MDR1 Flea Product Toxicosis in Cats

Hello, Summarians!

Wow. Sometimes information is slow to spread or maybe sometimes I just miss it. It’s hard to tell sometimes… MDR1 does occur in about 4% of cats and there is a commercially available test that has been available through WSU since 2022. The following article is why that is useful knowledge.

Please give me feedback on ways I can make it more useful to you.

If it is valuable to you please consider sending it on to a friend 😄 

Vitamin D and Survival Prediction.

This comprehensive study explored the roles of vitamin D metabolites and acute-phase proteins (APPs) as biomarkers for predicting survival in hospitalized cats and dogs. It specifically investigated the concentrations of 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]_2D), haptoglobin (HPT), C-reactive protein (CRP) in dogs, and serum amyloid A (SAA) in cats, aiming to assess their correlation with survival and disease severity. 

Key findings include: 

 Vitamin D metabolite and APP concentrations were frequently abnormal in the studied cohort, yet they did not predict survival 

The study observed longitudinal changes in serum vitamin D metabolites over a 48-hour period post-admission, finding no statistically significant differences, possibly due to the small cohort size and uncontrolled treatment variables. 

A moderate negative correlation between 1,25(OH)_2D and CRP in dogs was found, suggesting a greater depletion of 1,25(OH)_2D during critical illness, possibly due to increased enzymatic activity by immune cells in inflammatory states. 

 Previous veterinary studies indicated that low serum 25(OH)D concentrations might predict survival in certain conditions, contrasting with the findings of this study, where no direct prediction of survival based on 25(OH)D concentrations was observed. 

 The study also highlighted several limitations, such as the small patient cohort, potential enrollment bias towards patients with lower disease severity, discrepancies in methodologies for measuring 25(OH)D, and the absence of a reference interval for the 1,25(OH)_2D assay. 

In conclusion, while vitamin D metabolites and APPs were frequently abnormal in hospitalized cats and dogs, they were not effective predictors of survival in this study. The research underlines the necessity for larger, longitudinal studies to better understand the dynamics of these biomarkers in critical illness and their potential role in patient management and outcomes. Additionally, the study calls for a more personalized approach in interpreting these biomarkers, taking into account the patient’s specific disease and clinical status. 

 Rose, H., Jaffey, J. A., Cammarano, K., Ringold, R., Turner, H. D., McArdell, K., Sender, D., & Loftus, J. P. (2024). Serum vitamin D metabolite and acute-phase protein concentrations are frequently abnormal in a cohort of hospitalized dogs and cats. Journal of the American Veterinary Medical Association https://doi.org/10.2460/javma.23.12.0676 

Bottom line — Vitamin D and APP’s not effective predictors of survival.

MDR1 Flea Product Toxicosis in Cats

This detailed examination highlights significant concerns regarding the use of macrocyclic lactones (ML), specifically eprinomectin, in cats, focusing on the risks posed by genetic variants affecting P-glycoprotein function. P-glycoprotein, encoded by the ABCB1 gene, is crucial for preventing certain drugs, including ML, from crossing the blood-brain barrier into the central nervous system. Variants in the ABCB1 gene can lead to increased susceptibility to drug toxicity, as seen in some cats exposed to eprinomectin, leading to severe neurological toxicosis. 

The report underlines the findings of a case review following reports of adverse events in cats treated with a new eprinomectin-containing product. This review identified a significant overrepresentation of cats homozygous for the ABCB11930_1931del TC mutation among those experiencing neurological toxicosis. This mutation, found in a small percentage of the general cat population, significantly increases the risk of serious adverse reactions to eprinomectin. 

Additionally, the study addresses the role of acquired P-glycoprotein deficiency, suggesting that the concurrent administration of certain drugs with eprinomectin may inhibit P-glycoprotein function, further increasing the risk of toxicosis, even in cats without the genetic mutation. 

The findings highlight the critical need for ABCB1 genotyping in cats before administering eprinomectin-containing products to identify those at high risk of adverse reactions. This proactive approach could prevent serious health outcomes in susceptible cats. The study also suggests that further research is needed to fully understand the implications of both genetic and acquired P-glycoprotein deficiencies in cats treated with MLs. 

Clinical recommendations include careful monitoring of cats for 48 hours post-treatment with eprinomectin-containing products and considering the potential for drug interactions that may exacerbate the risk of neurological toxicosis. Additionally, a novel clinical sign of ML toxicosis was identified, where affected cats exhibit difficulty retracting or using their tongues, which could impact their ability to eat and necessitates specific therapeutic interventions. 

Overall, this report underscores the importance of weighing the genetic and environmental risks when using eprinomectin in feline patients, advocating for a cautious and informed approach to its application in veterinary practice. 

Mealey, K. L., Burke, N. S., Villarino, N. F., Court, M. H., & Heusser, J. P. (2024). Application of eprinomectin-containing parasiticides at label doses causes neurological toxicosis in cats homozygous for ABCB11930_1931del TC. Journal of Veterinary Pharmacology and Therapeutics, 00, 1–5. https://doi.org/10.1111/jvp.13431 

Bottom line — Important information to share with all cat owners.

Feeding and Pancreatitis.

The role of nutrition in the management of pancreatitis in both humans and animals has evolved significantly from the traditional approach of fasting or "resting the gut" to mitigate the condition. Historically, this method was believed to prevent the stimulation of pancreatic secretions, thus minimizing inflammation and autodigestion. However, contemporary research indicates that pancreatic secretions are actually decreased during pancreatitis, suggesting that the practice of fasting may not only be unnecessary but potentially harmful due to risks such as intestinal mucosal atrophy, enterocyte apoptosis, gut barrier dysfunction, and bacterial translocation. 

In contrast, current evidence supports the benefits of nutritional support, either enteral or parenteral, to mitigate the effects of pancreatitis. Enteral nutrition (EN) is particularly emphasized over parenteral nutrition, as it is associated with fewer complications and helps maintain gut integrity. For both dogs and cats, nutritional management strategies are now focusing on the provision of low-fat diets or hydrolyzed protein diets to manage the condition, depending on the species. 

Specific nutritional recommendations include: 

• Energy Requirements: Meeting the daily energy requirements is crucial to avoid negative impacts on the pancreas and overall health. In cats, this is especially important due to their risk of developing hepatic lipidosis. 

• Fat Intake: High-fat diets have been linked to induced pancreatitis in dogs in experimental settings, leading to a general recommendation to reduce fat intake in the initial management phase. However, the effect of dietary fat in naturally occurring disease remains less clear, suggesting a need for a more individualized approach. 

• Protein Intake: Dietary protein stimulates pancreatic secretion, so diets should be balanced to avoid excess protein while ensuring adequate intake for tissue repair and recovery. Hydrolyzed protein diets are recommended for cats to minimize pancreatic stimulation. 

• Carbohydrates and Fiber: Carbohydrates are less stimulating to the pancreas than fats and proteins, though adjustments may be necessary for animals with glucose intolerance or diabetes. High-viscous fiber diets should be avoided in animals with vomiting due to their effect on gastric emptying. 

When pancreatitis occurs alongside other conditions like hypertriglyceridemia, obesity, chronic enteropathy, diabetes mellitus, or chronic kidney disease, the nutritional strategy must be adjusted to address all concurrent issues. This highlights the importance of a comprehensive nutritional assessment and management plan tailored to each patient's specific needs and conditions. 

In hospitalized animals, the use of assisted enteral nutrition (EN) is recommended if voluntary food intake is insufficient, with a preference for enteral methods due to their association with quicker recovery and fewer complications compared to parenteral nutrition. 

Overall, the shift from fasting to proactive nutritional support in pancreatitis management reflects a deeper understanding of the disease's pathophysiology and the critical role nutrition plays in recovery and overall health. Further research is needed to refine these recommendations and develop new dietary formulations to better support animals with pancreatitis, considering the complexities of individual cases and comorbid conditions. 

Cridge, H., Parker, V. J., & Kathrani, A. (2024). Nutritional management of pancreatitis and concurrent disease in dogs and cats. Journal of the American Veterinary Medical Association https://doi.org/10.2460/javma.23.11.0641 

Bottom line — Proactive nutritional support is essential

Just putting things in perspective …