DIURETICS+III

In very simple terms, diuretics inhibit the reabsorption of Na, Cl, and/or K and water is retained in the tubular fluid to "balance out" the increase in salt content of the developing urine. The figure below is to remind you that renal tubules are 3D structures and are tubes through which the tubular fluid is modified. When blood is filtered at the glomerulus, the fluid which enters the proximal tubule (i.e. the //tubular fluid//) is really the developing urine. As the tubular fluid passes down the tubule, solutes (Na, K, Cl, etc...) are removed from the fluid and returned to the blood (**reabsorption**) or removed from the blood and added directly to the fluid (**secretion**). The right side of the figure shows 2 tubule epithelial cells (their positions are indicated by the **blue arrows**) in the absence (top) and presence of a diuretic. In very simplistic terms, the inhibition of transporter activity by a diuretic prevents reabsorption of solute and water is retained in the tubular fluid. The effects of various diuretics are listed in the table that follows. Use the diagram to help you understand how they work. **DIURETIC** inhibit carbonic anhydrase preventing HCO3- absorption. HCO3 remains in the tubular fluid increasing pH. Na is retained in the tubule, attracting water serious toxicity is uncommon
 * Diuretics** are drugs which increase the rate of urine flow. However, clinically useful diuretics also increase excretion of Na+ and an accompanying anion (negatively charged) ion like Cl-. Since NaCl is the major determinant of extracellular fluid volume, diuretics reduce extracellular fluid volume by decreasing total body NaCl content. Although continued use of a diuretic causes sustained net loss of Na, the time course for this effect is limited by compensatory mechanisms including activation of the renin-angiotensin-aldosterone pathway and the SNS.
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 * How do diuretics exert their effects on salt and water excretion?**
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 * How do diuretics exert their effects on salt and water excretion?**
 * How do diuretics exert their effects on salt and water excretion?**
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 * MECHANISM**
 * USES**
 * SIDE EFFECTS**
 * proximal tubule diuretics**
 * SIDE EFFECTS**
 * proximal tubule diuretics**
 * proximal tubule diuretics**
 * proximal tubule diuretics**
 * 1) treatment of glaucoma
 * 2) alkalinization of the urine
 * 3) ttreatment of altitude sickness ||
 * 1) ttreatment of altitude sickness ||
 * loop diuretics**
 * 1) inhibit Na/Cl/K reasorption in the Loop of Henle
 * 2) increase GFR by stimulating local production of prostaglandins ||
 * 3) acute pulmonary edema
 * 4) edema associated with CHF
 * 5) hypertension (not 1st choice)
 * 6) refractory edema ||
 * 7) hypokalemia (K wasting)
 * 8) hypovolemia
 * 9) hyponatremia
 * 10) hypotension || ||
 * 1) hyponatremia
 * 2) hypotension || ||

inhibit Na/Cl reabsorption in the diluting segment of the distal tubule. Since there is less Na in the diluting segment than in the Loop, these diuretics are less effective loop diuretics at increasing salt and water excretion K+-sparing diuretics 1. **Na channel blockers** - prevent the increase Na in the tubular fluid (due to the action of loop or diluting segment diuretics) from stimulating K+ secretion 2. **aldosterone receptor antagonists** - aldosterone enhances Na/water reabsorption and stimulates K secretion in the distal tubule weak diuretics used in con- juction with loop or diluting segment diuretics to prevent K wasting weak diuretics used with loop diuretics of diluting segment diuretics to reduce/prevent K wasting. Response is related to the amount of aldosterone in the circulation hyperkalemia - requires reduction in K intake substances which are freely filtered but are not reabsorbed nor secreted. rapid administration can cause excessive fluid shift into blood causing congestive heart failure
 * Diluting segment diuretics**
 * 1) edema due to heart failure (1st choice)
 * 2) cirrhosis with ascites
 * 3) hypertension ||
 * 4) hypokalemia (K wasting)
 * 5) hypovolemia
 * 6) hyponatremia
 * 7) hypotension || ||
 * 1) hypotension || ||
 * osmotic diuretics**
 * osmotic diuretics**
 * 1) inc. tonicity of the tubular fluid and cause water to be retained in the tubule
 * 2) inc blood tonicity, drawing water from intracellular spaces into the blood ||
 * 3) maintain kidney function and urine flow rate during hypotension
 * 4) cerebral edema
 * 5) decrease intraocular pressure in glaucoma ||