January 27, 2023

Whiteboard session on furosemide (lasix) including explanation of bioavailability, IV vs PO, pharmacokinetics, threshold dosing, and mechanism of action.

Hey everybody welcome back to the whiteboard doctor your host for today i appreciate you tuning in if this is the first thing we’ve been at the channel welcome if you have been here a number of times welcome back today we’re going to talk about furiosa meyde or lasix so i draw out a little picture here already to save us some time and we’ll dive into that picture

In a bit but initially you just wanted to talk to generally about lasix so lasix is a loop diuretic what that means is that it acts on the loop of henle in the nephron which is drawn below it is not the only diuretic we also have tor some id and budesonide which are both loop diuretics as well but today we’ll just be talking about lasix oral lasix and iv lasix have

A different onset of action peak bioavailability etc etc because the oral bioavailability so poa six bioavailability is highly variable so anywhere from 10 to 90 percent of oral lasix becomes bioavailable after taking it and it’s based on a number of different reasons so when talking about pio lasix and the bioavailability it has to be understood that 95 percent

Of lasix is protein bound this is important because these protein bound 0 cement molecules get into the proximal convoluted tubule through organic acid transporters and once they are in the proximal convoluted tubules about 50% of them are excreted protein bound whereas the rest are actually degraded through glucuronidase but 95 percent of protein bound and thus

Albumin can affect the amount of a bio availability so one thing that affects bio availability is albumin if your hypoalbuminemia canned you have less protein to make lasix protein bound you will have less protein bound lasix getting into the proximal convoluted tubule to do its job in addition to that theros amide has to be transported into the proximal convoluted

Tubule to then get to loop of henle to do its job so the second thing that can affect it is a renal function right because if your kidney if you have ckd or an aki and your kidneys not functioning properly you’re not going to be able to get fat shiro so not to where it needs to go to do with job in addition to that the absorption of the gi absorption of furosemide

Can be decreased in patients who have significant edema because they can get gi edema bowel edema and thus absorb less lasix and then you took all this over lasix but did not absorb all of it and thus you do not have that full poa six load to do its job so variable bioavailability 10 to 90 percent of pa lasix iv lasix the traditional teaching is that iv lasix is

Two times as potent as p o lasix this though is based on this highly variable bioavailability they say hey 10 to 90% bioavailable let’s just say it’s about 2 times as potent so this is actually somewhat of a misnomer honestly i still use it in clinical practice but it’s a rough estimate it is not a firm rule okay so you took some iv lasix because you don’t want

This highly variable bioavailability in one of your acutely ill patients iv lasix the diaeresis starts usually within about thirty minutes i’m just going to draw this arrow iv over here so you know i’m talking about the peak is about two hours and it lasts for about six to eight hours this though is under the assumption that you have reached these threshold what

I mean by the threshold is i’m going to draw a little graph here so there is a dose threshold that you have to hit i’m going to do t4 threshold for lasix to have an effect and once you hit that threshold you will get an exponential diuretic effect but your dose of lasix even if it comes right up close to the threshold you will still get no diuresis so in order to

Get diuresis you have to hit this threshold and then you will so this above here is diuresis below is no so this one could be a dose of let’s say 20 milligrams iv and you didn’t hit the threshold this could literally be a dose and no one doses lasix this way but for the sake of point 25 milligrams and because you got just above that threshold now you’re getting

Your diuresis whereas the 20 milligrams you might not have gotten any diuresis so in order to get these effects you have to make sure the dose it’s the threshold to cause diuresis in a patient you give 20 milligrams of iv lasix to and they have no diuresis giving them another 20 milligrams it’s not going to do anything because they did not hit the threshold you

Have to increase the dose to make sure that they get past this threshold and diuresis will then persist good so i am going to delete all this to the right i’m going to erase it because i want to free up some space and we’ll continue talking the next thing we’re going to talk about before we dive into the mechanism of action is the adverse effects and i’m gonna

Leave the adverse effects over here to the right of our drawing because we can actually talk about all the adverse electrolyte effects based on the mechanism of action and it helps to kind understand things we’re just get my pen back out here okay so adverse effects of lasix oh electrolyte and the different electrolyte adverse effects are hypo nutri mia kaleem

Iya magnus amoeba and calcium yes additional adverse effects are hyper uris emia it is actually a sulfonamide so you can get acute interstitial nephritis or hypersensitivity and you can also get tivity sensitivity there we go and you can also get odo toxicity this is often reversible though good so i wanted to leave electrolytes underlined because we’re going to

Use these to help understand the mechanism of action of lasix so furiosa mater lasix is a loop diuretic this drawing here is just part of a nephron so the part we are talking about we have the proximal convoluted tubule it goes into the loop of henle and you have the descending portion of the loop of henle and the a sending portion into the proximal portion of the

Distal convoluted tubule the other things i have here in green are awesomes so within the tube you will coming out of the proximal convoluted tubule you essentially i’m going to use the terms reabsorb for molecules going from the to be wall into the interstitial because once they’re in the interstitial they are reabsorbed into the bloodstream so within the proximal

Convoluted tubules you already reabsorbed a large portion of your sodium of your chloride of your potassium of your mag almost all of your glucose amino acids bicarb and more so we’re not going to focus on this because that’s not what the lecture is about but i just wanted to make a point so what is coming through your to buell is a smaller percentage of all these

Molecules including sodium chloride mag potassium calcium in the interstitial you have this gradient of awesome’s because as you are traveling you re absorbing all of these salts and because of that as you go more distal into the descending loop of henle you have an increased osmolarity of the interstitial which means that while the inter tubular awesomes are 300

And the external awesomes in the interstitial are 900 that’s when you’re gonna get all your h2o so i know i drew that five assaults but this is h2o but that means that as you travel down the tube you’ll you actually are increasing your toe nyssa t because all your h2o is going from the two buell to the interstitial and once you get to the ascending loop of henle

You actually hypertonic what that now means is that there is a push towards reabsorbing more of your salts and that’s where we get to our sodium potassium chloride transporter in the ascending loop of henle this is where furiosa line acts so there’s a transporter that moves sodium potassium and ii chloride from the tube you will out into the interstitial and by

Doing so creates a gradient where potassium actually a percentage of it will go back into the tube you will and that creates a positive charge on the basolateral membrane of some of these cells which then leads to a passive remember reabsorption is out into the interstitial of calcium and magnesium that are positively charged ions so what this transporter does

The sodium potassium dichloride transporter is it ria’s sodium chloride potassium calcium and magnesium all to end up in the interstitial so when theros amide comes in and inhibits this what it is doing is decreasing the amount of awesome’s that can be in the interstitial right because all of these salts here even though it’s not oh sorry about that even though

It doesn’t show them going over here they’re all over here as well causing this gradient of awesome’s so without the sodium potassium chloride calcium magnesium there is going to be lower awesome’s in the interstitial which then means there’s going to be a smaller gradient for water h2o to follow so that means is that the two tubules are retaining more water this

Is less hypertonic and what you’re delivering to the distal convoluted tubules has significantly more water in it in addition to that and remember that the distal convoluted tubule goes into eventually the collecting duct i’m just a new cd and eventually this is what is excreted so in addition to that the two buell is going to have more sodium potassium chloride

Calcium and magaz you’re inhibiting this mechanism so you’re going to have increased excretion of water calcium sodium potassium and mag does that look familiar exactly so the adverse effects of hyponatremia polly mia magna samia and kelsey mia are all because you’re inhibiting the sodium potassium chloride transporter thus there’s less sodium and chloride in the

Interstitial more in the tube you will to be excrete had been addition to that you have less potassium diffusing back across the membrane leading to this positive azo cell charge that drives the passive diffusion of calcium and magnesium into the interstitial so those all stay in the tube you will as well and the two buell contents including the sodium potassium

Chloride calcium magnesium as well as more h2o are all excreted which obviously you wanted the h2o excreted because that’s the goal but then you also get the adverse effects of electrolyte abnormalities such as those does that make sense i hope that makes sense obviously nephrology and the nephron is a extremely complex beast we could talk more about the different

Parts and even just the general physiology if you guys are interested leave any questions in the comments leave any thoughts and leave any additional videos you want us to make but i will you know think about making more videos just on the general physiology of the nephron if people are interested in that and we can talk more about the basics if people have

Additional questions so if you found some value and this feel free to subscribe we’re trying to get videos out every week and they’re on a diverse set of topics so you guys drive the content here leave us comments leave us questions and we will make some videos about them appreciate you want viewing and hope you all have a good day

Transcribed from video
Loop Diuretic (Furosemide/Lasix) Explained (mechanism, bioavailability, threshold, PO/IV) By Whiteboard Doctor