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P A R T 6
Drugs acting on the endocrine system
G
rowth hormone antagonists
GH hypersecretion is usually caused by pituitary
tumours and can occur at any time of life. This is often
referred to as hyperpituitarism. If it occurs before the
epiphyseal plates of the long bones fuse, it causes an
acceleration in linear skeletal growth, producing
gigan-
tism
of over 2 metres in height with fairly normal body
proportions. In adults, after epiphyseal closure, linear
growth is impossible. Instead, hypersecretion of GH
causes enlargement in the peripheral parts of the body,
such as the hands and feet, and the internal organs,
especially the heart.
Acromegaly
is the term used to
describe the onset of excessive GH secretion that occurs
after puberty and epiphyseal plate closure.
Most conditions of GH hypersecretion are treated
by radiation therapy or surgery. Drug therapy for GH
excess can be used for those people who are not candi
dates for surgery or radiation therapy. The drugs include
a dopamine agonist (bromocriptine [
Parlodel
]), and the
prototype drug (bromocriptine mesylate); somatostatin
analogue (lanreotide [
Somatuline
] (not available in
New Zealand) and octreotide [
Sandostatin
]); and a GH
analogue (pegvisomant [
registered for use in Australia
but not readily available
]).
Therapeutic actions and indications
Somatostatin is an inhibitory factor released from the
hypothalamus. It is not used to decrease GH levels,
although it does do that very effectively. Because it
has multiple effects on many secretory systems (e.g. it
inhibits release of gastrin, glucagon and insulin) and a
short duration of action, it is not desirable as a thera
peutic agent. Analogues of somatostatin, lanreotide
and octreotide, are considerably more potent in inhibit
ing GH release with less of an inhibitory effect on
insulin release. Consequently, they are used instead of
somatostatin.
Bromocriptine, a semisynthetic ergot alkaloid, is a
dopamine agonist frequently used to treat acromegaly.
It may be used alone or as an adjunct to irradiation.
Dopamine agonists inhibit GH secretion in some indi
viduals with acromegaly; the opposite effect occurs in
normal individuals. Bromocriptine’s GH-inhibiting
effect may be explained by the fact that dopamine
increases somatostatin release from the hypothalamus.
Pegvisomant is a GH analogue that was approved
in late 2003 for the treatment of acromegaly in individ
uals who do not respond to other therapies. It binds to
GH receptors on cells, inhibiting GH effects. It must be
given by daily subcutaneous injection. While registered
for use in Australia, this drug is not available under the
Pharmaceutical Benefits Scheme (PBS). Table 35.2 shows
usual indications for each of these agents.
Pharmacokinetics
Octreotide must be administered subcutaneously. The
drug is rapidly absorbed and widely distributed through
out the body, and it is metabolised in the tissues with
about 30% excreted unchanged in the urine.
Lanreotide is administered by either deep subcu
taneous or intramuscular injection, peaking between
10 and 16 hours after administration.
Bromocriptine is administered orally and effectively
absorbed from the gastrointestinal (GI) tract. The drug
undergoes extensive first-pass metabolism in the liver
and is primarily excreted in the bile.
Pegvisomant is given by subcutaneous injection
and is slowly absorbed, reaching peak effects in 33 to
77 hours. It also clears from the body at a slow rate,
with a half-life of 6 days. The drug is excreted in the
urine.
Contraindications and cautions
Bromocriptine should not be used during pregnancy or
breastfeeding
because of effects on the fetus and because
it blocks breastfeeding.
There are no adequate studies
of effects of octreotide and pegvisomant in pregnancy
and during breastfeeding; use of these drugs should
be reserved for situations in which the benefits to the
mother clearly outweigh any potential risks to the fetus
or neonate. Growth hormone antagonists are contra
indicated in the presence of any known allergy to the
drug
to prevent hypersensitivity reactions.
They should
be used cautiously in the presence of any other endocrine
drug therapy and promote compliance.
Instruct a
family member or caregiver in the following points:
–– Storage of the drug (refrigeration is required)
–– Preparation of the drug (the reconstitution
procedure varies depending on the brand name
product used)
–– Administration techniques (sterile technique,
need to rotate injection sites and need to monitor
injection sites for atrophy or extravasation).
Evaluation
■
■
Monitor response to the drug (return of GH levels
to normal; growth and development).
■
■
Monitor for adverse effects (hypothyroidism,
glucose intolerance, nutritional imbalance).
■
■
Evaluate the effectiveness of the teaching plan
(person can name drug, dosage, adverse effects
to watch for and specific measures to avoid them;
family member can demonstrate proper technique
for preparation and administration of the drug).
■
■
Monitor the effectiveness of comfort measures and
compliance with the regimen.
