11.1 Diuretics

Question 1

What are diuretics?

Answer 1

Are drugs that increase renal excretion of sodium and water resulting in increase in urine volume and elimination of water from the body.
Things that stimulate diuresis by natriuresis

Question 2

What is the function of diuretics?

Answer 2

• Reduce plasma volume + cardiac output
• Reduce blood pressure
• Reduce oedema/ascites (remove excess extracellular fluid)

Question 3

What what is diuresis?

Answer 3

• Diuresis: is the process of excretion of water in the urine.

Question 4

What is natriuresis?

Answer 4

Process of excretion of sodium in urine

Question 5

What are the 5 main classes of diuretics?

Answer 5

• Carbonic anhydrase inhibitors (PCT)
• Osmotic diuretics
• Loop diuretics (LoH)
• Potassium sparing diuretics (DCT)
• Thiazide and thiazide-like diuretics (late DCT and CD)

Question 6

How do diuretics affect sodium reabsorption?

Answer 6

Reduced sodium reabsorption by affecting carriers or transporters in the luminal membrane or renal tubular cells.

Question 7

Where do carbonic anhydrase inhibitors operate?

Answer 7

In the proximal convoluted tubule of the nephron

Question 8

Where do osmotic diuretics act?

Answer 8

Work throughout the tubule of the nephron

Question 9

Where do loop diuretics work?

Answer 9

In the loop of henle

Question 10

Where do thiazides and thiazides-like diuretics work?

Answer 10

In the distal convoluted tubule and into the collecting duct

Question 11

Where do potassium sparing diuretics work?

Answer 11

In the late distal convoluted tubule and into the collecting duct

Question 12

How do carbonic anhydrase inhibitors work?

Answer 12

Inhibit carbonic anhydrase, stopping carbonic acid being broken down into water and carbon dioxide.
This stops bicarbonate ions being reabsorbed into the proximal tubule. Sodium reabsorption is coupled with bicarbonate ion reabsorption. If less bicarbonate ione reabsorbed, less sodium ions are reabsorbed

Question 13

Describe the action of SGLT-2 inhibitors?

Answer 13

Inhibit the action of SGLT-2 transporters in the proximal tubule. As reabsorption of glucose is coupled with reabsorption of sodium. Not technically a diuretic

Question 14

What are flozins?

Answer 14

SGLT-2 inhibitors

Question 15

What is mannitol?

Answer 15

So osmotic diuretic, delivered via IV. Is freely filtered at glomerulus

Question 16

How does mannitol work?

Answer 16

Freely filtered into tubule at glomerulus. No transporters within the tubule to remove mannitol, so it stays there. Has high osmotic affect, drawing water into the tubule.

Question 17

How doe mannitol differ from other diuretics?

Answer 17

Is an osmotic diuretic and works by drawing water into the nephron tubule. Has little effect on sodium secretion, does not cause natriuresis

Question 18

What are the disadvantages of using osmotic diuretics?

Answer 18

• administered by IV
• have high osmotic effect in blood supply whilst being transported to the kidney, initially causes fluid retention
• inhibits renin release and increases renal blood flow
• cannot be used in patients with congestive cardiac failure

Question 19

When are osmotic diuretics used?

Answer 19

• Acute renal failure due to shock or trauma (maintain urine flow – preserve kidney function)
• Acute drug poisoning – To eliminate drugs that are reabsorbed from the renal tubules
• To ↓intracranial and intraocular pressure before ophthalmic or brain procedures.

Question 20

What are the side affects of osmotic diuretics?

Answer 20

Headaches, nausea, vomiting - due to dilution allergies hyponatraemia
Extracellular volume expansion, complicates HF and pulmonary oedema
Contraindicated in chronic heart failure
Excessive use leads to dehydration and hypernatraemia. Adequate water replacement required

Question 21

How do loop diuretics work?

Answer 21

By inhibiting the Na+/K+/2Cl- cotransporter.
Less sodium, potassium and chloride reabsorbed, more stay in the filtrate and are excreted.
Most potent diuretics ‘high ceiling’

Question 22

What are the most potent diurectics?

Answer 22

Loop diuretics

Question 23

Give examples of loop diuretics

Answer 23

Furosemide

Bumetanide

Question 24

How are loop diuretics administered?

Answer 24

IV or orally

Question 25

When are loop diuretics used?

Answer 25

Suitable for emergency situations due to fast onset of actions. • Severe oedema associated with congestive heart failure, nephrotic syndrome. • Treatment for Oliguric ARF. • Treatment of hypercalcemia • Acute pulmonary oedema. • Acute hyperkalaemia. Acute hypercalcemia. • To x i c i t y of Br, F & I

Question 26

What are common side affects of loop diuretics?

Answer 26

``` • Hypovolemia • Hyponatraemia (↓ blood Na+) • Hypokalemia (↓ blood K+). Dietary K supplementation or K-sparing diuretics should be used to avoid hypokalemia • Hypomagnesaemia (↓ blood Mg2+) • Hypocalcaemia (↓ blood Ca2+) • Metabolic alkalosis • Postural hypotension ```

Question 27

Why can patients on loop diuretics get metabolic alkalosis?

Answer 27

Patients on loop diuretics frequently get hypokalaemia as more potassium is excreted. Cells in the body will swap potassium ions for hydrogen ions. H+ ions taken into cells, increasing the pH of blood

Question 28

How do thiazides and thiazides like diuretics work?

Answer 28

Block the Na+/Cl- transporter in the distal convoluted tubule. Reduces amount of sodium and chloride reabsorbed.

Question 29

How can thiazides and thiazides like diuretics cause hypercalcaemia?

Answer 29

As on basement membrane of the cells of the distal convoluted tubule there are Na+/Ca2+ exchanger. If sodium levels in the cells are low, this will stimulate the exchanger to work, drawing Na+ in whilst pumping Ca2+ out into circulation

Question 30

When are thiazide and thiazide like diuretics used?

Answer 30

1st line antihypertensive • Essential hypertension • Mild heart failure • Calcium nephrolithiasis due to hypercalciuria • Osteoporosis • Nephrogenic diabetes insipidus polyuria

Question 31

How do thiazide and thiazide like diuretics affect the composition of urine?

Answer 31

``` Increase excretion of Na+ and Cl- Decreased excretion of Ca2+ (more reabsorbed - hypercalcaemia) Increased K+ excretion Increased Mg2+ excretion Decreased uric acid excretion ```

Question 32

How do aldosterone antagonists work?

Answer 32

Block aldosterone receptor, stopping upregulationg of ENAC channels and ROMK channels. This means that there isnt more K+ moved out into the filtrate and excreted.

Question 33

How to potassium sparing diuretics work?

Answer 33

Block the ENAC channels. Stops Na+ being reabsorbed into cells of the DCT. This reduces the functioning of the 3Na+/2K+ ATPase on the basolateral surface. Less K+ absorbed into the cells of the DCT from the blood. Less available to be excreted into the filtrate. Hence K+ sparing

Question 34

Name a potassium sparing diuretic

Answer 34

Amiloride

Question 35

Name an aldosterone antagonist

Answer 35

Spironolactone

Question 36

How is the composition of urine altered by aldosterone antagonists and potassium sparing diuretics?

Answer 36

Increased sodium excretion | Decreased K+ and H+ excretion

Question 37

What are potassium sparing diuretics and aldosterone antagonists used to treat?

Answer 37

* Secondary hyperaldosteronism. * CHF, hepatic cirrhosis, nephrotic syndrome * Treatment of hypertension (combined with thiazide or loop diuretics to correct for hypokalemia)

Question 38

What are the contraindications of aldosterone antagonists and potassium sparing diuretics?

Answer 38

* Hyperkalaemia: as in chronic renal failure, K+ supplementation, b-blockers or ACEinhibitors. * Liver disease (dose adjustment is needed).