Page 797 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 42 Agents That Affect Bone Mineral Homeostasis 783

of toxicity permits frequent administration at high doses (200 vitamin D–mediated intestinal calcium transport and increase
MRC units or more). An effect on serum calcium is observed renal excretion of calcium. An action of glucocorticoids to reduce
within 4–6 hours and lasts for 6–10 hours. Calcimar (salmon vitamin D–mediated bone resorption has not been excluded,
calcitonin) is available for parenteral and nasal administration. however. The effect of glucocorticoids on the hypercalcemia of
cancer is probably twofold. The malignancies responding best to
Gallium Nitrate glucocorticoids (ie, multiple myeloma and related lymphoprolif-
erative diseases) are sensitive to the lytic action of glucocorticoids.
Gallium nitrate is approved by the FDA for the management of Therefore part of the effect may be related to decreased tumor
hypercalcemia of malignancy. This drug inhibits bone resorp- mass and activity. Glucocorticoids have also been shown to inhibit
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tion. At a dosage of 200 mg/m body surface area per day given the secretion or effectiveness of cytokines elaborated by multiple
as a continuous intravenous infusion in 5% dextrose for 5 days, myeloma and related cancers that stimulate osteoclastic bone
gallium nitrate proved superior to calcitonin in reducing serum resorption. Other causes of hypercalcemia—particularly primary
calcium in cancer patients. Because of potential nephrotoxicity, hyperparathyroidism—do not respond to glucocorticoid therapy.
patients should be well hydrated and have good renal output
before starting the infusion.
HYPOCALCEMIA

Phosphate
The main features of hypocalcemia are neuromuscular: tetany, par-
Intravenous phosphate administration is probably the fastest esthesias, laryngospasm, muscle cramps, and seizures. The major
and surest way to reduce serum calcium, but it is a hazardous causes of hypocalcemia in the adult are hypoparathyroidism,
procedure if not done properly. Intravenous phosphate should vitamin D deficiency, chronic kidney disease, and malabsorption.
be used only after other methods of treatment (bisphosphonates, Hypocalcemia can also accompany the infusion of potent bisphos-
calcitonin, and saline diuresis) have failed to control symptomatic phonates and denosumab for the treatment of osteoporosis, but
hypercalcemia. Phosphate must be given slowly (50 mmol or 1.5 g this is seldom of clinical significance unless the patient is already
elemental phosphorus over 6–8 hours) and the patient switched hypocalcemic at the onset of the infusion. Neonatal hypocalcemia
to oral phosphate (1–2 g/d elemental phosphorus, as one of the is a common disorder that usually resolves without therapy. The
salts indicated below) as soon as symptoms of hypercalcemia have roles of PTH, vitamin D, and calcitonin in the neonatal syndrome
cleared. The risks of intravenous phosphate therapy include sud- are under investigation. Large infusions of citrated blood can pro-
den hypocalcemia, ectopic calcification, acute renal failure, and duce hypocalcemia secondary to the formation of citrate-calcium
hypotension. Oral phosphate can also lead to ectopic calcifica- complexes. Calcium and vitamin D (or its metabolites) form the
tion and renal failure if serum calcium and phosphate levels are mainstay of treatment of hypocalcemia. However, in patients with
not carefully monitored, but the risk is less and the time of onset hypoparathyroidism, teriparatide or rhPTH 1-84 may prove use-
much longer. Phosphate is available in oral and intravenous forms ful (only rhPTH 1-84 has been FDA approved for this condition).
as sodium or potassium salts. Amounts required to provide 1 g of
elemental phosphorus are as follows: Calcium
Intravenous: A number of calcium preparations are available for intravenous,
In-Phos, 40 mL; or Hyper-Phos-K, 15 mL intramuscular, and oral use. Calcium gluceptate (0.9 mEq
Oral: calcium/mL), calcium gluconate (0.45 mEq calcium/mL), and
Fleet Phospho-Soda, 6.2 mL; or Neutra-Phos, 300 mL; or calcium chloride (0.68–1.36 mEq calcium/mL) are available for
K-Phos-Neutral, 4 tablets intravenous therapy. Calcium gluconate is preferred because it
is less irritating to veins. Oral preparations include calcium car-
Glucocorticoids bonate (40% calcium), calcium lactate (13% calcium), calcium
phosphate (25% calcium), and calcium citrate (21% calcium).
Glucocorticoids have no clear role in the immediate treatment of Calcium carbonate is often the preparation of choice because of
hypercalcemia. However, the chronic hypercalcemia of sarcoid- its high percentage of calcium, ready availability (eg, Tums), low
osis, vitamin D intoxication, and certain cancers may respond cost, and antacid properties. In achlorhydric patients, calcium
within several days to glucocorticoid therapy. Prednisone in oral carbonate should be given with meals to increase absorption, or
doses of 30–60 mg daily is generally used, although equivalent the patient should be switched to calcium citrate, which is some-
doses of other glucocorticoids are effective. The rationale for what better absorbed. Combinations of vitamin D and calcium
the use of glucocorticoids in these diseases differs, however. The are available, but treatment must be tailored to the individual
hypercalcemia of sarcoidosis is secondary to increased production patient and the individual disease, a flexibility lost by fixed-dosage
of 1,25(OH) D by the sarcoid tissue itself. Glucocorticoid therapy combinations.
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directed at the reduction of sarcoid tissue results in restoration of Treatment of severe symptomatic hypocalcemia can be accom-
normal serum calcium and 1,25(OH) D levels. The treatment plished with slow infusion of 5–20 mL of 10% calcium gluco-
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of hypervitaminosis D with glucocorticoids probably does not nate. Rapid infusion can lead to cardiac arrhythmias. Less severe
alter vitamin D metabolism significantly but is thought to reduce hypocalcemia is best treated with oral forms sufficient to provide