VTechWorks staff will be away for the Thanksgiving holiday beginning at noon on Wednesday, November 27, through Friday, November 29. We will resume normal operations on Monday, December 2. Thank you for your patience.

Browsing by Author "Mercer, Melissa Ann"

Now showing 1 - 2 of 2
  • Thumbnail Image
    The Clinical Pharmacology of Acetaminophen in Adult Horses
    Mercer, Melissa Ann (Virginia Tech, 2022-08-18)
    Non-steroidal anti-inflammatory drugs (NSAIDs) are a mainstay of the management of pain and inflammation associated with musculoskeletal disorders and systemic inflammation in horses. The most utilized NSAIDs in equine practice are non-selective cyclooxygenase (COX) inhibitors, such as flunixin meglumine and phenylbutazone, which act through global inhibition of prostaglandin synthesis and release. While non-selective COX inhibitors are effective as anti-inflammatory agents, they are mired with complications with prolonged or high-dose use, particularly in critically ill patients. Therefore, non-selective COX-inhibitors have been displaced by selective COX-2 inhibitors for many practitioners due to the perceived reduced risk of gastrointestinal complications. It should be noted, however, that the use of COX-2 selective inhibitors in horses is not without risk. Due to the potential for significant adverse events in horses with critical illness treated with traditional NSAIDs, there is clinical need for safe, and effective anti-inflammatories and anti-pyretics for administration in these patients. The studies presented in this dissertation explore the pharmacokinetics, efficacy, and safety of acetaminophen in adult horses for use in musculoskeletal pain and pyrexia. In the first study, the pharmacokinetics and efficacy of oral acetaminophen at two different doses (20 mg/kg and 30 mg/kg) were examined in an experimentally induced lameness model and the analgesic efficacy of acetaminophen was compared to placebo and the non-selective COX inhibitor phenylbutazone. Acetaminophen when administered at 30 mg/kg produced a more rapid onset of greater improvement in subjective lameness scores and heart rate compared to other treatments in this model, and therefore would be more suitable as a monotherapy than acetaminophen dosed at 20 mg/kg. Acetaminophen dosed at 30 mg/kg resulted in a more rapid improvement in lameness scores than phenylbutazone at 2.2 mg/kg and was equivalent to phenylbutazone in lameness score reduction. However, results of this study necessitated further evaluation of the pharmacokinetics and safety of repeated oral dosing of acetaminophen at 30 mg/kg orally every 12 hours to determine clinical utility. In the second study, the pharmacokinetics, efficacy, and safety of oral acetaminophen (30 mg/kg) were examined in adult horses with naturally occurring chronic lameness. In that study, following 21 days of twice daily oral dosing at 30 mg/kg, acetaminophen was found to be safe with no evidence of gastric ulceration or hepatopathy in horses. Acetaminophen at 30 mg/kg twice daily for 21 days provided transient improvement in subjective and objective lameness evaluation when compared to baseline evaluation; however, the study concluded that acetaminophen may not be suitable as a monotherapy for management of moderate to severe orthopedic pain in horses In the third study, the pharmacokinetics and efficacy of oral acetaminophen (30 mg/kg) was examined in adult horses with experimentally induced endotoxemia when compared to placebo and the nonselective COX inhibitor flunixin meglumine. That study found that acetaminophen was superior to placebo and not statistically different from flunixin meglumine in reducing rectal temperature in adult horses with experimentally induced endotoxemia and may be an option for antipyresis in clinical cases, particularly when administration of traditional NSAIDs is contraindicated. Furthermore, acetaminophen administered at 30 mg/kg orally to adult horses with experimentally induced endotoxemia is an effective antipyretic but is unlikely to provide any alteration in systemic inflammatory response.
  • Thumbnail Image
    Pharmacokinetics and Safety of Acetaminophen in Adult Horses
    Mercer, Melissa Ann (Virginia Tech, 2018-10-15)
    Due to the detrimental side effects of NSAID administration, such as gastrointestinal ulceration and renal papillary necrosis, there is a profound need for clinical pain relief in horses with long term orthopedic disease whereby gastrointestinal side effects are obviated. Acetaminophen is one of the most commonly used analgesic drugs in humans, and is readily available as an inexpensive generic over-the-counter preparation. Acetaminophen has a number of mechanisms of action that differ from NSAIDs, including actions on the serotonergic, opioid, endocannabinoid and lipoxygenase pathways. These alternate pathways may provide greater efficacy against chronic or neuropathic pain in equine patients. Acetaminophen was preferred by physicians over COX-2 and nonselective NSAIDs, even when those drugs were coupled with proton-pump inhibitors to reduce gastrointestinal side effects; due to cost considerations and the occurrence of adverse side effects from those drugs. In horses, acetaminophen has been reported to be efficacious as an adjunct treatment for laminitis in one pony, and was an effective analgesic agent when combined with NSAIDs in a model of inducible foot pain. However, no studies have been performed to validate a dose-response curve in horses. A study recently completed by our group demonstrated rapid absorption following oral administration of acetaminophen. Reported human therapeutic plasma concentrations were achieved within 30 minutes of administration, with no clinical or clinicopathologic evidence of adverse side effects after two weeks of repeated dosing. Dose simulation trials indicate that a change in dosage schedule may be required in order to provide adequate plasma concentrations.