Diuretics…getting to the very last drop

Management of diuretics can seem a lot like a guessing game, and sometimes it is when trying to actively diurese and land on the most effective dose for a patient.

Most of the time when we talk about diuretics, they fall into one of two categories: those used for blood pressure (i.e. thiazides) and those used for fluid/edema management (i.e. pretty much everything else).

Did you know that thiazide diuretics are really not very good diuretics at all? It’s been demonstrated that the diuretic activity declines to baseline after 30 days of continuous use (the reference is out there somewhere, but I’m sitting here with dinner getting cold, so, I’m not going to chase it down).

So, why are diuretics a guessing game? They depend on so many things, like renal function, cardiac output, systemic vascular resistance, time of day, body position, levels of endogenous antidiuretic hormone and natriuretic peptide, and the list goes on and on.

Then, how can we even make an educated decision on what to do? Well, there are rules of thumb and there are pharmacokinetics. Pharmacokinetics is a single course I took in pharmacy school, and because it is so complex, another course in Clinical Pharmacokinetics was created. So, I can sum it up for you in two, two-and-a-half words: it’s complicated. Actually, if you can get an idea of the duration of action, comparative potency, and IV-to-PO dosing (i.e. bioavailability), then you’ve got a pretty good understanding.

That brings me to another point: efficacy. Efficacy is often used interchangeably with bioavailability, potency, and effectiveness. Yes, it’s true, furosemide is not as potent as torsemide, but only if you’re looking at a milligram to milligram basis. However, if you adjust for the differences in potency, you get similar efficacy. Same thing goes for bioavailibility. Yes, torsemide is more bioavailable than furosemide, but is mostly relevant when you switch a patient from PO to IV. With torsemide, it’s easy because the dose used orally is the same dose you’d use IV. However, with furosemide, because it is not as bioavailable, you make adjustments. You need only about 1/2 the dose IV to be equivalent to your oral dose. This fact does not make furosemide any less efficacious.

Of course, these are only a few concepts regarding the pharmacology and pharmacokinetics of diuretics. Yep, pharmacology. That is another 2 or so courses in pharmacy school.

I gave this lecture to the residents several months ago, but I updated it with one of several recent meta-analyses that have been published regarding torsemide and furosemide. It’s funny that the results of these meta-analyses are very similar, but the authors’ conclusions are somewhat different. I just gave you one example with my caveats listed. Enjoy!