SAEVA Proceedings 2015 | Page 65

South African Equine Veterinary Association Congress 2015  Protea Hotel  Stellenbosch Horses with PPID have also been shown to have a more rapid rise in faecal egg counts following anthelmentic administration, in comparison to normal, aged horses. Thus, attention to parasite burden by monitoring fecal egg counts and implementing appropriate anthelmentic practices should warrant greater attention in PPID-affected equids. Medications for treatment of PPID: Medications that have been used to treat equids with PPID include serotonin antagonists (cyproheptadine), dopamine agonists (bromocriptine and pergolide), and trilostane, an inhibitor of adrenal steroidogenesis. Cyproheptadine was one of the initial drugs used because serotonin had been shown to be a secretagogue of ACTH in isolated rat pars intermedia tissue and because the medication was available at a reasonable cost. Early reports that cyproheptadine (0.5-1.0 mg/kg, PO, q 24 h) resulted in clinical improvement and normalization of laboratory data within 1-2 months have been disputed as similar clinical improvement has been achieved with improved nutrition, preventive care, and management alone. Further, two studies comparing both clinical improvement and endocrine test results have clearly shown that pergolide is more effective than cyproheptadine as monotherapy for treatment of PPID. Because loss of hypothalamic dopaminergic innervation appears to be an important mechanism for development of PPID, treatment with dopaminergic agonists is a logical approach to therapy. Pergolide, a first generation dopamine agonist used for treatment of Parkinson‟s Disease (PD), was found to acutely lower plasma concentrations of immunoreactive adrenocorticotropin (ACTH) and other pro-opiomelanocortin peptides in an early report. Subsequently, pergolide treatment produced clinical improvement in 23 of 25 PPID-affected equids; however, the dosage was quite high (6-10 μg/kg, PO, q 24 h [3-5 mg to a 500 kg horse]) and the expense of treatment precluded routine use of the drug. When Peters and colleagues (1995 AAEP Convention) later reported that using a lower dose of pergolide (2 μg/kg, PO, q 24 h [1 mg/day for a 500 kg horse]) was clinically effective in a series of horses and ponies with PPID, use of pergolide became more widespread as cost was no longer prohibitive. Reported adverse effects of pergolide include anorexia, diarrhoea, and colic; however, the latter problems are more often associated with higher doses of the drug. Usually, only transient anorexia is recognized during the initial few weeks of “low dose” pergolide treatment and can be overcome by stopping treatment for a few days and starting back at half the dose, slowly increasing to the desired dose. Although pregnant mares have been treated with the drug, safety of pergolide use during pregnancy has not been studied in equids. Many pregnant mares treated with pergolide have been anecdotally reported to deliver healthy, term foals and produce adequate milk. Consequently, it does not appear that discontinuation of pergolide treatment prior to foaling is warranted unless udder development does not appear to be progressing as expected prior to the expected parturition date. Limited information exists on pharmacokinetics of pergolide although the initial study performed reported plasma concentrations of the drug that were 4-10 times greater in horses than in humans after administration of a similar oral dose (10 μg/kg), suggesting greater bioavailability in equids. The authors of that study concluded that a daily dose of 1-2 μg/kg (0.5-1 mg to a 500 kg horse) would be expected to produce drug levels in equids similar to therapeutic plasma concentrations in humans with PD, yet twice daily administration would more likely provide sustained plasma concentrations of the drug. More recent pharmacological studies have yielded conflicting results with pergolide half lives of 5.6 and 24 h reported. Another recent study found no difference in the decrease in plasma ACTH concentration between once or twice daily pergolide dosing. Consequently, the question of the “best” dosing interval remains unresolved at present. 65