Diuretics I and II

Question 1

Diuretics do what?

Answer 1

Increase urine volume by altering ion transport in the nephron.

Question 2

When and why do we use diuretics?

Answer 2

They are a first line defense in the treatment of HTN and edematous states such as CHF, nephrosis, and cirrhosis

Question 3

What are our osmotic agents?

Answer 3

Mannitol and urea

Question 4

Mechanism of Mannitol? Uses?

Answer 4

Mannitol is filtered into the tubular lumen but not reabsorbed, increasing osmotic pressure in the lumen and retaining water in the urine.We do it in order to reduce intraocular or intracranial pressure. It increases excretion of water more than Sodium, urinary excretion and metabolic toxins

Question 5

Side effects of osmotic agents like Mannitol and Urea

Answer 5

Dehydration if you don’t drink enough water

Increased ECF volume, leading to pulmonary edema (thus contraindicated in CHF patients)

Question 6

What is acetazolamide and how does it work

Answer 6

Carbonic Anhydrase Inhibitor

Blocks carbonic anhydrase primarily in the Proximal tubule, preventing reabsorption of sodium bicarbonate and leading to diuresis

Question 7

What are the uses and side effects of acetazolamide?

Answer 7

We use acetazolamide for:

1. Glaucoma to decrease production of aqueous humor
2. Acute Mountain sickness to stimulate ventilation via metabolic acidosis
3. Elimination of acidic toxins (Alkalinizes urine, leading to increased excretion of weak acids)
4. Corrects Alkalosis

Side effects

1. Renal stones: increases urine concentration of Ca2+ and phosphates
2. Potassium wasting (increased HCO3- in tubules attracts K+)
3. Hypercholemic metabolic acidosis

Question 8

What are furosemide, bumetanide, ethacrynic acid and how do they work

Answer 8

They are loop agents.

They work by inhibiting Na+ K+ 2Cl- transporter in thick ascending limb (specifically the 2Cl portion, which shuts down the pump). This keeps all of the ions in the lumen which leads to water being lost with the ions. Eventually as you take them more, Ca stops being reabsorbed through the lumen into the blood as well, so you’llstart peeing it out.

They also stimulate PGE release which causes a vasodilatory effect of afferent arterioles

Question 9

What do we use loop diuretics for and what are the side effects

Answer 9

We use it for Edematous states, HTN, and Hypercalcemia

Side Effects? OH DANG!

Ototoxicity
Hypokalemia
Dehydration
Allergy (Sulfa)
Nephritis (interstitial)
Gout

Question 10

What are HCTZ and Metolazone and how do they work?

Answer 10

Thiazide Diuretics

Work by inhibiting Na+-Cl- cotransporter in DCT leading to decreased reabsorption of these ions, which decreases the diluting capacity of the nephron and decreases Ca excretion.

Also, these have special effects. The first is that they increase secretion of Mg, and the second is that it acts secondarily on the PCT to increase reabsorption of urea = higher uric acid in the blood = Gout

Question 11

Uses and side effects of thiazide diuretics

Answer 11

First line agent for treatment of HTN, CHF, nephrosis, hypercalciuria, and nephrogenic DI.

Side effects: Dehydration, hypokalemia, hypercalcemia, hyperglycemia, hyperlipidemia, hyperuricemia, hyponatremia, allergic reactions

Question 12

Spironolactone, Eplerenone, are what? How do they work?

Answer 12

Potassium sparing agents

Spironolactone and eplerenone directly antagonize the mineralcorticoid receptor (target of aldosterone), thereby reducing Na+ reuptake in the late DCT and collecting duct. Both drugs prevent the aldosterone-mediated increase in apical membrane permeability to K+ (ROMK channels) and therefore are considered “potassium-sparing”

Question 13

What do we use the potassium sparing agents spironolactone and eplerenone for?

Answer 13

Spironolactone and eplerenone we use primarily in hyperaldosteronism (Conn syndrome) and edematous states caused by secondary hyperaldosteronism like cirrhosis, nephrotic syndrome and cardiac failure. Antiandrogen activity can be useful for treatment of polycystic ovary syndrome and hirsutism

Question 14

Amiloride and Triamterene are what? How do they work?

Answer 14

Amiloride and triamterene directly inhibit ENaCs in the late DCT and collecting duct which aso reduces Na+ reabsorption. This renders the charge in the lumen more positive, which is unfavorable for K+ secretion. Hence, these ENaC antagonists are also considered “potassium-sparing”

Question 15

What do we use amiloride and triamterene for?

Answer 15

Counteract the K+ loss caused by other diuretics, adjunct therapy to other diuretics to treat edema or HTN

Question 16

Side effects of Potassium-sparing agents

Answer 16

Hyperkalemia (yea no shit)
Hyperchloremic metabolic acidosis,
 gynecomastia with spironolactone,
 impotence in males 
abnormal menses in females

Question 17

When would we use ethacrynic acid over furosemide? What is each made of?

Answer 17

If the patient is allergic to sulfa drugs since ethacrynic acid is not a sulfonamide, but a phenoxyacetic acid derivative