Drugs and the kidney

Question 1

What makes the kidneys susceptible to drug/ chemical induced damage?

Answer 1

Highly vascular
Large surface area for binding and transport
Reabsorption of water concentrates some drugs in nephron
Excretion route for most drugs

Question 2

What needs to be considered when prescribing for a patient with impaired renal function?

Answer 2

1. Ability to excrete drug (impaired ability can lead to build up to toxic levels)
2. Toxicity of drug (nephrotoxic drugs should be avoided if possible as may worsen impairment)

Question 3

What is a diuretic?

Answer 3

Substance that promotes the formation (and excretion) of urine, usually by promoting renal excretion of sodium (natriuresis)
Commonly used for conditions associated with oedema and hypertension

Question 4

What are the classes of diuretics?

Answer 4

Loop diuretics 
Thiazide diuretics 
Potassium sparing diuretics 
Carbonic Anhydrase inhibitors 
Osmotic diuretics

Question 5

Where is water reabsorbed throughout the nephron?

Answer 5

65% proximal convoluted tubule

20% thin descending limb

Question 6

Where is sodium reabsorbed throughout the uriniferous tubule?

Answer 6

65% proximal convoluted tubule
25% thick ascending limb
8% distal convoluted tubule/ collecting duct

Question 7

What is the MoA of carbonic anhydrase inhibitors?

Answer 7

Inhibits Carbonic Anhydrase in tubular cells of PCT preventing reabsorption of HCO3- (as HCO3- cannot be transported across luminal membrane)
Weak diuretic effect as means only a small amount of sodium can be reabsorbed

Question 8

What are the potential side effects of Carbonic Anhydrase inhibitors?

Answer 8

Metabolic acidosis as it prevents secretion of H+

Question 9

When are Carbonic Anhydrase inhibitors typically used?

Answer 9

Reduction of intraocular pressure (e.g. in glaucoma)

Mountain sickness prophylaxis

Question 10

Name a Carbonic Anhydrase inhibitor

Answer 10

Acetalozamide

Question 11

What is the MoA of osmotic diuretics?

Answer 11

Increase filtrate osmolarity preventing water reabsorption

[work best in PCT and descending limb]

Question 12

Name an Osmotic Diuretic

Answer 12

Mannitol

Question 13

What are osmotic diuretics typically used to treat?

Answer 13

Raised intracranial pressure and raised intraocular pressure

Question 14

How is glucose used as an osmotic diuretic?

Answer 14

In disease states (e.g. uncontrolled DM), glucose reaches a transport maximum (where no more glucose can be reabsorbed) leading to excretion of glucose (and water) in the urine

Question 15

What is the MoA of loop diuretics?

Answer 15

Inhibit the Na+K+2Cl co-transporter (in the thick ascending limb) by competitively inhibiting Cl- binding

Question 16

Name a loop diuretic

Answer 16

Furosemide

Question 17

What are loop diuretics typically used to treat?

Answer 17

Peripheral oedema (e.g. heart failure)
Acute pulmonary oedema
Resistant hypertension

Question 18

What are the potential side effects of loop diuretics?

Answer 18

Hypovolaemia/ hypotension
Hyponatraemia/ hypokalaemia
Ototoxicity

Question 19

Name the Thiazide diuretics

Answer 19

Bendroflumethiazide
Hypochlorothiazide
Indapamide
Chlortalidone

Question 20

What is the MoA of thiazide diuretics?

Answer 20

Inhibit Na+Cl- Co-transporters in the early distal tubule by competitively inhibiting Cl- binding

Question 21

What are thiazide diuretics typically used for?

Answer 21

Peripheral oedema (e.g. heart failure) 
Hypertension

Question 22

What are the potential side effects of thiazide diuretics?

Answer 22

Hyponatraemia/ hypokalaemia
Gout (due to increased uric acid in plasma)
Erectile dysfunction
Hyperglycaemia

[Not ideal in renal impairment as they have to be filtered and secreted]

Question 23

How can loop and thiazide diuretics cause hypokalaemia?

Answer 23

Increase delivery of NaCl to distal nephron and decrease blood volume which increases potassium secretion by increasing tubular flow rate and activity of Na+/K+ ATPase and activating RAAS (increasing aldosterone)

Question 24

What potassium sparing diuretics are aldosterone antagonists?

Answer 24

Spironolactone

Elperenone

Question 25

What is the MoA of aldosterone antagonists (potassium-sparing diuretics)?

Answer 25

Competitively binds to intracellular mineralocorticoid receptors (preventing aldosterone from binding) in principal cells in the DCT and cortical collecting tubules - this prevents synthesis of proteins such as ENaC and ATPase thus reducing potassium secretion

Question 26

What potassium sparing diuretics are ENaC antagonists?

Answer 26

Amiloride

Question 27

What is the MoA of ENaC antagonists (potassium-sparing diuretics)?

Answer 27

Blocks ENaC by competing for Na+ binding site and decreases luminal permeability to Na+ meaning that K+ secretion is reduced into lumen

[Nb. weak diuretic, used in combination with loop or thiazide diuretics]

Question 28

What are potassium-sparing diuretics typically used for?

Answer 28

Chronic heart failure
Peripheral oedema/ ascites (caused by Cirrhosis)
Resistant hypertension
Primary hyperaldosteronism (Conn’s Syndrome)
ENaC antagonists often used in combination with Loop or Thiazide diuretics to prevent hypokalaemia

Question 29

What are the possible side effects of potassium-sparing diuretics?

Answer 29

Hyperkalaemia (need to be careful when prescribing with other RAAS drugs)
Gynaecomastia (aldosterone antagonists)

Question 30

What diuretics can be used in combination with eachother?

Answer 30

Loops + Thiazides (loops increase efficiency of thiazides as they increase the amount of NaCl delivered to distal nephron)
Loops/ Thiazides + Potassium-sparing (minimise loss of K+)

Question 31

What drugs affect GFR?

Answer 31

NSAIDs - inhibit prostaglandin production which normally causes dilation of afferent arterioles so NSAIDs reduce GFR
ACE inhibitors/ ARBs - prevent action of angiotensin II which normally causes efferent arteriole constriction so ACEi/ ARBs can reduce GFR