Session 7 - Diuretics

Question 1

Define diuresis

Answer 1

• Increased formation of urine by the kidney

Question 2

Define diuretics

Answer 2

• Block reabsorption of Na+ and therefore water by the kidney

Question 3

Give three main types of diuretics

Answer 3

• Loop diuretics
  
  • Thiazide diuretics
  • K+ sparing diuretics and aldosterone antagonists

Question 4

How do loop diuretics work?

Answer 4

• Acts on TAL of the loop of henle
  
  • Block Na-K-2Cl
  • Causes excretion of 10-25% of filtered Na+ ions (segments downstream also have limited capacity to reabsorb water, increasing diuresis)

Question 5

Name two loop diuretics

Answer 5

• Furosemide

* Bumetanide

Question 6

What do Thiazide diuretics do?

Answer 6

• Act on early DCT
  
  • Block Na-Cl co-transporter
  • Inhibits only 5% of Na+ reabsorption

Question 7

Give a thiazide diuretic

Answer 7

• Bendroflumethiazide

Question 8

Where do K+ sparing diuretics and aldosterone antagonists work?

Answer 8

• Late DCT and collecting duct
  
  • Reduce ENaC reabsorption of sodium
  • Inhibit 2% Na+ reabsorption

Question 9

Why are K+ sparing diuretics named thus?

Answer 9

Reduce the loss of K+ and can produce life threatening hyperkalaemia

Question 10

Give an example of a K+ sparing diuretic

Answer 10

• Amiloride

Question 11

Give an example of an aldosterone antagonist

Answer 11

• Spironolactone

Question 12

Give overall dangers of diuretics

Answer 12

• Hyper/hypokalaemia

* RAAS activation

Question 13

Outline the negatives of using K+ sparing diuretics/Aldosterone Antagonists

Answer 13

• Reduce loss of K+ and may produce life threatening hyperkalaemia

Question 14

Give a negative effect of loop diuretics

Answer 14

• Reduces calcium absorption, inducing urinary excretion

Patient may become hypocalcaemi

Question 15

What do loop and thiazide diuretics do?

Answer 15

• Increase the loss of potassium in the urine

Hypokalaemia

Question 16

Outline how loop and thiazide diuretics cause hypokalaemia

Answer 16

• Block Na+ and H20 reabsorption in LoH or early DCT
  
  • Increase Na+ and H20 delivery to late DT + CD
  • Increase Na+ absorption by principle cells/Faster flow rate of filtrate so K+ washed away faster
  • Favourable electrical gradient for K+ excretion/Low K+ concentration in lumen

Question 17

How do K+ sparing diuretics cause hyperkalaemia?

Answer 17

• Block epithelial Na+ channels
  
  • Reduce Na+ reabsorption
  • Reduce potassium loss in urine
  • Hyperkalaemia

Question 18

How do aldosterone antagonists cause hyperkalaemia?

Answer 18

• Block of action of aldosterone
  
  • Reduce activity of Na/K+ ATPase & epithelial Na+ channels
  • Reduce Na+ reabsorption
  • Reduce potassium loss in urine
  • Hyperkalaemia

Question 19

What do all diuretics do?

Answer 19

• Reduce ECF volume so activate RAAS

* This increases aldosterone secretion, increase Na+ reabsorption and K+ secretion, contributing to hypokalaemia

Question 20

List negative effects which come about as a result of diuretics use and abuse

Answer 20

• Hypokalaemia
  
  • Hyperkalaemia
  • RAAS activation
  • Hypovolaemia
  • Hyponatraemia
  • Increased uric acid levels in blood
  • Metabolic effects

Question 21

What is hypovolaemia?

Answer 21

• Decreased ECF volume due to excessive loss of Na+ and water

Question 22

What 3 things must be done to avoid hypovolaemia?

Answer 22

• Monitor weight
  
  • Look for signs of dehydration
  • Check BP

Question 23

What is hyponatraemia?

Answer 23

• Decreased sodium in blood

Multiple symptoms, including nausea, vomiting, headache and confusion

Question 24

What do increased uric acid levels in blood cause?

Answer 24

Gout

Question 25

What are two negative metabolic effect of diuretic use?

Answer 25

* Glucose intolerance | * Increased LDL levels

Question 26

What is a carbonic anhydrase inhibitor?

Answer 26

• Diuretic which acts in PCT by inhibitng enzyme carbonic anhydrase to interfere with Na+ and HCO3- reabsorption

Question 27

Why is carbonic anhydrase no longer used a diuretic?

Answer 27

• HCO3- loss leads to metabolic acidosis

Question 28

Give six conditions diuretics used to treat

Answer 28

* Conditions with ECF expansion and Oedema * Acute pulmonary oedema * Hypertension * Hypercalcaemia * Cerebral oedema (Osmotic diuretics) * Glaucoma (carbonic anydrase)

Question 29

Give four conditions which involve ECF expansion and oedema

Answer 29

* Congestive heart failure * Nephrotic syndrome * Kidney failure * Ascites and oedema due to liver cirrhosis

Question 30

What is acute pulmonary oedema usually due to?

Answer 30

• Left heart failure

Question 31

What is pulmonary oedema treated with?

Answer 31

• Loop diuretics

Question 32

What is hypertension treated with?

Answer 32

* Thiazide diuretics | * Spironolactone in primary hyperaldosteronism (Conn's syndrome)

Question 33

How is hypercalcaemia treated?

Answer 33

• Loop diuretics promote Ca2+ excretion in loop of henle

Question 34

Give three substances with diuretic actions

Answer 34

* Alcohol - Inhibits ADH release * Coffee - Increased GFR, decreased Na+ reabsorption * Lithium - Inhibits ADH action on collection ducts

Question 35

What is diuresis expressed as in the form of a symptom?

Answer 35

• Polyuria

Question 36

Give four causes of polyuria that are non drink related

Answer 36

• Diabetes mellitus ○ Glucose in filtrate -> Osmotic diuresis • Central diabetes insipidus ○ Decreased ADH release from posterior pituitary -> Diuresis • Nephrogenic diabetes insipidus ○ Poor response of collecting ducts to ADH -> Diuresis • Psychogenic polydypsia ○ Increased intake of fluid