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Potassium sparing diuretics

Potassium sparing diuretics


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Potassium sparing diuretics

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A 24-year-old woman presents to her dermatologist’s office with persistent cystic acne. She was successfully treated with a course of doxycycline in the past, but experienced a recurrence over the last two months. Her acne is worse in the post-luteal phase, and she also reports hair growth along her chin, neck, and chest. No other female relatives have the same symptoms. Physical examination shows cysts along the jawline, upper chest, and upper back, with extensive scarring. The dermatologist decides to prescribe a commonly-used medication, but warns the patient that she will need to come in regularly to monitor levels of a particular electrolyte. Which of the following electrolytes is likely to be affected by this medication?

External References

Diuretics are medications that act on the kidneys to increase production of urine, and to eliminate water, certain metabolic wastes, and electrolytes from the body.

There are 5 main types of diuretics; carbonic anhydrase inhibitors, osmotic diuretics, thiazide and thiazide-like diuretics, loop diuretics,, and last but not least, potassium sparing diuretics - which is the only class of diuretic that retains potassium, rather than wasting it.

Now, the basic unit of the kidney is called a nephron, and each nephron is made up of a glomerulus, which filters the blood. T.

The filtered content then goes through the renal tubule, where excess waste, and molecules, such as ions and water, are removed or filtered through an exchange between the tubule and the peritubular capillaries.

So the renal tubule plays a huge role in secretion and reabsorption of fluid and ions - such as sodium, potassium, chloride, and magnesium - in order to maintain homeostasis - or the balance of fluid and ions in our body.

The renal tubule has a few segments of its own: the proximal convoluted tubule, the U-shaped loop of Henle, with a thin descending, a thin ascending limb, and a thick ascending limb, and finally, the distal convoluted tubule, which empties into the collecting duct, which collects the urine.

Different kinds of diuretics act on different segments of the renal tubule. Now, potassium sparing diuretics act on the cortical collecting tubules. Here, there are principal cells and α-intercalated cells dispersed amongst the tubule cells.

The principal cell has two pumps on the apical surface, an ATP-dependent potassium pump that pushes potassium into the tubule, and an epithelial sodium channel pump, called ENaC for short, that pulls sodium into the cell.

There’s also a Na/K ATPase pump on the basolateral surface that again moves 2 potassium ions into the cell for every 3 sodium ions out.

Now, the alpha intercalated cells mainly get rid of hydrogen ions from the blood, and they use two pumps on their apical surface for this.

First, they have a H+/ATPase which uses ATP to pump hydrogen into the tubule. Second, they have a hydrogen potassium ATPase (H+K+ATPase) which uses ATP to push 1 hydrogen into the tubule in exchange for 1 potassium.

Sodium and potassium levels in alpha intercalated cells are also controlled by Na/K ATPase pumps on the basolateral surface, which move two potassium ions into the cell and three sodium ions out of the cell.

Now the reabsorption and secretion of these molecules in the distal convoluted tubule and collecting duct are hormonally regulated by aldosterone, a mineralocorticoid hormone made in the adrenal cortex.

In the principal cells, aldosterone diffuses across the basolateral membrane and binds to a mineralocorticoid receptor in the cytoplasm.

Then the aldosterone-receptor complex gets inside the nucleus of the cell where it triggers the increased synthesis of ENaCs, ATP-dependent potassium pumps, and the Na-K ATPase transporters.

Together, they work to increase sodium reabsorption into the blood and potassium secretion into the urine.

In the alpha intercalated cells, Aldosterone increases the synthesis of hydrogen potassium ATPase to increase H+ secretion.

Now, potassium sparing diuretics come in two flavors according to their mechanism of action: first, we’ve got those that directly inhibit the aldosterone receptor like spironolactone and eplerenone, then we have medications that indirectly inhibit the effects of aldosterone by blocking the ENaC channels on the cell membrane, like amiloride and triamterene.

This decreases the level of sodium inside the principal cells which decreases the action of the Na+/K+ ATPase on the basolateral membrane.

However, at the end of the day, both categories have the same effect; first, they increase the excretion of sodium, and since water flows where the sodium goes, they also increase water loss through the urine.

Next, they decrease the excretion of hydrogen and potassium, hence the name, potassium sparing.

Ok, so the major indication for diuretics is for the management of hypertension and edematous states.

These medications increase sodium and water loss through the urine, which leads to decreased plasma volume and cardiac output, resulting in lower blood pressure.

This also treats edematous states like pulmonary edema or ascites where fluid builds up in the extracellular space.

Potassium sparing diuretics are usually pretty weak, so they are used in combination with other diuretics, like loop or thiazides that would normally cause renal potassium wasting and hypokalemia.

The addition of a potassium sparing diuretic increases the reabsorption of potassium in the final stretches of the renal tubule, and therefore reduces potassium loss.

Aldosterone receptor antagonists like spironolactone and eplerenone are also useful in hyperaldosteronism.

Hyperaldosteronism can be primary, meaning too much aldosterone is secreted by the adrenal cortex itself; like with Conn syndrome, or when a tumor secretes too much ACTH, which then tells the adrenal cortex to make too much aldosterone.




Basic information

  • Agents that ↑ rate of urine flow (diuresis), net urinary excretion of Na+ salts (natriuresis) → ↓ extracellular fluid (ECF) volume without ↑ excretion of K+, H+

Mechanism of action

  • Act on distal convoluted tubule, collecting duct → inhibit aldosterone effects (stimulates Na+ reabsorption in exchange for K+, H+ excretion) → ↑ excretion of Na+, water; retention of K+, H+

Key points


Potassium-sparing diuretics

  • Indirectly inhibits aldosterone’s action by blocking sodium channel (ENaC) in principal cells in late distal tubule, collecting duct → ↓ actions of Na+-K+ ATPase

Potassium-sparing diuretics/mineralocorti-coid (aldosterone) receptor antagonists

  • Directly compete with aldosterone receptor sites in late distal tubule, collecting duct → inhibit aldosterone’s actions

Common indications



Drug-specific adverse effects

Boxed warnings

  • AMILoride, triamterene: potentially fatal hyperkalemia


  • Renal insufficiency: dosage reduction; ↑ risk of hyperkalemia

  • Hepatic impairment: fluid, electrolyte alterations may ↑ risk of hepatic coma


  • Administer diuretics early in day (avoids nocturia)

  • Suspension formulations: shake well (pre- administration)


  • Do not administer with potassium supplements

  • Avoid potassium-containing salt substitutes, potassium-rich diet

  • Grapefruit juice: ↑ serum eplerenone level


  • Eplerenone: major CYP3A4 substrate

Concomitant use



  1. "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
  2. "Rang and Dale's Pharmacology" Elsevier (2019)
  3. "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
  4. "Diuretic Therapy in Heart Failure – Current Approaches" European Cardiology Review (2015)
  5. "Managing resistant hypertension: focus on mineralocorticoid-receptor antagonists" Vascular Health and Risk Management (2017)