African Horse Sickness | EQUINE
1mg/kg PO q 12h, the drug has been demonstrated
to increase in cardiac output and fractional shortening
in horses with left-sided valvular regurgitation
when compared with horses receiving a placebo 24 .
Positive inotropic agents improve the contractility of
the myocardium and are used in conjunction with
diuretics and ACE inhibitors for the treatment of heart
failure. The most commonly used positive inotropes
in veterinary medicine are digoxin and more recently,
pimobedan. Digoxin is a cardiac glycoside that binds
to and inhibits the Na+K+ATPase pump exchanging
intracellular sodium for extracellular potassium,
thus causing sodium to accumulate in the cell. The
increased amount of sodium inside the cell prevents
the Na+Ca2+ exchanger from working efficiently
and calcium is therefore not pumped from the cell.
The extra calcium within the cell is taken up by the
sarcoplasmic reticulum and allows for more calcium to
be released during contraction.
The excess calcium binds to sarcomere and increases
the velocity and extent of sarcomere shortening,
thus increasing contractility. Cardiac glycosides also
decrease sympathetic nervous system activity and
increase vagal tone. This leads to a reduced heart rate,
prolonged effective refractory period and a decrease
in AV node conduction velocity. Because myocardial
perfusion occurs in diastole, a decrease in heart rate
will decrease myocardial ischaemia. Furthermore,
because myocardial perfusion occurs in diastole, a
decrease in heart rate will also improve stroke volume
by allowing increased time for ventricular filling and
decrease myocardial oxygen consumption. The
pharmacokinetics of digoxin has been extensively
studied in both normal horses and horses with heart
failure, and it has been demonstrated that both
intravenous and oral administration is effective 25-27 .
Unfortunately there is substantial individual variability
in digoxin disposition among horses, and because of
the narrow therapeutic window and the inherent risk
of toxicosis, drug concentration monitoring is advised
if possible in order to maintain serum concentrations
between 0.5 and 2.0ng/mL 27 . If drug concentration
monitoring is to be undertaken, serum samples should
be obtained at the time of the peak concentration
which would be expected to be approximately 2
hours after oral administration 27 . Other factors that
could potentially increase individual susceptibility to
digoxin toxicosis at maintenance doses is the presence
of hypokalaemia, hypoalbuminaemia and concurrent
administration of drugs that displace digoxin from
plasma-biding sites e.g. quinidine and phenylbutazone.
In the case of AHS, hypoalbuminemia is common,
and this may have a substantial effect of an individual
animal’s risk of digoxin toxicity.
Pimobendan is a benzimidazole-pyridazinone derivative
that increases the sensitivity of the myocardium to
the effects of calcium and inhibits phosphodiesterase
III, thus increasing cardiac contractility. In addition,
the drug induces vasodilation, thus reducing preload
by increasing venous capacitance and afterload by
decreasing systemic vascular resistance 28 . Pimobendan
is a very safe alternative to digoxin, and has been shown
to have significant ionotropic and chronotropic effects
in heathy horses when administered intravenously.
Unfortunately however, a similar effect was not seen
following oral administration, likely due to poor oral
bioavailability 29 .
Recommendations
Current recommendations for treatment based on this
study include:
• 1.1mg/kg flunixin megulmine iv SID
• 1mg/kg furosemide im or iv BID - continue
furosemide for 5 days or until oedema has resolved
• 1mg/kg benazepril po BID for 14 days - continue
with benazepril for 2 weeks in conjunction with
strict rest
• Volume 20 Issue 2 | July 2018 •
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