Projects in Small Animal Clinical Pharmacology for Masters in Veterinary Science (MVSc)
commencing 2005.
Project: Investigation into the long-term use of phenobarbitone in dogs with
idiopathic epilepsy; with particular emphasis on whether phenobarbitone
induced hypertriglyceridaemia increases the frequency and severity of
seizures in these dogs
Proposed supervisor: Dr Merran Govendir (02)93515442; mgovendi@vetc.usyd.edu.au
Canine idiopathic epilepsy (IE) is the most common neurological disorder in dogs. Presently
phenobarbitone (PB) is the most commonly used therapeutic agent for medical management of
canine IE. Traditionally, veterinarians initially treat canine epileptics with PB as it minimizes the
frequency or severity of seizures initially and is associated with acceptable side effects, is relative
inexpensive for life-time medication and there are few other effective canine anticonvulsant
agents. Unfortunately, approximately 20-50% of canine epileptics will eventually demonstrate
inadequate seizure control on PB even at high doses, and another therapeutic agent such as
potassium bromide (KBr) must be added to the therapeutic regime to improve seizure control.
In the past two years we have been carrying out the study Improving the control of seizures in
epileptic dogs and it was noticed that there is a subset of dogs with IE, whom have been treated
chronically with PB (longer than 6 months), that have fasting hypertriglyceridaemia; that is, they
had elevated concentrations of triglycerides in their blood not related to eating. Elevated
triglyceride concentrations have been associated with pancreatitis, lipaemia retinalis, cutaneous
xanthomas, behavioural changes, peripheral nerve paralysis and seizures in dogs. The fasting
triglyceride serum concentrations in our previous study were found to be statistically significantly
elevated compared to normal reference range. Interestingly, fasting hypertriglyceridaemia has
been recognized to result in serious clinical signs in dogs associated with a primary inherited
disorder known as Primary Idiopathic Hyperlipidaemia (PIH) in certain canine breeds (Beagles
and miniature Schnauzers) where affected animals are prone to high fasting triglyceride serum
concentrations which are associated with bouts of pancreatitis and seizures. So does
hypertriglyceridaemia induced by chronic PB administration also have the potential to
increase seizure activity in dogs with IE?
This project seeks to investigate how many dogs on chronic PB medication develop
hypertriglyceridaemia, and whether the hypertriglyceridaemia increases the incidence and
frequency of seizures in dogs. Further by manipulating the quantity of fat in the diet we can
ascertain whether the level of dietary fat is of some importance in controlling seizure frequency
and severity. Indeed this area of research is further complicated by the concept that children with
IE fed with high fat diets have more protection from seizures; however the mechanism by which
this occurs is still largely unknown. This study also seeks to investigate the mechanism by which
PB induces hypertriglyceridaemia in dogs by measuring the concentrations of the four lipoproteins
and regulatory hepatic enzymes involved in the biosynthesis of triglyceride.
I am seeking a veterinarian with at least two years practical experience and registered to practice
in NSW to assist me with this project and on submission of a thesis on this project will attain a
MVSc in the process. The project can be completed full or part time. A University or Faculty
scholarship may be available for full-time candidature but to be eligible you will need at least a
first class honours degree in veterinary science. There are other projects available. For further
information on the above projects or others available please contact Dr Merran Govendir
(02)93515442 M.Govendir@vetc.usyd.edu.au