Diuretics

Question 1

What are the general uses of diuretics?

Answer 1

(1) Edema (accumulation of fluid in body in cardiovascular, renal, endocrine disease)
(2) Hypertension
(3) Other diseases (described later)

Question 2

What is the functional unit of the kidney?

Answer 2

Nephron

Question 3

T/F Mechanism of Na re-absorption is the same the each segment.

Answer 3

FALSE; it diffes in various segments

Question 4

How much GFR do you have per minute? How much urine actually leaves the body?

Answer 4

125 ml/min; only <1ml/min

Question 5

What is the mechanism of Na re-absorption? (4)

Answer 5

(1) Unidirectional transport of Na is dependent on the polarity of the renal tubular cells
(2) Na transport proteins are present only in luminal or apical membrane
(3) Na-K-ATPase present only in basal and lateral membrane
(4) Two membranes are separated by tight junctions

Question 6

What drug works in the proximal tubule? What is its mechanism of action? Is this a direct or indirect effect?

Answer 6

Acetazolamide; carbonic anhydrase inhibitor inhibit NaHCO3 reabsorption; indirect effect (blocks the activity of bicarbonate transport which indirectly blocks the sodium transport)

Question 7

How much Na is reabsorbed in the proximal tubule?

Answer 7

~50% of filtered Na (and water)

Question 8

What drug works in the Thick Ascending Limb of the Loop of Henle? What is its mechanism of action? Is this a direct or indirect effect?

Answer 8

Furosemide; inhibits NaCl reabsorption from Na/K/2Cl cotransporter (inhibitor); direct

Question 9

What are the most powerful diuretics?

Answer 9

Loop diuretics (Furosemide)

Question 10

Furosemide- Uses

Answer 10

(1) Pulmonary edema, chronic heart failure
(2) Increases renal blood flow which is useful in patients with renal disease
(3) Increase urine flow in acute renal failure
(4) Increase Ca excretion, useful in hypercalcemia

Question 11

Furosemide- Adverse effects

Answer 11

(1) Increase K excretions, causes hypokalemia
(2) Increase Mg excretion, prolonged use causes hypomagnesemia
(3) Large doses may cause hypovolemia (circulatory collapse)
(4) Large doses may cause hearing loss, especially when given with aminoglycoside antibiotics

Question 12

How much NaCl is reabsorbed in the Loop of Henle?

Answer 12

~35%

Question 13

What drug works in the DIstal Tubule? What is its mechanism of action?

Answer 13

Thiazides (Hydrocholorthiazide); blocks the Na/Cl co-transporter

Question 14

How much NaCl is reabsorbed in the Distal Tubule?

Answer 14

~10%

Question 15

T/F Furosemide and Hydrocholorothiazide do not interact.

Answer 15

TRUE

Question 16

What is the difference between Furosemide and Hydrocholorothiazide?

Answer 16

Hydrochlorothiazide increases Ca retention instead of excretion which is important for calcium regulation

Question 17

What are the 2 ways in which Thiazides induce Ca retention?

Answer 17

(1) Increased passive paracellular reabsoprtion

(2) Increase reabsorption in the DCT

Question 18

Hydrochlorothiazide- Uses

Answer 18

• Hypertension, either alone or in combination with other drugs
• an increase in serum Ca with long-term use is useful for osteoporosis
• reduce Ca excretion and are useful in idiopathic hypercalciurea to prevent calcium stone formation
• useful in decreasing polyuria in nephrogenic diabetes insipidis (unknown mechanism)

Question 19

What is the difference between early fall (1-2 weeks) and late fall of Hydrochlorothiazide?

Answer 19

• Early fall in BP is due to decrease in extracellular fluid

- Late fall in BP is due to decrease in proximal reabsorption

Question 20

Hydrocholorothiazide- Adverse Effects

Answer 20

• Increase K excretion and cause hypokalemia

Question 21

T/F Hydrochlorothiazide is not effective in renal disease.

Answer 21

TRUE

Question 22

What drugs are used within the collecting duct? What is their mechanism of action?

Answer 22

Spironolactone (aldosterone receptor antagonist); triamterene & amiloride (block epithelial Na channels)

Question 23

How much NaCl is reabsorbed in the collecting duct? Why is it important to have a diuretic for such a small amount of NaCl reabsorption?

Answer 23

~3-5%; they are potassium sparing diuretics (when you are using other diuretics this is where the loss of potassium occurs)

Question 24

What is the transient natriuresis of diuretics? (3)

Answer 24

(1) Diuretics produce transient natriuresis
(2) After 1-2 days there is an activation of compensatory salt retaining mechanisms (release of angiotensin, aldosterone and ADH, and hyperactivity of distal segments)
(3) There is a new balance between intake and excretion of Na as long as the diuretic is continues

Question 25

How does hypokalemia occur in the collecting duct?

Answer 25

Renal compensation is going to reabsorb Na in the CCD which is coupled to K secretion which causes hypokalemia

Question 26

Spironolactone is an aldosterone antagonist. What does aldosterone receptor do?

Answer 26

The aldosterone receptor is a transcription factor that induces the genes encoding the epithelial sodium channel and the sodium/potassium ATPase

Question 27

Why are potassium-sparing drugs used in combination with thiazides or loop diuretics?

Answer 27

because they prevent K loss from the body

Question 28

Spironolactone- Uses

Answer 28

(1) Primary hyperaldosteronism (Conn's syndrome) and Secondary hyperaldosteronism due to hepatic cirrhosis complicated by ascites (2) slow onset of action, requiring several days for full effect

Question 29

Adverse effects of potassium sparing diuretics?

Answer 29

Hyperkalemia that is increased in patients with renal disease - the risk is increased when used with antihypertensive drugs (B blockers, ACE inhibitors)

Question 30

Mannitol- Mechanism of action

Answer 30

increase osmolarity of the plasma and attract water from the interstitial fluid

Question 31

Mannitol- Uses

Answer 31

(1) Used in cerebral edema to reduce intracranial pressure (2) Used in acute glaucoma to reduce intraocular pressure (3) Used as a diuretic to maintain renal function during acute renal failure (an increase in osmotic pressure retards water reabsorption in the proximal tubule)

Question 32

T/F Mannitol is metabolized in the body

Answer 32

FALSE; it is not and is filtered in the glomerulus and is not reabsorbed in the tubules

Question 33

Does Mannitol increase renal blood flow?

Answer 33

No

Question 34

Mannitol- Adverse effects

Answer 34

- if given too rapidly or in large amount, may lead to heart failure or pulmonary congestion due to an expansion of ECF volume

Question 35

Hypokalemia is associated with which drugs?

Answer 35

Thiazides and Furosemide

Question 36

Hyperglycemia is associated with which drugs?

Answer 36

Thiazides and Furosemide

Question 37

Hyperuricemia is associated with which drugs?

Answer 37

Thiazides and Furosemide

Question 38

Dehydration is associated with which drugs?

Answer 38

Furosemide (circulatory collapse)

Question 39

Deafness is associated with which drugs?

Answer 39

Furosemide

Question 40

Gynecomastia and menstrual abnormalities are associated with which drugs?

Answer 40

Spironolactone