Diuretics

Question 1

What are the different parts of the nephron?

Answer 1

• Bowmans Capsule
• Proximal convoluted tubule (PCT)
• Distal convoluted tubule (DCT)
• Thin descending limb
• Loop of Henle
• Thin ascending limb
• Thick ascending limb
• Collecting duct

Question 2

What are the types of diuretics that occur in the nephron?

Answer 2

• Osmotic diuretics
• Loop diuretics
• Carbonic Anhydrase Inhibitors
• Thiazides
• Aldosterone antagonists

Question 3

What do diuretics interfere with?

Answer 3

Ionic transport in the nephron to decrease tubular reabsorption

Question 4

How do diuretics work?

Answer 4

Act at different sites of the nephron causing Natriuresis (increase in Na+ excretion) which leads to diuresis (increase in urine volume)

Question 5

What is a diuretic?

Answer 5

Something that will increase the production of urine

Question 6

Why are diuretics useful?

Answer 6

Useful in the treatment of hypertension or oedema associated with congestive heart failure

• reduce blood pressure
• reduce oedema

Question 7

What are osmotic diuretics?

Answer 7

Drugs that alter the osmolality of the plasma, since very little drug is reabsorbed or metabolised so water follows the concentration gradient where more water is retained in the PCT and descending limb resulting in increased urinary output via osmosis

Question 8

What is an example of osmotic diuretics?

Answer 8

Mannitol

• Increases osmolality of tubular fluid at PCT
• Increases urinary output (diuresis)

Question 9

What are carbonis anhydrase inhibitors?

Answer 9

An enzyme that facilitates the exchange for H+ from Na+ and water in the proximal tubules
-Block this exchange of ions, thereby reducing the H+ concentration in the renal tubules (result is increased excretion of HCO3- , Na+ , K+ and Water

Question 10

What are carbonic anhydrase inhibitors used to treat?

Answer 10

Glaucoma, Oedema (secondary to heart failure), high altitude sickness and epilepsy

Question 11

What is an example of Carbonic Anhydrase inhibitors?

Answer 11

Acetazolamide
-Inhibit reabsorption of bicarbonate (HCO3-), a process normally driven by carbonic anhydrase

Has limited effectiveness:

• Increased Na+ and Cl- reabsorption in DCT
• Associated with metabolic acidosis
• Weak diuretic

Question 12

What are loop diuretics?

Answer 12

Drugs that prevent the creation of a hypotonic interstitium in the medulla by acting on the ascending limb of the loop of henle to block the Na+/K+/2Cl- symporter

• Increase Na+ delivery to DCT (promotes K+ loss)
• Decrease Na+ entry into macula densa (promote renin release and therefore increased angiotensin II activity)

Question 13

How effective are loop diuretics?

Answer 13

Sometimes referred to as ‘high ceiling’ diuretics due to their potent diuretic effects - can cause 15-25% of filtered Na+ to be excreted

Question 14

What are loop diuretics used to treat?

Answer 14

Pulmonary oedema (secondary to left ventricular failure and chronic heart failure)

Question 15

What is an example of Loop Diuretics?

Answer 15

Furosemide

• Solute added to peritubular fluid (water not reabsorbed)
• Act on thick ascending limb of loop of henle by blocking Na+/K+/2Cl- symporter

Question 16

What are Thiazides?

Answer 16

Third line drugs in hypertension

-Block Na+ and Cl- reabsorption in the DCT

Question 17

What are the used of thiazides?

Answer 17

• Used as a third line treatment for hypertension in patients over 55years old
• Secondary use is mild to moderate heart failure (particularly in the elderly)
• Ineffective in moderate renal impairment as the thiazides can’t go into the tubular system

Question 18

What example is there for Thiazides?

Answer 18

Bendroflumethiazide

• Moderately powerful diuretics
• Act on DCT to inhibit active Na+ reabsorption
• Increase solute in tubular fluid and decrease water reabsorption
• Reduce circulating volume

Uses: -Hypertension
-Mild to moderate heart failure

Question 19

What are K+ sparing diuretics?

Answer 19

• Block actions of aldosterone and/or block Na+ channels

- Help overcome the hypokalemic action of diuretics (which can develop in cardiac arrhythmia)

Question 20

When and why are K+ sparing diuretics used?

Answer 20

Used in conjunction with other diuretics
-Help maintain K+ balance in the body

May be used in the treatment of hyperaldosteronism, hypertension and heart failure

Question 21

What are the examples of K+ sparing diuretics?

Answer 21

Spironolactone

• Acts as aldosterone antagonist in the late DCT
• Blocks the action of aldosterone which would otherwise cause Na+ reabsorption and K+ and H+ secretion
• Prevents hypokalaemia caused by renal loss of K+ ions
• Secondary effect of several diuretics, including carbonic anhydrase inhibitors, loop diuretics and thiazides

Question 22

How do the electrolyte changes in in urine differ based on the administration of each diuretic drug?

Answer 22

Carbonic Anhydrase Inhibitors: Small increase in Na+
Small increase in K+
Large increase in HCO3-

Loop Diuretics:
Large increase in Na+
No change in HCO3-
Small increase in K+

Thiazides:
Medium increase in Na+
Small increase in K+
No increase in HCO3-

K+ sparing diuretics:
Small increase in Na+
No change in HCO3-
Small decrease in K+