Diuretics

Question 1

how do diuretics generally work

Answer 1

• diuretics increase the urine output by the kidney (i.e.promote diuresis)

• most diuretics – inhibit reabsorption of sodium at
different levels of the renal tubular system

• more sodium excreted, more water excreted

• sometimes combinations of diuretics are used
(synergistic effect)

Question 2

Give an example of an osmotic diuretic

Answer 2

Mannitol

Question 3

What is the mechanism of Mannitol

Answer 3

• Pharmacologically inert
• Filtered at glomerulus and poorly reabsorbed
• Decreases H2O reabsorption from nephron
• Increases osmotic pressure in glomerular filtrate
• Does not enter brain or eye - draws fluid from tissues

Question 4

When in Mannitol used?

Answer 4

• Forced diuresis e.g. in poisonings
• Acute glaucoma
• Cerebral oedema

Question 5

How is Mannitol administrated

Answer 5

Slow IV. Infusion of 5 – 20% solution

Question 6

Give an example of a diuretic that is a carbonic anhydrase inhibitor

Answer 6

Acetazolamide

Question 7

What is the mechanism of Acetazolamide

Answer 7

Suppresses H+ production and thus reduce Na+/H+ exchange
– less Na+ reabsorption

Increases excretion of HCO3 (accompanied by Na+, K+ and H2O)
– causes mildly alkaline urine
– causes metabolic acidosis

Question 8

When is Acetazolamide used?

Answer 8

Glaucoma
– inhibits CA in eyes to reduce the formation of aqueous humour

Adjunct therapy in metabolic alkalosis

Prevrnts altitude sickness

Question 9

What are the side effects of Acetazolamide?

Answer 9

Dizziness and light headache

Blurred vision

Loss of appetite

Stomach upset

Question 10

Give an example of a loop diuretic

Answer 10

Furosemide

Question 11

What is the mechanism of Furosemide?

Answer 11

Main action
Inhibit Na+/K+/2Cl- co-transporter in the thick ascending limb preventing the reabsorption of Na+

Cause 15-25% of filtered Na+ to be excreted –
“Torrential urine production”

Result in increased osmotic pressure in filtrate
delivered to distal tubule (decreases water reabsorption)

Question 12

When is Furosemide used?

Answer 12

• Heart failure – chronic/or acute pulmonary oedema
• Hypertension
• Hepatic cirrhosis complicated by ascites
• Nephrotic syndrome
• Renal failure
• Hypercalcaemia

Question 13

What are the side effects of Furosemide related to the drugs’ renal action?

Answer 13

-Hypovolaemia/Hypotension due to excessive Na+ loss and diuresis

Hypokalaemia – due to K+ loss

Metabolic or “contraction” alkalosis – due to Increase in plasma [HCO3-]

Question 14

What are the rare side effects of Furosemide unrelated to the drugs’ renal action

Answer 14

dose-related hearing loss

allergic reactions: rashes, bone marrow depression

Question 15

Give an example of a thiazide diuretic?

Answer 15

Hydrochlorothiazide

Question 16

What is the mechanism of action of Hydrochlorothiazide?

Answer 16

Block Na+/Cl- co-transporter in the distal convoluted tubule which results in a higher osmolarity of urine and decreased water reabsorption as less NaCl is reabsorbed

Question 17

How is Hydrochlorothiazide self-limiting?

Answer 17

It acts to lower blood volume

This causes Renine secretion

This causes Angiotensin formation and aldosterone secretion

This Limits the effect of thiazides

Question 18

When is Hydrochlorothiazide used?

Answer 18

Long term of diuretics

Adjunct in congestive heart failure / hypertension

Nephrogenic diabetes insipidus (“thiazide paradox”)

Question 19

What are the side effects of Hydrochlorothiazide that are directly related to drugs’ renal action (common):

Answer 19

Hypokalaemia, metabolic alkalosis (as in Loop diuretics)

Hypocalciuria

Hypomagnesaemia

Hyponatraemia

Question 20

What are the side effects of Hydrochlorothiazide that are unrelated to drugs’ renal action?

Answer 20

Hyperuricaemia precipitating gout (thiazide competes with uric acid for tubular secretion)

Hyperglycaemia – impaired pancreatic release of insulin and diminished tissue utilization of glucose

Higher plasma cholesterol level

Question 21

Give two examples of K+ sparing diuretic that are ENaC Blockers

Answer 21

Triamterene

Amiloride

Question 22

What is the mechanism of action of Triamterene & Amiloride?

Answer 22

Directly block epithelial Na+ channel (ENaC) in distal tubule, collecting tubules and collecting ducts (limited diuretic efficacy)

Question 23

When are Triamterene & Amiloride used?

Answer 23

Used in conjunction with loop and thiazide diuretics to maintain K+ balance

Question 24

What are the unwanted effects of Triamterene & Amiloride?

Answer 24

Hyperkalaemia

Gastrointestinal disturbance (rare)

Idiosycratic reactions: rashes (rare)

Question 25

Give an example of K+ sparing diuretic that is an Aldosterone Antagonist

Answer 25

spironolactone

Question 26

What are the Actions of Aldosterone on Na+ reabsorption?

Answer 26

Potassium-sparing diuretics are diuretic drugs that do not promote the secretion of potassium into the urine. Early phase: increasing opening of ENaC Late phase: promotes DNA transcription Increase synthesis of ENaC Increase synthesis of Na+, K+- ATPase

Question 27

When are K+ sparing diuretic (spironolactone) used?

Answer 27

- In conjunction with loop and thiazide diuretics to maintain K+ balance - Adjunct therapy in heart failure - Hyperaldosteronism (where too much aldosterone is produced by the adrenal glands, which can lead to lowered levels of potassium in the blood also known as hypokalemia)

Question 28

What are the sude effects of spironolactone?

Answer 28

- Hyperkalaemia (can be fatal if ACE inhibitor, angiotensin receptor antagonist or β-blocker are co-prescribed) - Gastrointestinal disturbance (common) -Menstrual disorders or testicular atrophy (acting on progesterone or androgen receptors)