In this video I have discussed the mechanism of action, examples, uses, adverse effects and contraindications for loop diuretics.
Okay so moving on to loop diuretics general information um do diuretics they work on the ascending loop of henle where 20 of our sodium is reabsorbed so again i have here a picture of the nephron just in case you forget so the ascending lipopending is this bit here again 20 of our total sodium is reabsorbed here um loop diuretics are um they can work in the
Renal function actually they are the drug of choice for moderate to severe renal failure because they do not alter the glomerular filtration rate so they’re you know they they’re good even if you even if your kidneys are not functioning very very well and they’re rarely used alone because they trigger compensatory mechanisms and um which i will explain later
And they have kind of a very short duration of action so um yeah they’re not used alone they’re used for hypertension specifically if thiazides are like inadequate so they have the synergistic effect with thiazide diuretics so examples include furosemide and furosemide has a vasodilatory action specifically veno dilation which is dilation of the veins um
Fluorosimide from what i’ve read they have no direct vasodilator effect on the arterioles actually so um if you give for some iv then it might provide quick relief for symptoms you know in left ventricular failure and it might resolve um pulmonary edema so twasimide is another example of a loop diuretic so among all of this it has the longest half-life so that
Might be an mcq question i don’t know so just remember tulsi mine has the longest half-life in all of the diuretics um so we have bumetanide as well which is the most potent one the most potent loot diuretic and it has less adverse effects compared to furicimide and then lastly we have um ether chronic acid so ethanic acid is highly toxic it’s toxic mainly to
The ear it’s autotoxic and to the auditory nerve so it’s actually not used that often mechanism of actions so loot diuretics they block the um sodium potassium two chlorides importa so we have a different simple to here guys bear that in mind and i will discuss this in the next slide they also produce prostaglandins which have vasodilatory effect so this means
That um nsaids would reduce their function because non-steroidal anti-inflammatory medications such as ibuprofen they block the production of prostaglandins by blocking the cox enzymes so just remember nsaids would reduce the function of loop diuretics they would make them less efficacious basically so effects as i said loop diuretics they are very powerful um
They are the high seeding diuretics which means that they create you know the maximum diuresis effect maximum water loss and they decrease calcium reabsorption they produce hypocalcemia in contrast with are thiazide diuretics that increase calcium reabsorption and actually produce hyper calcimia okay so now let’s discuss the mechanism of action of loop diuretics
So if you’ve seen my previous video this diagram would kind of make sense but i’ll just repeat myself anyway so here in blue we have the um cell membrane or the membrane of the lumen um here we have the ascending loop of henle and here it signifies that we’ve kind of moved downstream from the ascending loop of henle into the collecting duct or the late path of
The distal conveyor so here we are in the ascending loop of henle and here in green we have our little cells and in pink we have our peritribul capillary and between the peritubular capillary and our cells we have the interstitium okay so this is the apical membrane so basically it’s the membrane of the cell that’s orientated towards the tubule which is this
Bit and here we have the base lateral membrane which is the other membrane orientated towards the peritubular capillary so as you can see here we have loads and loads of different channels code transporters adpaces so let’s start okay so in a normal physiological setting we have our sodium potassium two chloride simple or co transport or whatever you wanna call
It here in the apical membrane so what it does it brings in sorry sodium potassium and two chloride into the cell okay so what happens is that the sodium concentration inside the cell builds up so how does the cell get rid of that you know extra sodium building up in the cell so our little guy here it’s still here our sodium potassium atpase so it pumps the um
Sodium out for the exchange of potassium into the cell so it pumps um three sodiums to be exact and then it bumps into potassium ions okay so that’s what happens to our sodium so now what happens to our chloride ions so chloride ions um they keep building up in the cell because you know through this um symporta so some of the co ions they actually leak out into
The interstitium and then eventually reaching the um peritubular capillary reaching our bloodstream and then with potassium here so potassium builds up in the cell as well because we’re actively pumping it in for the exchange of sodium and it’s coming in through this sodium potassium to chloride simpleta so the increased concentration of potassium means that
Some of them they leak out into the lumen or into the some leak out in the peritubular capillaries as well as depicted here so when they go to the lumen because they are positively charged they create a luminal charge they create a positive luminal charge so if you imagine lots of potassium coming out into into here right so we increase the charge here we make
It more positive so here we have um in our filtrate we also have magnesium and calcium are divalent cations so our diabetic cat ions you know positive and positive they repel each other they don’t want to be together so that means that our magnesium and calcium they just go back into the bloodstream because they won’t avoid that positive charge okay okay so
Now let’s discuss what happens when we give loop diuretics so loop diuretics as we know they inhibit the sodium potassium two chloride symbol so they inhibit this water on the apical membrane so that so what does that mean so that means that there’s less sodium that’s transported inside the cell so we increase sodium here right because it’s not coming in and
Then we also have less chloride coming in so we increase our chloride concentration in the filtrate and then we also have less potassium so we increase potassium here and we decrease the concentration of these three ions inside the cell all right and then less potassium means less um less potassium inside the cell means less potassium leaking out into the
Peritribular capillary or leaking back and that means that there is no positive luminal charge created here so the charge is actually neutral so that means that our dividend cap ions our magnesium and our calcium they you know they don’t get reabsorbed into the capillary they just stay in the filtrate because there’s no driving force there’s no reason for them
To leave because the charge is neutral so then what do we get here so in the peritribue capillary we have a decrease in sodium we have a decrease in chloride we have a decrease in potassium and we also have a decrease in magnesium so we get hyper magnesium and we get hypocalcemia sorry my handwriting is just nutritious today i’m using my mouse to write that’s
Why so anyway so that’s what we get in the peritubular side and inside the peritubular capillary we get a decrease in these ions these electrolytes and in the filtrate we increase them okay so same thing with dizzy diuretics you know we’ve discussed this these um ions they travel downstream so you know here we’re in we’re only in the ascending loop of henle
It goes towards the descending nuclear the dct and eventually ending up in the collecting dot so here in the collecting duct we have um the passive movement of sodium potassium and protons okay so um sodium is the main driving force for this passive movement so you know because we have an increase in sodium here then that sodium obviously wants to move into the
Cell to increase um that increases the sodium into the cell and this creates a positive charge inside the cell and that means that this increase in positive charge makes other positively charged ions want to come out so here in the luminal side we create a negative luminal charge because sodium is coming in and that means that potassium and hydrogen they want
To come here to neutralize this negative charge and they want to avoid this positive charge here created by the sodium so now we have an increase again in potassium in the filtrate an increase in hydrogen in the filtrate leading to alkalosis again because of the loss of protons and leading to hypokalemia because we’re losing our potassiums again right i just
Want to stress this point again so in loop diuretics we retain magnesium and more importantly we retain calcium in our filtrate which means we get hyper calciuria and increase in magnesium in our urine so if we have lots of those in the urine it just means we have less of them in our blood so this effect is basically the opposite of thiazide diuretics because
Implies eye diuretics we increase the absorption of calcium thereby decreasing you know the excretion of calcium in diuretics important very very important point to remember is that we increase the excretion of calcium and then we create you know the decrease in calcium in our bloodstream right so let’s discuss the major applications of loop diuretics so first of
All they are primarily used to treat um automatic state which basically means to you know treat edema of any form any fluid buildup so um specifically they are used for acute and chronic pulmonary edema in the lungs i think it’s usually given as iv to quickly relieve you know symptoms such as difficulty in breathing for these patients with pulmonary edema also
Because as i said before loop diuretics they produce prostaglandins which have vasodilatory action and that can also relieve symptoms of you know shortness of breath in patients with pulmonary edema and it’s used in treating other um automatic states such as you know in heart failure ascites basically if you have fluid buildup anywhere you could use um diuretics
So yeah treatment of mild to moderate heart failure very specific mild to moderate heart failure it’s also used in the treatment of hypercalcemia so hypercalcemia is you know increase in calcium and concentration in our blood because as we’ve discussed from the previous slide loop diuretics can increase the excretion of calcium so we could give give this drugs to
Patients with hypercalcemia okay so treatment of severe sorry that’s severe treatment of severe hypertension especially in hypertensive emergencies um we can give loop diuretics as well and they are used in hypertensive emergencies mainly because of their rapid onset of action right so adverse effects um electrolyte imbalances as we’ve seen in the previous slide
We create hyponatremia that’s a decrease in sodium hypocalcemia decrease in calcium hypokalemia and decrease in potassium and alkalosis and due to decrease in protons we also create hyperuricemia so this is the same with thiazide therapies the same mechanism same principle we create hyperuricemia when we use lip diuretics because they can inhibit or block the um
Organic anion transporters that transport uric acid from the bloodstream into the tribute which means that uric acid builds up in the body and that can exacerbate gout and you know things like that it can also be um oh adverse events it can cause acute hypovolemia because as i said these are very powerful um diuretics so they could really really decrease the
Fluid volume inside the body so acute hypovolemia we need to keep this in mind it can lead to cardiovascular complications because you know hypokalemia for example when we have less potassium that can trigger some arrhythmias in the heart um autotoxicity so this mainly applies to ethocrinic acid as i discussed you know two slides prior i think so ethanic acid
Is type of lip diuretic that has autotoxic effects so um it’s toxic to the ear and the audrey nerve that supplies you know the ear the innervates that you’re sorry supplies sorry um and the reason for that is because there are um sodium potassium including co-transporters inside their inner ear as well so these co-transporters are not just found in the tubule
They’re also found in the inner ear that’s why um ethanic acid you know and other loop diuretics can cause auto toxicity contraindications um obviously gout arthritis because as i said they can they can cause hyperuricemia
Transcribed from video
Diuretics part 2 – Loop Diuretics By Kristine Santos