Elder Care Interprofessional Provider Sheets

Medication-Induced Hypokalemia: A Common Problem

Barry D. Weiss, MD, College of Medicine, University of Arizona;
Jeannie K. Lee, PharmD, College of Pharmacy, University of Arizona

September 2019

TIPS ABOUT MEDICATION-INDUCED HYPOKALEMIA IN OLDER ADULTS

  • Keep in mind that older adults are at higher risk for medication-induced hypokalemia.
  • Be alert for hypokalemia when patients are taking common offending drugs - diuretics, laxatives, COPD medications, mineralocorticoids, high-dose antibiotics, or high-dose insulin - regularly monitor potassium level.

Hypokalemia is one of the most common electrolyte disorders seen in both outpatient and inpatient care. It is common among older adults, and increasing age is associated with a marked increase in the incidence of hypokalemia. In fact, compared with younger adults, an 80-year old has more than triple the risk of having a potassium level <3.0 mm/L. Women, African Americans, those with higher body mass index (BMI), and cancer patients are more likely to have hypokalemia also.  Additionally, polypharmacy (≥5 drugs) use increases risk.

A variety of medical conditions can cause hypokalemia (Table 1). Providers should screen for these conditions when evaluating patients who have hypokalemia. However, more commonly and particularly in older adults, hypokalemia is medication-induced. Multiple medications, even in therapeutic doses, can induce hypokalemia.

Table 1. Medical Conditions Causing Hypokalemia

  • Bartter's Syndrome and Gitelman's Syndrome (inherited disorders of renal tubule function) 
  • Cancer chemotherapy
  • Cushing syndrome
  • Delirium tremens
  • Diabetes mellitus, uncontrolled
  • Familial hypokalemic periodic paralysis 
  • Gastrointestinal infections 
  • Gastrointestinal tumors
  • Gastrointestinal malabsorption 
  • Hyperaldosteronism 
  • Hyperthyroidism, thyrotoxicosis
  • Hypomagnesemia
  • Leukemia
  • Malnutrition, severe (anorexia, dementia) 
  • Metabolic alkalosis 
  • Pernicious anemia 
  • Radiation enteropathy 
  • Renal tubular acidosis

This issue of Elder Care will review the most common hypokalemia-causing drugs. These and other medications are listed in Table 2. In addition to medications, hypokalemia can also be caused by the ingestion of large quantities of caffeine or licorice.

Hypokalemia is usually asymptomatic, though there have been reports of older adults experiencing profound weakness. Low potassium levels are most often discovered incidentally during routine blood tests. In the absence of blood testing, low potassium levels may go undetected and reduced to the point of disturbances in cardiac rhythm. Therefore, when patients are using medications known to cause hypokalemia, interval monitoring of potassium levels should be performed, especially upon initiation and dose changes.

Diuretics

Diuretic therapy causes renal loss of potassium and is the most common cause of hypokalemia. It can occur with both thiazide-type diuretics and loop diuretics such as furosemide. With loop diuretics, hypokalemia can occur even when potassium supplementation is given.

Laxatives and Enemas

Large doses of laxatives and enemas – particularly phenolphthalein laxatives and/or sodium polystyrene sulfonate – can cause loss of potassium in the stool. It is important to question patients about laxative use because they may not report it unless asked.

COPD Medications

Sympathomimetic drugs, such as beta-adrenergic bronchodilators, cause a shift of potassium from the serum into cells, thereby lowering serum potassium levels. The effect is potent, with a single nebulized albuterol treatment lowering potassium levels by 0.2-0.4 mmol/L, and a repeat dose within an hour dropping levels of by nearly 1 mmol/L.

Theophylline, also sometimes used for COPD treatment, stimulates release of sympathetic amines. Thus, similar to beta adrenergics, they cause a shift of potassium into cells and can lower serum potassium levels.

Oral or IV steroids with glucocorticoid properties, such as prednisone and hydrocortisone sometimes used to treat COPD, can increase renal potassium excretion.  When used  chronically, potassium levels can fall by up to 0.4 mmol/L. 

Mineralocorticoids

The mineralocorticoid fludrocortisone is used to treat orthostatic hypotension due to autonomic dysfunction in Parkinson’s disease or other conditions by causing renal sodium and fluid retention. A byproduct of sodium retention is renal potassium loss, which can cause hypokalemia.

Antimicrobials

Most providers do not think of antibiotics as a cause of hypokalemia. In large doses, however, penicillin, ampicillin, nafcillin and carbenicillin can induce renal potassium excretion. Such effect can occur with aminoglycoside therapy and amphotericin B also.

Insulin

Routine outpatient insulin treatment does not cause significant hypokalemia. But when administered in large doses,  such as for treatment of the non-ketotic hyperosmolar state that sometimes occurs in older diabetics, insulin shifts potassium into cells and can result in marked serum hypokalemia. Intravenous potassium supplementation is often needed for treatment.

Table 2.  Medications that Cause Hypokalemia
Medication Class Example of Specific Drugs Mechanism
Diuretics
 
  • Thiazides
  • Furosemide
  • Renal potassium loss
  • Renal potassium loss
Laxatives
 
  • Phenolpthalein
  • Sodium polystyrene sulfonate
  • Gastrointestinal potassium loss
  • Gastrointestinal potassium loss
COPD Medications
 
  • Beta adrenergics
  • Theophylline
  • Steroids
  • Shift of potassium from serum to cells
  • Shift of potassium from serum to cells
  • Renal potassium loss
Mineralocorticoids/ Glucocorticoids
  • Fludrocortisone
  • Renal potassium loss
Antimicrobials
 
  • Penicillins (penicillin G, nafcillin, ampicillin, carbenicillin)   
  • Aminoglycosides
  • Amphotericin B
  • Renal potassium loss   
  • Renal potassium loss 
  • Renal  potassium loss
Insulin
  • High dose
  • Shift of potassium from serum to cells
Other Medications
 
  • Pseudoephedrine
  • Verapamil (in overdose)
  • Acyclovir
  • Shift of potassium from serum to cells
  • Shift of potassium from serum to cells
  • Renal damage and reduced flow

References and Resources

  • Gilligan S, Raphael KL. Hyperkalemia and hypokalemia in CKD: Prevalence, risk factors, and clinical outcomes. Adv Chronic Kidney Dis. 2017;24(5):215-218. 
  • Veltri KT, Mason C.  Medication-induced hypokalemia. Pharmacy & Therapeutics. 2015;40(3):185-190.
  • Ramirez E, Rossignoli T, Campos AJ, et al.  Drug-induced life-threatening potassium disturbances detected by a pharmacovigilance program from laboratory signals. European Journal of Clinical Pharmacology. 2013;69:97-110