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.

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). Lippincott’s Illustrated Reviews: Pharmacology. (5th
ed).Wolters Kluwer, Philadelphia.

15. Thank you!