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Diuretics also known as water pills simply promote the elimination of water review the basic physiology of nephron so as you may already know nephron is the distinct regions that has specific function first we have bowman’s capsule the afferent arteriole where components of the blood get filtered out of the glomerulus by efferent arteriole next glomerular filtrate which
Contains through proximal convoluted tubule in this region almost 100% of the amino about 65% of electrolytes such as sodium and potassium along with water tend to follow the next major region through which the filtrate travels is the kidney now the descending limb has walls permeable to water but impermeable making the filtrate more concentrated on the other hand the
Opposite takes place sodium but impermeable to water so as the filtrate travels up about 25% the sodium-potassium-2-chloride cotransporter next the filtrate travels chloride gets reabsorbed mainly via sodium-chloride cotransporter this part more diluted finally the filtrate travels through the late distal tubule the intercalated cells now the functions of the principal
Cells are regulated by potassium secretion and antidiuretic hormone which increases water intercalated cells are regulated by aldosterone but their primary function let’s talk about diuretics diuretics simply increase the volume of produced us to remove salt and water from the body which makes them very useful for based on their mechanism of action diuretics can be divided
Into five major diuretics potassium sparing diuretics and class in more detail starting with carbonic anhydrase inhibitors carbonic reducing reabsorption of bicarbonate in the proximal convoluted tubule now exactly do that so to the left of the epithelial cell which contains blood vessels now here bicarbonate reabsorption is initiated by the action of sodium-hydrogen ion
Exchanger which allows pumped by sodium potassium atpase out of combines with the luminal bicarbonate ion to form carbonic acid carbonic anhydrase now carbon dioxide enters the epithelial cell by simple anhydrase finally intracellular carbonic acid dissociates to form hydrogen ion which can be transported by sodium-hydrogen exchanger to the lumen and enzyme and as a result
Bicarbonate gets retained in the lumen of carbonic anhydrase leads to significant reduction in proximal the reason why the diuretic effect is only mild is because the majority of by distal parts of the nephron however this late reabsorption also associated with this class additionally because bicarbonate is a leads to increase in plasma acidity known as metabolic acidosis
Now one of due to its relatively weak diuretic effect other pharmacologic actions now let’s move on to loop diuretics so loop in the ascending limb where they inhibit sodium-potassium-2-chloride diuretic effect because as much as 25% limb and at this point other parts of nephron can no longer compensate for the thick ascending limb to see what exactly happens there so upon
Reaching get reabsorbed by sodium-potassium-2-chloride cotransporter this among other potassium also tends to leak out through potassium channels back into the lumen lumen produces electrical driving force for paracellular reabsorption of blocks sodium-potassium-2-chloride cotransporter we not only lose sodium and potassium loss takes place mainly in the late distal tubule
This more later drugs that belong to this furosemide and torsemide now when it comes to side effects besides causing blood volume also known as acute hypovolemia this can lead to hypotension sodium-potassium-2-chloride cotransporter which their use has been associated with the damage to the hearing also referred to compete with a transport of uric acid at the same site thus
Blocking its symptoms now let’s move on to thiazide diuretics so thiazides are probably the distal tubule where they increase sodium chloride excretion by inhibiting reabsorbed before reaching the distal tubule in general thiazides produce vasodilation which reduces peripheral vascular resistance by mechanism that cell of the early distal tubules to see what exactly happens
There so here inside the cell sodium gets transported to the blood via the sodium-potassium when thiazide diuretic comes around and inhibits this sodium-chloride ultimately since water follows the salt we get increased urine output drugs that belong to this class include chlorothiazide and hydrochlorothiazide which are metolazone and indapamide which are often referred to
As thiazide-like drugs because they don’t have true thiazide ring but share the same mechanism of cause hypokalemia which results from increased delivery of sodium can also lead to hyperuricemia by interfering with uric acid transport excretion leading to hypocalcemia thiazides on the other hand can cause be responsible for this first takes place in the proximal tubule
Where thiazide reabsorption which in turn produces electrical gradient which leads to exchanger located on the basolateral side of the distal tubule so because concentration of sodium inside the cell which then in turn causes the sodium then excreted into the bloodstream lastly thiazides may worsen glucose leading to hyperlipidemia some of the mechanisms thought to be
Responsible for well as increased hepatic glucose production now let’s move on to potassium-sparing diuretics so potassium-sparing diuretics work primarily in potassium excretion although these potassium-sparing agents are relatively now let’s zoom in on the collecting tubule principal cell to see what potassium as well as sodium-potassium atpase on the basolateral side
Under transported by sodium-potassium atpase into the bloodstream in exchange for electrical potential is generated and chloride is driven into the bloodstream cell through potassium channel so as a side note here this illustration should loss so increased sodium load caused by loops and thiazides enhances sodium force for increased potassium secretion and ultimately lower
Potassium levels in potassium-sparing diuretics agents within this class can be separated into two works simply by blocking sodium channel which results in decreased sodium second group on the other hand works by antagonizing aldosterone aldosterone is stimulates transcription of genes encoding sodium channel and sodium aldosterone leads to increased reabsorption of sodium
And water and for binding to that intracellular receptor the result is reduced synthesis potassium atpases which ultimately leads to potassium retention drugs that belong to this group include spironolactone and eplerenone now when it especially when these diuretics are combined with other drugs that can also our natural steroid hormones spironolactone can stimulate receptors
For testosterone and gynecomastia in males now before we end i wanted to briefly interfering directly with osmosis as you water has tendency to move across membrane from lower osmolarity or the agents are filtered from glomerulus they are very water soluble or hydrophilic tubular fluid and thus decreased water reabsorption sodium excretion they’re not very effective for
Treating edema caused by pressure promotion of urinary excretion urine production in patients with acute kidney failure side effects use of osmotic diuretics can lead to significant fluid changes such that i wanted to thank you for watching i hope you enjoyed this lecture and as
Transcribed from video
Pharmacology – DIURETICS (MADE EASY) By Speed Pharmacology