Diuretics - Thiazide and Thiazide like Diuretics

Question 1

What are diuretics?

1 - drugs that increase water, Na+ and Cl- excretion
2 - drugs that decrease water, Na+ and Cl- excretion
3 - drugs that increase water, K+ excretion
4 -drugs that decrease water, K+ excretion

Answer 1

1 - drugs that increase water, Na+ and Cl- excretion

• reduce fluid retention by increasing urine production

Question 2

Where in the kidneys is blood filtered to form the filtrate?

1 - efferent arteriole
2 - afferent arteriole
3 - glomerulus
4 - juxtaglomerular

Answer 2

3 - glomerulus

Question 3

Once the filtrate is formed from the glomerulus, what happens to the fluid as it move through the tubules and out of the collecting duct as urine?

1 - only glucose is reabsorbed
2 - Na+ and K+ only are reabsorbed
3 - lots of ions and fluids are reabsorbed

Answer 3

3 - lots of ions and fluids are reabsorbed

• H2O, ions (K+, Na+, Cl-)
• what is left is urine

Question 4

Where are ions mainly re-absorbed in the renal system?

1 - loop of henle
2 - distal convoluted tubule
3 - proximal tubule
4 - collecting duct

Answer 4

3 - proximal tubule

• glucose, amino acids, ions, uric acid
• excretion of phosphate and H+

Question 5

Water passively follows ion re-absorption in the distal tubules of the renal system, which ion specifically does it follow?

1 - Na+
2 - K+
3 -Cl-
4 - HCO3-

Answer 5

1 - Na+
- due to osmosis (H2O dilutes Na+ in blood)

Question 6

Labels the parts of the renal tubules using the labels below:

1 - loop of henle
2 - distal convoluted tubule
3 - proximal tubule
4 - collecting duct

Answer 6

1 - proximal tubule
2 - loop of henle
3 - distal convoluted tubule
4 - collecting duct

Question 7

Where do thiazide and thiazide like diuretics get secreted into the renal tubules?

1 - loop of henle
2 - distal convoluted tubule
3 - proximal tubule
4 - collecting duct

Answer 7

3 - proximal tubule
- this is how they enter lumen of the renal tubules
- these medications compete with uric acid (causes gout) to be secreted into tubules
- if these medications are taken hric acid is not secreted into tubules and increases risk of gout

Question 8

Thiazide and thiazide like diuretics are secreted into the renal tubules at the proximal tubules. Which molecule to these diuretics compete with to be excreted?

1 - uric acid
2 - glucose
3 - Na+
4 - K+

Answer 8

1 - uric acid

• results in increased uric acid in the blood and risk of gout

Question 9

In the distal convoluted tubules there are transporters that are important in the reabsorption of Na+, Cl- and Ca2+. In normal physiology the following occurs:

• Na+/Cl- co-transporter on apical membrane reabsorbs 1 Na+ and 1 Cl-
• Ca2+ transport absorbs 1 Ca2+
• Na+/Ca2+ transporter on basolateral membrane exchanges 1 Na+ (into cell) and 1 Ca2+ into interstitium

Question 10

What is the mechanism of action of thiazide and thiazide like diuretics?

1 - inhibition of the Na+/K+/Cl- co-transporter
2 - inhibition of the Na+/K+ ATPase
3 - inhibition of the Na+/Cl- co-transporter

Answer 10

3 - inhibition of the Na+/Cl- co-transporter
- happens in the distal convoluted tubule

Question 11

If thiazides and thiazide like diuretics decrease Na+ reabsorption, what happens to the Ca2+ reabsorption from lumen and Na+ levels in the interstitium?

Answer 11

• Ca2+ reabsorption increases from lumen
• Ca2+/Na+ exchanged on the basolateral membrane goes into overdrive
• reduces Na+ réabsorption and thus water follows it into the filtrate

Question 12

Calcium channel blockers are one alternative first line drug for hypertension in a patient aged >55 y/o and black ethnicity. What is the other alternative

• Stage 3: SBP >180 mmHg Treat immediately
• Stage 2: BP >160/100 mmHg Treat once confirmed on 24hr BP
• Stage 1: BP > 140/90 mmHg Treat if end-organ damage or if diabetic

1 - ace inhibitors (ACE-I)
2 - thiazide like diuretics
3 - alpha blockers
4 - angiotensin receptor2 blockers

Answer 12

2 - thiazide like diuretics

• indapemide
• essentially when an ACE-I or ARB-II are unsuitable

Question 13

Which of the following drugs is the first line drug for hypertension, using the cuts offs below in a patient aged >55 y/o and black ethnicity?

• Stage 3: SBP >180 mmHg Treat immediately
• Stage 2: BP >160/100 mmHg Treat once confirmed on 24hr BP
• Stage 1: BP > 140/90 mmHg Treat if end-organ damage or if diabetic

1 - ace inhibitors (ACE-I)
2 - thiazide or thiazide like diuretics
3 - alpha blockers
4 - angiotensin receptor2 blockers

Answer 13

2 - thiazide or thiazide like diuretics

• Indapamide = thiazide
• bendroflumethiazide = thiazide like diuretic
• essentially when an ACE-I or ARB-II are unsuitable, but can also be added to other medication if they have failed treat hypertension

Question 14

Which of the following is the core thiazide we need to be aware of?

1 - Bumetanide
2 - Furosemide
3 - Indapamide
4 - Bendroflumethiazide

Answer 14

4 - Bendroflumethiazide

• prescribed at 2.5mg orally
• should be advised to take in the mornings

Question 15

Which of the following is the core thiazide like diuretic we need to be aware of?

1 - Bumetanide
2 - Furosemide
3 - Indapamide
4 - Bendroflumethiazide

Answer 15

3 - Indapamide

Question 16

All of the following are common adverse events of thiazide and thiazide like diuretics, EXCEPT which one?

1 - hyponatraemia
2 - hypokalaemia
3 - impotence
4 - dehydration
5 - cardiac arrhythmias

Answer 16

4 - dehydration

Question 17

How can thiazide and thiazide like diuretics lead to hypokalaemia?

1 - K+ is exchanged from Na+
2 - exchanged for Ca2+
3 - leaks out as no Na+ to keep it in cells
4 - distal tubule secretes more K+ and H+ in response to high Na+

Answer 17

4 - distal tubule secretes more K+ and H+ in response to high Na+

• can lead to metabolic alkalosis

Question 18

How can thiazide and thiazide like diuretics lead to hypokalaemia and cardiac arrhythmias. What might we see on an ECG trace?

1 - flat T wave
2 - prolonged PR wave
3 - prolonged QT interval and U waves
4 - shortened QRS

Answer 18

3 - prolonged QT interval and U waves
- K+ responsible for re polarisation, so less K+ means longer QT interval

• leads to dangerous cardiac dysrhythmia

Question 19

Should thiazide and thiazide like diuretics be used in a patient with hyponatraemia, hypokalaemia or gout?

Answer 19

• no

Question 20

Which class of drugs should be avoided with thiazide and thiazide like diuretics?

1 - NSAIDs
2 - anti-coagulants
3 - anti-platelets
4 - anti-hypertensives

Answer 20

1 - NSAIDs

• can attenuate

Question 21

Which class of drugs should be avoided with thiazide and thiazide like diuretics for risk of lower K+ levels further and increasing the risk of hyponatraemia?

1 - NSAIDs
2 - anti-coagulants
3 - anti-platelets
4 - loop diuretics

Answer 21

4 - loop diuretics

Question 22

Thiazide like diuretics are commonly used for hypertension. What is one other common use for this medication?

1 - fluid retention
2 - tachycardia
3 - bradycardia
4 - headaches

Answer 22

1 - fluid retention

• commonly referred to as a water tablet

Question 23

When administering thiazide and thiazide like diuretics we need to carefully monitor U&Es at baseline and then how long from initiation of the drug?

1 - 1-2 days
2 - 3-5 days
3 - 1 week
4 - 2-4 weeks

Answer 23

4 - 2-4 weeks

• should be discontinued if patients symptoms improve or further comorbidities develop

Question 24

Do thiazide and thiazide like diuretics activate or inhibit the renin-angiotensin-aldosterone system (RAAS)?

Answer 24

• activate RAAS
• loss of Na+ and fluid reduces decreased extracellular fluid (ECF)
• this activates the RAAS system

Question 25

Are ACE-I or ARB-II combined with thiazide or thiazide like diuretics a good treatment option?

Answer 25

• yes
• thiazide and thiazide reduce Na+ and water absorption BUT activate RAAS
• ACE-I and ARB-II inhibit RAAS