Page 173 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Disorders of Calcium: Hypercalcemia and Hypocalcemia 163

normal dogs at 25 mg/kg/hr did not have detrimental of humans. Treatment with gallium nitrate may be more
effects on the kidneys. 578 effective than bisphosphonates in cancer-related hyper-
Hemodialysis or peritoneal dialysis with calcium-free calcemia in those with the highest concentrations of
dialysate may be used to lower serum calcium concentra- PTHrP. 327 The cytoprotectant amifostine (investiga-
tion when other methods fail. 98,306 Dialysis may be par- tional drug WR-2721) inhibits PTH secretion and may
ticularly helpful in animals with severe intrinsic renal have effectiveness in animals with hyperparathyroid-
failure caused by hypercalcemia. Clinical experience with ism. 604 Use of amifostine has been limited to humans,
this method of treatment in animals is limited. and its adverse effects include nausea, vomiting, somno-
lence, and hypotension. 48
Future Considerations
Additional Specific Treatments for
Calcimimetics are a new class of compounds that are able
to activate the calcium receptor, stopping PTH secre- Hypervitaminosis D
tion. 170,588 Cinacalcet (Sensipar) has been marketed for In hypervitaminosis D associated with cholecalciferol
use in human renal secondary hyperparathyroid- intoxication, treatment may be necessary for several weeks
ism. 55,198,407 This drugis expensive, and itis available only because of the long half-lives of cholecalciferol and vita-
as a solid tablet, making its use in small animals problem- min D metabolites. Consequently, aggressive fluid ther-
atic because creating smaller doses is very difficult. Despite apy for 1 week or more may be required to correct the
their action on calcium receptors throughout the body severe hypercalcemia that is often encountered. Predni-
rather than exclusively on the calcium receptors of the sone and furosemide therapy should be continued as
parathyroid glands, calcimimetics may have promise in maintenance therapy for 1 month. In addition, a low-cal-
treating hypercalcemia of most types, including idiopathic cium diet is important to reduce intestinal absorption of
hypercalcemia of cats. However, the calcimimetic calcium. The diet provided can be a commercially available
cinacalcet is contraindicated if renal disease is present veterinary food or a homemade diet consisting mostly of
due to hyperphosphatemic consequences. 131,284 In the macaroni and lean ground beef. Dairy products should be
future, calcimimetics for veterinary use may be developed. strictly avoided. Non–calcium-containing intestinal phos-
The calcium channel blocker diltiazem reduces the phorus binders may also be beneficial to counteract the
magnitude of hypercalcemia and soft tissue mineraliza- effects of hyperphosphatemia. This treatment may be par-
tion in vitamin D toxicosis in chicks 162 and may be effec- ticularly important because the magnitude of soft tissue
tive in hypercalcemia of other causes. The toxic effects of mineralization is most severe in animals with hypercalce-
hypercalcemia on the cardiovascular system of dogs can mia induced by vitamin D toxicosis. Aluminum hydroxide
be blunted by verapamil, 33,637,639 and this drug may at 30 to 90 mg/kg/day in divided doses is recommended
prove useful for stabilizing dogs and cats with severe during the first 2 weeks, with dosage and duration of treat-
hypercalcemia until other measures to decrease serum cal- ment adjusted based on serial measurements of serum
cium concentration become effective. phosphorus concentration. Other unproven methods
Most treatments for HHM have focused on for treatment include anticonvulsants to increase hepatic
counteracting the effects of excess PTHrP rather than metabolism of cholecalciferol, intestinal calcium binders
inhibiting PTHrP secretion. Somatostatin congeners to reduce intestinal calcium absorption, and calcium chan-
inhibit secretion of certain hormones, and one congener, nel blockers to decrease the toxic intracellular effects of
lanreotide, successfully reduced serum calcium and persistent hypercalcemia. 162
PTHrP concentrations in a human patient with When hypervitaminosis D is caused by excess calcitriol
HHM. 14 Similar results were observed in other tumors in patients with granulomatous disease, chloroquine,
in humans treated with octreotide. 383,395,450,584 hydroxychloroquine, and ketoconazole may be used as
Nonhypercalcemic analogues of calcitriol have been supplemental therapeutic agents or as substitutes for
reported to inhibit cell proliferation and PTHrP produc- glucocorticoids because they impair conversion of
tion by neoplastic tissue in vitro. 366,634 These new 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D by
modalities for treating hypercalcemia in conditions macrophages. 164,478
associated with increased PTHrP appear to be safe, are
easy to use, and are effective. 314 HYPOCALCEMIA
Gallium nitrate is an antineoplastic, radioprotectant
drug that has hypocalcemic properties related to its ability
to reduce the solubility of hydroxyapatite in bone and INTRODUCTION
inhibit osteoclast function. Gallium nitrate has been con- Hypocalcemia based on serum tCa is a relatively common
sidered for treatment of refractory hypercalcemia, but it laboratory abnormality and was observed in 13.5% of
requires constant infusion. 48,315,420,599 Gallium nitrate serum biochemical profiles of dogs in one clinical
was more effective in control of hypercalcemia for longer study. 115 Based on serum iCa measurement in 1633 sick
periods than etidronate or pamidronate in a recent study dogs, the prevalence of hypocalcemia was 31%, 519 and in