Diuretics

Question 1

Where do Osmotic diuretic act

Answer 1

Proximal tubules, Loop of Henle, Collecting duct

Question 2

Osmotic diuretics mechanism of action

Answer 2

They create an osmotic pressure which draws water from cells and the interstitium into the tubule lumen = Inhibition of water and Na+ reabsorption

Question 3

Name some osmotic diuretics

Answer 3

Mannitol, isosorbide, glycerine and urea

Question 4

Side effects of osmotic diuretics

Answer 4

CV toxicity immediately after injection, they can cause an increase in blood volume and so increases workload of the heart.

Question 5

When not to use osmotic diuretics

Answer 5

If they have congestive heart failure

Question 6

Carbonic anhydrase inhibitors site of action

Answer 6

Proximal tubules

Question 7

Carbonic anhydrase inhibitors mechanism of action

Answer 7

Inhibition of bicarbonate reabsorption, preventing H+ formation and Na/H transported wont reabsorb any Na. They block the CA enzyme

Question 8

Name some Carbonic anhydrase inhibitors

Answer 8

Acetazolamide, Methazolamide

Question 9

When to use Carbonic anhydrase inhibitors

Answer 9

Raised intra-ocular pressure in open-angle glaucoma (they reduce aqueous humour secretion)
Ocular hypertension when monotherapy is inadequate

Question 10

Side effects of Carbonic Anhydrase inhibitors

Answer 10

Metabolic acidosis
Renal stones (Calcium and phosphate)
Renal potassium wasting (enhanced K+ secretion due to NaHCO3)

Question 11

When to use osmotic diuretics (Mannitol mainly)

Answer 11

1) it is inherently non-toxic,
2) it is freely filtered,
3) it is non-reabsorbable,
4) it is not metabolised,
5) the other agents may pass into cells to a limited extent.

Question 12

Loop Diuretics site of action

Answer 12

Thick ascending limb of Loop of Henle

Question 13

Loop Diuretics mechanism of action

Answer 13

Inhibit the Na+/K+/2Cl- co-transporter (NKCC2) in the thick ascending loop of Henle → decrease in Na+, K+ and Cl- reabsorption (blocks transport of NaCl out of the tubule into the interstitial tissue)

Question 14

Name some Loop diuretics

Answer 14

Furosamide, Torasamide

Question 15

When to use Loop diuretics

Answer 15

Treat water imbalances in Congestive HF, KF and pulmonary oedema

Question 16

Loop diuretics contraindications

Answer 16

Don’t use if hypokalaemia
Don’t use with aminoglycoside antibiotics (e.g. Gentamicin) - cause HL and Kidney damage
NSAIDs reduce the effect of loop diuretics

Question 17

Thiazide diuretics site of action

Answer 17

Early distal tubule

Question 18

Thiazide diuretics mechanism of action

Answer 18

Block the thiazide-sensitive Na/Cl co-transporter - inhibit reabsorption of Na+ and Cl− from the distal convoluted tubules in the kidneys
Also increase Ca2+ reabsorption at distal tubules - lowering Na+ conc increases activity of Na/Ca co-transporter
Also cause a loss of K+

Question 19

Thiazide diuretics contraindications

Answer 19

Hypotension
Gout (reduce clearance of uric acid)
Renal failure
Lithium therapy
Hypokalemia
May worsen diabetes

Question 20

Name some thiazide diuretics

Answer 20

Hydrochlorothiazide, clorothiazide, bendroflumethiazide

Question 21

Where do K+ sparing diuretics act

Answer 21

Late distal tubule
Collecting duct

Question 22

K+ sparing diuretics side effects

Answer 22

Hyperkalaemia , so potassium supplements should not be co-prescribed.
Caution when used with drugs such as ACE inhibitors that increase blood potassium levels. Increases in K+ can lead to cardiac arrythmias

Question 23

Aldosterone agonists (K+ sparing diuretics) mechanism of action

Answer 23

Aldosterone receptor antagonists reduce this expression of Na+/K+ATPase and ENaC thus reducing both Na+ reabsorption and K+ secretion

Question 24

Name some Aldosterone agonists (K+ sparing diuretics)

Answer 24

Spironolactone, Eplerenone

Question 25

Na+ channel inhibitors (K+ sparing diuretics) mechanism of action

Answer 25

Inhibit Na+ reabsorption by blocking ENaC on the apical membrane and reduce K+ secretion by a downstream reduction in Na+/K+ATPase activity on the basolateral membrane.

Question 26

Name some Na+ channel inhibitors (K+ sparing diuretics)

Answer 26

Amiloride, triamterene

Question 27

When to use K+ sparing diuretics

Answer 27

Used in combination with loop diuretics and thiazides to reduce K+ loss particularly where hypokalaemia is a concern.

Question 28

What is Digoxin

Answer 28

An inhibitor of the Na+/K+ ATPase pump and binds to the alpha subunit that comes from Foxgloves

Question 29

Digoxin mechanism of action

Answer 29

inhibits the Na+/K+ ATPase pump and binds to the alpha subunit.
This causes an increase in intracellular Na+.
This reduces the action of the Na+/Ca2+ exchanger in the resulting in increased intracellular Ca2+ which is then stored in the sarcoplasmic reticulum.
The Ca2+ is released during a cardiac action potential thus increasing the force of a contraction

Question 30

When to not use Digoxin

Answer 30

Hypokalaemia resulting from loop diuretics and thiazides will potentiate the effect digoxin, thus increasing the risk of cardiac arrythmias