Drugs which affect the kidney: diuretic agents

Question 1

What are the 3 types of AKI

Answer 1

Pre-renal (due to blood loss) can be due to ACEi
intrinsic (nephrotoxic AKI) can be due to anti-cancer drugs
post-renal (due to blockage) typically due to kidney stones or a tumour.

Question 2

What are diuretic agents

Answer 2

Any compound that causes excretion of an increased volume of urine from the body.

natriuretic: increases Na excretion
kaliuretic: increases K excretion, promotes hypokalemia which is an unwanted effect

Question 3

What are two modes of action of diuretics

Answer 3

1) direct action on the cells of the nephron (more common)

2) modification of the content of the filtrate.

Question 4

What are two major applications of diuretic agents

Answer 4

reduce circulating fluid volume and reduce excess body fluid (oedema)

Question 5

How can diuretics help

Answer 5

via actions on the kidney: hypertension, CHF, liver cirrhosis, renal disease, premenstrual oedema and toxic oedema.

Question 6

What part of the nephron does osmotic diuretics affect

Answer 6

The PCT and descending loop of Henle

Question 7

What part of the nephron does loop diuretics affect

Answer 7

ascending loop of Henle

Question 8

What part of the nephron does thiazides and thiazide-like diuretics affect

Answer 8

early distal tubule

Question 9

What part of the nephron does k-sparing diuretics affect

Answer 9

late distal tubule and early collecting duct.

Question 10

Outline the function of loop diuretics

Answer 10

Inhibit the NKCC2 transporter in the thick ascending limb of the loop of Henle which reduces the reabsorption of Na, K, Cl which leads to fluid loss.

Question 11

What clinical conditions do loop diuretics aid in and what are some unwanted effects

Answer 11

acute pulmonary oedema, chronic heart failure, cirrhosis of the liver, resistant hypertension, nephrotic syndrome and AKI

unwanted effects: dehydration, hypokalemia, deafness (when used with aminoglycoside antibiotics), metabolic alkalosis

Question 12

Outline the function of thiazide diuretics

Answer 12

Act in the DCT to inhibit the apical Na/CL co-transporter, can cause moderate but sustained sodium excretion, it is well absorbed from the GI tract and has a long duration of up to 24 hrs.

Question 13

What clinical conditions do thiazide diuretics aid in and what are some unwanted effects

Answer 13

clinical uses: hypertension, oedema and mild HF.
unwanted effects: plasma K depletion, metabolic alkalosis, gout, hyperglycemia, increased plasma cholesterol, male impotence (Reversible)

Question 14

What is hypokalaemia

Answer 14

due to increased loss of K+ in the urine, loop diuretics and thiazide can cause hypokalemia.

milk hypokalemia: fatigue, drowsiness, dizziness, muscle weakness.
severe hypokalemia: abnormal heart rhythm, muscle paralysis and death.

Question 15

What are potassium-sparing diuretics

Answer 15

acts on distal tubule to inhibit sodium reabsorption
two types
aldosterone antagonists: spironolactone
non-aldosterone antagonists: triamterene.

Question 16

What are the unwanted effects of spironolactone

Answer 16

hyperkalaemia, metabolic acidosis, GI upsets, gynaecomastia, menstrual disorders, testicular atrophy.

Question 17

Why are diuretics combined

Answer 17

To achieve a synergistic effect as some patients don’t respond well to one diuretic and to avoid hypokalaemia.

Question 18

How do carbonic anhydrase inhibitors produce a diuretic effect

Answer 18

Blocks sodium bicarbonate reabsorption in the PT and this gives it the diuretic action.

Question 19

How do osmotic diuretics work

Answer 19

They are excreted and take water with them in their structures (like a sponge) e.g. mannitol