Tutor : Anwesh Vats
Hello friends welcome to the channel gyri and sulci continuing with the pharmacology of diuretics today we are going to discuss about – i’m sparing diuretic first of all let’s break this world potassium speery and diuretic so diuretic other drugs which cause a net loss of sodium and water in the urine we know actually there’s loss of sodium and what i just
Follows it dose of sodium in the urine is known as natural unisys so diuretics are also known as natural genetics protection spell it means these drugs conserve reserve potassium inside the body by decreasing potassium excretion protection excretion in the urine is known as kelly unisys so we can see that these drugs decrease tell your uses we will talk about
Their potassium spinning action later in the video site of action of potassium sparing diuretic is destined to blue and collecting that of nephrons now we must understand that normal sodium reabsorption that occurs at collecting duct and distal tip you because when this sodium reabsorption is inhibited increased sodium passes in the unit and we get our desired
Diuretic action sodium absorption at the distal tubule and collecting that is physiologically under the influence of l dosterone that is it is normally controlled by aldosterone in the body and westerman is a potent mineralocorticoid hormone which is secreted by granulosa cells of adrenal cortex and its major function is as follows first it helps in sodium
Reabsorption second it promotes k+ excretion or secretion into the lumen and third h+ excretion or secretion into the lumen now let us observe a single cell tracing at the distal tubule or collecting that this cell is known as principle cell and those they won’t enters the principal self from interstitial site to be selected membrane and combines with an
Intra cellular receptor nunez mineralocorticoid receptor the mineralocorticoid receptor aldosterone complex translocates to the nucleus and promotes gene mediated mrna synthesis through transcription the mrna then directs synthesis of aldosterone induced proteins to translation the ai piece is the major protein responsible for all aldosterone actions it helps
In the translocation of na+ k+ atp’s and sodium channels from the cytosolic site where they are synthesized to basolateral membrane and luminal membrane respectively we can therefore say that a ips are responsible for the proper functioning of sodium potassium atpase and sodium channels we will now see the function of sodium potassium atpase it promotes a
Flux of three sodium ions for every two potassium ions influx into the cells this mainly serves two purposes first it decreases sodium concentration inside the cell which creates a sodium gradient on the luminal side that is increased sodium on the human side and decreased sodium inside the cell this results in easy entry of sodium into the cell through sodium
Channels these channels are also known as a miller light sensitive sodium channels and renal epithelial sodium channels and the second increased k+ concentration inside the cell so principal cells have high intracellular potassium concentration which causes easy secretion of k+ into the lumen through k+ channels also some amount of k+ e flux is there into
The interstitial space through he ki k+ channels for easy functioning of any k plus atp s because it requires adequate amount of k+ at the interstitial site of the basolateral membrane we can thus see sodium entry occurs at the luminal side through sodium channels and long the gradient created by sodium potassium atpase present at the basolateral membrane this
Sodium is transported to the interstitial site by na k plus atp s and this is how the sodium is reabsorbed now the sodium entry excludes chloride or any other anion present at the luminal side this causes development of partial depolarization on the luminal membrane now there is formation of negative lumen trans epithelial potential difference due to increased
Concentration of anions on the luminal side of the membrane it is approximately equal to minus 15 millivolts now this is a very very important point that development of this negative lumen to answer material potential difference is responsible for the proper functioning of k+ channels and h-class channels so sodium entry causes development of negative looming
Trans epithelial potential difference and this is responsible for secretion of k+ into the newman by k+ channels and secretion of h+ into the lumen by atp driven h+ pump by this information we now understand that without sodium reabsorption potassium and h+ secretion cannot take place and also we can understand that if sodium reabsorption increases luminal
Membrane is depolarized to a greater extent there is increased formation of negative lumen trans epithelial potential difference and pleasant expresses secreted into the lumen it is also important to notice that the source of h+ inside the principal cell is h2 co3 through an enzyme known as kalpana and hydrates and decreased activity of this enzyme causes
Less h+ inside the cell and less h+ secretion i shall talk more about it later in the video so whatever we have learnt is the normal function of aldosterone that is sodium reabsorption k+ secretion and h+ secretion into the lumen two major protection spamming diuretics are spironolactone which act at the em i mean ml o corticoid receptor and amiloride which
Act at the immuno light-sensitive sodium channels we can we shall see this later in the video let us now try to understand why is there a need for conserving potassium why a whole new class of drugs is made when we already had significant number of diuretics the other diuretics such as loop diuretic which act at medullary part of thick ascending limb of loop
Of henle carbonic anhydrase inhibitor which attacked pct thiazide which attacked cortical part of thick as in the name of loop of henle we can see that these diuretics act at such sites in the nephron which are proximal to keithley ncd and the increase the amount of sodium that arrives at the dtmc division there is increased sodium reabsorption at the distal
Tubules and collecting that compared to normal condition due to compensatory mechanisms it causes because we have already learnt that if sodium reabsorption is increased luminal membrane is depolarized to protect state and there’s formation of more negative lumen transit ethereal potential difference this causes increased secretion of k+ + h+ in the urine let us
Understand this with the help of an example in the normal condition suppose sodium hundred sodium arrives at the deviancy division out of which 40 na+ is reabsorbed and 60 na+ is secreted into the lumen to maintain the charge to 240 na + 20 k + + 20 x places secreted into the lumen now the second condition in which a diuretic is being used the decreased sodium
Reabsorption proximal to dt ncd region and hence increased sodium now arrives at dp ncd supposing this of 100 sodium now 200 sodium arrives at this region and 80 any place is absorbed and 120 any place is secreted in spite of increased sodium reabsorption now in place of 60 na + 120 na + is secreted into the lumen so our diuretic action has been achieved but
It is important to note that now 40 k+ + 4 th place is secreted into the lumen this increased potassium secretion in the lumen is the major cause of hypokalemia now important point for carbonic anhydrase inhibitor it is important to note that h+ can not be generated in the principal cells which are present in that dt and c d region because source of h+ is h2
Co3 which is converted to h less with the help of an enzyme carbonic anhydrase and this enzyme is inhibited by the carbonic anhydrase inhibitor so only k+ and no h+ can be secreted now in place of 40 k + 8 t k+ is secreted in the lumen so we see that if we take diuretic loop diuretic thiazide and carbonic anhydrase inhibitor at similar natural unitec doses
That is if both if all three of them secrete 120 na + carbonic anhydrase inhibitors causes maximum hypokalemia that is maximum carrier basis for the same degree of natural unisys so we see that there is a problem of hypokalemia with these diuretics and in order to prevent k+ loss we must use potassium sparing diuretic and how potassium sparing diuretic prevents
Potassium loss this is discussed with individual drugs coming to the classification of potassium spelling diuretic we have two groups aldosterone antagonist and the renal epithelial sodium channel inhibitor the first one include spironolactone and a player or not and the second one include and will arrive and triamterene it can also be remembered with the help
Of a mnemonic seat sat the first one is aldosterone antagonist we will be discussing this considering spironolactone as the third drug spironolactone is a competitive antagonist to aldosterone it means that it has a similar structure like aldosterone and binds to same site in the mineralocorticoid receptor the mineralocorticoid receptor spironolactone complex
Fails to translocate to the nucleus this inhibits the formation of aip aldosterone induced poutines na+ k+ atp’s and sodium channels are non-functional there is decreased reabsorption of sodium this causes no formation of negative lumen plants epithelial potential difference and the k+ channel and h+ pump fails to function therefore there is less k+ secretion
And less h+ equation and we see that potassium is spared which was our prime concern it is also important to note that the spironolactone is the only diuretic which act from the basolateral membrane which act from the basolateral membrane all other diuretics they first come in the lumen and they act from the luminal side coming to the uses of a spironolactone
It is used for its potential bearing action for this it is combined with a loop diuretic or thiazide to decrease potassium loss note that potassium swelling diuretics are not used alone it is not of high efficacy if we observed the total amount of sodium being reabsorbed at different portions of the nephron and the normal conditions we find that at ect there
65 to 70 percent reabsorption thick ascending limb 20 to 25% dt82 9% and cd 2 to 3% we see that very small fraction of sodium reaches dt and cb and preventing reabsorption at this site doesn’t make very big difference in the sodium status of the body ii lose dima these decreases sodium in the blood by promoting dialysis water content of the blood is also
Reduced blood volume decreases there is rapid mobilization of edema fluid into the blood it is mainly used in edema due to liver cirrhosis and nephrotic syndrome because in these conditions there is increased aldosterone levels it is also used in hypertension because they decrease blood volume decreases cardiac output and reduces blood pressure now here it is
Important to understand the meaning of the resistant hypertension and refractory edema if we use loot diuretics or thiazide in the treatment of edema or hypertension the aldosterone levels are increased due to compensate with mechanisms and try to reach to sodium levels in the body by increasing its reabsorption this results in development of a refractory edema
Or resistant hypertension this is treated by combining spironolactone to loop diuretic or thiazide because they suppress normal aldosterone action the other use is heart failure these drugs decreased blood volume decreases venous return and hence decreases 3-node when three load decreases heart has to do less work it is also used in primary hyperaldosteronism
Known as cons physics as the name suggests it is a condition where aldosterone is increased interactions of spironolactone potassium supplements plus pi 1 electron results in dangerous hypokalemia because both of them increases potassium in the body sp wind blows spironolactone action is inhibitors or aips plus a spironolactone results hyperkalemia why is in
Beta or ai be either drugs which block hera’s system every knee in shootings in l dosterone system so aldosterone is blocked and spironolactone also decreases aldosterone function so there is hyper telomere spironolactone increases plasma digoxin concentrations adverse effect of a spironolactone there is a risk of hypokalemia it increases on conversion to ash
Troy diode in males this results in kanyakumari erectile dysfunction loss of libido in female this results in breast tenderness menstrual irregularities now the second group having an epithelial sodium channel inhibitors as the name suggests these drugs block luminal sodium channels these channels are also known as mu low light sensitive sodium channels or renal
Epithelial sodium channels when these channels are plugged all the subsequent actions are similar to the spironolactone absolutely similar why because in this condition also there is no formation of negative lumen trans epithelial potential difference the sodium channels actually the potassium channels and the h+ pump they both and not function and if they do
Not function there is decreased potassium secretion and decreased h+ situation and we see that potassium is spared which was our primary concern the users of renal epithelial sodium channel blockers i similar to spironolactone absolutely similar there is one more use in cystic fibrosis where they increase fluidity of a respiratory secretions interactions are
Also similar and they have less adverse effects like nausea diarrhea and headache thank you for watching that’s all for today hit the like and subscribe button and stay tuned for the journey of advanced cognition
Transcribed from video
Potassium Sparing Diuretic- Spironolactone and Amiloride By GYRI N SULCI
