Drugs acting on the kidneys 1

Question 1

Define in general terms what a diuretic is

Answer 1

Agents that increase urine output through causing a net electrolyte (mainly sodium) and water loss.

Question 2

How do diuretics enter the glomerular filtrate to have there effect ?

Answer 2

1. Glomerular filtration
2. Secretion via transport process in the proximal tubule

Question 3

What diuretics are secreted into the tubule via The organic anion transporters (OATs)?

Answer 3

Loop and thiazide diuretics

Question 4

What diuretics are secreted into the tubule via The organic cation transporters (OCTs)?

Answer 4

Triamterene and amiloride

Question 5

Where in the glomerulus and on what does loop diuretics act ?

Answer 5

Inhibits the Na+/K+/2Cl- cotransporter in the thick ascending loop of henle by binding to Cl- site in the transporter

Question 6

Describe the mechanism of action of loop diuretics

Answer 6

1. Acts on Na+/K+/2Cl- cotransporter, preventing the transporter from being able to reabsorb Cl-
2. This then prevents the transporter from working correctly so Na+ and K+ are then also not reabsorbed
3. In the long-term Ca2+ and Mg2+ are also not reabsorbed

Increased Na+, H20, Cl-, K+, Ca2+ and Mg2+ excretion

Question 7

What is the secondary affect of loop diuretics ?

Answer 7

They have a secondary venodilator action which is beneficial in pulmonary oedema caused by HF

Question 8

Give some examples of loop directics and how you remember them

Answer 8

• Furosemide and Bumetanide
• Think ‘mide and nide’

Question 9

What is the typical responsiveness of patients to furosemide and what affects it?

Answer 9

Responsiveness to furosemide is very variable from 20-100% and depends on drugs, liver function (approx. 50% is metabolised by the liver) and amount of bile salts

Question 10

What are the clinical uses of loop diuretics ?

Answer 10

• Acute pulmonary oedema
• Chronic HF
• Chronic KD
• Nephrotic syndrome
• Hepatic cirrhosis with ascites
• Acute kidney failure
• Hypercalcaemia and stones

Question 11

What is the equivalent doses of furosemide to bumetanide ?

Answer 11

1mg of bumetanide is equivalent to 40mg of furosemide

Question 12

What is the action of thiazide diuretics and where in the glomerulus does this occur ?

Answer 12

Inhibit the Na+/Cl- symporter in the distal tubule ==> inhibiting Na+ reabsorption

Question 13

Describe the mechanism of action of thiazide diuretics

Answer 13

1. Inhibit the Na+/Cl- symporter in the distal tubule, and since H20 follows salt then water is excreted also
2. In the long-term there is increased Ca2+ reabsorption and Mg2+ secretion (excretion)

There is increased Na+, K+, Cl- and H20 excretion

Increased Ca2+ reabsorption

Increased Mg2+ secretion (excretion)

Question 14

Why is there still increased K+ loss with thiazide diuretics when they do not act directly on a transporter involving K+ ?

Answer 14

This is because as they act on the Na+/Cl- transporter in the distal convoluted tubule ==> this results in increased levels of Na+ in the distal part of the tubule (as more Na+ is getting excreted) which in turn the increased conc. of Na+ stimulates the aldosterone sensitive Na+ pump in the distal part of the tubule to reabsorb Na+ in exchange for K+ and H+ ions ==> this is also therefore the mechanism by which it can cause metabolic alkalosis.

Question 15

What are the clinical uses of thiazide diuretics ?

Answer 15

Widely used in mild HF and hypertension

Question 16

What is the secondary action of thiazide diuretics?

Answer 16

Vasodilator action that contributes to there effectiveness in treatment of hypertension

Question 17

Which diuretic is still effective in patients with severe renal failure ?

Answer 17

Loop diuretics (thiazide are not)

Question 18

Give some examples of thiazide diuretics and the way to remember them

Answer 18

• Bendroflumethazide
• Think ‘thiazide’

Question 19

How do loop and thiazide diuretics cause hypokalaemia ?

Answer 19

1. They increase Na+ load in filtrate
2. This causes increased reabsorption of Na+ in the late distal tubule and collecting ducts (through activation of aldosterone sensitive sodium pump)
3. This leads to enhanced secretion of K+ and H+ due to low Na+ stimulating RAAS

Note that loop diuretics will also be directly resulting in loss of K+ through inhibition of the triple co-transporter (also the loss in their Cl- ions also due to an inverse relationship with HCO3- bicarb will mean bicarb will increase which is why loop diuretics can also cause metabolic alkalosis)

Question 20

What are the signs of hypokalaemia ?

Answer 20

• Weakness/fatigue
• Myalgia
• Arrhythmias

Question 21

What is done to prevent hypokalaemia in patients on diuretics ?

Answer 21

• Potassium supplements
• Use of potassium sparing diuretics e.g. spironolactone

Question 22

Give a rough overview of the doses if furosemide and when you would switch to IV furosemide and further then IV to an infusion.