3. Diuretic Drugs

Front 1

How do most diuretics except osmotic diuretics work?

Back 1

They decrease tubular reabsorption of Na+, which also decreases reabsorption of Cl- and water.

Front 2

What osmotic diuretics do we have?

Back 2

Mannitol, urea, glycerine and isosorbide. Mannitol is the most important.

Front 3

Mechanism of action of mannitol?

Back 3

Enters ECS and induces a slight hyperosmolarity which causes water to move from the ICS to the ECS. This will make the RFB and GFR increase, and diuresis increases.

It is freely filtered in the glomeruli and pulls water from the interstitium by increasing the osmolarity in the filtrate.

Front 4

Indications for mannitol?

Back 4

- Preventing of anuria during acute renal failure.

- Treatment of cerebral edema and glaucoma

- Decreases viscosity of the bronchial fluid in cystic fibrosis.

Front 5

Contraindications for mannitol?

Back 5

Heart failure

Front 6

Why is mannitol contraindicated in heart failure?

Back 6

It increases the preload, and can cause pulmonary oedema.

Front 7

Name carbonic anhydrase inhibitors

Back 7

Acetazolamide, brinzolamide, dichlorphenamide, methazolamide.

Front 8

Indications for carbonic anhydrase inhibitors?

Back 8

Glaucoma, altitude sickness.

Front 9

Mechanism of action of carbonic anhydrase inhibitors?

Back 9

Carbonic anhydrase increases HCO3- and Na+ reabsorption and increases the H+ secretion. By inhibiting this, the decreased reabsorption of Na+ and HCO3- will increase the diuresis.

HCO3- is a component in aqueous humor, and the intraocular pressure will decrease when carbonic anhydrase is inhibited.

Front 10

How can carbonic anhydrase inhibitors cause somnolence?

Back 10

They reduce the RBCs ability to carry CO2 to lungs. The CO2 level in the tissues increases and gives a weak anaesthetic effect on the CNS.

Front 11

Pharmacokinetics of acetazolamide?

Back 11

Has 100 % oral bioavailability and extensive protein binding.

Is eliminated by tubular secretion.

Front 12

Drug interactions with carbonic anhydrase inhibitors?

Back 12

Increases reabsorption of weak basic drugs like amphetamine.

Decrease reabsorption of weak acidic drugs like aspirin and phenobarbital.

Front 13

Name loop diuretics

Back 13

Furosemide, bumetanide, torasemide.

Front 14

Indications of loop diuretics?

Back 14

Pulmonary oedema, acute hypertensive crisis, heart failure, acute renal failure, acute hypercalcemia and acute hyperkalemia.

Front 15

Mechanism of action of loop diuretics?

Back 15

They are secreted into the filtrate through drug transporters OAT1, OAT4 and MRP4.

They inhibit the Na+/K+/2Cl symporter (NKCC2) in the ascending limb of Henle. This symporter creates the cortico-medullary osmotic gradient. Loop diuretics makes it smaller, and therefore the water reabs decreases in the descending loop and collecting ducts.

Front 16

Which ions are lost with loop diuretics?

Back 16

Ca2+ and Mg2+

Front 17

How can loop diuretics decrease tubologlomerular feedback and why is this beneficial?

Back 17

They block Cl- from entering macula densa cells, so GFR does not get reduced in acute tubular injury.

Front 18

How are loop diuretics beneficial in cardiac failure?

Back 18

Reduce preload by increasing the diuresis.

They're the first-line drug for pulmonary edema due to heart failure.

Front 19

Bioavailability in loop diuretics?

Back 19

50 % in furosemide. Nearly 100 % in bumetanide.

Front 20

Pharmacokinetics of loop diuretics?

Back 20

Extensive plasma protein binding. Eliminated mainly by tubular secretion but some by biotransformation.

Front 21

Side-effects of loop diuretics?

Back 21

Deafness and dizziness because the inner ear has a NKCC1 symporter. (Ototoxicity)

Front 22

Contraindications in loop diuretics?

Back 22

NSAIDs as they decrease the effect of loop diuretics and reduce renal blood flow, rising the cortico-medullary osmotic gradient.

Contraindicated in anuria since they would never reach the ascending limb.

Front 23

Name thiazides and thiazide-like drugs

Back 23

Thiazide: Hydrochlorothiazide

Thiazide-likes: chlorothalidone, clopamide.

Front 24

Indications of thiazides and thiazide-like drugs?

Back 24

Hypertension, oedema, calcium stones and osteoporosis, nephrogenic diabetes insipidus.

Front 25

Mechanism of action of thiazides and thiazide-like drugs?

Back 25

Secreted into prox. convoluted tubules by OAT1, OAT4 and MRP4.

Inhibit Na+/Cl- symporter in the distal convoluted tubule.

They inhibit NaCl reabs, increase K+ and H+ excretion and reabsorb Ca2+.

Front 26

Name Na+ channel inhibitors

Back 26

Amiloride and triamterene

Front 27

Indications of Na+ channel inhibitors?

Back 27

Same as for thiazides since they are always combined because Na+ channel inhibitors are K+-sparing.

Front 28

Action of Na+-channel inhibitors?

Back 28

Secreted by OCT2 and MATE in the prox tubule. Travel to collecting duct and inhibit epithelial Na+ channels.

Front 29

Name aldosterone antagonists

Back 29

Spironolactone and eplerenone.

Front 30

Side effects of aldosterone antagonists?

Back 30

Is not selective for mineralocorticoid receptors and can act on other steroid receptors as well. The drug will therefore have antiandrogenic and glucocorticoid effects.

This leads to side-effects, especially in men.

Front 31

Indications of aldosterone antagonists?

Back 31

Hypertension, edema and primary and secondary hyperaldosteronism.

Front 32

Mechanism of action of aldosterone antagonists?

Back 32

Aldosterone binds to mineralocorticoid receptors in the kidney to increase Na+ reabsorption and increase K+ and H+ secretion. By blocking these receptors with aldosterone antagonists can we cause diuresis.