Medication Summary
Potassium
Oral potassium chloride is the usual choice for replenishment of potassium levels and for maintenance of potassium levels in patients with ongoing potassium loss (eg, those on thiazide diuretics). Potassium chloride is absorbed easily and can be given several times per day if needed, especially if high-dose diuretic therapy is required.
In patients with hypokalemia and diabetic ketoacidosis, part of the potassium dose should be administered as potassium phosphate.
ACE inhibitors
ACE inhibitors have gained significantly in popularity because of their excellent tolerability and benefit in a variety of disease conditions. In particular, these drugs have demonstrable clinical benefit for the treatment of hypertension, heart failure, and a variety of kidney diseases, including diabetic nephropathy.
Because they inhibit renal potassium excretion, ACE inhibitors can ameliorate some of the hypokalemia that can occur with use of thiazide or loop diuretics.
Cough is the most common complaint with ACE inhibitors. Other types of adverse effects commonly seen with other antihypertensives (eg, exercise intolerance, fatigue, dry mouth, impotence, drowsiness) are not reported as commonly with ACE inhibitors.
Caution
Often, individuals with cirrhosis or chronic heart failure have subtle decreases in renal function that may not be apparent from routine laboratory studies. In addition, patients with heart failure often are treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), classes of drugs that inhibit renal potassium excretion.
In patients with mild renal insufficiency, the combination of an ACE inhibitor, a potassium-sparing diuretic, and a potassium supplement can very easily result in life-threatening hyperkalemia. Frequent follow-up is necessary to avoid this outcome.
Selective aldosterone antagonists
Potassium-sparing diuretics are generally used only in patients with normal renal function who are prone to significant hypokalemia. Some evidence indicates that spironolactone is particularly useful in patients with cirrhosis and in those with heart failure. Exercise caution in using potassium-sparing diuretics in either of these populations. Frequent determination of potassium levels is mandatory.
Treatment with the more selective aldosterone receptor inhibitor eplerenone is associated with fewer side effects than treatment with spironolactone and may be more effective for hypertension related to primary hyperaldosteronism. [60] Eplerenone in patients with chronic heart failure after acute myocardial infarction has been associated with improved mortality and a low incidence of hyperkalemia. [61]
Electrolytes
Class Summary
Potassium is essential for transmission of nerve impulses, contraction of cardiac muscle, maintenance of intracellular tonicity, skeletal and smooth muscles, and maintenance of normal renal function. Gradual potassium depletion may occur via renal excretion, through gastrointestinal loss, or because of low intake. In general, a 1 mEq/L drop in potassium correlates to a loss of 100-200 mEq of total body potassium. However, hypokalemia may result from the movement of potassium into cells without loss of potassium from the body.
Electrolytes can be used as oral or parenteral therapy for potassium replacement. Most patients respond well to low-dose supplements.
Potassium chloride (K-Dur, Klor Con, Klor-Con M, KTab, MicroK, Kaon CL 10, K-Lyte Cl, Kay Ciel)
Potassium chloride is the preferred salt for patients with preexisting alkalosis. It is the first choice for IV therapy. Oral preparations include 8 mEq slow-release tablets, 20 mEq elixir, 20 mEq powder, and 25 mEq tablets. Any of these forms may irritate the stomach and cause vomiting; consequently, they should be taken with food or after meals to minimize gastrointestinal discomfort.
Unflavored liquid potassium chloride has an unpleasant taste, so pills may be conducive to better compliance. Long-acting supplements often are not as well absorbed, but microencapsulated forms often are better tolerated. Tailor the dose to the patient's needs.
Urinary Alkalinizing Agents
Class Summary
Potassium citrate is an orally administered alkalinizing agent. This and other potassium salts may be used as supplements to maintain potassium homeostasis; however potassium chloride is usually the drug of choice.
Potassium citrate (Urocit K)
This is an oral preparation with a base instead of an acid anion. Potassium citrate is generally used for patients who form calcium stones or for those with severe metabolic acidosis. It is not as effective as potassium chloride for replacement in the general population. Tailor the dose to the patient's needs.
ACE Inhibitors
Class Summary
These agents inhibit the production of aldosterone and decrease renal potassium losses. All of the drugs in this category work in the same way. Differences are in the duration of action and the ability to inhibit locally produced and circulating ACE.
Captopril (Capoten, Captoril)
This agent prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion and increased renin activity. Captopril is the shortest-acting ACE inhibitor; it must be given 2 or 3 times daily, while other drugs in this class can be taken once daily.
Enalapril (Vasotec)
Enalapril is a competitive inhibitor of ACE. It reduces angiotensin II levels, decreasing aldosterone secretion and increasing renin secretion.
Fosinopril
Fosinopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion and increased renin secretion.
Ramipril (Altace)
Ramipril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.
ARBs
Class Summary
ARBs competitively inhibit the ability of angiotensin II to interact with and stimulate angiotensin II receptors. This action results in decreased aldosterone secretion and, consequently, decreased renal potassium excretion.
Valsartan (Diovan)
Valsartan is a prodrug that produces direct antagonism of angiotensin II receptors. It displaces angiotensin II from the AT1 receptor and may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses.
Valsartan may induce more complete inhibition of the renin-angiotensin system than ACE inhibitors, it does not affect response to bradykinin, and it is less likely to be associated with cough and angioedema. It can be used as an alternative therapy, especially in patients who are unable to tolerate ACE inhibitors.
Candesartan (Atacand)
Candesartan produces direct antagonism of angiotensin II receptors. It displaces angiotensin II from the AT1 receptor and may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses.
This agent may induce more complete inhibition of the renin-angiotensin system than ACE inhibitors, it does not affect response to bradykinin, and it is less likely to be associated with cough and angioedema. It can be used as an alternative therapy, especially in patients unable to tolerate ACE inhibitors.
Losartan (Cozaar)
Losartan is an angiotensin II receptor antagonist that blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. It may induce more complete inhibition of the renin-angiotensin system than ACE inhibitors, it does not affect response to bradykinin, and it is less likely to be associated with cough and angioedema. It can be used as an alternative therapy, especially in patients unable to tolerate ACE inhibitors.
Diuretics, Potassium-Sparing
Class Summary
Potassium-sparing diuretics are excellent for adjunctive therapy when ongoing renal losses are anticipated. These agents may be used in conjunction with thiazide or loop diuretics.
Triamterene (Dyrenium)
Triamterene is a potassium-sparing diuretic with relatively weak natriuretic properties. It exerts a diuretic effect on the distal renal tubule, inhibiting reabsorption of sodium in exchange for potassium and hydrogen. It is not a competitive antagonist of mineralocorticoids, and a potassium-conserving effect is observed in patients with Addison disease (ie, without aldosterone).
Amiloride (Midamor)
This agent is a pyrazine-carbonyl-guanidine unrelated chemically to other known antikaliuretic (potassium-sparing) or diuretic agents. It is a potassium-sparing drug that, compared with thiazide diuretics, possesses weak natriuretic, diuretic, and antihypertensive activity.
Aldosterone Antagonists, Selective
Class Summary
These agents selectively block aldosterone binding at mineralocorticoid receptors. They may be used as potassium-sparing diuretics.
Spironolactone (Aldactone)
Spironolactone is used to manage edema resulting from excessive aldosterone excretion. It competes with aldosterone for receptor sites in distal renal tubules, resulting in increased water excretion and retention of potassium and hydrogen ions.
Eplerenone (Inspra)
Eplerenone selectively blocks aldosterone at the mineralocorticoid receptors in epithelial (eg, renal) and nonepithelial (eg, heart, blood vessel, and brain) tissues; thus, it decreases blood pressure and sodium reabsorption. It is more selective for mineralocorticoid receptors than spironolactone and thus has a lower incidence of side effects associated with androgen antagonism, such as gynecomastia.
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A model of transport mechanisms in the distal convoluted tubule. Sodium-chloride (NaCl) enters the cell via the apical thiazide-sensitive NCC and leaves the cell through the basolateral Cl− channel (ClC-Kb), and the Na+/K+-ATPase. Indicated also are the recently identified magnesium channel TRPM6 in the apical membrane, and a putative Na/Mg exchanger in the basolateral membrane. These transport mechanisms play a role in familial hypokalemia-hypomagnesemia or Gitelman syndrome.
