Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 21 DRUGS USED IN THE TREATMENT OF DISORDERS OF PANCREATIC FUNCTION
Special considerations
Due to the relatively slow onset of action of ultralente
insulin, in most situations it may be advisable to use a
diet relatively high in fiber and/or to encourage the
patient to eat small amounts frequently rather than one
or two large meals per day.
Insulin glargine
Clinical applications
Insulin glargine has been shown in humans to be a longlasting,
peakless insulin more closely resembling the
profile of constitutive basal endogenous insulin secretion.
In humans it has been shown to be beneficial in
the management of both type 1 and type 2 (or insulindependent
and insulin-independent respectively) diabetes
mellitus with decreased incidence of hypoglycemic
episodes and improved control when compared to
at least one traditional intermediate-acting insulin
(NPH).
In dogs and cats, insulin glargine generally lasts longer
than either lente or protamine zinc insulins although
this extended duration generally is not sufficient to
justify once-daily administration. Consequently, it is
generally used in those patients where the duration of
activity of the so-called intermediate-acting insulins is
insufficient to provide adequate glycemic control for
12-h periods. As insulins generally last for a shorter
period of time in cats than dogs and a greater proportion
of diabetic cats tend to have ‘grazing feeding’ patterns,
making their insulin requirement more suited to
an insulin with a relatively consistent effect over its
duration of action, insulin glargine is more commonly
used for treating diabetes mellitus in cats than dogs.
Indeed, preliminary data suggest that when combined
with appropriate dietary control, 12-hourly administration
of subcutaneous insulin glargine to cats with diabetes
mellitus is more likely to produce remission than
similarly administered either lente or protamine zinc
insulin.
Formulations and dose rates
Insulin glargine was developed by recombinant DNA technology and
differs from human insulin by the substitution of glycine for asparagine
at position 21 of the A-chain and the addition of two positively
charged arginine molecules at the C-terminus of the B-chain. These
changes result in glargine being relatively insoluble at neutral pH,
leading to its microprecipitation in neutral pH, as is found in normal
subcutaneous tissue. This microprecipitation delays absorption,
resulting in insulin glargine being released from its subcutaneous site
relatively consistently over an extended period. It is because of this
tendency for a relatively stable activity profi le over a reasonable period
that glargine has been recommended for use in cats as either once- or
twice-daily insulin. One recent preliminary study showed no difference
in glycemic control between diabetic cats dosed with similar
total daily doses of lente insulin given 12 hourly and glargine 24
hourly. Other investigators have reported improved remission rates in
diabetic cats given 12-hourly glargine compared to those given either
protamine zinc or lente 12 hourly. In both studies the numbers of
animals enrolled were small and the results interpreted with caution.
First, the small sample size may not have allowed for the contribution
of confounding factors to the apparent differences and second, the
studies may have been underpowered and thus unable to demonstrate
real differences.
Nevertheless insulin glargine can effectively control diabetes mellitus
in cats and offers a suitable alternative to the more traditional
prolonged action insulins. Its apparent relatively peakless activity
profi le might make it particularly suitable for cats that tend to consume
their daily caloric intake in regular amounts over a 24-h period. When
administered once daily, it is at least as effective as twice-daily lente
but the most recent results tend to suggest that optimum control is
most likely to be achieved with twice-daily dosing.
DOGS
No published information is available on the use of glargine in dogs.
Consequently currently its use should be considered as experimental
and close monitoring would be strongly recommended.
• A standard dose of 0.5–2.0 IU/kg/24 h generally divided and
given 12 hourly is recommended although the dose MUST be
individualized on the basis of either serial blood glucose
estimations or regular estimates of circulating glycated proteins
such as fructosamine or glycosylated hemoglobin
CATS
• A starting dose of 1.0 IU/kg/24 h divided and given 12 hourly is
recommended although as with all insulin therapy in diabetic
cats, the dose must be individualized and close monitoring is
essential
ORAL HYPOGLYCEMIC AGENTS
The so-called ‘oral hypoglycemic agents’ have been variably
successful in treating canine and feline diabetes
mellitus. Generally, they are unlikely to be effective in
patients with an irreversible, absolute insulin deficiency.
Consequently they have not been considered a worthwhile
treatment option in dogs as, by the time canine
diabetics present to a veterinarian, most have an irreversible
absolute insulin deficiency. As this is not the
case with feline diabetes mellitus, it is in this species
that the use of oral hypoglycemics is most likely to be
effective.
Sulfonylureas
Chemical structure
All drugs in this class are substituted arylsulfonylureas.
They differ by substitution at the para position on the
benzene ring and also at one nitrogen residue on the
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