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Old 05-07-2015
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Default Amiodarone and Warfarin drug interaction

can anyone explain the mechanism behind amiodarone causing warfarin toxicity? UW says it inhibits its metabolism but i want to know the mechanism behind it
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Old 05-07-2015
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Quote:
Originally Posted by sm3356 View Post
can anyone explain the mechanism behind amiodarone causing warfarin toxicity? UW says it inhibits its metabolism but i want to know the mechanism behind it
Short answer: amiodarone is a Cytochrome P450 inhibitor. Warfarin is metabolized via this system, so it is metabolized more slowly in the presence of amiodarone.

From the clinical side, warfarin is a terribly difficult and finicky drug to dose appropriately. Even under ideal circumstances, patients need to have frequent blood tests of their PT/INR and continual adjustment of their dose until they reach and maintain a therapeutic and non-toxic level of anticoagulation. So it's a pain, but it's really effective and continues to be the standard by which all other anticoagulants are measured.

Because of this, warfarin is a favorite drug examiners like to use for test questions because you can use it for pretty much any discipline and it's something you will definitely encounter almost every day in practice.

Remember that any CYP inhibitor, not just amiodarone, can give you toxic levels of warfarin. Conversely, any CYP inducer will give you sub-therapeutic levels (you can imagine a test question where a person on warfarin suddenly gets a DVT, and you have to identify that she was taking a new drug that was a CYP inducer). Along those same lines, any DISEASE process that impairs liver function will also impact warfarin dosing.

I think it's always a good idea when reviewing missed questions to ask yourself: how else might they ask me about this? For Step 1:
1) mechanism -- inhibits epoxide reductase --> lower vit k clotting factors
2) affected clotting factors -- II, VII, IX, X, C, S
3) Warfarin-induced necrosis - C & S have short half-lives, so hypercoagulable; must bridge with heparin or other anticoag.
4) CYP inducers/inhibitors and drug level
5) Labs for checking efficacy - PT/INR
6) Treatment for toxicity -- must give FFP (not vitamin K, which will be a distractor almost guaranteed)

etc.

If you think about each topic like that, there's no way they can ask you a question about it that you can't answer.
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Old 05-07-2015
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cool thanks so much for the info!!
and thanks for the idea for reviewing missed questions, def. gonna start doing that!!
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Old 05-07-2015
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Quote:
Originally Posted by sm3356 View Post
cool thanks so much for the info!!
and thanks for the idea for reviewing missed questions, def. gonna start doing that!!
No problem!

One of the most empowering moments for me was when I realized that there are only so many things they could ask me about.

If I learned the mechanisms and concepts surrounding each topic, then I could answer any possible question on it no matter how much the test writers tried to disguise it.
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Old 05-07-2015
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lol ya thats so true, good point
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