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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
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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? An agent that promotes excretion of urine
In the glomerulus where is the majority of sodium reabsorbed? • Proximal convoluted tubule • Loop of Henle • Distal convoluted tubule • Collecting duct
Which of these is NOT a class of diuretic? • Loop diuretic • Carbonic anhydrase inhibitor • Sodium-sparing diuretic • Potassium-sparing diuretic • Thiazide diuretic
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
What is the commonest clinical use of thiazide diuretics? • Heart failure • Hypertension • Cerebral oedema • Renal failure
Hypertension • Thiazide diuretics • ↓ systolic BP by 10-15 mmHg • ↓ diastolic BP by 5-10 mmHg
Hypertension MAP = CO x SVR CO = HR x SV Preload Contractility Afterload ~ 1 r4
Hypertension MAP = CO x SVR CO = HR x SV Preload Contractility Afterload ~ 1 r4
Hypertension MAP = CO x SVR CO = HR x SV Preload Contractility Afterload ~ 1 r4
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
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
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
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
Summary Cvpharmacology.com
