Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

EXOCRINE PANCREATIC INSUFFICIENCY
Adverse effects
There is no information available on the adverse effects
of troglitazone in cats. In humans, a proportion of
patients develop variably severe hepatocellular damage.
As this has been associated with an unacceptable
number of fatalities, troglitazone has not been licensed
for human use in either the UK or Australia and the
prevalence of this problem resulted in its withdrawal
from the US market. More recent thiazolidinediones
such as pioglitazone and rosiglitazone appear to have
similar potency to troglitazone and have not been associated
with idiosyncratic hepatopathies in humans.
However, their long-term administration has been
linked to mild nonregenerative anemias and interestingly,
in one report where darglitazone was administered
to normal and obese cats, the investigators
commented on a mild but significant reduction in the
hematocrit of cats receiving darglitazone over a 42-d
period.
Special considerations
Additional studies are needed to determine the efficacy
and safety of the various commercially available
thiazolidinediones in the treatment of feline diabetes
mellitus.
a-GLUCOSIDASE INHIBITORS
Chemical structure
The α-glucosidase inhibitors acarbose and miglitol are
complex oligosaccharides of microbial origin.
Mechanism of action
α-Glucosidase inhibitors bind competitively to the α-
glucosidases glucoamylase, sucrase, maltase and isomaltase
located within the brush borders of the small
intestinal mucosa, inhibiting the conversion of complex
carbohydrates and disaccharides to monosaccharides.
These inhibitory effects delay and reduce postprandial
glucose concentrations as well as decreasing insulin
secretion.
Acarbose alone does not appear to be effective in
treating diabetes mellitus but it can be used in conjunction
with insulin and/or other oral hypoglycemic agents
to achieve better diabetic control. However, a recent
report suggests that while acarbose resulted in a demonstrable
improvement in diabetic control in diabetic cats
receiving a standard commercial diet, there was no significant
effect of acarbose when the cats were fed a
standard low-carbohydrate diet.
Formulations and dose rates
CATS
• The recommended dose is 12.5–25 mg/cat/12 h orally given
with food. It is generally recommended to start at a lower dose
and increase it to achieve a satisfactory effect. Doses need to
be adjusted on the basis of changes in overall diabetic control
and on the prevalence of side effects. As the effect of acarbose
is entirely dependent upon its interaction with intestinal enzyme
during the post prandial period, it is essential that it is only
administered at the time of feeding
DOGS
• It is generally recommended to start with a low dose of 12.5–
25 mg per animal per meal and increase this to 50–100 mg per
meal over a 2-week period. Dose adjustment will be based on
appropriate modifi cation of diabetic control and the prevalence
of side effects. As the effect of acarbose is entirely dependent
upon its interaction with intestinal enzyme during the
postprandial period, it is essential that it is only administered at
the time of feeding
Adverse effects
Adverse effects of acarbose are common although, as it
is not absorbed, they are predominantly confined to
reversible gastrointestinal problems such as poorly
formed stools, diarrhea, flatulence and weight loss. The
prevalence and severity of the signs appear to be dose
related. Although gastrointestinal signs were evident in
approximately 35% of normal dogs receiving acarbose
regardless of dose, these signs tended to resolve within
2–3 d of discontinuing the medication.
Special considerations
As mentioned above, the effect of acarbose requires it
to be administered at the same time as the meal. While
it may have a role to play in facilitating some level of
improved control in diabetic dogs, recent reports suggest
that the addition of acarbose is only likely to improve
control of diabetes in cats if they are not being fed a
low-carbohydrate diet.
EXOCRINE PANCREATIC INSUFFICIENCY
Relevant physiology/pathophysiology
The exocrine pancreas is an accessory digestive organ
which, under complex neuroendocrine control, secretes
fluid containing digestive enzymes and sodium bicarbonate
into the intestinal lumen, resulting in digestion
of food and neutralization of HCl of gastric origin.
Three types of enzymes are secreted by the pancreas:
amylases, lipases and proteases. The reserve capacity of
the pancreas is enormous. Consequently, in the dog,
protein digestion is not impaired until more than 90%
of the gland is removed or destroyed.
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