Week 3 - C - Drugs acting on the kidney 1 - Thiazide and loop diuretics

Question 1

What is the function of diuretics?

Answer 1

To increase the urine output by causing increase in an electrolye loss (mainly sodium) andwater

Question 2

What are the three main type of diuretics?

Answer 2

Loop diuretics
Thiazide diuretics
Potassium-sparing diuretics

Question 3

What are the uses of the main diuretics usually?

Answer 3

Loop diuretics - usually used to treat heart failure
Thiazide diuretics - used to treat fluid in the legs and hypertension
Potassium sparing diuretics - Used for ascites and to make sure potassium levels do not drop to much

Question 4

What is the volume of fluid filtered every day by the kidneys and how much is this per minute?

Answer 4

The kidneys filtred approx 180L of fluid per day
They filter 125mls/min

Question 5

The kidneys only produce about 1.5L of urine per day (1ml/min) however so what does this means with regards to the tubular reabsorption?

Answer 5

This must mean that more than 99% of the fluid filtered in the kidneys are reabsorbed into the tubules

Question 6

How is it that the diuretics in the blood are able to be secreted into the nephron?

Answer 6

They are secreted via tranpsort processes into the proximal tubule

Question 7

The organic anion transporters transport acidic drugs such as (thiazide and loop agents) and the organic cation drugs transport basic drugs such as (potassium sparing diuretics) Why can the loops/thiazides have an effect on gout?

Answer 7

Diuretics can cause gout as it stops as much uric acid being transported into the tubular lumen as they are competetivie inhibtors of the transporter – the diuretics bind to the sodium/hydrogen exhanger which stops the acids from being ecxcreted - increased uric acid

Question 8

What transporter to loop diuretics work on to have their effect?

Answer 8

Loop diuretics work on the Na+/K+/2Cl- co-transporter in the thick ascending loop of Henle

Question 9

What in the Na+/K+/2Cl- co transporter do the loop diuretics bind to to have their effect?

Answer 9

They bind to the chloride site in the transporter therefore decreasing sodium reabsorption and leading to water loss osmotically into the tuble

Question 10

Why are loop diuretics known as high ceiling drugs?

Answer 10

This is because the greater the dose of loop diuretics, the greater the effect it has

Question 11

How does the loop diuretic cause potassium loss?

Answer 11

It increases the levels of sodium and water in the nephron tubule
This means that further down the tubule in order to try and compensate for the sodium loss, the tubule tries to reabsorb sodium therefore secreting potassium which cause the hypokalaemia

Question 12

How do the loop diuretics increase the calcium and magnesium excretion leading to hypomagnesaemia and hypocalcaemia?

Answer 12

The loop diuretics causes the loss of the lumen positive potential as the potassium remains in the tubular cell This causes a decrease in paracellular calcium and magnesium reabsorption leading to low levels of these in the blood Futher down the tubule the decreased sodium is recognized and the potassium is therefore secreted into the lumen to be excreted

Question 13

Why is loop diuretics good for quick use?

Answer 13

There is good absorption from he GI tract and rapid onset following IV adminsitration

Question 14

Name some different loop diuretics?

Answer 14

Furosemide,Torsemide Bumetanide, Ethacrynic acid

Question 15

What type of diseases are loop diuretics good for use in?

Answer 15

Heart failure
Liver failure
Acute pulmonary oedema
Kidney failure
Nephrotic syndrome

Question 16

What are at least 5 adverse affects of loop diuretics?

Answer 16

Hypokalaemia
Metabolic alkalosis
Hypomagnesaemia
Hypocalcaemia
Hyperglycaemia
Hyperuricaemia
Hearing loss

Question 17

How can the loop diuretic cause metabolic alkalosis?

Answer 17

Due to the low sodium concentration in the blood, at the collecting duct the K+ and H+ ion transporters cause loss of these ions in order to try and retain sodium
This leads to a hypokalaemia and and alkalsosis

Question 18

Hyperuricaemia – loop diuretics are a substrate for the acid (uric acid) transporter and is therefore competitive, when the kindeys start to transport the loop diuretics into the tubular lumen instead, can cause a wosrning of gout due to the uric acid build up in the blood How can loop diuretics cause hearing loss and what can they not be used with?

Answer 18

There is a Na+/K+/2Cl- transporter in the inner ear endolymph and therefore it can affect this
As aminoglycosides are ototxic should not be used in adjunct with this

Question 19

What do thiazide diuretics bind to?

Answer 19

They bind to the Na+/Cl- symporter in the distal convoluted tubule

Question 20

How does thiazide diuretics cause hypokalaemia?

Answer 20

They increase the load of sodium travelling to the collecting duct therefore causing potassium excretion in an effort to maintain sodium concentration
This cause hypokalaemia

Question 21

Loop diuretics possess an additional, indirect, venodilator action (before diuresis) that is beneficial in pulmonary oedema cause by heart failure Possess an additional, indirect, vasodilator action that contributes to their effectiveness in the treatment of hypertension How does venodilation help in pulmonary oedema caused by heart failure?

Answer 21

It reduces the preload into the heart

Question 22

What is the other difference between loop and thiazide diuretics? (apart from the transporters they act on and the veno and vasodilatory effect respectively)

Answer 22

Loop diuretics cause hypocalcaemia
Thiazide diuretics cause hypercalcaemia

Question 23

Due t the fact less sodium is being absorbed at the apical membrane, this means there is less sodium transport at the basolateral membrane via Na+/K+/ATPase pump What does this mean for calcium in thiazide diuretics?

Answer 23

This means that as the interstitium is positively charged because the thiazide blocks the entry of sodium into the tubular epithelium, there is therefore a decrease in the osmotic flow of calcium leading to hypercalcaemia

Question 24

What are the two main times thiazide diuretics are used?

Answer 24

Mild heart failure and hypertension mainly

Question 25

What line of treatment are thiazide diuretics inhypertension?

Answer 25

It is third line treatment in hypertension

Question 26

Why can thiazide diuretics be used to treat nephrolithiasis (hypercalciuria - kidney stones)?

Answer 26

Nephrolithiasis - decreases calcium excretion into the urine meaning less calcium for stone fromation

Question 27

Why can thiazides be used in nephrogenic diabetes insipidus? paradoxical use (kidneys are not responding to the ADH - diagnose with vasopressin test)

Answer 27

Nephrogenic diabetes insipidus is a paradoxical use – can prescribe it as along with NSAIDs they can increase urine output, which leads to shrink the afferent arteriole therefore reducing the filtration rate and causing more absorption in the proximal tubule can be used to create mild hypovolemia which encourages salt and water uptake in proximal tubule and thus improve nephrogenic diabetes insipidus.

Question 28

What eGFR are thiazide diuretic powerless in? and how can they predispose to diabetes?

Answer 28

ineffective if eGFR is less than 30 mL/minute And can reduce insulin secretion (due to decreased potassium) and sensitivity – therefore can precipitate diabetes And have an increased glucose

Question 29

What is the main thiazide diuretic and which is the only thiazide diuretic that can bu used with a loop diuretic for renal failure?

Answer 29

Bendrafluomethiazide Metolazone is the only thiazide diuretic able to help in acute kindey failure

Question 30

What are the same side effects that thiazide diuretics have as loop diuretics?

Answer 30

Hypokalaemia Metabolic alkalosis - sodium and chloride loss leads to increased H+ ion loss in collecting duct as an attempt to correct the loss Hyponatraemia Hypomagnesaemia Hyperuricaemia and gout Hyperglycaemia

Question 31

What is the difference between effect on calcium in loop diuretics and thiazide?

Answer 31

Loop diuretics cause hypocalcaemia Thiazide cause hypercalcaemia

Question 32

Increased Na+ load in the filtrate caused by loop or thiazide diuretic produces enhanced reabsorption of Na+ in late distal and collecting duct Leads to enhanced secretion of K+ and H+ How can low potassium present? (also what does it look like on ECG)

Answer 32

Present with muscle cramps, fatigue, arythmias Flattened Twaves on ECG

Question 33

Due to the diuretics causing a loss of sodium, the RAAS system may be activated Describe how this effect can cause hypokalaemia?

Answer 33

Renin produced by juxtaglomerular cells in response to low sodium in the blood, this cause conversion of angitotensinogen (produced by liver) to AT1. Converted by ACE to AT2. AT2 causes aldosterone secretion from the adrenal cortex which causes sodiu reabsorption due to potassium loss

Question 34

What cells of the adrenal cortex secrete aldosterone?

Answer 34

Zona glomerulosa

Question 35

What is an example of a potassium sparing diuretic? They act on the collecting duct by aldosterone mediated sodium reabsorption and potassium excretion

Answer 35

Spironolactone - potassium sparing diuretic known as an aldosterone antagonist