This is video #2 in our free teaching series on diuretics, this time it’s all about loop diuretics. The video was taken from our upcoming course on fluids & electrolytes.
We’re gonna go through every diuretic and each aspect of the kidney to understand how these diuretics work and we’re not gonna do them in an atomic order because in truth the proximal tubules and the cortical collecting duct diuretics they’re just not very strong diuretics and so we’re gonna start with the strongest diuretics of all the loop diuretic in order to
Understand the loop diuretic you need to understand how the thick ascending limb of the loop of henle works the principle molecule here is the sodium potassium ii chloride cotransporter here two molecules of chloride a molecule of sodium and a molecule of potassium all bind this and are transported into the cell one should quickly look and see that sodium and
Chloride are at much higher concentrations in a tubular fluid and if as this molecule runs and transports these ions across cell membrane potassium would be quickly depleted in order to avoid that potassium is recycled out of the cell through something called the rom k channel but when that happens what is normally an electro neutral movement to cations sodium and
Potassium and to anions chloride now becomes electrogenic because there’s no net movement of potassium you get a positive charge on the tubular side of the membrane this positive charge is a byproduct of the potassium recycling but the kidney uses this byproduct to force the reabsorption of other cations magnesium calcium and sodium specifically a reabsorbed will
Pair a cellular pathway that means a pathway between the cells not through the cells and it is driven by that positive charge generated from the recycling of potassium let’s take a closer look at the loop diuretics so loop diuretics are active in the tubular fluid they don’t act from the basolateral membrane they don’t get to their active site via the blood they
Need to get into the tubular fluid to work now loop diuretics are highly protein bound and any molecule is protein bound can’t be filtered at the glomerulus so the way that it enters the tube you’ll is it secreted in the proximal tubular now that secretion is gfr dependent hence the lower the gfr the less diuretic that makes it to the tube you’ll we’re always
Talking about dosing for kidney disease and usually when we talk about renal dosing we talk about decreasing the dose that as your kidney function deteriorates you either need less of the drug or you need to use the drug less often that’s not the case with diuretics here when we talk about renal dosing we use more and more of the drug as the kidneys get weaker
And weaker there’s a number of ways to figure out a starting dose for furosemide but i like to take the serum creatinine and milligrams per deciliter and just multiply it by 20 with a ceiling of around 80 milligrams once i’m at 80 milligrams i’ll stop the sense there give a test dose and see what kind of response if no response is you can go even higher let’s
Take a look at how the loop diuretics actually work at the thick ascending limb of the loop of henle here the lasix is a green dot and it blocks the chloride slot fits into the chloride slot and shuts down the sodium potassium to chloride transporter this will increase the renal excretion of sodium potassium hydrogen ions causing metabolic alkalosis calcium and
Magnesium now there are three loop diuretics and they have all of different characteristics the one we’re most familiar with is furosemide caused by the trade name lasix but there’s two others bumetanide and course amide now they vary primarily from lasix in terms of bioavailability i want to talk a little bit bioavailability later but essentially bioavailability
Is the ratio of a iv dose to what you need orally so as you can see with lasix if you give this much iv you’ll either need the equivalent amount orally or a whole bunch more and it’s hard to predict what the case is on any individual patient where the bioavailability of bumex in horsham id is much more predictable the low dose to the high dose is almost identical
To the iv dose and that makes it much easier to convert patients from iv to oral bumetanide and taurus amide the other big difference is half-life and you can see that the half-life of lasix goes from one and a half to two hours much shorter half-life would be met an id and a longer half-life with taurus amide let’s go back to the bioavailability and talk about
What the implications are for patients so here’s a patient case this is a gentleman with a known history of heart failure he’s been taking his medications regularly but despite that he has a thirty pound weight gain over the last month and today he was unable to put on his regular shoes and is forced to wear his slippers he comes to the emergency room with dyspnea
And shortness of breath and in the emergency room he’s given a dose of iv lasix and promptly begins making copious amounts of urine now the cynic includes that with such a brisk diuresis the patient must not have been taking his diuretics but another possibility that you conclude that this may be a case where the bioavailability of furosemide has fallen in this
Individual from 100 percent to 10 percent now how may that occur it can occur because the edema that we see throughout the body also occurs in the intestinal tract and as you get increased intestinal edema that can decrease the absorption of furosemide so that what was a appropriate dose at one point is no longer appropriate for giving him the diaeresis he needs
Moving on to half-life so the half-life for furosemide is one and a half to two hours the meta knight is quicker it has a half-life of one hour that means it’s gonna have a very quick onset of action you give the drug and you immediately see a response this is useful in the icu horsham odds on the other half of that stick it has a long half-life from three to four
Hours this allows once daily dosing it is optimal for hypertension and heart failure and there are clinical studies that have shown that you can decrease hospitalization where the only change you do is switch patients from furosemide horsham i’d reduction in hospitalization for heart failure and all causes
Transcribed from video
Loop diuretics By Medmastery
