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