Diuretics

1. Applied Sciences Lecture Course Diuretics Dr Cathy Armstrong SpR In Anaesthesia & Clinical Fellow in Undergraduate Medical Education Manchester Royal Infirmary March 2011

2. Aims & Objectives Define the term diuretic Classify diuretics into groups Describe mechanisms of action Describe relevant pharmacokinetic aspects Discuss common clinical uses

3. What is a diuretic?

4. What is a diuretic? An agent that promotes excretion of urine

6. In the glomerulus where is the majority of sodium reabsorbed? • Proximal convoluted tubule • Loop of Henle • Distal convoluted tubule • Collecting duct

7. Cvpharmacology.com

8. Which of these is NOT a class of diuretic? • Loop diuretic • Carbonic anhydrase inhibitor • Sodium-sparing diuretic • Potassium-sparing diuretic • Thiazide diuretic

9. Cvpharmacology.com

10. Thiazide diuretics Main action on distal convoluted tubule Bendroflumethazide hydrochlorothiazide Inhibit sodium & chloride reabsorption www.mc.uky.edu

11. 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

12. Cvpharmacology.com

13. What is the commonest clinical use of thiazide diuretics? • Heart failure • Hypertension • Cerebral oedema • Renal failure

14. Hypertension • Thiazide diuretics • ↓ systolic BP by 10-15 mmHg • ↓ diastolic BP by 5-10 mmHg

15. Hypertension MAP = CO x SVR CO = HR x SV Preload Contractility Afterload ~ 1 r4

16. Hypertension MAP = CO x SVR CO = HR x SV Preload Contractility Afterload ~ 1 r4

17. Hypertension MAP = CO x SVR CO = HR x SV Preload Contractility Afterload ~ 1 r4

18. Hypertension – NICE guidance A = ACE inhibitor, C = calcium channel blocker, D = thiazide diuretic

19. Loop diuretics Act on thick ascending limb of loop of Henle Sodium-potassium-chloride cotransporter Handles 25% of sodium reabsorption www.mc.uky.edu

20. Loop diuretics Induce renal synthesis of prostaglandins ↑ renal blood flow Redistribution of renal cortical blood flow Quick onset, shorter duration of action

21. 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

22. Cvpharmacology.com

23. Pulmonary oedema • Presentation • Dyspnoea • Hypoxia • Sweating • Tachycardia (gallop rhythm) • Elevated JVP • Pink frothy sputum • Crepitations on auscultation of lung fields

24. Pulmonary oedema • Immediate management • Oxygen • Sit patient up • IV access • Furosemide (40 – 80mg IV) • Diamorphine • GTN infusion (if BP will tolerate) • Consider CPAP

25. Pulmonary oedema Cvpharmacology.com

26. Chronic Heart Failure – NICE Guidance

27. Potasium sparing diuretics Block sodium channels distal end of DCT www.mc.uky.edu

28. 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

29. Aldosterone Antagonists Spironolactone Aldosterone enhances expression of sodium channel in distal end of DCT

30. Cvpharmacology.com

31. Aldosterone Antagonists Uses Oedema & ascites in cirrhosis of the liver Chronic heart failure Primary hyperaldosteronism Conn’s syndrome side effects Hyperkalaemia N&V gynaecomastia

32. Carbonic anhydrase inhibitors Prevent reabsorption of bicarbonate in proximal convoluted tubule www.mc.uky.edu

33. Carbonic anhydrase inhibitors • Weak diuretics • Not used for diuretic properties • Uses • Prophylaxis against altitude sickness • glaucoma

34. 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

35. Diuretics in acute renal failure?

36. Summary Cvpharmacology.com

37. ?