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P A R T 6
Drugs acting on the endocrine system
these hormones have not been clearly identified. Not
all of the hypothalamic hormones are used as phar
macological agents. A number of the hypothalamic
releasing hormones described here are used for diag
nostic purposes only, and others are used primarily as
antineoplastic agents.
Agonists
CRH stimulates the release of adrenocorticotropic
hormone (ACTH) from the anterior pituitary and is
used to diagnose Cushing’s disease (a condition char
acterised by hypersecretion of adrenocortical hormones
in response to excessive ACTH release). Goserelin is an
analogue of GnRH. Following an initial burst of follicle-
stimulating hormone (FSH) and luteinising hormone
(LH) release, this drug inhibits pituitary gonadotropin
secretion, with a resultant drop in the production of the
sex hormones. See Table 35.1 for usual indications for
each of these agents.
Antagonists
Cetrorelix, ganirelix, leuprorelin and nafarelin are
antagonists of GnRH. Leuprorelin occupies pituitary
GnRH receptor sites so that they no longer respond to
GnRH; as a result, there is no stimulation for release of
LH and FSH. Nafarelin, a potent agonist of GnRH, is
used to decrease the production of gonadal hormones
through repeated stimulation of their receptor sites.
After about 4 weeks of therapy, gonadal hormone
levels fall, and the cells they normally stimulate are
quiet. See Table 35.1 for usual indications for each of
these agents.
Pharmacokinetics
For the most part, these drugs are absorbed slowly when
given intramuscularly (IM), subcutaneously (SC) or in
depot form. Nafarelin is given in a nasal form. They tend
to have very long half-lives of days to weeks. Metabolism
is not understood, but it is thought that they are meta
bolised by endogenous hormonal pathways. Because
they are hormones or similar to hormones, they cross
the placenta and cross into breast milk. Most of them
are excreted in the urine.
Contraindications and cautions
These drugs are contraindicated with known hyper
sensitivity to any component of the drug
because of the
risk of hypersensitivity reactions
, and during pregnancy
and breastfeeding
because of the potential adverse
effects to the fetus or baby.
Caution should be used with
renal impairment,
which could interfere with excretion
of the drug
; with peripheral vascular disorders,
which
could alter the absorption of injected drug
; and with
rhinitis when using nafarelin,
which could alter the
absorption of the nasal spray.
Adverse effects
Adverse effects associated with these drugs are related
to the stimulation or blocking of regular hormone
control. Agonists can lead to increased cortisol and
aldosterone levels, causing fluid retention, electro
lyte imbalance, impaired healing and elevated glucose
levels, or to increased release of sex hormones, leading
to ovarian overstimulation, flushing, increased tem
perature and appetite and fluid retention. Antagonists
can lead to a decrease in testosterone levels, leading to
loss of energy, decreased sperm count and activity and
potential alterations in secondary sex characteristics, or
to a decrease in female sex hormones, leading to lack of
menstruation, fluid and electrolyte changes, insomnia
and irritability.
Prototype summary: Leuprorelin
Indications:
Treatment of advanced prostatic cancer,
endometriosis, uterine leiomyomata.
Actions:
LHRH agonist that occupies pituitary
gonadotropin-releasing hormone receptors and
desensitises them; causes an initial increase and
then profound decrease in LH and FSH levels.
Pharmacokinetics:
Route
Onset
Peak Duration
IM depot 4 hours Variable 1, 2, 3 or 4 months
T
1/2
:
3 hours; metabolism and excretion are
unknown.
Adverse effects:
Dizziness, headache, pain, peripheral
oedema, myocardial infarction, nausea, vomiting,
anorexia, constipation, urinary frequency,
haematuria, hot flushes, increased sweating.
Care considerations for people receiving
drugs affecting hypothalamic hormones
The specific care of the person who is receiving
a hypothalamic releasing factor is related to the
hormone (or hormones) that the drug is affecting
(see Chapter 36 for adrenocorticoid hormones and
Chapters 40 and 41 for sex hormones). Drugs used
for diagnostic purposes are short lived; information
about these agents should be included in any
teaching about the diagnostic procedure. Guidelines
for other agents can be found with the therapeutic
drug class to which they belong (e.g. antineoplastic
agents, Chapter 14).
