Diuretics
- 1. LECTURE NO-26 UNIT – II 10 Hours Drugs acting on Cardiovascular system b) Diuretics: Carbonic anhydrase inhibitors: Acetazolamide, Methazolamide, Dichlorphenamide. Thiazides: Chlorthiazide, Hydrochlorothiazide, Hydroflumethiazide, Cyclothiazide Loop diuretics: Furosemide, Bumetanide, Ethacrynic acid. Potassium sparing Diuretics: Spironolactone, Triamterene, Amiloride. Osmotic Diuretics: Mannitol Diuretics S D Magar PRCOP October 14, 2021 1
- 2. Drugs acting on Cardiovascular system b) Diuretics: MC2.pdf Diuretics S D Magar PRCOP October 14, 2021 2
- 3. Diuretics S D Magar PRCOP October 14, 2021 3 Diuretics ("water pills") increase the kidneys' excretion of salt (sodium) and water, decreasing the volume of fluid in the bloodstream and the pressure in the arteries. Diuretics are the oldest and most studied antihypertensive agents. Diuretics
- 4. Diuretics S D Magar PRCOP October 14, 2021 4 Drugs promoting urine output are known as diuretic drugs, which refer only to those agents that act directly on the kidneys. These drugs primarily increase the excretion of water and ions like sodium (Na +), chloride ( Cl- ), or bicarbonates ( HCO3-) from the body. Glomerular filtration , tubular reabsorption , and tubular secretion in kidneys determine the excretion of substances. Tubular reabsorption is a process which involves active transport of electrolytes and other solutes from tubular urine to tubular cells, and then to extra cellular fluid. As a result, glomerular filtration is increased. The mechanism of action of diuretic drugs also involves a decrease in tubular reabsorption. However, these drugs have no effect on glomerular filtration rate or on the action of Anti-Diuretic Hormone (ADH) on the distal portion of nephron. Diuretics effectively treat cardiac oedema (accumulation of fluid in extra vascular tissues), especially the one which is associated with congestive heart failure. It is also employed in the treatment of various disorders like nephrotic syndrome, diabetes insipidus, hypertension, nutritional oedema, oedema of pregnancy, and liver cirrhosis. They also decrease the intracellular and cerebrospinal fluid pressure.
- 5. Diuretics S D Magar PRCOP October 14, 2021 5 Carbonic anhydrase inhibitors: Acetazolamide, Methazolamide, Dichlorphenamide. Thiazide: Chlorthiazide, Hydrochlorothiazide, Hydroflumethiazide, Cyclothiazide Loop Furosemide, Bumetanide, Ethacrynic acid Potassium-sparing Spironolactone, Triamterene, Amiloride. Osmotic Diuretics: Mannitol CLASSIFICATION
- 6. Diuretics S D Magar PRCOP October 14, 2021 6
- 7. Diuretics S D Magar PRCOP October 14, 2021 7 Study of Individual Drugs The following carbonic anhydrase inhibitors are discussed below: 1) Acetazolamide, 2) Methazolamide, 3) Dichlorphenamide. Acetazolamide Acetazolamide is the prototype carbonic anhydrase inhibitor. This type of diuretics inhibit carbonic anhydrase enzyme in the membrane and cytoplasm of epithelial cell.
- 8. Diuretics S D Magar PRCOP October 14, 2021 8 Mechanism of Action Carbonic anhydrase enzyme is inhibited by acetazolamide; thus, preventing the formation of H+ ions. As a result, the exchange of Na + ions with H+ ions does not take place. The Na+ and HCO3¯ ions undergo urinary excretion. Increased exchange of Na + and K+ ions in the distal convoluted tubule resulted in the loss of K+ ions. On the whole, the urine produced is alkaline in nature as the Na +, K+, and HCO3¯ ions are lost. Uses Acetazolamide is self-limiting in nature. It produces adverse effects like acidosis and hypokalaemia. Thus, it is not used as a diuretic anymore; instead, it is currently being employed in the treatment of: 1) Glaucoma: As an adjuvant to other ocular hypotensives. 2) Alkalinising Urine: For urinary tract infection or to promote excretion of certain acidic drugs. 3) Epilepsy: As an adjuvant in absence seizures when primary drugs are not fully effective. 4) Acute Mountain Sickness: Symptomatic relief as well as prophylaxis.
- 9. Diuretics S D Magar PRCOP October 14, 2021 9 Methazolamide Methazolamide is a carbonic anhydrase inhibitor. It is used as a diuretic and for treating glaucoma
- 10. Diuretics S D Magar PRCOP October 14, 2021 10 Mechanism of Action Methazolamide is a potent inhibitor of carbonic anhydrase enzyme. It inhibits the enzyme in the ciliary processes of eye , thus reduces aqueous humor secretion by delaying the formation of bicarbonate ions and reducing sodium and fluid transport. Uses 1) It is used for treating chronic open-angle glaucoma and acute angle –closure glaucoma. 2) It is used in cystoid macular oedema and pseudotumour cerebri.
- 11. Diuretics S D Magar PRCOP October 14, 2021 11 Dichlorphenamide Dichlorphenamide is a carbonic anhydrase inhibitor. It is used for treating glaucoma.
- 12. Diuretics S D Magar PRCOP October 14, 2021 12 Mechanism of Action Carbonic anhydrase inhibitors decrease intraocular pressure by partially suppressing aqueous humor secretion. The mechanism behind this is however not known completely. It has been proved that HCO3− ions are formed in the ciliary body by hydration of carbon dioxide catalysed by carbonic anhydrase . The HCO3− ions formed diffuse into the hypertonic posterior chamber containing more Na + and HCO3− ions than the plasma . Then, w ater is attracted to the posterior chamber by osmosis, thereby causing a pressure drop. Uses 1) It is used for adjunctive treatment of chronic simple (open -angle) glaucoma and secondary glaucoma. 2) It is used pre-operatively in acute angle closure glaucoma in which surgery is delayed so that the intraocular pressure decreases
- 13. Diuretics S D Magar PRCOP October 14, 2021 13 THIAZIDES Introduction Thiazide diuretics are referred to as moderately efficacious diuretics as a majority (nearly 90%) of the filtered sodium is already re -absorbed before it reaches the distal tubule. These diuretics comprise of two distinct groups: 1) Diuretics containing a benzothiadiazine ring; these agents are referred to as thiazide diuretics and include agents like chlorothiazide, hydrochlorothiazide, polythiazide, etc. 2) Diuretics not containing benzothiadiazine ring , but containing an un - substituted sulphonamide group ; these agents are termed as thiazide-like diuretics and include chlorthalidone, indapamide, metolazone, etc.
- 14. Diuretics S D Magar PRCOP October 14, 2021 14 Mechanism of Action Thiazide diuretics inhibit the reabsorption of Na+ and Cl– ions at the first portion of the distal tubules. They block a Na + Cl– symport in the luminal membrane of the epithelial cells in the distal convoluted tubule, thus, blocking the reabsorption of NaCl. Thiazide diuretics exert a minor effect on NaCl reabsorption in the proximal tubule. They block the entry of Na + ions and enhance the activity of Na+-Ca++ exchanger in the basolateral membrane of epithelial cells. Thus, the reabsorption of Ca++ ions in the distal convoluted tubule is enhanced . Thiazide diuretics also inhibit the carbonic anhydrase enzyme. The resulting diuretics are supplemented by increased excretion of potassium, bicarbonates, chloride, and water The anti-hypertensive action of thiazide diuretics is influenced by the following two factors: 1) Reduced plasma concentration of sodium due to its depletion, and 2) Decrease in peripheral resistance
- 15. Diuretics S D Magar PRCOP October 14, 2021 15 Mechanism of Action
- 16. Diuretics S D Magar PRCOP October 14, 2021 16 Study of Individual Drugs The following thiazide diuretics are discussed below: 1) Chlorothiazide, 2) Hydrochlorothiazide, 3) Hydroflumethiazide, 4) Cyclothiazide. Chlorothiazide Chlorothiazide is 4H-1,2,4-benzothiadiazine 1,1-dioxide in which the hydrogen at position is substituted by chlorine and that at position 7 is substituted by a sulfonamide group. A diuretic, it is used for treatment of oedema and hypertension. It has a role as a diuretic and an antihypertensive agent.
- 17. Diuretics S D Magar PRCOP October 14, 2021 17 Like other thiazides, chlorothiazide promotes water loss from the body (diuretics). It inhibits Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Mechanism of Action Uses 1) It is used as an adjunct in oedema related to congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. 2) It is used alone in the management of hypertension, but in combination with other antihypertensive drugs in the more severe forms of hypertension.
- 18. Diuretics S D Magar PRCOP October 14, 2021 18 Hydrochlorothiazide Hydrochlorothiazide is a benzothiadiazine that is 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1- dioxide substituted by a chloro group at position 6 and a sulfonamide at 7. It is a benzothiadiazine, a sulfonamide and an organochlorine compound. Hydrochlorothiazide reduces the reabsorption of electrolytes from renal tubules. This causes an increase in the excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium.
- 19. Diuretics S D Magar PRCOP October 14, 2021 19 Uses 1) It reduces sodium and water retention in preeclampsia during pregnancy. 2) It is used for the management of hypertension, and as an adjunct in oedema related to congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Hydrochlorothiazide inhibits the Na+-Cl– symporter in the distal convoluted tubule (responsible for 5% of total sodium reabsorption), thus blocks the reabsorption of water in nephron s. Hydrochlorothiazide prevents the reabsorption of sodium and water from the distal convoluted tubule, allowing for the increased elimination of water in the urine. Mechanism of Action
- 20. Diuretics S D Magar PRCOP October 14, 2021 20 Hydroflumethiazide Hydroflumethiazide is a benzothiadiazine consisting of a 3,4-dihydro-HH-1,2,4 benzothiadiazine bicyclic system dioxygenated on sulfur and carrying trifluoromethyl and aminosulfonyl groups at positions 6 and 7 respectively. A diuretic with actions and uses similar to those of hydrochlorothiazide. It has a role as a diuretic and an antihypertensive agent. It is a benzothiadiazine and a thiazide.
- 21. Diuretics S D Magar PRCOP October 14, 2021 21 Mechanism of Action Hydroflumethiazide inhibits the Na +-Cl– symporter in the distal convoluted tubule (responsible for 5% of total sodium reabsorption), thus blocks the reabsorption of water in nephrons. The Na +-Cl– symporter transports Na+ and Cl–ions from the lumen into the epithelial cell lining the distal convoluted tubule. A sodium gradient established by Na +-K+ ATPases on the basolateral membrane provides energy for transporting Na+ and Cl– ions. Uses 1) It is used as an adjunct in oedema related to congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. 2) It is used alone in the management of hypertension, but in combination with other antihypertensive drugs in the more severe forms of hypertension.
- 22. Diuretics S D Magar PRCOP October 14, 2021 22 Cyclothiazide is 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide substituted at positions 3, 5 and 6 by a 2-norbornen-5-yl group, chlorine, and a sulfonamide group, respectively. A thiazide diuretic, it has been used in the management of hypertension and oedema. Cyclothiazide
- 23. Diuretics S D Magar PRCOP October 14, 2021 23 As a diuretic, cyclothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like cyclothiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. Mechanism of Action Uses 1) It is used as an adjunctive therapy in oedema related to congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. 2) It is used alone in the management of hypertension, but in combination with other antihypertensive drugs in the more severe forms of hypertension.
- 24. Diuretics S D Magar PRCOP October 14, 2021 24 Loop diuretics Loop or high efficacy diuretics exhibit their effects by acting on the ascending limb of the loop of Henle. They are the most effective of all diuretic agents since the reabsorptive capacity of the ascending limb of the loop of Henle is very high. The loop diuretics are also known as high ceiling diuretics, or Na+-K+-2Cl– cotransporter inhibitors.
- 25. Diuretics S D Magar PRCOP October 14, 2021 25 Mechanism of Action Loop diuretics inhibit the Na +-K+-2Cl– symport in the luminal membrane of the Thick Ascending Limb (TAL) of loop of Henle, thus inhibit the reabsorption of NaCl and KCl. The TAL is responsible for the reabsorption of 35% of filtered sodium and there no downstream compensatory reabsorption mechanisms, thus the loop diuretics are highly efficacious and are also termed as high ceiling diuretics.
- 26. Diuretics S D Magar PRCOP October 14, 2021 26 The Na+-K+-2Cl– symport along with the sodium pump generate a positive lumen potential that initiates the reabsorption of Ca ++ and Mg ++ ions. Therefore, the inhibition of Na+-K+- 2Cl– symport also results in the inhibition of Ca++ and Mg++ ions reabsorption. Loop diuretics also have direct effect on vasculature including increased renal blood flow and increased systemic venous capacitance through unknown mechanisms (prostaglandin-mediated probably). Study of Individual Drugs The following loop diuretics are discussed below: 1) Furosemide, 2) Bumetanide, 3) Ethacrynic acid.
- 27. Diuretics S D Magar PRCOP October 14, 2021 27 Furosemide Furosemide is a benzoic -sulfonamide-furan with fast onset and short duration of action. It is used for treating oedema and chronic renal insufficiency. Furosemide is a chlorobenzoic acid that is 4-chlorobenzoic acid substituted by a (furan-2- ylmethyl)amino and a sulfamoyl group at position 2 and 5 respectively. It is a diuretic used in the treatment of congestive heart failure. It has a role as a xenobiotic, an environmental contaminant and a loop diuretic. It is a sulfonamide, a chlorobenzoic acid and a member of furans.
- 28. Diuretics S D Magar PRCOP October 14, 2021 28 4-chloro-2-(furan-2-ylmethylamino)-5-sulfamoylbenzoic acid
- 29. Diuretics S D Magar PRCOP October 14, 2021 29 Mechanism of Action Furosemide competitively inhibits the binding of Cl– ions at the Na+-K+-2Cl– cotransporter in the thick ascending limb of Henle’s Loop. This in turn inhibits the reabsorption of water in nephron. As a result, the sodium transport from the lumen of the loop of Henle into the basolateral interstitium is prevented. Hence, the hypertonicity of lumen increases (due to more sodium) while that of the interstitium decreases (as the sodium is lesser). This altered concentration of sodium reduces the osmotic gradient for the reabsorption of water all over the nephron. Uses 1) It is used for the treatment of oedema related to congestive heart failure, liver cirrhosis, and renal disease. 2) It is also used either alone or with other antihypertensive agents for the management of hypertension. Toxicity Summary Clinical consequences from overdose depend on the extent of electrolyte and fluid loss and include dehydration, blood volume reduction, hypotension, electrolyte imbalance, hypokalemia, hypochloremic alkalosis, hemoconcentration, cardiac arrhythmias
- 30. Diuretics S D Magar PRCOP October 14, 2021 30 Bumetanide Bumetanide is a loop diuretic of sulfamyl category. It is used for treating heart failure. It is used by the people who are not responding to high doses of furosemide or other diuretics. Bumetanide is a member of the class of benzoic acids that is 4-phenoxybenzoic acid in which the hydrogens ortho to the phenoxy group are substituted by butylamino and sulfamoyl groups. Bumetanide is a diuretic, and is used for treatment of oedema associated with congestive heart failure, hepatic and renal disease. It is a sulfonamide, an amino acid and a member of benzoic acids.
- 31. Diuretics S D Magar PRCOP October 14, 2021 31 Mechanism of Action Bumetanide inhibits renal cAMP and/or the Na+-K+ ATPase pump. It also inhibits the active reabsorption of Cl– and Na+ ions i n the ascending loop of Henle, thus disturbing the electrolyte transfer in proximal tubule. This causes excretion of Cl– and Na+ ions, and water, and results in diuresis. Uses It is used for treating oedema related to congestive heart failure, hepatic and renal disease including nephrotic syndrome. Toxicity Summary Overdosage can lead to acute profound water loss, volume and electrolyte depletion, dehydration, reduction of blood volume and circulatory collapse with a possibility of vascular thrombosis and embolism. Electrolyte depletion may be manifested by weakness, dizziness, mental confusion, anorexia, lethargy, vomiting and cramps. Treatment consists of replacement of fluid and electrolyte losses by careful monitoring of the urine and electrolyte output and serum electrolyte levels.
- 32. Diuretics S D Magar PRCOP October 14, 2021 32 Ethacrynic Acid Ethacrynic acid is an unsaturated ketone derivative of aryloxyacetic acid without a sulfonamide substituent. It belongs to the class of loop diuretics. Ethacrynic Acid is an unsaturated ketone derivative of aryloxyacetic acid without a sulfonamide substituent belonging to the class of loop diuretics. Ethacrynic acid is extensively bound to plasma proteins; both ethacrynic acid in its unchanged form as well as its metabolites are excreted in bile and urine.
- 33. Diuretics S D Magar PRCOP October 14, 2021 33 Mechanism of Action Ethacrynic acid blocks Na+-K+-2Cl– symport in the ascending limb of Henle loop and in the proximal and distal tubules. This causes excretion of Na+, K+, and 2Cl– ions, increases urinary output, and decrease d extracellular fluid. Ethacrynic acid also reduces the blood pressure by lowering the plasma and extracellular fluid volume, which in turn reduces the cardiac output . Ultimately, the cardiac output returns to normal with a reduction in peripheral resistance. Uses It is used in the treatment of high blood pressure and oedema caused by diseases like congestive heart failure, liver failure, and kidney failure. Toxicity Summary Overdosage may lead to excessive diuresis with electrolyte depletion.
- 34. Diuretics S D Magar PRCOP October 14, 2021 34 POTASSIUM SPARING DIURETICS Introduction Potassium sparing diuretics include triamterene and amiloride. Only less than 5% of total filtered (amount of a substance filtered per unit time) Na+ load is excreted by the use of these agents, and this is its maximal effect. As the name suggests, these agents ( triamterene and amiloride) form sparing diuretics for K + ions contrary to loop and thiazide diuretics, which are K+ ion depleting agents. Mechanism of Action The late distal tubule and the collecting duct comprise of principal cells and intercalated cells. A Na + ion channel, present in the luminal membrane of the principal cells, forms a pathway for the entry of Na + ions into the cells mediated by the basolateral Na+ ion pump, against the electrochemical gradient.
- 35. Diuretics S D Magar PRCOP October 14, 2021 35 The luminal membrane is highly permeable to Na + ions, thereby, creating a lumen negative trans- epithelial potential difference. This potential difference between the lumen and epithelium forms an important driving force enabling the secretion of K+ ions into the lumen. The H+ ion is secreted into the tubular lumen by the intercalated cells. This secretion is mediated by the H +-ATPase pump or proton pump and the lumen negative trans-epithelial voltage difference acts as the driving force. The potassium sparing diuretics (triamterene and amiloride) act by blocking the Na+ ion channels in the luminal membrane of the principal cells (within the late distal tubule and collecting duct). This inhibits the transport of Na + ions through the cells, thereby, reducing the luminal secretion of H + ions from the intercalated cells and K + ions from the principal cells. The net effect is increase in the excretion of Na+ ions through urine, and retention of K+ and H+ ions.
- 36. Diuretics S D Magar PRCOP October 14, 2021 36
- 37. Diuretics S D Magar PRCOP October 14, 2021 37 Study of Individual Drugs The following potassium sparing diuretics are discussed below: 1) Spironolactone, 2) Triamterene, 3) Amiloride. Spironolactone Spironolactone is a potassium sparing diuretic which acts by antagonizing aldosterone in the distal renal tubules. Spironolactone is a steroid lactone that is 17alpha-pregn-4-ene-21,17-carbolactone substituted by an oxo group at position 3 and an alpha-acetylsulfanyl group at position 7. It has a role as a diuretic, an aldosterone antagonist, an antihypertensive agent, an environmental contaminant and a xenobiotic. It is a steroid lactone, an oxaspiro compound, a thioester and a 3-oxo-Delta(4) steroid.
- 38. Diuretics S D Magar PRCOP October 14, 2021 38 Mechanism of Action Spironolactone is a specific pharmacologic antagonist of aldosterone. It acts by competitive binding of receptors at the aldosterone -dependent Na+- K+ exchange site in the distal convoluted renal tubule. Spironolactone increases the amounts of Na+ ions and water to be excreted, while retaining the K+ ions. Through this mechanism, spironolactone acts as a diuretic as well as an antihypertensive drug. It is administered either alone or along with other diuretics that act more proximally in the renal tubule. Aldosterone improves the expression of Na +-K+- ATPase and the Na+ ion channel involved in Na+-K+ transport in the distal tubule by interacting with a cytoplasmic mineralocorticoid receptor. Spironolactone binds to t his receptor and inhibits aldosterone actions on gene expression. Aldosterone hormone retains Na+ ions and excrete s K+ ions in the kidneys. Uses 1) It is used for treating refractory oedema in patients having failure, nephrotic syndrome, or hepatic cirrhosis. 2) It is also used for treating hypokalaemia, Conn’s syndrome, and low –renin hypertension
- 39. Diuretics S D Magar PRCOP October 14, 2021 39 Triamterene Triamterene is a potassium -sparing diuretic. It is used with thiazide diuretics in the treatment of hypertension and swelling. Triamterene is a pteridine derivative with potassium-sparing diuretic property.
- 40. Diuretics S D Magar PRCOP October 14, 2021 40 Mechanism of Action Triamterene blocks the sodium-potassium exchange pump (Na-K-ATPase) in the luminal membrane of principal cells in the late distal tubule, cortical collecting tubule and collecting duct in the kidney. This reversible inhibition of the electrogenic sodium transport decreases the lumen-negative transepithelial potential difference and thus reduces the driving force for K+ movement into the tubular lumen resulting in the inhibition of sodium reabsorption in exchange for K+ and H+. Uses 1) It is used for treating oedema related to congestive heart failure, liver cirrhosis, and nephrotic syndrome. 2) It is also used for treating steroid-induced oedema, idiopathic oedema, and oedema caused by secondary hyperaldosteronism. Overdosage of triamterene may cause electrolyte imbalance, especially hyperkalemia. Nausea, vomiting, other GI disturbances, and weakness may also occur. Hypotension may also result, especially when the drug is used concomitantly with hydrochlorothiazide or other diuretics or hypotensive agents. Toxicity Summary
- 41. Diuretics S D Magar PRCOP October 14, 2021 41 Amiloride Amiloride is a pyrazine compound that inhibits sodium reabsorption through sodium channels in renal epithelial cells. Amiloride is a member of the class of pyrazines resulting from the formal monoacylation of guanidine with the carboxy group of 3,5-diamino-6-chloropyrazine-2-carboxylic acid. It has a role as a sodium channel blocker and a diuretic. It is a member of pyrazines, an organochlorine compound, an aromatic amine and a member of guanidines. It is a conjugate base of an amiloride(1+).
- 42. Diuretics S D Magar PRCOP October 14, 2021 42 Mechanism of Action Amiloride binds to the amiloride -sensitive sodium channels and inhibits sodium reabsorption in the distal convoluted tubules and collecting ducts in the kidneys. As a result, sodium and water loss from the body occurs, while retaining potassium. Amiloride inhibits sodium reabsorption at the distal convoluted tubule, cortical collecting tubule, and collecting duct; and this explains its potassium sparing effect. This effect of amiloride reduces the net negative potential of the tubular lumen and decreases the secretion and excretion of potassium and hydrogen. Amiloride is not an aldosterone antagonist, and can acetven in the absence of aldosterone . Uses It is used with thiazide diuretics or other kaliuretic -diuretic agents in the treatment of congestive heart failure or hypertension.
- 43. Diuretics S D Magar PRCOP October 14, 2021 43 OSMOTIC DIURETICS Introduction Osmotic diuretics are pharmacologically inert agents. They are comparatively large in size (though they are smaller than albumin); yet, they are filtered freely through the glomerulus. They show poor reabsorption by the renal tubules. Mechanism of Action Osmotic diuretics are filtered at the glomerulus. They are not reabsorbed by the renal tubule. The primary sites of action for osmotic diuretics are the loop of Henle and the proximal tubule (membrane is most permeable to water). They prevent water absorption due to its osmotic action in the proximal tubules and impair sodium reabsorption by decreasing sodium concentration in the tubular fluid. Osmotic diuretics decrease medullary hypertonicity in the loop of Henle by raising the medullary blood flow. They decrease sodium and water reabsorption in the collecting duct due to papillary washout and high flow rate.
- 44. Diuretics S D Magar PRCOP October 14, 2021 44 Mannitol Mannitol is a naturally occurring alcohol found in fruits and vegetables. It is used as an osmotic diuretic. It undergoes glomerulus filtration and poor renal tubule reabsorption, thus increases osmolarity of the glomerular filtrate.
- 45. Diuretics S D Magar PRCOP October 14, 2021 45 Mannitol is freely filtered by the glomerulus and poorly reabsorbed from the renal tubule, thereby causing an increase in osmolarity of the glomerular filtrate. An increase in osmolarity limits tubular reabsorption of water and inhibits the renal tubular reabsorption of sodium, chloride, and other solutes, thereby promoting diuresis. In addition, mannitol elevates blood plasma osmolarity, resulting in enhanced flow of water from tissues into interstitial fluid and plasma. Uses 1) It is used for producing diuresis before irreversible renal failure becomes established. 2) It is also used for reducing intracranial pressure, in treating cerebral oedema, and for facilitating urinary excretion of toxic substances. Mannitol overdose may result in bronchoconstriction and should be counteracted using a short-acting bronchodilator and other symptomatic and supportive care, as necessary. Mechanism of Action Toxicity Summary