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New Treatments for Hypokalemia

A low serum potassium concentration is perhaps the most common electrolyte abnormality encountered in clinical practice. When defined as a value of less than 3.6 mmol of potassium per liter, hypokalemia is found in over 20 percent of hospitalized patients. The majority of these patients have serum potassium concentrations between 3.0 and 3.5 mmol per liter, but as many as one quarter have values below.

Comparable data are not available for outpatients, but a low serum potassium concentration has been found in 10 to 40 percent of patients treated with thiazide diuretics. Hypokalemia is usually well tolerated in otherwise healthy people, but it can be life-threatening when severe.

Normal Regulation of Potassium Balance

Both the total body stores of potassium and its distribution within the body are closely regulated by key hormones. The normal transcellular distribution of potassium (a high ratio of intracellular).

Clinical Spectrum

Patients with hypokalemia often have no symptoms, particularly when the disorder is mild (serum potassium, 3.0 to 3.5 mmol per liter). With more severe hypokalemia, nonspecific symptoms, such as generalized weakness, lassitude, and constipation, are more common.

Hypokalemia is rarely suspected on the basis of clinical presentation; the diagnosis is made by measurement of serum potassium. A low serum potassium concentration indicates disruption.

Hypokalemia is almost always the result of potassium depletion induced by abnormal losses of potassium. More rarely, hypokalemia occurs because of an abrupt shift of potassium from the extracellular compartment into cells. In either case, drugs prescribed by physicians.

In the absence of an inciting drug, hypokalemia can result from an acute shift of potassium.

Drug-Induced Causes Due to Transcellular Shifts

2-Sympathomimetic Drugs

A wide range of drugs have/32-sympathomimetic activity, including decongestants, bronchodilators, and inhibitors of uterine contraction (Table 1). A standard dose of nebulized albuterol reduces serum potassium by 0.2 to 0.4 mmol per liter, and a second dose taken within one hour reduces.


Theophylline and caffeine are not sympathomimetic drugs, but these agents stimulate the release.

Other Drugs

Although calcium-channel blockers increase cellular uptake of potassium in experimental studies, these drugs have no effect on serum potassium concentrations at usual doses. Intentional ingestion.

Drug-Induced Causes Due to Abnormal Losses of Potassium


The most common cause of hypokalemia is diuretic therapy. Both the thiazide and loop diuretics block chloride-associated sodium reabsorption (with each inhibiting a different membrane-transport protein) and, as a result, increase delivery of sodium to the collecting tubules.

Drugs with Mineralocorticoid or Glucocorticoid Effects

Fludrocortisone is an oral mineralocorticoid that promotes renal potassium excretion and can cause potassium wasting if used inappropriately. Glucocorticoids, such as prednisone and hydrocortisone,.

Other Drugs

Penicillin and its synthetic derivatives, when given intravenously in large doses, promote renal potassium excretion by increasing sodium delivery to the distal nephron. The aminoglycoside antibiotics, the antitumor drug cisplatin, and the antiviral drug foscarnet.

Laxatives and Enemas

Large doses of laxatives cause excessive potassium loss in the stool and can cause hypokalemia.

Nondrug Causes Due to Transcellular Shifts

Severe hypokalemia (serum potassium, <3.0 mmol per liter) can occur, although rarely, in association with hyperthyroidism, resulting in a clinical syndrome characterized by the sudden onset of severe hypokalemia.

Familial hypokalemic periodic paralysis is a rare autosomal dominant disease that has been associated with mutations of the gene encoding the dihydropyridine receptor, a voltage-gated calcium channel) The disorder is characterized by sudden attacks of muscle paralysis.

Nondrug Causes Due to Inadequate Dietary Intake

When the dietary intake of potassium is reduced to less than 1 g per day (25 mmol per day), depletion of potassium and hypokalemia result because the renal excretion of potassium fails to decrease promptly. An isolated reduction of this magnitude in the dietary intake of potassium requires a specially prepared diet, and therefore, hypokalemia is rarely the result of decreased intake. With starvation or near-starvation, body potassium stores become depleted but the breakdown of tissues releases potassium into the extracellular compartment, mitigating the hypokalemia.

Nondrug Causes Due to Abnormal Losses of Potassium

Losses in Stool

The concentration of potassium in stool is 80 to 90 mmol per liter, but because of the low volume of water in normal stool, only about 10 mmol is usually lost each day. In diarrheal states, the potassium concentration in stool decreases.

Metabolic Acidosis

Hypokalemia is a cardinal feature of type I or classic distal renal tubular acidosis. The degree of hypokalemia in this disorder is not directly correlated to the degree of acidosis but more likely reflects dietary sodium and potassium intake and serum aldosterone concentrations.

Other Disorders

Magnesium depletion, induced either by dietary restriction or by abnormal loss, reduces the intracellular potassium concentration and causes renal potassium wasting, The depletion of intracellular potassium stores appears to be due to impairment of the activity of cell-membrane.

Severe and often refractory hypokalemia due to renal potassium wasting occurs in patients with acute myelogenous, monomyeloblastic, or lymphoblastic leukemia. The cause of the defect.

In uncontrolled diabetes mellitus, renal glucose loss causes osmotic diuresis, increasing sodium delivery to the distal nephron and promoting potassium excretion. With prolonged glycosuria.

Principles of Potassium Replacement

Potassium replacement is the cornerstone of therapy for hypokalemia. Unfortunately, supplemental potassium administration is also the most common cause of severe hyperkalemia.