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P A R T 6
Drugs acting on the endocrine system
Insulin
Insulin
is the hormone produced by the pancreatic beta
cells of the islets of Langerhans. The hormone is released
into circulation when the levels of glucose around
these cells rise. It is also released in response to
incre-
tins
, peptides that are produced in the gastrointestinal
(GI) tract in response to food. One of these incretins,
glucagon-like polypeptide-1 (GLP-1)
, increases insulin
release and decreases glucagon release (in preparation
for the nutrients that will soon be absorbed). GLP-1 also
slows GI emptying to allow more absorption of nutrients
and stimulates the satiety centre in the hypothalamus to
decrease the desire to eat because food is already in the
GI tract. GLP-1 has a very short half-life and is metabo-
lised by the enzyme
dipeptidyl-peptidase-4 (DPP-4)
.
Insulin circulates through the body and reacts with
specific insulin receptor sites to stimulate the transport
of glucose into the cells to be used for energy, a process
called facilitated diffusion. Insulin also stimulates the
synthesis of
glycogen
(glucose stored for immediate
release during times of stress or low glucose), the conver-
sion of lipids into fat stored in the form of adipose tissue
and the synthesis of needed proteins from amino acids.
Insulin is released after a meal, when the blood
glucose levels rise. It circulates and affects metabolism,
allowing the body to either store or use the nutrients
from the meal effectively. As a result of the insulin
BOX 38.1
Drug therapy across the lifespan
Hypoglycaemic agents
CHILDREN
Treatment of diabetes in children is a difficult challenge
of balancing diet, activity, growth, stressors and insulin
requirements. Children need to be carefully monitored for
any sign of hypoglycaemia or hyperglycaemia and treated
quickly because their fast metabolism and lack of body
reserves can push them into a severe state quickly.
Insulin dose, especially in infants, may be so small that
it is difficult to calibrate. Insulin often needs to be diluted
to a volume that can be detected on the syringe. A second
person should always check the calculations and dose of
insulin being given to small children.
Teenagers often present a real challenge for diabetes
management.The desire to be “normal” often leads to a
resistance to dietary restrictions and insulin injections.
The metabolism of the teenager is also in flux, leading to
complications in regulating insulin dose. A team approach,
including the child, family members, teachers, coaches,
and even friends, may be the best way to help the child
deal with the disease and the required therapy. New
delivery methods for insulin may help this age group cope
with the drug therapy in the future.
Metformin is the only oral hypoglycaemic drug
approved for children. It has established dosing for
children 10 years of age and older. With the increasing
number of children being diagnosed with type 2 diabetes,
the use of other agents in children is being tested.
ADULTS
Adults need extensive education about the disease, as well
as about the drug therapy. Warning signs and symptoms
should be stressed repeatedly as the adult learns to juggle
insulin needs with exercise, stressors, other drug effects
and diet. Adults maintained on oral agents need to be
monitored for changes in response to the drugs. Often
additional drugs are added or doses are changed as the
disease progresses over time.
Exercise and diet should always be emphasised as
the mainstay of dealing with diabetes. Adults need to be
cautioned about the use of over-the-counter and herbal
or alternative therapies. Many of these products contain
agents that alter blood glucose levels and will change
insulin or oral agent requirements. Adults should always
be asked specifically whether they use any of these agents
and adjustments should be made accordingly.
PREGNANCY AND BREASTFEEDING
Insulin therapy is the best choice for women with diabetes
mellitus during pregnancy and breastfeeding, which are
times of high stress and metabolic demands. Needs may
change on a daily basis, and the mother should have
ready support and extensive teaching about what to do
if hypoglycaemia or hyperglycaemia occurs.The period
of labour and birth is often a critical time in diabetes
management because of the stress and sudden changes
in body fluid volume and hormone levels.The obstetrician
and the endocrinologist or primary care provider should
consult frequently about the best way to support the
woman through this period.
OLDER ADULTS
Older adults can have many underlying problems that
complicate diabetes management. Poor vision and/or
coordination may make it difficult to prepare a syringe.
A week’s supply of syringes can be prepared and
refrigerated for the usual dose of insulin.
Dietary deficiencies related to changes in taste,
absorption or attitude may lead to wide fluctuations in
blood sugar levels, making it difficult to control diabetes.
Many areas have nutritional assistance programs for older
adults (e.g. Meals onWheels) or have places that can refer
people to appropriate agencies that might be able to offer
assistance.
Older adults have a greater incidence of renal or
hepatic impairment, and kidney and liver function
should be evaluated before starting any of these drugs.
Combinations of oral agents may not be feasible with
severe dysfunction and the person may need to use
insulin to control blood glucose levels.
Older adults should receive periodic educational
reminders about diet, the need for exercise, skin and foot
care, and warning signs to report to the healthcare provider.
The older person is also more likely to experience end
organ damage related to the diabetes—loss of vision,
kidney problems, coronary artery disease, infections—
and the drug regimen of these people can become quite
complex. Careful screening for drug interactions is an
important aspect of the assessment of these people.
