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