S4) Diuretics & Renal Pharmacology

Question 1

What are the four broad functions of the kidney?

Answer 1

• Regulatory
• Excretory
• Endocrine
• Metabolism

Question 2

What are the three regulatory functions of the kidney?

Answer 2

• Fluid balance
• Acid-base balance
• Electrolyte Balance

Question 3

What does the kidney excrete?

Answer 3

• Waste products
• Drug elimination (glomerular filtration & tubular secretion)

Question 4

Identify four endocrine secretions of the kidney

Answer 4

• Renin
• Erythropoetin
• Prostaglandins
• 1-alpha calcidol

Question 5

Which substances does the kidney metabolise?

Answer 5

• Vitamin D
• Polypeptides e.g. insulin
• Drugs e.g. morphine, paracetamol

Question 6

What are the seven different types of diuretic drugs acting on the kidney?

Answer 6

• Carbonic anhydrase inhibitors
• Osmotic diuretics
• Loop diuretics
• Thiazides
• K⁺ sparing diuretics
• Aldosterone antagonists
• ADH Antagonists

Question 7

Describe the actions and effects of carbonic anhydrase inhibitors

Answer 7

• Sodium bicarbonate diuresis
• Excretion of Na⁺, K⁺ and PO₃
• Metabolic acidosis / hypokalemia

Question 8

Describe the actions and effects of osmotic agents

Answer 8

• Filtered at glomerulus
• Increase osmotic gradient throughout nephron
• Excessive water loss
• Hypernatraemia

Question 9

Describe the actions and effects of loop agents

Answer 9

• Thick ascending limb loop of Henle
• Inhibit NaCl reabsorption
• Concurrent Ca/Mg excretion
• Hypokalaemia (CD)

Question 10

Describe the actions and effects of thiazides

Answer 10

• Inhibits NaCl reabsorption
• Promotes Ca reabsorption
• Hypokalaemia
• Hyperuricaemia

Question 11

Describe the actions and effects of aldosterone antagonists e.g. spironolactone

Answer 11

• Inhibits Na⁺ retention (Na-K ATPase / Na⁺ flux)
• Blunts K⁺ and H⁺ secretion
• Androgenic cross-reactivity

Question 12

What is the action of aldosterone on the kidney

Answer 12

Aldosterone increases expression of ENaC and Na/K/ATPase in principal cells of the collecting duct

Question 13

Describe the actions and effects of ADH antagonists e.g. lithium

Answer 13

ADH antagonists reduce concentrating ability of urine in collecting ducts

Question 14

Explain how the following substances have diuretic action:

• Alcohol
• Caffeine

Answer 14

• Alcohol – inhibits ADH release
• Caffeine – ↑GFR and ↓ tubular Na⁺ reabsorption

Question 15

Identify four generic adverse drug reactions from diuretics

Answer 15

• Anaphylaxis / photosensivity rash
• Hypovolaemia & hypotension
• Electrolyte disturbance (Na⁺, K⁺, Mg²⁺, Ca²⁺)
• Metabolic abnormalities

Question 16

Identify 5 common specific ADRs from thiazides

Answer 16

• Gout
• Hyperglycaemia
• Erectile dysfunction
• ↑LDL & TG
• Hypercalcaemia

Question 17

Identify 3 common specific ADRs from spironolactone

Answer 17

• Hyperkalaemia
• Impotence
• Painful gynaecomastia

Question 18

Identify 4 common specific ADRs from furosemide (loop diuretic)

Answer 18

• Ototoxicity
• Alkalosis
• ↑LDL & TG
• Gout

Question 19

Identify a common specific ADRs from bumetanide (loop diuretic)

Answer 19

Myalgia

Question 20

Explain the effect of ACE Inhibitors interacting with K⁺ sparing diuretics

Answer 20

Increased hyperkalaemia → cardiac problems

Question 21

What is the effect of aminoglycosides interacting with loop diuretics?

Answer 21

• Ototoxicity
• Nephrotoxicity

Question 22

Explain the effect of digoxin interacting with thiazide and loop diuretics

Answer 22

Hypokalaemia → increased digoxin binding & toxicity

Question 23

What is the effect of β- Blockers interacting with thiazide diuretics?

Answer 23

• Hyperglycemia
• Hyperlipidemia
• Hyperuricaemia

Question 24

What is the effect of steroids interacting with thiazide & loop diuretics?

Answer 24

Increased risk of hypokalaemia

Question 25

What is the effect of lithium interacting with thiazide & loop diuretics?

Answer 25

- Lithium toxicity (thiazides) - Reduced lithium levels (loop)

Question 26

What is the effect of carbamazepine interacting with thiazide diuretics?

Answer 26

Increased risk of hyponatraemia

Question 27

Which diuretics are commonly used to treat hypertension?

Answer 27

- Thiazide diuretics (vasodilatation as well as diuresis) - Spironolactone

Question 28

Which diuretics are commonly used to treat heart failure?

Answer 28

- Loop diuretics - Spironolactone (non-diuretic benefits)

Question 29

Which diuretics are commonly used to treat decompensated liver disease?

Answer 29

- Spironolactone - Loop diuretics

Question 30

Which diuretics are commonly used to treat nephrotic syndrome?

Answer 30

- Loop diuretic (often big doses needed) - ± Thiazides - ± K⁺ sparing diuretic / K⁺ supplements

Question 31

Which diuretics are commonly used to treat Chronic Kidney Disease?

Answer 31

- Loop diuretics - ± Thiazide-like - Generally avoid K⁺ sparing diuretics

Question 32

Describe the process and requirements for diuretic delivery to renal tubule *e.g. furosemide*

Answer 32

- **Blood flow** to proximal tubule must be intact (transport via albumin) - **Proximal tubule** must be functioning to transport furosemide across - **TAL** must be intact to respond to furosemide

Question 33

In four steps, describe the clinical approach to treat a patient with refractory oedema

Answer 33

⇒ Check salt intake ⇒ IV furosemide (if gut oedema likely) ⇒ Find minimum effective dose ⇒ Give repeated bolus or infusion (short t_1/2)

Question 34

Describe the relationship between diuretic drugs and kidney function in terms of adverse reactions

Answer 34

- Drugs may reduce kidney function by **direct/indirect toxicity** - Drugs may **accumulate to toxic levels** if they are excreted through the kidneys and renal function is impaired

Question 35

Identify four potentially nephrotoxic drugs

Answer 35

- Aminoglycosides *e.g gentamicin* - Vancomycin (IV only) - Aciclovir - NSAIDs

Question 36

Identify four drugs which can exacerbate renal dysfunction

Answer 36

- ACE-Inhibitors - Diuretics - NSAIDs - Metformin

Question 37

What are the three steps involved in managing hyperkalaemia?

Answer 37

⇒ Identify a cause ⇒ ECG ⇒ Treatment

Question 38

Describe the three steps in the emergency treatment of hyperkalaemia

Answer 38

⇒ Protect the heart → calcium gluconate ⇒ Lower serum K⁺ → insulin / dextrose ⇒ Remove K⁺ from body → calcium resonium