Ned Patterson, DVM, advisor to the Canine Epilepsy Network and University of Missouri's College of Veterinary Medicine states that 20% of the dogs on phenobarbital develop liver damage.  Knowing what to look for and what laboratory tests should be done to monitor Phenobarbital therapy is vital to the health of any dog taking this anti-seizure medication.  Although with proper monitoring the risk of Phenobarbital induced liver disease is low, the risk does exist.  The following are some of the things you can do to reduce that risk:

1.    Have a chemistry panel with the liver enzymes ALT, GGT and alkaline phosphate done every 3 to 4 months.

2.     If all three liver enzymes are severely elevated (more than just a few points above normal) then you should do a urine bile acid test or a pre- and post-meal bile acid test to see what kind of damage has been actually done to the liver so you can change the diet to the liver cleansing diet and/or reduce the Penobarbital.

3.    Monitor Phenobarbital levels every 6 months, more frequently if you do not have seizure control or if there are any signs of toxicity like ataxia, wobbliness, hind end weakness (not after a seizure) or your epi is walking around like a drunken sailor.

4.     Unfortunately by the time liver disease signs show up it may be too late.

Maintain target serum levels:  

Target serum levels should be maintained between 20 and 35 for adequate seizure control and the least risk of liver disease.  When starting therapy with Phenobarbital serum levels are usually monitored frequently until target serum levels are reached and seizure control is achieved.  However, it is extremely important to continue to monitor blood serum levels every six to twelve months throughout the course of Phenobarbital use as changes in pharmacokinetcs may cause the levels to drift out of the targeted range.  An increase in serum concentrations of Phenobarbital without an increase in dose is one of the indications of liver disease.  Chronic administration of Phenobarbital can cause the liver to produce enzymes that reduce the half life of the drug.  When this happens a higher dose of Phenobarbital will be required to maintain seizure control. 

Monitor Liver enzymes:

A blood chemistry panel checks the level of enzymes produced by many of the body's organs including the liver, however, it is not conclusive in relation to liver disease. For example, Phenobarbital causes an elevation in several liver enzymes, particularly Alkaline Phosphatase (ALK or ALP). An elevated Alkaline Phosphatase level is not indicative of liver disease in a dog who is taking Phenobarbital or one of several other drugs which induce the liver to produce Alkaline Phosphatase. However, if blood work reveals an elevation in Alkaline Phosphatase in conjunction with abnormal values in other liver enzymes (ALT and GGT), swift follow-up in the form of a urine bile acid or a fasting bile acid test should be performed. A urine bile acid or fasting bile acid test is much more accurate than testing liver enzymes because Phenobarbital does not increase bile acids and elevations are usually seen early in the course of most liver diseases.

The following are some of the enzymes that are tested in a chemistry panel that may indicate liver disease (for a complete listing of blood chemistry please see Reading Laboratory Results):

ALBUMIN - Albumin is a common blood protein produced by the liver. Decreased albumin levels are commonly encountered in liver disease (i.e.,  cirrhosis), certain types of kidney disease or parasitic infections such as hookworm.  High levels indicate dehydration and loss of protein.  

ALP OR ALKP - ALKALINE PHOSPHATASE - this enzyme is found in many different tissues within the body, primarily liver, bone, intestines, and kidneys. Increased ALP levels can be seen with liver disease and gallbladder disorders. In addition, drugs such as corticosteroids and Phenobarbital can cause increased ALP levels. Very high ALP levels can be seen in dogs with adrenal gland disease as well.

ALT - ALANINE AMINOTRANSFERASE - This enzyme is considered to be liver specific in the dog. Increased levels of ALT are an indicator of damage to liver cells, as this enzyme is contained within the liver cell itself. When the cell is injured, the enzyme is released into the bloodstream and the increased level can be measured.

AST - Aspartate Aminotransferase - an enzyme seen in the liver, heart, kidney, skeletal muscle and brain. The half life of the AST in the blood stream is much shorter than that of ALT, therefore the values of AST tend to drop more rapidly once liver function is resumed.  AST elevations and ALT elevations should parallel each other in liver disease.

BUN - Blood urea nitrogen, is produced by the liver and excreted through the kidneys.    Elevated levels can indicate kidney disease, but can also be caused by dehydration or urinary tract obstruction.  Low BUN levels are seen in patients with chronic liver disease.

CHOLESTEROL - Cholesterol values in the dog are not thought to have as much significance with regards to the heart as they do in humans.  Decreased levels are often found in an overactive thyroid gland or intestinal mal-absorption.  Elevated levels of cholesterol are seen in a variety of disorders including hypothyroidism and diseases of the liver, kidneys, cardiovascular, diabetes and stress.

GGT - Gamma Glutamyltransferase - This enzyme is has it's highest concentration in the kidneys and pancreas, but it is also found in the liver and other organs. The major proportion of GGT in the serum seems to come from the liver. Elevations of GGT in disease seem to stem from new synthesis rather than leakage, therefore the changes seen due to disease are not spectacular. Large elevations of GGT are more commonly associated with pancreatitis and bile duct obstruction.

TBIL - Total Bilirubin is a component of bile; bilirubin is secreted by the liver into the intestinal tract. High levels can lead to jaundice and indicate destruction in the liver and bile duct.

TOTAL PROTEIN - Total protein levels are increased in patients with dehydration or chronic inflammatory conditions.  Increases indicate dehydration or blood cancer, bone marrow cancer.  Decreases indicate malnutrition, poor digestion, liver disease, kidney disease, bleeding or burns.

GLOB - Decreased levels indicate problems with antibodies, immunodeficiency viruses or risk of infectious disease.  Increased levels may indicate stress, dehydration, blood cancer, allergies, liver disease, heart disease, arthritis or diabetes.

Watch for the signs of liver disease:

The following are some of the physical symptoms of liver disease.  If any of these symptoms occur please see your veterinarian:

1.    Chronic weight loss

2.    Pain in the abdomen

3.    Orange urine.  Orange urine is the result of improper processing of bile causing the excretion of bilirubin in the urine.

4.    A yellow cast to the skin and eyes, known as jaundice or icterus.  This is caused by biliary pigments accumulating in the blood and is usually visible on the stomach and eyes.

5.    Gastrointestinal upsets such as loss of appetite, vomiting, diarrhea or constipation.

6.    A swollen belly with a fluid-filled look.  This is known as ascites and is actually fluid accumulation in the belly due to circulation alterations in the abdomen.

7.    Pale gray feces which results from a lack of bile pigments.

8.    Increased water consumption and urination.

9.    Progressive depression or lethargy

10.  Severe neurological signs, such as behavioral changes, seizures, aimless pacing or circling and head pressing.

When liver damage has been determined by a urine bile acid test or a pre- and post-meal bile acid test or chemistry panels, which show elevated values of Alk Phos, Alt (SGPT), and GGT, our Guardian Angels have had great success in reversing liver damage by doing three things:

  1. Reducing the amount of Phenobarbital on a program determined by your vet or Dr. Dodds.
  2. Feeding the liver cleansing diet
  3. Adding Milk Thistle to the diet