Diuretics

Question 1

What is a diuretic?

Answer 1

a drug that increases excretion of both fluids and electrolytes

Question 2

Natriuretic

Answer 2

increases Na+ secretion

Question 3

Kaliuretic

Answer 3

increases K+ secretion

Question 4

Aquauretic

Answer 4

increases water secretion

Question 5

Most diuretics act by

Answer 5

• increased excretion of Na+ and
  water by the kidneys
• natriuretic
• decreased reabsorption of Na+ from
  filtrate, and increasing water loss
  secondary
• generally on luminal side of
  nephron
• some modify the content of the
  filtrate

Question 6

When do we use diuretics?

Answer 6

• chronic heart failure
• cirrhosis
• nephrotic syndrome
• glaucoma (high pressure in the eye)

Question 7

Is water a diuretic?

Answer 7

under normal conditions, increased water intake leads to increase in volume of urine excreted

process controlled by ADH

Question 8

Results of reduced expression of aquaporin 2 channels results in

Answer 8

• water excretion
• if on apical surface of DCT and
  collecting duct

Question 9

Drugs that act via ADH:

Answer 9

• alcohol (inhibit ADH, urinate
  more)
• nicotine and morphine (increase
  ADH)
• demeclocycline (ADH
  antagonist’(SIADH))
• Tolvaptan (SIADH)

Question 10

Nephron and fluid re-absorption

Answer 10

insert

Question 11

5 drug classes of diuretics and where they act:

Answer 11

insert

Question 12

Where do diuretics act?

Answer 12

insert

Question 13

Core Drug: Furosemide: Which drug class?

Answer 13

Loop Diuretics

Question 14

Core Drug: Furosemide: Molecular Mechanism of Action:

Answer 14

• blockage of Cl- channel of
  NA+/K+/2Cl co- transported in thick
  ascending limb of loop of henle
• prevents Na+ and Cl- entering
  interstitial fluid
• increased loss of Na,K,Cl and water
• hence water also remains in LOH
  lumen
• very powerful

Question 15

Core Drug: Furosemide: Pharmacological Effect Lasts:

Answer 15

6 hours

Question 16

Core Drug: Furosemide (loop Diuretic): Side Effects:

Answer 16

• **hypokalaemia (arrhythmias)
• **ototoxicity (auditory nerve
  damage)
• Hyperuricaemia (gout)
• dehydration
• renal impairment

Question 17

Core Drug: Furosemide (loop diuretics): Cause of hypokalaemia:

Answer 17

• increase Na+ delivery to DCT where
  it is exchanged for K+, which is then
  excreted in the urine

Question 18

Core Drug: Furosemide (loop diuretics): most used for:

Answer 18

• peripheral oedema
• pulmonary oedema

Question 19

Core Drug: Bendroflumethiazide: Drug Class:

Answer 19

• Thiazide Diuretic

Question 20

Core Drug: Bendroflumethiazide (thiazide diuretic): Molecular Mechanism of Action:

Answer 20

• blocks apical Na+/Cl- co-transported
  both leaving lumen into interstitial
  space) in DCT
• K+ is also involved
• less powerful than loop diuretics

Question 21

Core Drug: Bendroflumethiazide (thiazide diuretic): Molecular Mechanism of Action:

Answer 21

• blocks Na+/Cl- co-transported (both
  leaving lumen into interstitial space)
• K+ is also involved

Question 22

Core Drug: Bendroflumethiazide (thiazide diuretic):

Question 23

Core Drug: Bendroflumethiazide (thiazide diuretic: Effect lasts for:

Answer 23

Upto 24 hours

Question 24

Core Drug: Bendroflumethiazide (thiazide diuretic): Clinical Uses:

Answer 24

antihypertensive

Question 25

Core Drug: Indapamide: Drug Class:

Answer 25

Thiazide-like diuretics

Question 26

Core Drug: Indapamide (thiazide-like diuretic): Molecular Mechanism:

Answer 26

• activates K+ATP channels in smooth
  muscle of blood vessels to dilate
  arterioles: decreased BP
• in kidney acts upon Na/Cl co-
  transporter:
  - increased Na+ loss
  - increased water loss
  - decreased blood pressure

Question 27

Core Drug: Indapamide (thiazide-like diuretic): Side Effects:

Answer 27

Kidney:
- hypercalcaemia (high Ca2+)
- hyponatraemia and kalaemia
- gout

Insulin Resistance:
- increase glucose (diabetes)

Lipids:
- increases lipids (arterial disease)

Question 28

Core Drug: Indapamide (thiazide-like diuretic): Clinical Uses: (thiazide too)

Answer 28

• urinary tract stones
• nephrogenic diabetes insipidus

Question 29

Why are thiazides better for hypertension then furosemide?

Answer 29

have a vasodilator effect too; sometimes more than the renal effect

Question 30

Core Drug: Spironolactone: Drug Class:

Answer 30

aldosterone antagonist/potassium sparing diuretic

Question 31

Core Drug: Spironolactone: (aldosterone antagonist/potassium sparing diuretic): Molecular Mechanism:

Answer 31

• blocks the upregulation of Na+
  channels in the DCT by aldosterone
• prodrug: metabolised to active form
  canrenone

-

Question 32

Core Drug: Spironolactone: (aldosterone antagonist/potassium sparing diuretic): effect:

Answer 32

takes a few days to develop

Question 33

Core Drug: Spironolactone: (aldosterone antagonist/potassium sparing diuretic): Clinical Use:

Answer 33

• add on in resistant hypertension
• first line in hyperaldosteronism
• first line in cirrhosis

helps those with poor LV function and post MI

Question 34

Core Drug: Spironolactone: (aldosterone antagonist/potassium sparing diuretic): Side Effects:

Answer 34

• impaired renal function
• hyperkalaemia
• gynaecomastia (breasts) and
  testicular atrophy (similar structure
  to oestregen)

Question 35

Amiloride is a direct inhibitor of epithelial Na+ channels in the DCT. Amiloride is a potassium sparing diuretic and is mostly used in a fixed dose combination with furosemide.

Explain why.

Answer 35

Furosemide will decrease potassium levels, amiloride will increase potassium

Question 36

Osmotic Diuretics:

Answer 36

• mannitol
• IV
• undergoes glomerular filtration and
  is not re-absorbed; does not cross
  BBB
• increases water in circulating
  plasma and urine
• increase in blood vol

Question 37

Osmotic diuretics are used for cerebral oedema:

Answer 37

• swelling of the brain
• sucks fluid out of the brain into the
  blood
• lowers intra-cranial pressure