Page 941 - Small Animal Internal Medicine, 6th Edition

CHAPTER 52 Hyperlipidemia 913

acid [EPA] and docosahexaenoic acid [DHA]) in the amount in people. One study described positive effects of chitosan in
of 200 to 220 mg/kg body weight/day to assist in the man- cats with hyperlipidemia not exceeding 300 mg/dL, which
VetBooks.ir agement of hypertriglyceridemia, especially in dogs refrac- was induced by feeding cholesterol orally; however, there are
no studies reported in cats with naturally occurring hyper-
tory or incompletely responsive to dietary fat restriction. The
efficacy is questionable in severe cases, and overall dietary fat
Hypercholesterolemia is most likely associated with the
restriction remains the priority. lipidemia, or in any dogs.
Treatment with medications, all of which have the poten- presence of an underlying disease and generally resolves with
tial for toxicity, should be undertaken with particular care. control of the altered metabolic state. Unlike the situation
In general, drugs should not be used in animals whose serum with humans, hypercholesterolemia is rarely a significant
triglyceride concentration is less than 500 mg/dL. Several health concern in dog or the cat as they are at lower risk of
classes of drugs are used to treat hypertriglyceridemia in atherosclerosis. Specific therapy is indicated only for those
humans including statins; however, few reports have animals with a prolonged marked increase in the serum cho-
described their use in cats and dogs. Until further studies lesterol concentration (i.e., >800 mg/dL) that may be associ-
have evaluated dose, effect, and toxicity, drug therapy is indi- ated with the development of atherosclerosis, which is
cated only in animals that have clinical signs associated with typically secondary to endocrinopathy. Nutritional therapy
severe elevations in triglyceride concentrations that cannot with a diet lower in fat compared with the current and his-
be ameliorated by dietary therapy. torical intake is the initial treatment of choice for severe
Niacin (100 mg/day in dogs) reduces serum triglyceride hypercholesterolemia. The addition of soluble fiber to the
concentration by decreasing fatty acid release from adipo- diet may also help to reduce plasma cholesterol concentra-
cytes and reducing the production of VLDL particles. tions by as much as 10%, because it interferes with the enteric
Adverse effects are frequent, mainly because of the associ- reabsorption of bile acids. Consequently, the fecal excretion
ated release of the prostaglandin prostacyclin, and include of cholesterol increases and the liver uses intrahepatic cho-
vomiting, diarrhea, erythema, pruritus, and abnormalities in lesterol to increase the synthesis of bile acids.
liver function test results. In addition, niacin has been shown Pharmacologic agents that can be considered for the
to positively impact hyperlipidemia in only a small number management of severe hypercholesterolemia include bile
of dogs; larger clinical trials are lacking. acid sequestrates, HMG-CoA reductase inhibitors, and pro-
Fibric acid derivatives (clofibrate, bezafibrate, gemfibro- bucol. Bile acid sequestrates are ion exchange resins that
zil, ciprofibrate, fenofibrate) lower plasma triglyceride con- interrupt the enterohepatic circulation of bile acids.
centrations by stimulating lipoprotein lipase activity, in Decreased reabsorption of bile acids stimulates the liver to
addition to reducing the free fatty acid concentration, which synthesize bile acids, thereby reducing intrahepatic choles-
decreases the substrate for VLDL synthesis. In humans the terol stores. Depletion of intrahepatic cholesterol stores
fibrates generally lower plasma triglyceride concentrations stimulates the hepatic LDL receptor to increase the removal
by 20% to 40%. Gemfibrozil has been used in the dog and of LDL and HDL particles from the circulation. Cholestyr-
cat (10 mg/kg q12h), and bezafibrate has been used in the amine (1-2 g, administered orally q12h) is effective for low-
dog (4-10 mg/kg/day). Reported adverse effects in humans ering cholesterol concentrations; however, its use has been
include abdominal pain, vomiting, diarrhea, and abnormal associated with constipation, it interferes with the absorp-
liver function test results. A recent study in dogs demon- tion of several oral medications, and it may increase hepatic
strated that bezafibrate was effective in hypertriglyceridemic VLDL synthesis, resulting in an increase in plasma triglyc-
dogs, although ALT activity decreased over time; other eride concentrations. It may also increase the dietary require-
adverse effects were not reported. ment for sulfur amino acids because they serve as precursors
The statins (lovastatin, simvastatin, pravastatin, fluvas- for taurine synthesis in the dog, which conjugates bile acids
tatin, cerivastatin, atorvastatin) are hydroxymethyl-glutaryl exclusively with taurine. In cats the requirement for dietary
coenzyme A (HMG-CoA) reductase inhibitors and therefore taurine may be similarly increased. HMG-CoA reductase is
primarily suppress cholesterol metabolism. As a conse- the rate-limiting enzyme for cholesterol synthesis. The
quence of lower intracellular cholesterol concentrations, the HMG-CoA reductase inhibitors (lovastatin, simvastatin,
hepatic LDL receptor is upregulated, thereby increasing the pravastatin, fluvastatin, cerivastatin, and atorvastatin) are
removal and clearance of LDL (VLDL remnant particles) the most potent cholesterol-lowering agents, and in humans
from the circulation. In addition, the statins decrease hepatic may reduce cholesterol concentrations by 20% to 40%. Lov-
production of VLDL. In humans, the statins can lower tri- astatin (10-20 mg, administered orally q24h) may be tried in
glyceride concentrations by 10% to 15%. Adverse effects dogs with persistent, severe idiopathic hypercholesterolemia
include lethargy, diarrhea, muscle pain, and hepatotoxicity. that does not respond to diet alone. Potential adverse effects
These are not commonly used, and clinical experience in include lethargy, diarrhea, muscle pain, and hepatotoxicity.
dogs and cats is limited. Lovastatin should not be administered to dogs with hepatic
Chitosan has been explored as an option for controlling disease. Probucol is a cholesterol-lowering agent whose
hyperlipidemia secondary by reducing absorption of lipids mechanism of action is not completely clear. Probucol is no
and bile salts in the intestinal lumen. It appears to be effective longer recommended for the management of hypercholes-
in lowering serum lipid concentrations in rodent models and terolemia because its effect on lowering cholesterol