Week 13: Chapter 41 - Diuretics

Question 1

State the common mechanism or mechanisms by which all diuretics increase urine production

Answer 1

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Question 2

Potassium Sparing Diuretics

Answer 2

spironolactone and triamterene

Question 3

Potassium Wasting Diuretics

Answer 3

furosemide, hydrochorothiazide, mannitol

Question 4

state why a knowledge of the effects of diuretics on renal potassium excretion is important clinically

Answer 4

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Question 5

State factors that should be considered when selecting a diuretic, focusing on the efficacy of the various agents, dose-response relationships, and the potential for adverse effects in patients with other disorders.

Answer 5

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Question 6

discuss for which pathologies the various diuretics are suitable.

Answer 6

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Question 7

Describe the adverse effects, contraindications, or precautions for the various diuretics.

Answer 7

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Question 8

the expected effects of thiazides and loop diuretics on blood levels of glucose, lipids, uric acid, calcium, and magnesium and identify the preexisting conditions that might require extra caution if use of these diuretics is anticipated.

Answer 8

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Question 9

State how changes in the serum potassium level influence the effects of digoxin and the likely impact of hypokalemia or hyperkalemia on therapy with a cardiac glycoside.

Answer 9

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Question 10

State whether combinations of named diuretics are rational and give a reason why. For example, is it reasonable and rational to administer two thiazides or two loop diuretics to the same patient?

Answer 10

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Question 11

Compare and contrast the mechanisms of action, clinical uses, and typical adverse effects of mannitol with those of a thiazide or loop diuretic.

Answer 11

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Question 12

Active Tubular Secretion

Answer 12

The kidney has two major kinds of “pumps” for active secretion. These pumps transport compounds from the plasma into the lumen of the nephron. One pump transports organic acids and the other transports organic bases. Together, these pumps can promote the excretion of a wide assortment of molecules, including metabolic wastes, drugs, and toxins. The pumps for active secretion are located in the proximal convoluted tubule.

Question 13

Aldosterone

Answer 13

the principal mineralocorticoid of the adrenal cortex, stimulates reabsorption of sodium from the distal nephron. At the same time, aldosterone causes potassium to be secreted. Although not directly coupled, these two processes—sodium retention and potassium excretion—can be viewed as an exchange mechanism. Aldosterone promotes sodium-potassium exchange by stimulating cells of the distal nephron to synthesize more of the pumps responsible for sodium and potassium transport.

Question 14

Antidiuretic Hormone

Answer 14

The distal nephron is the site of two important processes. The first involves exchange of sodium for potassium and is under the influence of aldosterone. The second determines the final concentration of the urine and is regulated by antidiuretic hormone (ADH). Although sodium-potassium exchange is discussed in more detail, we will not continue discussion of ADH, as it has little to do with the actions of diuretics.

Question 15

Diuretics

Answer 15

drugs that increase the output of urine. These agents have two major applications: (1) treatment of hypertension and (2) mobilization of edematous fluid associated with heart failure, cirrhosis, or kidney disease. In addition, because of their ability to maintain urine flow, diuretics are used to prevent renal failure.

Question 16

Glomerular Filtration Rate

Answer 16

In contrast to thiazide diuretics, loop diuretics are effective even when the glomerular filtration rate is low. Furosemide is especially useful in patients with severe renal impairment, since, unlike the thiazides (see below), the drug can promote diuresis even when renal blood flow and glomerular filtration rate are low. Thiazide diuretics are ineffective when glomerular filtration rate is low.

Question 17

High-Ceiling (Loop) Diuretics

Answer 17

aka loop diuretics. The loop agents are the most effective diuretics available. These drugs produce more loss of fluid and electrolytes than any other diuretics. They are known as loop diuretics because their site of action is in the loop of Henle.

Question 18

Osmotic Diuretics

Answer 18

Osmotic diuretics differ from other diuretics with regard to mechanism and uses. At this time, mannitol is the only osmotic diuretic available in the United States. Three related drugs—urea, glycerin, and isosorbide—have been withdrawn.

Question 19

Ototoxicity

Answer 19

Rarely, loop diuretics cause hearing impairment. With furosemide, deafness is transient. With ethacrynic acid (another loop diuretic), irreversible hearing loss may occur. The ability to impair hearing is unique to the loop diuretics. Diuretics in other classes are not ototoxic. Because of the risk of hearing loss, caution is needed when loop diuretics are used in combination with other ototoxic drugs (eg, aminoglycoside antibiotics).

Question 20

Potassium Sparing Diuretics

Answer 20

The potassium-sparing diuretics can elicit two potentially useful responses. First, they produce a modest increase in urine production. Second, they produce a substantial decrease in potassium excretion. Because their diuretic effects are limited, the potassium-sparing drugs are rarely employed alone to promote diuresis. However, because of their marked ability to decrease potassium excretion, these drugs are often used to counteract potassium loss caused by thiazide and loop diuretics.

There are two subcategories of potassium-sparing diuretics: aldosterone antagonists and nonaldosterone antagonists. In the United States, only one aldosterone antagonist—spironolactone—is used for diuresis.* Two nonaldoste­rone antagonists—triamterene and amiloride—are currently employed.

Question 21

Reabsorption

Answer 21

More than 99% of the water, electrolytes, and nutrients that are filtered at the glomerulus undergo reabsorption. This conserves valuable constituents of the filtrate while allowing wastes to undergo excretion. Reabsorption of solutes (eg, electrolytes, amino acids, glucose) takes place by way of active transport. Water then follows passively along the osmotic gradient created by solute reuptake. Specific sites along the nephron at which reabsorption takes place are discussed below. Diuretics work primarily by interfering with reabsorption.

Question 22

Thiazides

Answer 22

The thiazide diuretics (also known as benzothiadiazides) have effects similar to those of the loop diuretics. Like the loop diuretics, thiazides increase renal excretion of sodium, chloride, potassium, and water. In addition, thiazides elevate plasma levels of uric acid and glucose. The principal difference between the thiazides and loop diuretics is that the maximum diuresis produced by the thiazides is considerably lower than the maximum diuresis produced by the loop diuretics. In addition, whereas loop diuretics can be effective even when urine flow is decreased, thiazides cannot.

Question 23

Furosemide

Answer 23

Category: loop diuretic
MOA: acts in the thick segment of the ascending limb of Henle’s loop to block reabsorption of sodium and chloride
Therapeutic Use: pulmonary edema associated with congestive heart failure, edema of hepatic, cardiac, or renal origin that has been unresponsive to less efficacious diuretics, and hypertension that cannot be controlled with other diuretics.
Adverse Effects: Hyponatremia, Hypochloremia, and Dehydration, Hypotension, Hypokalemia, Ototoxicity, Hyperglycemia, Hyperuricemia, and can cause maternal death and abortions in pregnancy.

Question 24

Hydrochlorothiazide

Answer 24

Category: thiazide diuretic
MOA: promotes urine production by blocking the reabsorption of sodium and chloride in the early segment of the distal convoluted tubule
Therapeutic use: essential hypertension, edema, diabetes insipidus, protection against postmenopausal osteoporosis
Adverse Effects: Hyponatremia, Hypochloremia, and Dehydration, Hypokalemia, Hyperglycemia, Hyperuricemia, increase LDLs and cholesterol, increase secretion of magnesium

Question 25

Spironolactone

Answer 25

Category: potassium sparing diuretic - aldosterone antagonist
MOA: blocks the actions of aldosterone in the distal nephron. Since aldosterone acts to promote sodium uptake in exchange for potassium secretion, inhibition of aldosterone has the opposite effect: retention of potassium and increased excretion of sodium. The diuresis caused by spironolactone is scanty because most of the filtered sodium load has already been reabsorbed by the time the filtrate reaches the distal nephron. (Recall that the degree of diuresis a drug produces is directly proportional to the amount of sodium reuptake that it blocks.)
Therapeutic Use: Hypertension and Edema, Heart Failure, primary hyperaldosteronism, premenstrual syndrome, polycystic ovary syndrome, and acne in young women
Adverse Effects: Hyperkalemia, Endocrine Effects, Benign and Malignant Tumors.

Question 26

Triamterene

Answer 26

Category: potassium spring diuretic - nonaldosterone antagonist
MOA: disrupts sodium-potassium exchange in the distal nephron. However, in contrast to spironolactone, which reduces ion transport indirectly through blockade of aldosterone, triamterene is a direct inhibitor of the exchange mechanism itself.
Therapeutic Use:
Adverse Effects: