drugs which affect the kidney

Question 1

what are diuretics?

Answer 1

a drug that increases the excretion of both fluids and solutes

Question 2

what does a natriuretic do?

Answer 2

increases Na+ excretion

Question 3

what does a kaliuretic do?

Answer 3

increases K+ excretion

Question 4

what are the 2 ways in which most diuretics increase excretion of Na+ and water by the kidneys?

Answer 4

1) they reduce reabsorption of Na+ from the filtrate

2) increase water loss is secondary to Na+ excretion

Question 5

what are aquaretic agents?

Answer 5

new diuretics that increase urine excretion without increasing Na+ excretion

Question 6

what are the 2 modes of action of diuretics?

Answer 6

1) direct action of the cells of the nephron

2) modification of content of the filtrate

Question 7

what are the 2 major applications of diuretic agents?

Answer 7

1) reduce circulating fluid volume

2) removal of excess body fluid (oedema)

Question 8

what are possible of side effects of diuretics due to actions they have on the kidneys?

Answer 8

• hypertension
• chronic heart failure
• liver cirrhosis
• renal disease
• premenstrual oedema
• toxic oedema
• increase elimination of drugs
• rapid weight loss

Question 9

what are other side effects of diuretics?

Answer 9

• glaucoma

- epilepsy

Question 10

where do carbonic anhydrases act?

Answer 10

proximal tubule

Question 11

where do osmotic diuretics act?

Answer 11

proximal tubule, descending loop of Henle

Question 12

where do loop diuretics act?

Answer 12

ascending loop of Henle

Question 13

where do thiazides and thiazide-like diuretics act?

Answer 13

early distal tubule

Question 14

what are the 2 types potassium sparing diuretics?

Answer 14

• aldosterone antagonists

- non-aldosterone antagonists

Question 15

where do potassium sparing diuretics act?

Answer 15

late distal tubule, early collecting duct

Question 16

what are the most effective diuretics?

Answer 16

loop diuretics

Question 17

how do loop diuretics work?

Answer 17

they inhibit the Na+/K+/2Cl- transporters (NKCC2) in the thick ascending limb of the loop of Henle which reduces reabsorption of Na+, K+ and Cl-

Question 18

what can a single dose of loop diuretics do to the urine volume?

Answer 18

increase urine volume from 200 to 1,200ml over 3 hours

Question 19

what are the clinical uses of loop diuretics?

Answer 19

• acute pulmonary oedema
• chronic heart failure
• cirrhosis of liver
• resistance hypertension
• nephrotic syndrome
• acute kidney injury

Question 20

what are the unwanted effects of loop diuretics?

Answer 20

• dehydration
• K+ loss leading to low plasma K+
• metabolic alkalosis
• hypokalaemia can potentiate effects of cardiac glycosides
• deafness

Question 21

how does sodium-potassium exchange change due to loop diuretics?

Answer 21

• loop diuretics cause increased Na+ delivery to distal tubule
• this is exchanged for K+ in the DT which is excreted in the urine
• this K+ loss contributes to hypokalaemia associated with loop diuretics

Question 22

how do thiazide diuretics work?

Answer 22

• act in the distal tubule to inhibit the apical Na+/Cl- co-transporter
• cause moderate but sustained Na+ excretion with increased water excretion

Question 23

how long do thiazide diuretics work?

Answer 23

up to 24 hours

Question 24

what are the clinical uses for thiazide diuretics?

Answer 24

• hypertension
• oedema
• mild heart failure

Question 25

what are the unwanted effects of thiazide diuretics?

Answer 25

- plasma K+ depletion - metabolic acidosis - increased plasma uric acid: gout - hyperglycaemia - increased plasma cholesterol - male impotence (reversible)

Question 26

what is currently the preferred diuretic for resistance hypertension and why?

Answer 26

- indapamide | - lower incidence of unwanted effects

Question 27

what are the symptoms of mild hypokalaemia?

Answer 27

fatigue, drowsiness, dizziness, muscle weakness

Question 28

what are the symptoms of severe hypokalaemia?

Answer 28

abnormal heart rhythm, muscle paralysis, death

Question 29

how do potassium sparing diuretics work?

Answer 29

act on distal tubules to inhibit Na+ reabsorption but K+ isn't secreted into the distal tubule

Question 30

what is spironolactone metabolised to?

Answer 30

canrenone

Question 31

what is canrenone?

Answer 31

a competitive antagonist of aldosterone

Question 32

how does spironolactone work?

Answer 32

reduces Na+ channel formation and its absorption from distal tubule

Question 33

what are the clinical uses of spironolactone?

Answer 33

- heart failure | - oedema

Question 34

what are the unwanted effects of spironolactone?

Answer 34

- hyperkalaemia - metabolic acidosis - GI upsets - gymaecomastia, menstrual disorder, testicular atrophy *eplernone produces less unwanted effects

Question 35

how do triamterene and amiloride work?

Answer 35

- weak diuretic: act on distal tubule to inhibit Na+ reabsorption and decrease K+ excretion - block luminal Na+ channel by which aldosterone produces its main effects

Question 36

what are the main unwanted effects of triamterene and amiloride?

Answer 36

- hyperkalaemia - metabolic acidosis - GI upsets - skin rashes

Question 37

what are the 2 main reasons diuretics are used in combination?

Answer 37

1) to increase diuretic effect | 2) to avoid the unwanted effects of hypokalaemia

Question 38

what is the best combination of diuretics to use to avoid hypokalaemia?

Answer 38

use loop diuretics or thiazides with potassium sparing diuretics

Question 39

what is the main example of a carbonic anhydrase inhibitor?

Answer 39

azetozolamide

Question 40

how do carbonic anhydrase inhibitors work?

Answer 40

- blocks sodium bicarbonate reabsorption in the proximal tubule -

Question 41

what are carbonic anhydrase inhibitors used to treat?

Answer 41

- glaucoma | - epilepsy

Question 42

what are the unwanted effects of carbonic anhydrase inhibitors?

Answer 42

- metabolic acidosis | - enhances renal stone formation

Question 43

what is the main example of an osmotic diuretic?

Answer 43

mannitol

Question 44

what are the clinical uses of osmotic diuretics?

Answer 44

- treatment of raised inter cranial pressure - treatment of intraoccular pressure - cause osmotic diarrhoea if given orally - can treat acute renal failure

Question 45

what is the unwanted effector osmotic directs?

Answer 45

increased plasma volume

Question 46

what volume of urine does ADH usually maintain?

Answer 46

1.5L/day

Question 47

what happens with toxicity of ADH antagonists?

Answer 47

1) diabetes insipidus 2) renal failure 3) Li+ can cause tremors, mental confusion, cardiotoxcicity, thyroid dysfunction and leukocytosis 4) demeclocylcine shouldn't be used in patients with liver disease

Question 48

what are the 2 non-selective agents used in potential ADH antagonists?

Answer 48

- lithium | - demeclocyline

Question 49

how doe Xanthines work?

Answer 49

- produce weak diuretic effect by increasing cardiac output - possible also some vasodilation of the glomerular afferent arteriole - results in increased renal and glomerular blood flow which increases glomerular filtration rate and urine output