Diuretics

1. Diuretics Dr Gareth Noble (and Dr Sue Jordan)

3. Overview of Kidney

4. 3 Functions of the Urinary System Excretion: removal of organic wastes from body fluids Elimination: discharge of waste products Homeostatic regulation: of blood plasma volume and solute concentration

5. Homeostatic Functions of Urinary System Regulate blood volume and blood pressure: by adjusting volume of water lost in urine releasing erythropoietin and renin Regulate plasma ion concentrations: sodium, potassium, and chloride ions (by controlling quantities lost in urine) calcium ion levels (through synthesis of calcitriol) Help stabilize blood pH: by controlling loss of hydrogen ions and bicarbonate ions in urine

6. Homeostatic Functions of Urinary System Conserve valuable nutrients: by preventing excretion while excreting organic waste products Assist liver to detoxify poisons

7. The Structure of the Kidney

11. Kidneys Help to regulate the blood pressure by increasing or decreasing the blood volume The renin-angiotensin system They are the most important organs for the long-term control of blood pressure.

13. Diuretics

14. Therapies

15. Commonly prescribed diuretics include: thiazides (bendroflumethiazide/ bendrofluazide, chlortalidone,indapamide) loop diuretics (furosemide/frusemide, bumetanide) potassium-sparing diuretics (amiloride, triamterene)

16. Therapeutics Thiazides are used to relieve oedema due to chronic heart failure and, in lower doses, to reduce blood pressure. Loop diuretics are used in pulmonary oedema due to left ventricular failure and in patients with chronic heart failure. Combination diuretic therapy may be effective in patients with oedema resistant to treatment with one diuretic. Vigorous diuresis, particularly with loop diuretics, may induce acute hypotension; rapid reduction of plasma volume should be avoided.

17. ACTIONS These are the 'transport-inhibiting diuretics‘ because they block the enzymes which reabsorb electrolytes (sodium, potassium and chloride) from urine into the circulation. As electrolytes are lost in the urine, water is lost with them. This doesn't work so well if the patient takes a high salt diet or smokes. Diuretics also dilate blood vessels.

18. INDICATIONS Diuretics are prescribed when the body contains too much fluid, in conditions associated with oedema and hypertension. Thiazides: long-term: hypertension, heart failure, oedema Loop diuretics: acute therapy: pulmonary oedema, renal failure; long term: heart failure, occasionally hypertension Potassium-sparing diuretics are prescribed with other diuretics to reduce potassium loss.

19. ADMINISTRATION AND DOSES Oral administration should be linked to meal-times. In some patients, food reduces furosemide-induced diuresis by up to 66%. If heart failure worsens, absorption may decrease, making the diuretic less effective.

20. Thiazide (overview) Largest, most commonly prescribed class MoA: act on the distal tubule to block Na+ reabsorption to increase K+ and water excretion (urine) Primary use: mild to moderate hypertension Mild to moderate heart failure, liver failure and renal failure

21. Thiazides Thiazides and related compounds are moderately potent diuretics; act within 1 to 2 hours of oral administration and duration of action of 12 to 24 hours; Mx Hypertension: a low dose of a thiazide, 2.5 mg daily, produces a maximal or near-maximal blood pressure lowering effect, with very little biochemical disturbance. Higher doses cause more marked changes in plasma potassium, sodium, uric acid, glucose, and lipids, with little advantage in blood pressure control. Mild to moderate heart failure: Bendroflumethiazide (bendrofluazide) is widely used Controlling oedema : Chlortalidone (chlorthalidone), a thiazide-related compound, has a longer duration of action than the thiazides and may be given on alternate days Useful if patients dislike the altered pattern of micturition promoted by other diuretics.

22. Adjuncts Other thiazide diuretics (including benzthiazide, clopamide, cyclopenthiazide, hydrochlorothiazide and hydroflumethiazide) do not offer any significant advantage over bendroflumethiazide and chlortalidone. Metolazone is particularly effective when combined with a loop diuretic (even in renal failure); profound diuresis may occur and the patient should therefore be monitored carefully. Xipamide and indapamide are chemically related to chlortalidone. Indapamide is claimed to lower blood pressure with less metabolic disturbance, particularly less aggravation of diabetes mellitus.

23. Loop Diuretics Used in pulmonary oedema due to left ventricular failure; IV administration produces relief of breathlessness Used in patients with chronic heart failure. Diuretic-resistant oedema can be treated with a loop diuretic combined with a thiazide or related diuretic (e.g. bendroflumethiazide 5–10 mg daily or metolazone 5–20 mg daily). Sometimes used to lower blood pressure especially in hypertension resistant to thiazide therapy. MoA: Loop diuretics inhibit reabsorption from the ascending limb of the loop of Henlé in the renal tubule and are powerful diuretics. Hypokalaemia (K+ loss) may develop, and care is needed to avoid hypotension. If there is an enlarged prostate, urinary retention may occur; this is less likely if small doses and less potent diuretics are used initially.

24. Furosemide (frusemide) and bumetanide are similar in activity; both act within 1 hour of oral administration and diuresis is complete within 6 hours can be given twice in one day without interfering with sleep. IV: peak effect within 30 minutes. Torasemide has properties similar to those of furosemide and bumetanide, and is indicated for oedema and for hypertension.

25. Adverse Effects (loop) Increased calcium excretion, hypotension; Less commonly nausea, gastro-intestinal disturbances, gout; Hyperglycaemia (less common than with thiazides); Photosensitivity and bone marrow depression (withdraw treatment), Pancreatitis (with large parenteral doses), Tinnitus and deafness (usually with large parenteral doses and rapid administration and in renal impairment)

26. ADMINISTRATION: furosemide Oral furosemide induces diuresis within 1 hour and continues to do so for 6 hours. Administration <6 hours before bedtime may disturb sleep. Discuss with patient the most convenient time for administration and suggest flexibility to accommodate social engagements. Usual dose is 20-40mg, but this may be increased if oedema cannot be controlled any other way. Intravenous furosemide acts within 20-60 minutes. Rapid administration (>4mg./minute) risks damage to hearing and balance.

27. Elderly patients receive lower initial doses, which are subsequentlyadjusted according to renal function tests. serum creatine, urea, glomerular filtration rate (GFR), and urinalysis.

28. Potassium-sparing diuretics Major problem with diuretics is Hypokalemia Amiloride and triamterene on their own are weak diuretics. cause retention of potassium and are therefore used as a more effective alternative to giving potassium supplements with thiazide or loop diuretics. Potassium supplements must not be given with potassium-sparing diuretics. Administration to a patient receiving an ACE inhibitor or an angiotensin-II receptor antagonist can cause severe hyperkalaemia.

43. Cautions and contra-indications include: Previous hypersensitivity responses. People allergic to sulphonamides may be allergic to thiazides and furosemide. Impaired renal function. Most thiazides are ineffective in renal failure (GFR<20ml./min.). Contra-indicated if GFR<10 ml./min. Impaired liver function. Diuretics increase potassium and magnesium loss and may precipitate coma. Pre-existing fluid and electrolyte imbalances will be intensified. Exacerbation of: Addison's disease, gout, diabetes, lupus, porhyria Potassium-sparing diuretics are not recommended in severe, acute illness, renal failure or pregnancy. Pregnancy. Diuretics jeopardise the blood supply to the placenta. Used only under specialist supervision. Furosemide may cause severe respiratory problems in the neonate. Lactation. Diuretics impair formation of breast milk.

44. Interactions include Some drugs accentuate the adverse effects of diuretics: Hypotension: all anti-hypertensives, general anaesthetics, alcohol, benzodiazepines, phenothiazines, anti-depressants, nitrates Loss of sodium: carbamazepine, aminoglutethimide Loss of potassium: digoxin, corticosteroids, bronchodilators, amphetamines, reboxetine, terfanadine, 'cold cures', liquorice. Cardiac arrhythmia due to hypokalaemia: amisulpride, pimozide, sertindole, terfanidine, thioridazine, sotalol Dangerously high potassium concentrations may occur if potassium-sparing diuretics are co-administered with: any potassium-rich food, herbal preparations or supplements, ciclosporin, NSAIDs (non-steroidal anti-inflammatory drugs), ACE inhibitors, tacrolimus, oestrogen and progestogens

45.  Organ damage may occur if diuretics are combined with certain drugs: NSAIDs, cisplatin, cephalosporins affect: kidney amiodarone, anti-arrhythmics affect: heart aminoglycosides, vancomycin affect: ear Diuretics cause lithium, quinidine and amphetamines to accumulate. Diuretics can be rendered ineffective by: corticosteroids, oestrogens, NSAIDs.

46. Textbook References Karch AM (2006) Focus on Nursing Pharmacology, 3rd Edition. Lippincott Williams & Wilkins Rang et al (2003) Pharmacology, 5th Edition. Churchill Livingstone. Lilley et al (2005) Pharmacology and the Nursing Process, 4th Edition. Mosby Page et al (2002) Integrated Pharmacology, 2nd Edition. Mosby. Martini (2005) Principles of Anatomy and Physiology, Pearson Education Publishers