakthroughs or episodes. If the medicine is keeping one in normal sinus rhythm all of the time, then afib is not occuring, and thus the condition cannot get worse. At least that is my humble view. I think when the medicine begins to lose its effectiveness (as the body adapts to it), and breakthroughs begin, then the condition starts deteriorating. Without breakthroughs I don't think AF can be getting worse.

If afib begets afib, does normal sinus rhythm beget normal sinus rhythm?

To both Jim's....


I think that is a good observation. My opinion is the longer one can stay in NSR, the healthier and less irritated the heart cells become and therefore less likely to go into afib. The test is finding what keeps one in NSR... be it a higher dose of drugs or supportive nutrients. Each person has to find his own solution and balance. Lord knows we've all tried every conceivable combination of things with the approach being sooner or later, something is going to work.

I like that statement that NSR begets NSR. That's a goal for everyone - one way or another.

Jackie

Greetings

Yes the question is, and what my cardio implied to the on demand approach is;
Why not take them to prevent AF as opposed to once the AF has started.
However;
1. If you take them daily then you could build up resistance. Does however NSR beget NSR?
2. If you take them on demand and get attacks, does AF beget AF?
3.Do you take them daily and ignore (within reason) triggers? (Providing you then get no AF).
4. Do the triggers put strain on the system and eventually break it down.?

Han's reports seem to indicate that taking the drugs daily does not seem to influence the frequency of attacks, assuming all triggers are avoided. This would suggest the on demand approach.
However if triggers are not avoided then possibly daily would be more suitable.

Personally I think one should keep a diary and monitor attacks without triggers. If the frequency of attacks is of a certain rate (possibly twice a month??? ANY IDEAS HERE??). Then take it daily. If less then on demand. Of course if attacks do not change in frequency then switch to on demand.
If you cannot or refuse to avoid your triggers then possibly take it on demand to limit the time in AF, that is if of course taking it daily doesn't control AF, although it will be asking much of the drug as you are supplying triggers for it to fight against.
I know people will say that you should be avoiding triggers completely as a matter of course but life and what people get out of life differs from person to person. It is easy for some harder for others it depends on so many factors, social, historical cultural, psychological etc. Everything in moderation sob!!.

Hmm everyone is different, triggers are different, suck it and see methinks.
I would be interested in what people see as an acceptable frequency if there is such a thing.

Be seeing you
Chris H