Page 1126 - Small Animal Clinical Nutrition 5th Edition

1172 Small Animal Clinical Nutrition

VetBooks.ir Box 68-3. Adjunctive Use of Copper Chelating Agents for Patients with
Hepatic Copper Toxicosis.

For Bedlington terriers with subclinical or clinical liver disease, in tine and zinc regimen with apparently good results. Affected dogs
addition to selection of a low-copper (<5 mg/kg, [dry matter]) vet- should be fed copper-restricted foods and be given the faster act-
erinary therapeutic food (Table 68-11), adjunctive treatment with ing copper chelator.When hepatic copper concentrations approach
copper chelating agents is clearly indicated. Chelator treatment is normal levels, switching to zinc therapy alone may prevent further
used for breeds of dogs with copper-associated chronic hepatitis copper accumulation.
and cirrhosis and other breeds in which copper accumulation is The initial report in dogs used 100 mg of elemental zinc acetate
documented by liver histopathology and/or elevated hepatic copper b.i.d. for one to two months during an induction phase followed by
concentrations (generally >1,000 to 2,000 ppm dry weight). a maintenance dose of 50 mg of elemental zinc b.i.d., thereafter.
Adjunctive treatment of hepatic copper toxicosis involves use of Serum zinc concentrations should be monitored with a goal of
zinc or copper chelating agents such as D-penicillamine or trien- approximately a twofold increase in serum concentrations (<200
tine (Figure 1). Zinc blocks copper absorption. Chelating agents µg/ml). Hemolysis can occur if serum zinc concentrations increase
bind to copper and increase its excretion in urine. D-penicillamine, significantly (>750 µg/ml). Zinc can be given as an acetate, sul-
the copper chelating agent most frequently recommended for use fate, gluconate or methionine salt but should be administered on
in dogs, should be given at a dosage of 10 to 15 mg/kg body an empty stomach to ensure adequate absorption. Common prob-
weight twice daily, on an empty stomach. Vomiting is the most lems encountered with zinc therapy include anorexia, nausea and
common side effect in dogs, but can be alleviated by giving the vomiting shortly following administration. If concurrent chelator
agent more frequently in reduced doses. D-penicillamine therapy therapy is used, dosing should be staggered to ensure adequate
also has been associated with pyridoxine deficiency in people. absorption of the chelator.
However, this problem has not been recognized in dogs.
a
Trientine (2,2,2-tetramine) is another chelating agent. In a clin- ENDNOTE
ical trial, chelation results with trientine (10 to 15 mg/kg body a. Syprine. Merck & Company, Inc., Rahway, NJ, USA.
weight, per os, twice daily) were comparable to those of D-penicil-
lamine and fewer side effects were noted. Modification of 2,2,2- The Bibliography for Box 68-3 can be found at
tetramine to 2,3,2-tetramine increases the potency as a copper www.markmorris.org.
chelating agent. Use of 2,3,2-tetramine in affected Bedlington ter-
rier dogs significantly re-
duced liver copper con-
centrations after 200 days
of treatment at a dose of
15 mg/kg body weight.
This drug is not commer-
cially available but can be
obtained from chemical
supply companies in the
form of N,N’-bis(2-amino-
ethyl)-1,3-propanedi-
amine and prepared as a
salt for oral administra-
tion.
Oral zinc therapy blocks
copper absorption from
the intestine. In early
human studies, therapy
with combined zinc and
copper chelators found no
benefit over single chela-
tor therapy suggesting the
chelator most likely binds
zinc in the intestinal tract.
However, more recently,
human patients having
Wilson’s disease who are
intolerant to penicillamine
Figure 1. Algorithm for treating copper hepatotoxicosis in dogs. (Adapted from Center SA. Chronic liver dis-
are sometimes treated
eases. In: Guilford WG, Center SA, Strombeck DR, et al, eds. Strombeck’s Small Animal Gastroenterology,
with a combination trien-
3rd ed. Philadelphia, PA: WB Saunders Co, 1996; 749.)