Page 172 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

162 ELECTROLYTE DISORDERS

hypercalcemia. Based on these findings, pamidronate at adverse effects; one cat with idiopathic hypercalcemia did
multiple doses may safely and effectively lower both serum develop hypocalcemia and clinical signs. The salutary
total and iCa concentrations in patients with hypercalce- response during bisphosphonate treatment indicates that
mia resulting from various disease processes. blunting of osteoclastic bone resorption can be effective
There is limited information about the use of oral in decreasing serum iCa, but it does not prove that
bisphosphonates in general, and none for control of accelerated bone resorption is the underlying cause of idi-
hypercalcemia specifically reported in dogs or cats. Oral opathic hypercalcemia. The long-term safety and effec-
bisphosphonate therapy is generally designed for mainte- tiveness of this treatment remain to be proven. 120
nance treatment after a course of intravenous Both clodronate and pamidronate have safely and
bisphosphonates has been effective in the control of effectively been given subcutaneously for the control of
hypercalcemia. Less than 5% of orally administered hypercalcemia in people. 158,475 Use of subcutaneous
bisphosphonate is absorbed from the gastrointestinal clodronate was better tolerated than subcutaneous
tract, 192 which limits the usefulness of oral forms of eti- pamidronate. 593,594 The subcutaneous route has not
dronate, clodronate, and alendronate. 224 Food in the yet been investigated for use in dogs or cats with
stomach markedly reduces the oral absorption of some hypercalcemia.
bisphosphonates. 211 Increasing the dose can slightly
increase the oral absorption of bisphosphonates. 384 Other Miscellaneous Treatments
High-dose oral bisphosphonate treatment can achieve Mithramycin is a potent inhibitor of osteoclastic bone
similar results as the IV route in some instances in peo- resorption. 483,486 Significant toxicity, including throm-
ple. 436 Etidronate is generally administered orally to dogs bocytopenia, hepatic necrosis, renal necrosis, and hypo-
at 10 to 40 mg/kg/day in divided doses, and it has had calcemia, unfortunately has been reported with the use
some effectiveness in reduction of hypercalcemia of this drug. 115,184,314 Mithramycin was safe when two
associated with lymphoma, myeloma, primary hyperpara- doses of 0.1 mg/kg were administered intravenously 1
thyroidism, and hypervitaminosis D in dogs (Drs. Dennis week apart to eight normal beagle dogs. Mithramycin
Chew and Guillermo Couto, unpublished observations). decreased serum iCa concentration in these normal dogs
A puppy with hypercalcemia and primary hyperparathy- without adverse side effects such as hepatotoxicity, neph-
roidism was also successfully treated using etidronate. 568 rotoxicity, or bone marrow hypoplasia, but some shiver-
There is concern about the oral administration of some ing occurred during the infusion. Osteoclastic bone
bisphosphonates to humans because nausea, vomiting, resorption was significantly reduced. 486 Mithramycin
abdominal pain, dyspepsia, esophagitis, and esophageal was used to treat cancer-associated hypercalcemia in cli-
reflux can be the adverse effects. 52 Both clodronate and ent-owned dogs. 487 A single infusion of 0.1 mg/kg to
alendronate have been used orally in humans. 37,269 A two dogs resulted in normal serum tCa concentration
small number of cats with odontoclastic resorptive dental within 24 hours, but severe hepatocellular necrosis
lesions were treated with oral alendronate at 9 mg/kg associated with marked vomiting, diarrhea, and fever
twice weekly orally for 27 weeks without development resulted in death shortly thereafter. To decrease addi-
of adverse effects. 388 In a pilot study conducted at Ohio tional episodes of toxicity, the dosage of mithramycin
State University, once weekly oral alendronate reduced was decreased to 25 mg/kg for the remaining dogs in this
serum iCa concentration in most cats with idiopathic study. Serum calcium concentration returned to the nor-
hypercalcemia (Dr. Brian Hardy, unpublished mal range in six of nine dogs within 24 to 48 hours of
observations). No side effects were documented over treatment. Toxicity at this dosage was minimal, but the
the 6 months of the study with an average weekly dose calcium-lowering effect lasted only 24 to 72 hours in
of 10 mg alendronate per cat. Care should be taken to three dogs. PTHrP concentrations and tumor size
ensure that tablet medication does not stick in the esoph- remained unchanged after treatment, and the lowering
agus, as this is a known risk for erosive esophagitis in of serum calcium concentration was attributed to
humans. Tap water given PO following pilling is decreased osteoclastic bone resorption. Mithramycin is
recommended to help lessen the possibility of esophagi- seldom prescribed because of its toxicity in hypercalcemic
tis; “buttering” of the lips to encourage salivation, dogs at higher dosages and the short-lived effect at lower
swallowing, and increased transit of pills into the stomach dosages.
is also recommended. In cats that fail to return to During a hypercalcemic crisis, EDTA can be infused at
normocalcemia with diet and prednisolone treatment, a dosage of 25 to 75 mg/kg/hr. Administered EDTA
oral bisphosphonate therapy may restore normocalcemia. combines with circulating calcium to form a soluble com-
Some cats have required up to 30 mg weekly per cat to plex that then is excreted by the kidneys. 115 This treat-
achieve normocalcemia. In a small number of cats with ment is considered a rescue method designed to allow
idiopathic hypercalcemia, oral bisphosphonate treatment other modalities time to take effect. Use of EDTA should
has failed to achieve normocalcemia. Several cats have be reserved for crisis situations because EDTA is nephro-
been on alendronate treatment for years without known toxic at higher dosages. A 2-hour infusion of EDTA in