Diuretics.

Front 1

Define a diuretic?

Back 1

Diuretics are agents that increase the production of urine.

Front 2

Main uses of diuretics?

Back 2

In the management of cardiac failure to control oedema and congestion.

Front 3

Where is the main site of action of the thiazide diuretics?

Back 3

First they are excreted into the PCT.

The early distal convoluted tubule is main site of action.

Front 4

Thiazide mechanism of action?

Back 4

Inhibit the sodium/ chloride co-transport system by binding to it.

Prevent sodium and chloride ion reabsorption.

Reduce loss of CA2+.

Increase loss of potassium.

Front 5

What occurs to the effectiveness of a diuretic as you move along the tubule?

Back 5

Become less and less effective as diuretics as most H2O been absorbed by this point.

Front 6

Name some thiazides?

Back 6

Chlorothiazide.

Hydrochlorothiazide.

Bendroflumethazide.

Trichlormethiazide.

Front 7

When do we use thiazides?

Back 7

Mild cardiac failure to manage oedema.

Combined with other diuretics e.g. furosemide.

Oedema secondary to hypoproteinaemic disorders.

Diabetes insipidus thats nephrogenic in origin.

Front 8

Side effects of Thiazides?

Back 8

Hypokalaemia.

Decreased effect of insulin.

Man potentiate anaesthetics, cardiac glycosides like digoxin.

Front 9

Pharmokinetics of thiazides?

Back 9

Orally bioavailable and is variable between them. 10% chlorothiazide and 70% for hydrochlorothiazide.

Half life 1.5- 2 hours.

Rapid effect within 1 hour.

Front 10

What is the site of action of the loop diuretics?

Back 10

Site of action of the loop diuretics is the thick ascending loop of Henle.

Front 11

What does a loop diuretic target on the thick ascending loop of Henle?

Back 11

It targets the NA/K/2CL- contransport from lumen into tubule cell.

This reduces the hypertonicity of the medulla so less water moves out from the collecting duct and descending loop of Henle.

Front 12

What are the effects of loop diuretics on electrolyte balance? Is there any other effect which may be of benefit to you with a patient with cardiovascular disease?

Back 12

1) Because there is increased sodium presented in the collecting duct there is an effort to excrete potassium. Hypokalaemia.

2) Ca loss increase- Useful in hypercalcaemia like that caused by lymphoma

3) Intravenously has a vasodilatory effect.

Front 13

Pharmokinetics of loop diuretics?

Back 13

Orally bioavailable.

Highly protein bound.

Secreted in PCT.

Metabolised in the liver by P450 pathways.

Furosemide undergoes type II glucuronidation.

Rapid onset of action.

Half life about 90 mins and durations 3-6 hours.

Front 14

When do we use loop diuretics and name one example?

Back 14

Heart failure for management of oedema.

Given i/v for vasodilation, reduce preload and increase renal perfusion.

Treating hypercalcaemia.- lymphosarcoma for instance.

Name one example: Furosemide.

Front 15

Side effects of the loop diuretics?

Back 15

Hypovolaemia and hypokalaemia.

Ototoxicity especially if used with the aminoglycosides.

Front 16

Name an aldosterone antagonist and what it does?

Back 16

Spironolactone--> loss of sodium and retention of potassium.

Front 17

Spironolactone pharmokinetics?

Back 17

Orally bioavailable 70%

First pass hepatic metabolism.

Highly protein bound.

Canrenone is an active metabolite.

Half life short.

Carenoate the inactive metabolite which is converted to Canrenone half life 16 hours.

Onset of active

Front 18

What do loop diuretics function depend on ? Is there a drug which may decrease loop diuretic function as a result?

Back 18

Depend on the action of Prostaglandins.

Corticosteroids.

Front 19

Side effects of spironolactones?

Back 19

Hyperkalaemia especially if used with ACE inhibitors.

Front 20

Name other potassium sparing diuretics and how they function?

Back 20

Other potassium sparing diuretics include amiloride and triamterene--> prevent reabsorption of sodium through the luminal sodium channels and reduce the loss of potassium and increase the loss of sodium.

Front 21

What are pharmokinetics properties of potassium sparing diuretics?

Back 21

Moderately oral bioavailability 50%

Triameterene 60% plasma bound much less binding with amiloride.

Triamterene metabolised in liver and some excreted unchanged in urine.

Amiloride most unchanged kidney.

Duration 12 hours triamterene and amiloride 24 hours.

Front 22

Side effects of potassium sparing diuretics?

Back 22

In conjunction with other diuretics for severe cardiac failure.

Used with loop diuretic as compliments potassium loosing effect.

Front 23

Name an osmotic diuretic and its important features?

Back 23

Mannitol

Filtered by glomerulus.

Reabsorption is limited.

Pharmacologically inert.

Front 24

MOA of Mannitol?

Back 24

1)As water and sodium are progressively removed along PCT mannitol becomes more and more concentrated.

2) Reduced water reabsorption in PCT.

3) Thus Na removal declines.

4)Decreases tonicity of medulla.

5) Less water is reabsorbed in DCT.

Front 25

Uses of Mannitol?

Back 25

Management of acute renal failure to restore urine production.

Used to reduce CSF pressure.

Used to reduce intraocular pressure in glaucoma.

Front 26

When are osmotic diuretics not indicated?

Back 26

Cardiac disease as elevate ECF volume.