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Potassium - sparing diuretics

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Potassium sparing diuretics work by interfering with sodium reabsorption in the collecting duct of the nephron, thereby inhibiting the indirect secretion of potassium. The main classes are aldosterone antagonists like spironolactone and eplerenone, and epithelial sodium channel inhibitors like amiloride and triamterene. They are used to treat edema and hypertension while preserving potassium levels. Adverse effects include hyperkalemia and hypokalemia, so monitoring of electrolyte levels is important when using these drugs.

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Potassium sparing diuretics Namulo Talohole Pharmacy student Lusaka Apex Medical University
INTRODUCTION Diuretics are drugs that increase the volume of urine excreted by the kidney as a result, reduce extracellular fluid. Their diuretic action is achieved by blockade of distal renal tubular sodium reabsorption In addition the major effect of each class of diuretics drugs is limited to specific nephron segment, and knowledge of their specific sites of action is important in selecting an appropriate drug and anticipating and preventing complications. Potassium sparing diuretics works at the collecting duct, where they interfere with Na+ reabsorption and indirectly with K+ secretion. Their diuretic activity is weak.
Potassium - sparing diuretics
Examples of potassium-sparing diuretics They are divided into : Aldosterone diuretics Spironolactone Eplerenone Epithelium Na+ channel inhibitors Amiloride Triamterene
Pharmacodynamics Normally the tubular fluid in the distal convoluted tubule part is hypotonic . The high celling diuretics and thiazides increases the sodium ion concentration and this induces the renin-angiotensin aldosterone system that results in substitution of sodium for potassium ions so that potassium is also excreted . Administration of Aldosterone antagonist hence prevent K + secretion by antagonizing the effects of aldosterone in collecting tubules. Spironolactone and eplerenone bind to mineralocorticoid receptors and blunt aldosterone activity. This prevent substitution of sodium for potassium.
Cont.. Amiloride and triamterene do not block aldosterone, but instead directly interfere with Na + entry through the epithelial Na + channels in the apical membrane of the collecting tubule. Hence, inhibiting reabsorption of sodium and promote loss of sodium and water without depleting potassium.
Pharmacokinetics Overall, spironolactone has a rather slow onset of action, requiring several days before full therapeutic effect is achieved. Spironolactone is completely absorbed orally and is strongly bound to proteins. It is rapidly converted to an active metabolite, canrenone. The action of spironolactone is largely due to the effect of canrenone, which has mineralocorticoid- blocking activity. Spironolactone induces hepatic cytochrome P450. Eplerenone is a spironolactone analog with much greater selectivity for the mineralocorticoid receptor. It is several hundredfold less active on androgen and progesterone receptors than spironolactone, and therefore, eplerenone has considerably fewer adverse effects
Cont.. Triamterene is metabolized in the liver, but renal excretion is a major route of elimination for the active form and the metabolites, approximately 80%. Because triamterene is extensively metabolized, it has a shorter half-life and must be given more frequently than amiloride (which is not metabolized).
Therapeutic uses Spironolactone and eplerenone are used for oedema associated with hyperaldonsteronism, for instance cirrhosis, nephrotic syndrome and congestive cardiac failure. Amiloride and triamterene, in combination with hydrochlorothiazide, are used for oedema and for hypertension where potassium sparing and magnesium sparing are indicated They also used to correct hypokalemia
Adverse effects Hyperkalemia excessive potassium can lead to cardiac arrthymias and occur mainly in renal dysfunction Hyponatraemia- encountered particularly when spironolactone is combined with other diuretics and in the treatment of liver cirrhosis. Oestrogen- like effects- gynecomastia, depressed libido, impotence menstrual irregularities, and postmenopausal haemorrhage may be encountered. Megaloblastic anemia in patients with cirrhosis may develop due shortage of folic acid because triamterene interferes with dihydrofolate reductase. CNS effects drowsiness and convolution can occur GIT disturbances- loss of appetite, vomiting, nausea, abdominal cramps, diarrhoea, etc..
Drug interaction Strong CYP3A4 inhibitors (e.g. erythromycin, fluconazole, diltiazem, and grapefruit juice) can markedly increase blood levels of eplerenone, but not spironolactone. Non- steroidal Anti-inflammatory Drugs (NSAIDs), especially indomethacin, may reduce the antihypertensive effects of potassium sparing diuretics. This is a result of decreased prostaglandins renal synthesis. Degreased clearance of digoxin, lithium, metformin, may result in elevated serum levels of these drugs (Christy L.,2001) K+ sparing diuretics are given with food to help decrease GI disturbance and spironolactone oral absorption is enhanced when taken with food.
Contraindications Patients with chronic renal insufficiency, including anuria, elevated serum creatinine, and elevated BUN Triamterene should not be used in patients with severe hepatic dysfunction.
Precautions These K+ sparing diuretics should be avoided in pregnancy due to the salt imbalances they cause e.g reduce Na and chlorine (hypochloremia). However, safety not confirmed in breastfeeding. Spironolactone is a potassium sparing diuretic and should be used with caution especially if used in combination with ACE inhibitors or angiotensin receptor blockers(ARBs), and should almost always be avoided with other potassium sparing diuretics, for example, amiloride.
References Christy l. (2001). Southern Medical Journal :potassium sparing diuretics. [online] available from: www.Medscape.com/viewarticle/421426_2 Roger, W, Cate, W. (2012). Clinical Pharmacy and Therapeutics. (5th Ed). Churchill, Livingstone. Katzung B, Susan B, Anthony T. (2012). Basic and Clinical Pharmacology (12th ed ). McGraw-Hill, New York. Richard A. (2012). Lippincotts Illustrated Reviews: Pharmacology. (5th ed).Wolters Kluwer, Philadelphia.
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Potassium - sparing diuretics

  • 1. Potassium sparing diuretics Namulo Talohole Pharmacy student Lusaka Apex Medical University
  • 2. INTRODUCTION Diuretics are drugs that increase the volume of urine excreted by the kidney as a result, reduce extracellular fluid. Their diuretic action is achieved by blockade of distal renal tubular sodium reabsorption In addition the major effect of each class of diuretics drugs is limited to specific nephron segment, and knowledge of their specific sites of action is important in selecting an appropriate drug and anticipating and preventing complications. Potassium sparing diuretics works at the collecting duct, where they interfere with Na+ reabsorption and indirectly with K+ secretion. Their diuretic activity is weak.
  • 4. Examples of potassium-sparing diuretics They are divided into : Aldosterone diuretics Spironolactone Eplerenone Epithelium Na+ channel inhibitors Amiloride Triamterene
  • 5. Pharmacodynamics Normally the tubular fluid in the distal convoluted tubule part is hypotonic . The high celling diuretics and thiazides increases the sodium ion concentration and this induces the renin-angiotensin aldosterone system that results in substitution of sodium for potassium ions so that potassium is also excreted . Administration of Aldosterone antagonist hence prevent K + secretion by antagonizing the effects of aldosterone in collecting tubules. Spironolactone and eplerenone bind to mineralocorticoid receptors and blunt aldosterone activity. This prevent substitution of sodium for potassium.
  • 6. Cont.. Amiloride and triamterene do not block aldosterone, but instead directly interfere with Na + entry through the epithelial Na + channels in the apical membrane of the collecting tubule. Hence, inhibiting reabsorption of sodium and promote loss of sodium and water without depleting potassium.
  • 7. Pharmacokinetics Overall, spironolactone has a rather slow onset of action, requiring several days before full therapeutic effect is achieved. Spironolactone is completely absorbed orally and is strongly bound to proteins. It is rapidly converted to an active metabolite, canrenone. The action of spironolactone is largely due to the effect of canrenone, which has mineralocorticoid- blocking activity. Spironolactone induces hepatic cytochrome P450. Eplerenone is a spironolactone analog with much greater selectivity for the mineralocorticoid receptor. It is several hundredfold less active on androgen and progesterone receptors than spironolactone, and therefore, eplerenone has considerably fewer adverse effects
  • 8. Cont.. Triamterene is metabolized in the liver, but renal excretion is a major route of elimination for the active form and the metabolites, approximately 80%. Because triamterene is extensively metabolized, it has a shorter half-life and must be given more frequently than amiloride (which is not metabolized).
  • 9. Therapeutic uses Spironolactone and eplerenone are used for oedema associated with hyperaldonsteronism, for instance cirrhosis, nephrotic syndrome and congestive cardiac failure. Amiloride and triamterene, in combination with hydrochlorothiazide, are used for oedema and for hypertension where potassium sparing and magnesium sparing are indicated They also used to correct hypokalemia
  • 10. Adverse effects Hyperkalemia excessive potassium can lead to cardiac arrthymias and occur mainly in renal dysfunction Hyponatraemia- encountered particularly when spironolactone is combined with other diuretics and in the treatment of liver cirrhosis. Oestrogen- like effects- gynecomastia, depressed libido, impotence menstrual irregularities, and postmenopausal haemorrhage may be encountered. Megaloblastic anemia in patients with cirrhosis may develop due shortage of folic acid because triamterene interferes with dihydrofolate reductase. CNS effects drowsiness and convolution can occur GIT disturbances- loss of appetite, vomiting, nausea, abdominal cramps, diarrhoea, etc..
  • 11. Drug interaction Strong CYP3A4 inhibitors (e.g. erythromycin, fluconazole, diltiazem, and grapefruit juice) can markedly increase blood levels of eplerenone, but not spironolactone. Non- steroidal Anti-inflammatory Drugs (NSAIDs), especially indomethacin, may reduce the antihypertensive effects of potassium sparing diuretics. This is a result of decreased prostaglandins renal synthesis. Degreased clearance of digoxin, lithium, metformin, may result in elevated serum levels of these drugs (Christy L.,2001) K+ sparing diuretics are given with food to help decrease GI disturbance and spironolactone oral absorption is enhanced when taken with food.
  • 12. Contraindications Patients with chronic renal insufficiency, including anuria, elevated serum creatinine, and elevated BUN Triamterene should not be used in patients with severe hepatic dysfunction.
  • 13. Precautions These K+ sparing diuretics should be avoided in pregnancy due to the salt imbalances they cause e.g reduce Na and chlorine (hypochloremia). However, safety not confirmed in breastfeeding. Spironolactone is a potassium sparing diuretic and should be used with caution especially if used in combination with ACE inhibitors or angiotensin receptor blockers(ARBs), and should almost always be avoided with other potassium sparing diuretics, for example, amiloride.
  • 14. References Christy l. (2001). Southern Medical Journal :potassium sparing diuretics. [online] available from: www.Medscape.com/viewarticle/421426_2 Roger, W, Cate, W. (2012). Clinical Pharmacy and Therapeutics. (5th Ed). Churchill, Livingstone. Katzung B, Susan B, Anthony T. (2012). Basic and Clinical Pharmacology (12th ed ). McGraw-Hill, New York. Richard A. (2012). Lippincotts Illustrated Reviews: Pharmacology. (5th ed).Wolters Kluwer, Philadelphia.