Hypercalcemia in Emergency Medicine Medication

Several classifications of medications are used to treat elevations of serum calcium. Some can be used in acute life-threatening elevations, while others are used to help control calcium elevations after the acute event has been treated. Agents that help treat hypercalcemia include plicamycin (also known as Mithracin), calcitonin, gallium nitrate, intravenous phosphate, bisphosphates, and glucocorticoids.

Class Summary

These compounds are analogs of pyrophosphate that act by binding to hydroxyapatite in bone matrix, thereby inhibiting the dissolution of crystals. These agents prevent osteoclast attachment to bone matrix and interfere with osteoclast recruitment and viability.

Pamidronate (Aredia)

Mechanism of action is inhibition of normal and abnormal bone resorption; appears to inhibit bone resorption without inhibiting bone formation and mineralization. Potent agent that has several regimens for administration. Adverse effects of IV administration include mild transient increases in temperature, leukopenia, and mild reduction in serum phosphate levels. PO maintenance therapy is available after acute event has resolved, but this therapy is experimental. With acute hypercalcemia, all of these agents are effective; pamidronate may be preferable because of its potency and efficacy.

Zoledronic acid (Zometa)

Inhibits bone resorption, possibly by acting on osteoclasts or osteoclast precursors. Median duration of complete response (maintaining normalized calcium levels) and time to relapse reported as 32 and 30 d, respectively. Indicated for hypercalcemia of malignancy.

Etidronate (Didronel)

Reduces bone formation; does not appear to alter renal tubular reabsorption of calcium. Does not affect hypercalcemia in patients with hyperparathyroidism where increased calcium reabsorption may increase blood calcium levels. Response generally observed within first 48 h; more effective if patient is well hydrated before initial dose. If patient responds well before 7 d, therapy can be discontinued. Generally well tolerated; most common adverse effect is a transient elevation of serum creatinine and phosphorous. PO therapy is experimental and not always effective.

Class Summary

Inhibit RNA synthesis in osteoclasts and effective in treatment of hypercalcemia.

Calcitonin (Miacalcin, Cibacalcin, Calcimar)

A naturally occurring hormone that inhibits bone reabsorption and increases excretion of calcium. Most rapid onset of action of anticalcemic agents. Effects may be observed within a few hours with peak response at 12-24 h; because of short duration of action, other more potent but slower-acting agents should be started in patients with severe hypercalcemia. Salmon calcitonin is used most often and is more potent than human calcitonin. Action of this agent is short-lived. If elevation of calcium is severe, coadminister 1-2 doses with fluids and Lasix to provide a rapid, although limited, reduction of the calcium level.

Gallium nitrate (Ganite)

Works by inhibiting bone reabsorption and altering structure of bone crystals.

Exerts hypocalcemic effect, possibly by reducing bone resorption; performs well against other anticalcium agents but has slow onset of action.

Plicamycin

No longer manufactured and distributed in the United States. Inhibits cellular ribonucleic acid (RNA) and enzymatic RNA synthesis. Possibly blocks hypercalcemic action of pharmacologic doses of vitamin D and may act on osteoclasts or block action of parathyroid hormone. Effect in lowering calcium is not related to tumoricidal activity.

Class Summary

Use of IV phosphate is very effective in lowering serum calcium levels most likely because of a precipitation phenomenon. Significant risk exists with use of this agent. This agent is reserved for hypercalcemia unresponsive to other agents.

Potassium phosphate

IV preparations are available as sodium or potassium phosphate (K₂ PO₄). Response to IV serum phosphorus supplementation is highly variable and is associated with hyperphosphatemia.

Class Summary

While these agents do not treat hypercalcemia directly, they are useful for treating hypercalcemia caused by vitamin D toxicity, certain malignancies (eg, multiple myeloma, lymphoma), sarcoidosis, and other granulomatous diseases. These agents generally are not effective in patients with solid tumors or primary hyperparathyroidism. Several different glucocorticoids may be used.

Hydrocortisone (Cortef)

Mineralocorticoid activity and glucocorticoid effects; onset of activity is rapid. Significant number of adverse reactions for those on long-term steroids. In acute phase, few severe reactions present.

Class Summary

Binds to and modulates the parathyroid calcium-sensing receptor, increases sensitivity to extracellular calcium, and reduces parathyroid hormone secretion.

Cinacalcet (Sensipar)

Directly lowers parathyroid hormone (PTH) levels by increasing sensitivity of calcium sensing receptor on chief cell of parathyroid gland to extracellular calcium. Also results in concomitant serum calcium decrease. Indicated for hypercalcemia with parathyroid carcinoma.