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Diuretics targets to lower sodium and water reabsorption that may lead to enhanced water excretion. The main aim of diuretics is to reduce the fluid volume inside the body and maintain the electrolyte and water equilibrium. These agents are used for managing the pathological conditions including hypertension and edema such as cardiac congestion failure, liver and kidney problems, and glaucoma. It also helps in processing and regulating the blood pressure by eliminating the excessive salt from the body which slows down the cardiac muscles to impel the blood. Diuretics influence and inhibit the tubular water and sodium reabsorption using the epithelial cells liner of the renal tubules system. Several diuretics such as carbonic anhydrase inhibitors, thiazide-like diuretics, loop diuretics and potassium-sparing diuretics repress the water and sodium reabsorption by blocking the function of proteins involved in the electrolyte transportation across the epithelial membrane. There are multiple types of diuretics that are Thiazide diuretics, osmotic diuretics, Loop diuretics, Potassium-sparing diuretics. In natriuresis excretion of sodium is conducted using atrial and ventricular natriuretic peptides, Aquaretics increase the blood flow to the kidney and improves the urine production without influencing sodium and chloride reabsorption (Wang & Gottlieb, 2008).
2. Carbonic anhydrase inhibitors such as acetazolamide
Carbonic anhydrase is involved in catalysis of carbonic acid which is found in RBCs and various other tissues like kidneys etc. It reduces the pH of tissues breaking the carbonic acid into carbon dioxide and water leading to an acidic milieu. Carbonic anhydrase inhibitor based diuretics such as acetazolamide directly interact with renal proximal tubule which is the main site of carbonic sodium, bicarbonate, and chloride reabsorption. The inhibition of Carbonic anhydrase by diuretic agent results in increased excretion of ions with extra water. This occurrence results in lowered blood pressure with low pH, hyperventilation which in turn increases oxygen amount and decreased carbon dioxide as well as low serum potassium level (Puscas et al., 1998).
3. Loop diuretics such as furosemide
Furosemide is a prototype of Loop Diuretics that inhibit co-transport structure (1Na+, 1K+, 2Cl-) present of the thick ascending appendage of Henle’s loop. It is the most efficient class of diuretics. Loop diuretics act through suppressing water and sodium reabsorption by restraining certain proteins accountable for the electrolyte transportation across the epithelial membrane. These agents induce the condition of hypokalemia. The outcome of these agents is excretion of Na+, K+, and Cl-. Ascending loop segment facilitates the 25% of Cl- and Na+ reabsorption as well as it is accountable for sustaining the medullary-osmolarity-gradient. Loop diuretics results in reduced sodium, potassium, and Chloride, while increasing the pH through elevating the excretion of divalent cations like NaCl (Xiaoping, 2016).
4. Mechanism of Thiazides diuretics and effects on pH and calcium and potassium
Thiazides such as hydrochlorothiazide are also known as called diluting segment diuretics that directly act on the distal tubule. Thiazide diuretics hinder the Na+Cl- symporter existing in the luminal membrane through contending for the Cl- binding site. Mechanism of action of Thiazide diuretics involves inhibition of Na+-Cl- symport that leads to the reduction in Na+ and Cl- reabsorption which in turn increases their excretion. These agents reduce the levels of potassium and magnesium inside body as well as in urine while increases the uric acid level in the blood causing a reduction in pH of blood. These agents strengthen the renal function linked to the parathyroid hormone which results in calcium retention (Middler et al., 1973).
5. Spironolactone and amiloride
Spironolactone and amiloride are potassium-sparing diuretics that inhibit Na+ and water reabsorption through inhibiting the aldosterone binding to the receptor thus they proceed as aldosterone antagonist. These agents interact directly with early collecting tubules and late distal convoluted tubule division of nephron. Through inhibiting the Na+ re-absorption by 2-3% they assist in lowering the driving force for K+ secretion. Thus, they increase the potassium levels in blood and lower it in urine. They belong to the third class of diuretics that do not intervene with sodium transport. They help in passing more water and sodium into the collecting duct and eliminating by urine. It also pushes excessive sodium towards the collecting ducts that result in the freer aldosterone. The pH level of blood increases severely as an effect of Spironolactone and amiloride. Due to its steroidal 5 Carbon ring structure, it also enforces antiandrogen effects. It is also used in combination with thiazide and loop diuretics for treating hypertension and edema. It enhances the excretion of sodium and prevents K+ wasting (Carey et al., 1972).
6. Why Spironolactone and amiloride are known as potassium-sparing diuretics
Spironolactone and amiloride are popular potassium-sparing diuretics. It directly intervenes with the functioning of Na+–K+–H+ exchanger located at the distal tubules and collecting ducts through inhibiting it. It enhances the diuresis through such mechanism where it operates as an antagonist for the aldosterone receptor. That is why these agents are called potassium-sparing diuretics because these agents do not cause hypokalemia like other diuretics including thiazides and loop diuretics. Aldosterone shows the capability of improving sodium and water excretion. Such agents obstruct the sodium channels associated with aldosterone-sensitive Na+ pump resulting in increased sodium and water and sodium. The spironolactone causes hyperkalemia due to its specific effects. Thus, it is preferred to administer in combination with other loop or thiazide diuretics (Xiaoping, 2016).
7. Mechanisms of Mannitol and vasopressin as osmotic diuretics
Osmotic diuretics create a hypertonic solution that helps water in passing into the tubules form all over a body that generates a diuretic effect. Mannitol and sorbitol agents are administered intravenously in the solutions of 5-50%. These agents work on the basis of the proximal tubule and Henle's loop permeability for water. It enhances the water withholding in this specific region causing a condition of water diuresis. The diuresis results in potassium, water as well as sodium loss. Osmotic diuretics reduce the increased intracranial pressure stimulating a quick toxin removal from kidneys. The side effects of Osmotic diuresis involved increases in urine volume and reduction in Na+ reabsorption. Serum potassium is observed escalating in these cases (Xiaoping, 2016).
8. Carbonic anhydrase inhibitors do not directly block the sodium transport in the proximal convoluted tubules. Firstly, in this section the Sodium reabsorption is operated by a Carbonic-anhydrase independent pathway and Sodium bicarbonate reabsorption is controlled by Na+/H+ exchanger present at proximal tubule. Carbonic anhydrase inhibitors block the bicarbonate transport nearby the proximal-convoluted tubule that results in lowered sodium reabsorption at this location. The result of this occurrence is the higher loss of bicarbonate, sodium and water loss into the urine. Carbonic anhydrase is the weakest diuretics. They are prescribed in various cardiovascular disease and glaucoma (Xiaoping, 2016).
References
Carey, R. M., Douglas, J. G., Schweikert, J. R., & Liddle, G. W. (1972). The syndrome of
essential hypertension and suppressed plasma renin activity: normalization of blood
pressure with spironolactone. Archives of Internal Medicine, 130(6), 849.
Puscas, I., Coltau, M., Baican, M., Pasca, R., & Domuta, G. (1998). The inhibitory effect of
diuretics on carbonic anhydrases. Research communications in molecular pathology and
pharmacology, 105(3), 213-236.
Middler, S., Pak, C. Y., Murad, F., & Bartter, F. C. (1973). Thiazide diuretics and calcium
metabolism. Metabolism, 22(2), 139-146.
Wang, D. J., & Gottlieb, S. S. (2008). Diuretics: still the mainstay of treatment. Critical care
medicine, 36(1), S89-S94.
Xiaoping, D. (2016). Diuretics. http://www.uic.edu. Retrieved 5 May 2016, from
http://www.uic.edu/classes/pcol/pcol425/restricted/Du/diuretics.PDF
