Applied Sciences Lecture Course
Diuretics
Dr Cathy Armstrong
SpR In Anaesthesia & Clinical Fellow in Undergraduate
Medical Education
Manchester Royal Infirmary
March 2011
Aims & Objectives
• Define the term diuretic
• Classify diuretics into groups
– Describe mechanisms of action
– Describe relevant pharmacokinetic aspects
• Discuss common clinical uses
What is a diuretic?
What is a diuretic?
An agent that promotes excretion
of urine
In the glomerulus where is the
majority of sodium reabsorbed?
1. Proximal 25% 25% 25% 25%
convoluted tubule
2. Loop of Henle
3. Distal convoluted
tubule
4. Collecting duct
1 2 3 4
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Which of these is NOT a class of
diuretic?
1. Loop diuretic 20% 20% 20% 20% 20%
2. Carbonic anhydrase
inhibitor
3. Sodium-sparing
diuretic
4. Potassium-sparing
diuretic
5. Thiazide diuretic
1 2 3 4 5
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Thiazide diuretics
• Main action on distal convoluted tubule
– Bendroflumethazide
– hydrochlorothiazide
• Inhibit sodium & chloride reabsorption
www.mc.uky.edu
Thiazide diuretics
• Maximal effects produced by small doses
• Duration of action 12-18 hours
• Side effect profile
– Hypokalaemia
• Particular caution with digoxin
– Increased uric acid levels
– Impaired glucose tolerance
– Increased cholesterol levels
Cvpharmacology.com
What is the commonest clinical use
of thiazide diuretics?
1. Heart failure 25% 25% 25% 25%
2. Hypertension
3. Cerebral oedema
4. Renal failure
1 2 3 4
Hypertension
• Thiazide diuretics
– ↓ systolic BP by 10-15 mmHg
– ↓ diastolic BP by 5-10 mmHg
Hypertension
MAP = CO x SVR
~ 1
r4
CO = HR x SV
Preload Contractility Afterload
Hypertension
MAP = CO x SVR
~ 1
r4
CO = HR x SV
Preload Contractility Afterload
Hypertension
MAP = CO x SVR
~ 1
r4
CO = HR x SV
Preload Contractility Afterload
Hypertension – NICE guidance
A = ACE inhibitor, C = calcium channel blocker, D = thiazide
diuretic
Loop diuretics
• Act on thick ascending limb of loop of Henle
• Sodium-potassium-chloride cotransporter
– Handles 25% of sodium reabsorption
www.mc.uky.edu
Loop diuretics
• Induce renal synthesis of prostaglandins
– ↑ renal blood flow
– Redistribution of renal cortical blood flow
• Quick onset, shorter duration of action
Loop diuretics
• Side effects
– Hypokalaemia
– Hyperglycaemia & hyperuricaemia
– Transient damage to CN VIII (esp with gentamycin)
• Uses
– Pulmonary oedema (Acute LVF)
– Chronic heart failure
– Hypertension
– Peripheral oedema
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Pulmonary oedema
• Presentation
– Dyspnoea
– Hypoxia
– Sweating
– Tachycardia (gallop rhythm)
– Elevated JVP
– Pink frothy sputum
– Crepitations on auscultation of lung fields
Pulmonary oedema
• Immediate management
– Oxygen
– Sit patient up
– IV access
– Furosemide (40 – 80mg IV)
– Diamorphine
– GTN infusion (if BP will tolerate)
– Consider CPAP
Pulmonary oedema
Cvpharmacology.com
Chronic Heart Failure – NICE
Guidance
Potasium sparing diuretics
• Block sodium channels distal end of DCT
www.mc.uky.edu
Potasium sparing diuretics
• Weak diuretics
• Examples
– Amiloride, Triamterene
• Often co-administered to reduce
hypokalaemic effects of loop / thiazides
– Co-amilofruse
– Co-triamterzide
• Side effects
– hyperkalaemia
Aldosterone Antagonists
• Spironolactone
• Aldosterone enhances expression of sodium
channel in distal end of DCT
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Aldosterone Antagonists
• Uses
– Oedema & ascites in cirrhosis of the liver
– Chronic heart failure
– Primary hyperaldosteronism
• Conn’s syndrome
• side effects
– Hyperkalaemia
– N&V
– gynaecomastia
Carbonic anhydrase inhibitors
• Prevent reabsorption of bicarbonate in proximal
convoluted tubule
www.mc.uky.edu
Carbonic anhydrase inhibitors
• Weak diuretics
• Not used for diuretic properties
• Uses
– Prophylaxis against altitude sickness
– glaucoma
Osmotic diuretics
• Mannitol
– Draws water from the extracellular & intracellular
spaces into the vascular compartment
– Easily filtered but not reabsorbed
– Continues to be osmotically active in tubules
causing diuresis
• Main use
– Cerebral oedema
Diuretics in acute renal failure?
Summary
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?