Diuretics Flashcards
What are the different classes of diuretics?
Thiazide diuretics Loop diuretics Potassium-sparing diuretics Carbonic anhydrase inhibitors Osmotic diuretics
How much of the blood plasma that enters the kidneys is filtered into the Bowman capsule?
16-20%
What substances are reabsorbed in the proximal convoluted tubule?
Nearly all glucose, bicarbonate, water, and amino acids. 2/3 of sodium is reabsorbed as well.
What substance modulates the reabsorption of bicarbonate?
Carbonic anhydrase
What type of drug (and specifically, what is the name of this drug) would inhibit bicarbonate reabsorption?
Carbonic anhydrase inhibitor; acetazolamide.
Which substances, if found in tubular fluid, would prevent water reabsorption?
Mannitol and glucose; this would result in osmotic diuresis.
Which part of the nephron contains the acid and base secretory systems?
Proximal convoluted tubule
What are a few organic acids that may be secreted through the acid secretory system?
Uric acid, antibiotics, diuretics
Why does hyperuricemia occur with certain diuretic drugs?
Most diuretics enter the nephron at the acid secretory system, competing with uric acids for secretion. This increases the levels of uric acid left in the blood.
Which specific substances are secreted by the base secretory system?
Creatine and choline
True or false: Although the filtrate that leaves the proximal convoluted tubule is isotonic, by the time it has passed through the descending loop of Henle, the salt concentration has increased 3x.
True, through countercurrent mechanisms.
True or false: The ascending loop of Henle is permeable to water.
False; it is impermeable to water (as is the distal convoluted tubule.
Sodium, potassium, chloride are actively reabsorbed in the ascending loop of Henle. What is the mechanism of reabsorption?
A Na+/K+/2Cl- cotransporter.
How much of the tubular sodium chloride is reabsorbed in the ascending loop of Henle, and what connotation does this have in choosing a diuretic drug?
25-30%; this makes the ascending loop of Henle a good target for diuretic drugs (loop diuretics, which are the most efficacious diuretics)
Which class of diuretics affects the distal convoluted tubule, and what is its specific target?
Thiazides; they target the Na+/Cl- transporter (responsible for reabsorption of about 10% of the filtered NaCl)
What factors influence calcium reabsorption or secretion?
Calcium is reabsorbed through a Na+/Ca2+ exchanger; its secretion is regulated by parathyroid hormone.
In the collecting tubule and duct, what substances inhibit the epithelial sodium channels, preventing sodium reabsorption?
Amiloride and triamterene.
What is the effect of aldosterone in the collecting tubule and duct?
It increases sodium reabsorption
What is the effect of ADH in the collecting tubule and duct?
It increases water reabsorption
What is the underlying cause of an edematous state?
Abnormally high amounts of sodium are reabsorbed, leading to high retention of water.
How does the kidney respond to the reduced CO of heart failure, and what class of diuretics are commonly used in this case?
As if there were a decrease in blood volume: more salt is reabsorbed, leading to water retention so as to increase blood volume. Loop diuretics are commonly used in this situation.
What is hepatic ascites?
Accumulation of fluid in the abdominal cavity as a complication of cirrhosis of the liver.
How does secondary hyperaldosteronism complicate hepatic ascites, and which drug is useful for this effect?
Fluid retention is promoted by aldosterone; aldosterone levels were increased in response to decreased blood volume. This increases the fluid accumulation. Spironolactone (potassium-sparing) is useful in this situation.
What is nephrotic syndrome?
Loss of proteins into the glomerular filtrate leads to loss of colloidal osmotic pressure, resulting in edema throughout the body. Aldosterone levels increase in response to the low blood volume, signalling retention of sodium and water, further aggravating the edema.
Which class of diuretics are commonly used to treat hypertension, and why?
Thiazides, due to their ability to reduce blood volume and stimulate ateriole dilation.
Which class of diuretics are commonly used to treat hypercalcemia, and why?
Loop diuretics, due to calcium excretion.
Which class of diuretics are commonly used to treat diabetes insipidus, and why?
Thiazides, because they reduce plasma volume, which causes a drop in glomerular filtration rate and subsequent reabsorption of sodium and water.
True or false: Thiazides are the most widely used class of diuretics.
True.
True or false: Thiazides are sulfonamide derivatives.
True (meaning they are structurally related to carbonic anhydrase inhibitors)
Which part of the nephron do thiazides affect?
The ascending loop and the distal tubule.
Which was the first thiazide?
Chlorothiazide
Which thiazides are most commonly used currently?
Hydrochlorothiazide (HCTZ) and chlorthalidone
Which “thiazides” are not actually true thiazides?
Chlorthalidone, indapamide, and metolazone.
What effects do thiazides have on sodium, chloride, potassium, magnesium, and calcium blood concentrations?
Decrease: sodium, chloride, potassium, magnesium
Increase: calcium (useful if pt has osteoporosis)
What conditions are commonly treated with thiazides?
Hypertension and diabetes insipidus
What are adverse effects of thiazide use?
**Hypokalemia
**Hyperuricemia
Hypotension
Hypercalcemia
Hyponatremia
Which of the loop diuretics is most commonly used?
Furosemide
Which of the loop diuretics is rarely used?
Ethacrynic acid
Which of the loop diuretics is most potent?
Bumetanide
True or false: Loop diuretics have the lowest efficacy in removing sodium and chloride from the body
False; their efficacy is the highest
What is the major site of action for loop diuretics?
Ascending loop of Henle
How do loop diuretics increase sodium and chloride excretion?
They inhibit the Na+/K+/2Cl- transporter
For which conditions are loop diuretics useful?
They are the drug of choice in reducing acute pulmonary edema of heart failure. They are also useful in treatment hypercalcemia and hyperkalemia.
What are adverse effects of loop diuretic use?
**Ototoxicity
**Hypokalemia
**Hyperuricemia
Hypotension
Hypomagnesemia
Where do potassium-sparing diuretics act?
In the collecting tubule
What is the major use of potassium-sparing diuretics?
Treatment of hypertension, often in combination with a thiazide
Which of the potassium-sparing diuretics are aldosterone antagonists, and where are the receptors they block?
Spironolactone and eplerenone; the aldosterone receptors they block are intracellular
Of the potassium-sparing diuretics, which may have less endocrine effects?
Eplerenone
Which diuretic is the drug of choice in patients with hepatic cirrhosis?
Spironolactone
Which drug prevents remodeling that occurs during progressive heart failure?
Spironolactone
Which potassium-sparing drugs block sodium/potassium exchange sites?
Triamterene and amiloride
Acetazolamide is a carbonic anhydrase inhibitor. In which cells is the carbonic anhydrase that it inhibits?
In proximal tubular epithelial cells
What ocular condition can acetazolamide be used to treat?
Open-angle glaucoma, by decreasing the production of aqueous humor
Which carbonic anhydrase inhibitors, used topically, can be used as an alternative to acetazolamide, and why?
Dorzolamide and brinzolamide; they do not cause any systemic effects
In what condition can acetazolamide be used as a prophylactic agent?
Mountain sickness, if used 5 days before the ascent and if the ascent is to above 10,000 feet
What are the adverse effects of acetazolamide use?
Metabolic acidosis (mild), potassium depletion, renal stone formation, drowsiness, paresthesia
Which substances are considered osmotic diuretics?
Mannitol and urea
What conditions are treated by oxmotic diuretics?
Increased ICP or acute renal failure due to shock, drug toxicities, and trauma
