Veterinary Science Collected Works - Theses
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ItemPrednisolone in canine medicine: How and why it is prescribed systemically and the impact of bodyweight on prescriptions and pharmacokinetics( 2022-11)Background: Prednisolone is a commonly used medication in canine medicine, for a variety of indications. It is prescribed for physiologic maintenance, as an anti-inflammatory and as an immunosuppressant. Unfortunately, it also comes with a variety of adverse effects. There is a lack of research describing what conditions prednisolone is prescribed for and what factors influence dose in dogs. Additionally, there is evidence to suggest that canine bodyweight influences risk of side effects, therefore published dosing recommendations for dogs over 25 kg recommend dosing by body surface area. However, there is no research on whether bodyweight influences dose prescribed by veterinarians and little research as to how bodyweight affects prednisolone pharmacokinetics. Objectives: The aims of this thesis were to review the current literature on prednisolone use and pharmacokinetics in dogs (Chapter 1); to describe prednisolone prescribing practices to for dogs in Australia, indication for prescription and to evaluate what factors influence dose prescribed (Chapter 2); to observe prednisolone pharmacokinetics in client-owned dogs and describe any effect of bodyweight (Chapter 3). Method: Chapter 2 was a cross-sectional study using individual canine clinical records acquired from the VetCompass Australia database. Dogs prescribed prednisolone between 1 July 2016 to 31 July 2018 were identified and a random sample of 2,000 dogs from this population were used for data acquisition. Chapter 3 was a prospective, observational study where dogs receiving prednisolone for medical reasons had a series of plasma samples taken after their normal prednisolone dose. Plasma prednisolone concentrations were measured via liquid- chromatography tandem mass spectrometry and the relationship between dog bodyweight, prednisolone dose and prednisolone area-under-the-curve (AUC) was described. Results: Prednisolone was found to be most prescribed for inflammatory conditions, at an anti-inflammatory dose to Australian dogs. Disease of the integument was the most common indication for prescription. Notably, 8% of dogs (n = 152) were prescribed an immunosuppressant dose, for an inflammatory condition, which was considered inappropriate. Bodyweight was found to have a small, independent, negative effect on dose prescribed. The pharmacokinetic study found that dosing by bodyweight (milligrams per kilogram) resulted in AUC being positively associated with bodyweight. Conclusions: This research describes, for the first time, prednisolone prescriptions for dogs in Australia and confirms that bodyweight influences dose prescribed and impacts prednisolone pharmacokinetics. Veterinary clinicians appear to reduce the prednisolone dose prescribed, in milligrams per kilogram, to larger dogs. Regarding pharmacokinetics, when dosed equivalently in milligrams per kilogram, a larger dog has larger plasma prednisolone AUC compared to a smaller dog. This is potentially a cause for the increased adverse effects experienced by larger dogs. This research will improve veterinary clinician awareness to the potential risk to larger dogs prescribed prednisolone and provide groundwork to further research on prednisolone pharmacokinetics in dogs.
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ItemCoagulation factor activity patterns in venom-induced consumption coagulopathy from naturally occurring tiger snake (Notechis scutatus) envenomation in dogs( 2020)Snake venom-induced consumption coagulopathy (VICC) is an important syndrome resulting from snake envenomation. The prothrombin activator notecarin D is responsible for this coagulopathy in tiger snake (Notechis scutatus) envenomation. In dogs, the presence of this coagulopathy is used to assist with the diagnosis of snake envenomation and, in some cases, can produce clinical signs associated with a coagulopathic envenoming. There are subtle differences in this syndrome between dogs and people, particularly concerning the development of clinical signs. Chapter two reviews tiger snake envenomation and the consequent VICC in Australian dogs with comparisons to human literature. The VICC syndrome between the two species share many clinical similarities; the key difference lies in the significance of clinical haemorrhage in people when compared with dogs. A brief overview of coagulation and coagulometry is provided. Chapter three is a prospective observational cohort study characterising the coagulation factor activity patterns in VICC from naturally occurring tiger snake envenomation in dogs. The changes in coagulation factors in a study cohort of tiger snake envenomed dogs were compared to a healthy control cohort. Fibrinogen, factor V and factor VIII were identified as the most consumed factors and displayed the fastest recovery to control values. Tests of coagulation times (i.e., prothrombin time and activated partial thromboplastin time) were similarly affected. Additionally, higher serum tiger snake venom concentrations were associated with greater reductions in factors II, V and VIII, and greater prolongations in both coagulation times. The elucidation of the consumption and recovery pattern of coagulation factors in dogs, contrasted with that of people, provides insight into the underlying mechanisms of tiger snake VICC and its treatment. This information can be used for further diagnostic and therapeutic endeavours.