February 1, 2023

High Ceiling Loop Diuretics – Furosemide (Mechanism of Action, uses and Adverse Effects) by Dr. Shikha Parmar

Hello students in today’s video we will discuss pharmacology of high ceiling loop diuretics and before starting discussing loop diuretics let’s first quickly revise function of kidneys and role of diuretics now look at this diagram uh this diagram shows a structure of nephron and these are the peritubular capillaries and these peritubular capillaries are

Also termed as vasa recta now the most important function of kidneys is to filter and purify blood and remove waste toxic products of the body in the form of urine now structural and functional unit of kidney is the nephron now each kidney consists of around 1 million nephrons and the main function of kidney is to produce urine now there are three main steps

In the formation of urine namely the glomerular filtration then selective reabsorption and secretion now blood in the glomerulus is filtered and the filtrate passes into the tubule of nephron now around 180 liters of filtrate is produced daily by both the kidneys now this filtrate uh consists of more than 90 water uh then waste toxic products like urea uric

Acid creatinine along with the useful substances like glucose amino acids vitamins electrolytes like sodium potassium calcium magnesium etc now all these essential substances that are required along with the water is reabsorbed it is reabsorbed from the lumen into the luminal epithelial cells and from the luminal epithelial cells all the required substances

They move to the peritubular capillaries or vasa recta and thus all these required substances they reach the blood circulation now thus around 99 of the filtrate is returned to the blood circulation and this reabsorption of filtrate maintains the blood volume and uh the ph of blood now reabsorption of water primarily depends on the reabsorption of sodium

Now water is reabsorbed iso osmotically that is for every molecule of sodium that is reabsorbed is accompanied by reabsorption of molecule of water and thus when the sodium is reabsorbed uh the water follows that means water follows higher sodium concentration now very important to remember that out of 180 liter of filtrate only one to one point five liter of

Urine is produced that mean uh rest of the filtrate that is 99 of the filtrate is reabsorbed in this renal tubule at the different sites like uh the proximal convoluted tubule here ah 65 to 70 percent of sodium and water is reabsorbed ah then this is the descending loop of henle here 15 percent of water is reabsorbed ah this is the ascending limb of loop of

Henle here around 25 percent of sodium is reabsorbed now this is an early distal tubule here around five percent of sodium and eight percent of uh the content water content of the filtrate is reabsorbed uh now this is the late distal convoluted tubule and collecting duct here around 3 percent of sodium is absorbed and apart from this water is also absorbed now

Absorption of water is tightly regulated by anti-diuretic hormone in the collecting duct whereas absorption reabsorption of sodium is regulated by the aldosterone so this is how at different sites uh water and sodium is reabsorbed from the renal tubule into the renal into the luminal epithelial cells and from the luminal epithelial cells sodium along with the

Water moves into the peritubular capillaries or vasa recta and from here ah sodium as well as water they reach the blood circulation and this is how the blood volume and the ph of blood is maintained now uh diuretics are the agents that act upon kidney and they increase the volume of urine thereby reducing the volume of blood now what the diuretics do is this that

Diuretics decrease uh the reabsorption of sodium as well as a reabsorption of water from the lumen into the peritubular capillaries thus diuretics are the agents that cause net loss of sodium and water in the urine now since these diuretics they increase the volume of urine they reduce the volume of blood they are primarily useful in the management of edema and

Hypertension now let’s talk about high ceiling loop diuretics these are sulfur mole derivatives examples are furosemide bu metanite dosamite and the prototype drug is furosemide now diuretics as discussed earlier are the agents that act on kidneys to make more urine and these agents they cause a net loss of sodium and water in the urine that means they prevent

The reabsorption of sodium and water from the tubular lumen into the peritubular capillaries now furysemide is a loop diuretic as its site of action is ascending limb of loop of henle and these agents are also called as a high ceiling diuretics since these agents are more effective than the other diuretics now fury semi primarily decreases sodium chloride

And potassium reabsorption from the tubule of nephron into the peritubular capillaries it is an inhibitor of sodium potassium chloride or transport now a furosemide is a rapidly acting highly efficacious overall diuretic and diuretic response increases with increasing dose and furosemide is effective even in patients with relatively severe renal failure and

Furysimide has a prompt onset of action iv furosemide reduces diuretic effect in two to five minute intramuscularly produces its effect in 10 to 20 minutes and the oral dosage form produces the response in 20 to 40 minutes it has a short duration of action of about three to six hours uh now let’s uh discuss ah mechanism of action of high ceiling loop diuretics

Now major site of action of these diuretics is the thick ascending limb of loop of henle now look at this diagram uh it shows a lumen of nephron then luminal epithelial cell of ascending limb of lupunella and peritubular capillaries now this luminal epithelial cell has two surfaces one is the apical surface this is the apical surfaces facing the lumen of nephron

And this is the basal lateral surface close to ah vasa recta that is a peritubular capillaries now this diagram shows sodium potassium chloride co transporter now this protein is responsible for the transportation of sodium chloride and potassium from the filtrate to the epithelial cell and these ions that is a sodium chloride and potassium they are further

Transported to the blood that means further transporter to the peritubular capillaries now very important to remember that around 25 percent of sodium is reabsorbed in thick ascending limb of loop of henle and furosemide inhibits uh sodium potassium to chloride co transport and this prevents it inhibits reabsorption of sodium and there is a net loss of sodium

And water in the urine now this increases the volume of urine and therefore furysemite by inhibiting sodium potassium 2 chloride co transport exerts its diuretic effect it increases the volume of urine now intravenous furosemide also increases local prostaglandin synthesis now as we all know these prostaglandins they are vasodilators they dilate the renal

Blood vessels and therefore furosemide increases renal blood flow apart from this ah there is dilation of veins now dilation of veins causes increase in systemic venous capacitance and dilation of other veins like superior vena cava inferior vena cava decrease left ventricular filling pressure and this provides relief in left ventricular failure and associated

Pulmonary edema now a furosemide also increases excretion of calcium and magnesium whereas it decreases the excretion of uric acid now this was about the prototype drug that is the furosemide other loop diuretics also exhibits the same mechanism of action now talking about the bumatinide it is 40 times more potent than furysemite and bumetanide is used in cases

Not responding to furosemide and in patients not tolerating furosemide apart from that tosamite is three times more potent than furosemide ah now let’s talk about the therapeutic uses of loop diuretics now first and the foremost is used in edema as uh loop diuretics reduce the blood volume uh loop diuretics are effective in adem irrespective of the etiology of

Edema uh they are very useful in pseurotic hepatic and renal edema now loop diuretics are the drug of choice in nephrotic and resistant edema now in impending or suspected case of acute renal failure loop diuretics may reduce uh the need of dialysis now apart from this as discussed earlier ah furosemide dilate the veins it dilates superior vena cava and inferior

Vena cava reducing the left ventricular filling pressure and provide a quick relief in left ventricular failure and associated pulmonary edema now apart from this very important diuretics reduce the blood volume fall in the blood volume reduces cardiac output now as we all know blood pressure is equal to cardiac output into peripheral resistance fallen blood

Volume reduces uh cardiac output reduces blood pressure so diuretics are useful in the management of hypertension now loop diuretics are effective in the management of hypertension in the presence of renal insufficiency congestive heart failure and also in hypertensive crisis ah now let’s understand the adverse effects of loop diuretics now one of the major

Adverse effect is hypokalemia now loop diuretics as we’ve already discussed inhibit reabsorption of sodium in ascending limb of loop of henle so sodium is not reabsorbed uh from the loop of henle so sodium is passed in the filtrate and this filtrate which is rich in the sodium reaches the distal convoluted tubule and the collecting duct and there the sodium

Is reabsorbed in exchange of potassium so sodium is reabsorbed while the potassium is excreted and therefore since this potassium is excreted in the urine this results in hypokalemia and additional use or adjuvant use of potassium sparing diuretics can reduce the incidence of hypokalemia now rarely these drugs can cause autotoxicity and hypokalemia has been

Found to reduce the secretion of insulin and which can cause hyperglycemia drop in the blood volume can cause hypovolemia and loss of electrolytes in urine can cause electrolyte imbalance loss of calcium causes hypocalcemia then hyperuricemia is also observed with these drugs and since these drugs are sulphur drugs allergy to sulfur drugs can also occur so this

Is in brief on pharmacology of loop diuretics and please note that the information provided in the seed video is exclusively for students from their examination point of view so kindly consult your physician with regards to the clinical use of diuretics now if you find the video useful kindly like subscribe and share this video thanks for watching this video you

Transcribed from video
High Ceiling Loop Diuretics – Furosemide (Mechanism of Action, uses and Adverse Effects) By Dr.Shikha Parmar Classes