Potassium-sparing diuretics

Potassium-sparing diuretics are diuretic drugs that do not promote the secretion of potassium into the urine.  They are used as adjunctive therapy, together with other drugs, in the treatment of hypertension and management of congestive heart failure.

Potassium-sparing diuretics are generally used in combination with other diuretic drugs (e.g. loop diuretics) that would otherwise tend to lower the potassium levels to potentially dangerous low levels (hypokalemia). The combination therefore helps maintain a normal reference range for potassium. 

On their own, this group of drugs may raise potassium levels beyond the normal range, termed hyperkalemia, which risks potentially fatal arrhythmias.  The risk is high in concurrent use of ACE inhibitors. People are often advised not to use potassium-containing salt replacements with these products. They also carry the risk of developing an acidosis.

There are two main types of drug within this class that have their effect at similar locations:

Aldosterone antagonists: these are competitive antagonists of aldosterone. These drugs prevent aldosterone from entering the principal cells, preventing sodium reabsorption.  They inhibit the effect of aldosterone by competing for intracellular aldosterone receptors in the cortical collecting duct. This decreases the reabsorption of sodium and water, while decreasing the secretion of potassium.

Epithelial sodium channel blockers:  these  work by directly blocking the epithelial sodium channel (ENaC) thereby inhibiting sodium reabsorption in the late distal convoluted tubules, connecting tubules, and collecting ducts in the kidneys. This promotes the loss of sodium and water from the body, but without depleting potassium.

By disrupting the reabsorption of ions, the fluid leaving the kidney is more ‘concentrated’ and there is an ‘osmotic driving force’ to dilute it, as it leaves the collecting duct system, ultimately resulting in increased urine production and reduction of water in the body.

The name of this class derives from the fact that these diuretics tend to decrease or prevent  the secretion of potassium into the urine; thus, potassium is spared and not lost as much as in other diuretics. The term "potassium-sparing" thus refers to an effect rather than a mechanism. However, although potassium  may be spared, calcium isn’t and this class of drug tends to increase the calcium lost in urine.

Drugs

This list is likely to change over time, but at least it provides you with an idea of which drugs come within which category.  The drugs which have caused hallucinations according to the ehealthme web site are listed separately under the observations whereas those in this list without any figures have no record on this site.

Amiloride [1] - was first approved for use in 1967 (then known as MK 870), and known by the trade name Midamor.  It is used in the management of hypertension and congestive heart failure.  The drug is often used in conjunction with thiazide (e.g. co-amilozide) or loop diuretics (e.g. co-amilofruse).

Benzamil or benzyl amiloride is a potent blocker of the ENaC channel  and also a sodium-calcium exchange blocker. It is a potent analog of amiloride, and is marketed as the hydrochloride salt (benzamil hydrochloride).

Canrenone is an aldosterone antagonist, the active form, and first metabolite of, Spironolactone.  Potassium canrenoate or canrenoate potassium is the potassium salt of canrenoic acid, and is also an aldosterone antagonist, as a prodrug, which is metabolized to canrenone in the body.

Eplerenone is an aldosterone antagonist used as an adjunct in the management of chronic heart failure. It is similar to the diuretic spironolactone, though it may be more specific for the mineralocorticoid receptor. It is marketed under the trade name Inspra.
Common adverse drug reactions (ADRs) associated with the use of eplerenone include: hyperkalaemia, hypotension, dizziness, altered renal function, and increased creatinine concentration.  Eplerenone is primarily metabolised by the cytochrome P450 enzyme CYP3A4. Thus the potential exists for adverse drug interactions with other drugs that induce or inhibit CYP3A4.

Spironolactone [66] - see the observation on the main website

Triamterene [24] - see the observation on the main website.