Lecture 5 - Diuretics

Question 1

What is the function of diuretics?

Answer 1

Increase production of urine to eliminate water from the body

Question 2

What is the purpose of diuretics removing excess water from the body?

Answer 2

Reducing plasma volume + cardiac output
Reduce BP
Reduce oedema/Ascites

Question 3

What are drugs called that increase excretion of sodium and water resulting in increased urine volume?

Answer 3

Diuretics

Question 4

What is Diuresis?

Answer 4

Excretion of water in urine

Question 5

What is natriuresis?

Answer 5

Excretion of sodium in the urine

Question 6

What are the 5 classes of diuretics?

Answer 6

Carbonic anhydrase inhibitors
Osmotic diuretics
LOOP DIURETICS
POTASSIUM SPARING DIURETICS
THIAZIDE AND THIAZIDE-LIKE DIURETICS

Question 7

What is the main ion which most diuretics interfere witht the normal reabsorption of?

What diuretic doesn’t do this?

Answer 7

Na+

Osmotic diuretics

Question 8

What part of the nephron do carbonic anhydrase inhibitor diuretics work on?

Answer 8

PCT

Question 9

What part of the nephron do osmotic diuretics work on?

Answer 9

Whole nephron (most effect at PCT)

Question 10

What part of the nephron do Loop Diuretics work on?

Answer 10

Loop of Henle

Question 11

What part of the nephron do Thiazide and thiazide like diuretics work on?

Answer 11

DCT

Question 12

What part of the Nephron do potassium sparing diuretics work on?

Answer 12

DCT and Collecting Duct

Question 13

How do carbonic anhydrase inhibitors act as diuretics?

Answer 13

Inhibit carbonic anhydrase
Less carbonic acid broken down into H20 and CO2
Less CO2 diffuses into PCT cell
Less H2CO3 made from CO2 + H20 so less HCO3- and H+ made

Since theres less H+ in the PCT cell the Na+/H+ exchanger works less so less Na+ reabsorbed into the PCT cell (more lost in urine)

Question 14

What are Flozins?

How are they similar to a diuretic but aren’t a diuretic?

Answer 14

Inhibit SGLT-2 reducing the absorption of Na+ since less glucose being reabsorbed
(Less Na+ reabsorbed = less water reabsorbed)

Question 15

What is an example of an osmotic diuretic?

Answer 15

Mannitol

Question 16

How do osmotic diuretics work?

Answer 16

Increase water excretion by acting as an osmole drawing and keeping water in nephron

Question 17

Why are osmotic diuretics not used in patients with heart failure and pulmonary oedema?

Answer 17

It expands the extracellular fluid volume initially as it travels to the kidneys

Question 18

When are osmotic diuretics used?

Answer 18

Acute renal failure due to shock or trauma (increase extracellular fluid volume)

Acute drug poisoning (elimates drugs reabsorbed from renal tubules)

Decreases intracranial and Intra ocular pressure before surgery

Question 19

How can using osmotic diuretics lead to hyponatraemia and hypernatraemia at different stages?

Answer 19

Initially causes hyponatraemia due to extracellular fluid expansion

Then excess use leads to dehydration and hypernatraemia

Question 20

What channels do Loop diuretics block in the loop of Henle?

Answer 20

NKCC channels

Question 21

How does loop diuretics block NKCC channels in the LOH lead to a diuretic affect?

Answer 21

Less Na+, K+ and 2Cl- reabsorbed into the cell so more stays in the LOH lumen

Water stays with the ions

Question 22

What other affect can loop diuretics have on the body?

Answer 22

Hypocalcaemia
Hypomagneseamia

Question 23

How can loop diuretics cause hypomagnesaemia and Hypocalcaemia?

Answer 23

The NKCC channel gets blocked means less Na+, Cl- and K+ reabsorbed, this means less K+ leak back across into the lumen via ROMK so the lumen doesn’t become positively charged

This means theres less repelling force so less Mg2+ and Ca2+ reabsorbed via paracellular transport

Question 24

What is the most potent type of diuretic and why?

Answer 24

Loop Diuretics

They block NKCC channels which maintains the osmotic gradient

Question 25

What are some loop diuretics?

Answer 25

Furosemide

Question 26

When are loop diuretics used?

Answer 26

Severe oedema from congestive heart failure Treating Hypercalcaemia Acute pulmonary oedema Acute Hyperkalaemia or acute Hypercalcaemia

Question 27

How can loop diuretics lead to metabolic alkalosis?

Answer 27

Loss of water leads to increased concentration of bicarbonate ions in blood making it more alkaline

Question 28

What are some side effects of loop diuretics?

Answer 28

Hypovolaemia Hyponatraemia Hypokalaemia Hypomagnesaemia Hypocalcaemia Metabolic alkalosis Postural hypotension

Question 29

What channel do Thiazide and Thiazide like diuretics block?

Answer 29

Na+/Cl- cotransporter in the DCT

Question 30

How does Thiazide/Thiazide like diuretics cause a diuretic effect?

Answer 30

Blockage of the Na+/Cl- cotransporter means less Na+ reabsorbed into DCT cell so less Na+ reabsorbed into vasa recta Less Na+ in vasa recta means less water follows it into the vasa recta

Question 31

How can thiazide lead to Hypercalcaemia?

Answer 31

Blocks the Na+/Cl- cotransporter of the DCT cell This dec conc of Na+ in cell (steeper grad from interstitium into cell) This is more favourable for the Na+/Ca2+ antiporter on the basolateral membrane of the cell so more Ca2+ reabsorbed into interstitium and then vasa recta

Question 32

What is an example of a Thiazide/thiazide like diuretic? These are 1st line antihypertenisves

Answer 32

Bendroflumethiazide Indapamide

Question 33

What can Thiazides be used to treat?

Answer 33

Essential hypertension Mild heart failure Osteoporosis (since increases calcium reabsorption) Nephrogenic diabetes Insipidus polyuria

Question 34

How do Potassium sparing diuretics work?

Answer 34

Block ENAC channels in the Collecting duct cells Means less Na+ reabsorbed into cell and vasa recta so more water lost

Question 35

How do aldosterone antagonists have a diuretic affect while also being Potassium sparing?

Answer 35

Aldosterone leads to more Na+/K+ ATPases to be expressed in the collecting duct so more Na+ reabsorbed so more water follows it Also decreases Expression of ROMK channels preventing K+ leaking back into the lumen of the collecting duct

Question 36

What is a potassium sparing diuretic?

Answer 36

Amiloride

Question 37

What is an example of an aldosterone antagonist?

Answer 37

Spironolactone

Question 38

What can aldosterone antagonists and potassium sparing diuretics be used to treat?

Answer 38

Secondary Hyperaldosteronism Chronic Heart Failure Cirrhosis Nephrotic syndrome Treats hypertension

Question 39

Why can aldosterone antagonists and potassium sparing diuretics not be used in patients with Chronic renal failure?

Answer 39

Can lead to hyperkalaemia Leads to less aldosterone being made This leads to less ROMK being created Means less K+ lost Since patients with renal failure have a decreased GFR plasma conc of K+ increase

Question 40

Where amino acids completely reabsorbed from the filtrate via active transport?

Answer 40

PCT

Question 41

When theres an increase in conc of potassium the conc of what hormone increases and why?

Answer 41

Inc aldosterone Leads to more ROMK being expressed so more K+ can be lost

Question 42

How can loop diuretics result in hypokalaemia?

Answer 42

NKCC blocked Less Na+ reabsorbed More Na+ delivered to DCT and CD More Na+ reabsorbed through ENAC channels K+ lost through ROMK Leads to hypokalaemia

Question 43

What part of the nephron is the glucose reabsorbed?

Answer 43

PCT

Question 44

Where is most of the Urate and creatinine secreted?

Answer 44

PCT

Question 45

What is the main hormone that affects K+ excretion?

Answer 45

Aldosterone (due to ROMK)

Question 46

What is the main transporter driving electrolyte reabsorption in the LOH?

Answer 46

NKCC transporter

Question 47

How does aldosterone affect membrane permeability to sodium?

Answer 47

Increases it