A Brief Review of the Pharmacology of Hyperkalemia: Causes and Treatment

James M. Wooten, PharmD; Fernanda E. Kupferman, MD; Juan C. Kupferman, MD, MPH


South Med J. 2019;112(4):228-233. 

In This Article

Abstract and Introduction


Hyperkalemia is a common problem in both inpatients and outpatients. Many disease states (eg, chronic kidney disease) and medications may precipitate hyperkalemia. There are several drugs now available to treat hyperkalemia. Many of these drugs are relatively new. This review provides information regarding drug-induced causes of hyperkalemia and provides detailed information on the medications used to treat this problem.


Hyperkalemia is a common and clinically relevant electrolyte abnormality. In adults, a normal potassium (K+) concentration is defined as a serum potassium level between 3.5 and 5.0 mEq/L (or millimoles per liter). Although a somewhat arbitrary measure, the general classification of hyperkalemia is mild (>5.0–5.9 mEq/L), moderate (6–<7.0 mEq/L), and severe (≥7 mEq/L);[1,2] other entities have published slightly different cutoffs for mild, moderate, and severe hyperkalemia.[1,4] Hyperkalemia also can be differentiated based on how quickly the potassium rises (ie, acute or chronic). This distinction is important because acute hyperkalemia is generally considered to be much more critical than chronic hyperkalemia.[1–3]

Acute hyperkalemia is defined as hyperkalemia that occurs as a single event, generally for hours or days, and usually requires emergency treatment. Acute elevations of potassium can be dangerous, especially to the cardiac system. Based on the potassium concentration and the condition of the patient, acute hyperkalemia should be considered a medical emergency and must be dealt with accordingly. Once treated, the potassium must be monitored closely, especially in patients with acute renal insufficiency, cardiac disease, and other comorbidities. These patients are almost always hospitalized and are monitored in an acute care setting with constant electrocardiographic monitoring.

Chronic hyperkalemia is defined as hyperkalemia that develops during the course of weeks or months, may occur persistently or periodically, and may require some type of outpatient management. Precise guidelines for monitoring serum potassium in patients with chronic hyperkalemia are less clear. Many patients with chronic mild hyperkalemia are managed as outpatients with appropriate therapies. In these patients, renal function and serum potassium concentrations are assessed regularly and are individualized based on a patient's comorbidities, changing renal function, potential drug interactions, and other indicators.

The incidence of hyperkalemia in the general population is unknown; however, in hospitalized patients in the United States, its incidence has been estimated to be between 1% and 10%.[4] The mortality rate in the United States for hyperkalemia in hospitalized patients is estimated at 1 in 1000 patients. Appropriate renal excretion or reabsorption of potassium is extremely important in maintaining potassium homeostasis. As renal function declines, the number of patients diagnosed as having hyperkalemia increases considerably. Although patients with mild chronic hyperkalemia (5.1–5.9 mEq/L) can be treated as outpatients, severe hyperkalemia is encountered most often in inpatients or treated in the emergency department.[3–5]

The pharmacologic influence on this electrolyte disorder is interesting. There are several commonly prescribed medications that can cause hyperkalemia, and understanding the pharmacology of these drugs will enable the practitioner to more accurately predict and monitor this potential adverse effect. There are also several medications that can be used to treat this disorder, and knowing the pharmacology of these drugs will enable the practitioner to select the appropriate pharmacotherapy regimen for the patient. This review focuses primarily on the pharmacologic causes and treatments of hyperkalemia.