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Diuretics Overview

Diuretics Overview. Francesca Burns. Different classes of diuretics Their sites and mechanisms of action How this explains their clinical use Important side effects and contraindications. What I’m going to cover. What are they?.

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Diuretics Overview

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  1. DiureticsOverview Francesca Burns

  2. Different classes of diuretics • Their sites and mechanisms of action • How this explains their clinical use • Important side effects and contraindications What I’m going to cover

  3. What are they? Drugs that act on the kidney to increase the excretion of salt and water. Have a variety of clinical applications, are some of the most commonly prescribed drugs in clinical practise. • What different sub-classes of diuretics are there? • Thiazides • Loop Diuretics • Aldosterone antagonists • Osmotic diuretics • Carbonic anhydrase inhibitors

  4. Nephron – the functional unit of the kidney • FILTRATION occurs in the glomerulus, and SELECTIVE REABSORPTION occurs through the tubular system. Normal urine output = 1500ml/day

  5. Different sites of action

  6. Thiazides Ultrafiltration DCT NA+/Cl- symporter PCT CT NA+/K+ antiporter Aldosterone receptor Cortex Reabsorption Medulla Aldosterone Antagonists NA+/K+/2Cl- symporter Nephron Loop diuretics Loop of Henle

  7. Thiazides Ultrafiltration DCT NA+/Cl- symporter PCT CT NA+/K+ antiporter Aldosterone receptor Cortex Reabsorption Medulla NA+/K+/2Cl- symporter • Moderately potent diuretics • Inhibit sodium reabsorption at early DCT • Act within 1-2 hours of oral administration (well absorbed from GI tract) • Typical duration of action of 12-24 hours Thiazides • Metalozone = thiazide related drug Loop of Henle

  8. Hypertension • Mild heart failure (loop usually preferred) • Severe resistant oedema (metolazone is often used together with loops) • Idiopathic hypercalciuria • Nephrogenic diabetes insipidus Indications

  9. SE/Cautions/C/i

  10. Ultrafiltration DCT NA+/Cl- symporter PCT CT NA+/K+ antiporter Aldosterone receptor Cortex Reabsorption Medulla NA+/K+/2Cl- symporter ‘torrential urine flow’ • The most powerful diuretics. • Act on thick limb of ascending • LOH. • Also venodilate and reduce • preload, which is useful for some • of their indications. • Act within 1 hour if given orally, (IV • peak is 30 minutes). • Lasts for 6 hours. (LaSix) Loop Diuretics Loop diuretics Loop of Henle

  11. Acute pulmonary oedema (IV) • Chronic heart failure • Cirrhosis of the liver complicated by ascites • Nephrotic syndrome • Treatment of hypertension complicated by renal impairment • Treatment of hypercalcaemia after rehydration Indications

  12. SE/Cautions/Ci

  13. Ultrafiltration DCT NA+/Cl- symporter PCT CT NA+/K+ antiporter Aldosterone receptor Cortex Reabsorption Medulla Aldosterone Antagonists NA+/K+/2Cl- symporter • K+ sparing • Weak diuretic – only 2% Na+ reabsorption occurs under aldosterone control. • Potentiates thiazide and loop diuretic action. • Well absorbed orally. • Half life of 10 mins. Potassium-sparing diuretics • Spironolactone – aldosterone antagonist • Amiloride – blocks Na+ channel Loop of Henle

  14. With K+ losing (i.e. loop or thiazide) diuretics to prevent K+ loss, where hypokalaemia is especially hazardous (e.g. patients requiring digoxin or amiodarone) • Heart failure (prognostic benefit) • Primary Hyperaldosteronism (Conn’s) • Resistant essential hypertension • Secondary hyperaldosteronism caused by hepatic cirrhosis complicated by ascites. Indications

  15. SE/Cautions/Ci

  16. Ultrafiltration DCT NA+/Cl- symporter PCT CT NA+/K+ antiporter Aldosterone receptor Cortex Reabsorption Medulla NA+/K+/2Cl- symporter • Cause an increase in plasma osmolarity. • Osmotic extraction of water from the brain. • Filtered but not reabsorbed by the kidney. • Leads to excretion of water. Osmotic Diuretics • E.g. Mannitol • Indicated in cerebral oedema. Loop of Henle

  17. SE/Cautions/Ci

  18. Ultrafiltration DCT NA+/Cl- symporter PCT CT NA+/K+ antiporter Aldosterone receptor Cortex Reabsorption Medulla NA+/K+/2Cl- symporter • Act on PCT • Inhibit actions of Carbonic anhydrase and therefore increase excretion of HCO3-. • Self limiting action therefore not used for their diuretic properties. • Indications: • Glaucoma to reduce formation of aqueous humour • Some unusual types of epilepsy Carbonic Anhydrase Inhibitors Loop of Henle

  19. Metabolic acidosis, sedation and paresthesia. Also, because of the structural similarity to sulfonamides, carbonic anhydrase inhibitors can cause bone marrow depression and allergic reactions. • Hyponatraemia Cautions and C/i

  20. References: • Rang and Dales • Pharmacology at a Glance • BNF • Wikipedia Questions?

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