Description
Hypothalamus and Pituitary Drugs
• • Discuss the clinical uses of major hypothalamus and pituitary hormones
• Identify commonly used drugs and hormone replacement
• State the major nursing consideration in the care of client receiving specific hypothalamic and pituitary hormones
• Calculate the drug dosage accurately for oral and parental drug/hormone used for hypothalamus and pituitary replacements
• Pituitary gland
• Pituitary Hormones
• Hypothalamic & Anterior Pituitary Hormones
• Clinical Uses of Major Hypothalamus & Pituitary Hormones
• Pharmacologic Applications of Thyroid & Pituitary Hormones
• Adrenocorticotropic hormone (corticotrophin)
• Therapeutic uses of ACTH
• Growth hormone (somatotropin)
• Therapeutic uses of Somatropin
• Somatostatin (Growth hormone-inhibiting hormone)
• Somatostatin
• Octreotide
• Lanreotide
• Gonadotropin-releasing hormone (GnRH)
• GnRH antagonists
• Gonadotropins (Gns)
• Uses
• Gonadotropin deficiency in males.
• Undescended testes.
• Amenorrhea and infertility.
• In vitro fertilization—to time the ovulation
• Prolactin
• Prolactin inhibitors
• Uses of Bromocriptine
• Hormones of the Posterior Pituitary
Vasopressin and oxytocin
• Oxytocin
• Vasopressin(antidiuretic hormone)
• Desmopressin
• Nursing Consideration
Unit I D:
Hypothalamus and Pituitary Drugs
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Objectives
By the completion of this unit learners will be able to:
• Discuss the clinical uses of major hypothalamus and pituitary hormones
• Identify commonly used drugs and hormone replacement
• State the major nursing consideration in the care of client receiving specific
hypothalamic and pituitary hormones
• Calculate the drug dosage accurately for oral and parental drug/hormone used for
hypothalamus and pituitary replacements
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Pituitary gland
• Pituitary gland often called as “ Master gland”
• Its function are primarily controlled by hypothalamus.
• Pituitary gland consist of 2 lobe:
– Anterior lobe
– Posterior lobe
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Pituitary Hormones
• Anterior pituitary hormones are produced by separate group of cells:
– Somatotrophs: Growth hormones
– Lactotrophs: Prolactin
– Gonadotrophs: FSH, LH
– Corticotrophs: ACTH
• Posterior lobe: Vasopressin and Oxytocin
• Anterior pituitary hormones are regulated by negative feedback mechanism.
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Hypothalamic & Anterior Pituitary Hormones
• The hormones secreted by the hypothalamus and the pituitary are all peptides or
low molecular weight proteins that act by binding to specific receptor sites on their
target tissues.
• The hormones of the anterior pituitary are regulated by neuropeptides that are
called either “releasing” or “inhibiting” factors or hormones.
• These are produced in the hypothalamus, and they reach the pituitary by the
hypophyseal portal system
• Each hypothalamic regulatory hormone controls the release of a specific hormone
from the anterior pituitary.
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Clinical Uses of Major Hypothalamus & Pituitary Hormones
• Although a number of pituitary hormone preparations are currently used
therapeutically for specific hormonal deficiencies, most of these agents have limited
therapeutic applications.
• Hormones of the anterior and posterior pituitary are administered intramuscularly
(IM), subcutaneously, or intranasally because their peptidyl nature makes them
susceptible to destruction by the proteolytic enzymes of the digestive tract.
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Pharmacologic Applications of Thyroid &
Pituitary Hormones
• Replacement therapy
• Antagonists for excess production of pituitary hormones.
• Diagnostic tools for endocrine abnormalities.
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Adrenocorticotropic hormone (corticotrophin)
• Normally, ACTH is released from the pituitary in pulses with an overriding diurnal
rhythm, with the highest concentration occurring in the early morning and the
lowest in the late evening.
• Stress stimulates its secretion, whereas cortisol acting via negative feedback
suppresses its release.
• Mechanism of action: ACTH binds to receptors on the surface
of the adrenal cortex, thereby activating G protein–coupled processes that
ultimately stimulate the synthesis and release of the adrenocorticosteroids and the
adrenal androgens.
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Therapeutic uses of ACTH
• Limited use of ACTH due to corticosteroids
• Used in the diagnosis of adrenocortical insufficiency.
• Therapeutic corticotrophin preparations are extracts from the
anterior pituitaries of domestic animals or synthetic human
ACTH.
Adverse effects:
• Short-term use of ACTH for diagnostic purposes is usually well
tolerated.
• With longer use, toxicities are similar to those of
glucocorticoids and include hypertension, peripheral edema,
hypokalemia, emotional disturbances, and increased risk of
infection
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Mainly to used as a diagnostic tool for differentiating between
primary adrenal insufficiency (Addison disease) and secondary
adrenal insufficiency (caused by the inadequate secretion of
ACTH by the pituitary).
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Growth hormone (somatotropin)
• Somatotropin is released by the anterior pituitary in response to growth hormone
(GH)-releasing hormone
• Somatotropin influences a wide variety of biochemical processes (for example, cell
proliferation and bone growth are promoted). Synthetic human GH (somatropin) is
produced using recombinant DNA technology.
• Mechanism of action: Although many physiologic effects of GH are exerted directly
at its targets, others are mediated through the somatomedins—insulin-like growth
factors 1 and 2 (IGF-1 and IGF-2).
[Note: In acromegaly (a syndrome of excess GH due to
hormone-secreting tumors), IGF-1 levels are consistently high,
reflecting elevated GH.]
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Secretion of GH is inhibited by another hypothalamic
hormone, somatostatin.
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Therapeutic uses of Somatropin
• GH deficiency or growth failure in children.
• Growth failure due to Prader-Willi syndrome,
• Management of AIDS wasting syndrome
• GH replacement in adults with confirmed GH deficiency.
Pharmacokinetics
• Somatropin is administered by subcutaneous or IM injection.
Although the half-life of GH is short (approximately 25
minutes), it induces the release of IGF-1 from the liver, which
is responsible for subsequent GH-like actions.
Adverse effects:
• Adverse effects of somatropin include pain at the injection
site, edema, arthralgias, myalgias, flu-like symptoms, and an
increased risk of diabetes. www.remixeducation.in
Somatostatin
(Growth hormone-inhibiting hormone)
• In the pituitary, somatostatin binds to receptors that suppress GH and thyroid-
stimulating hormone release.
• Originally isolated from the hypothalamus, somatostatin is a small polypeptide that
is also found in neurons throughout the body as well as in the intestine, stomach,
and pancreas.
• Somatostatin not only inhibits the release of GH but also that of insulin, glucagon,
and gastrin.
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Somatostatin:
• It is growth hormone release inhibiting hormone (GHRIH).
• Inhibits secretion of GH, also inhibits thyroid stimulating hormone, Insulin,
prolactin, glucagon.
• Uses:
– Use to prevent acute bleeding due to esophageal varices.
– Upper GIT bleeding from hemorrhagic gastritis, intestinal or pancreatic fistula.
– Hypersecretory tumor of intestinal tract.
• Limitation: short half life, lack of specificity, GH rebound after discontinuation.
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Octreotide [ok-TREE-ohtide] and lanreotide [lan-REE-oh-
tide] are synthetic analogs of somatostatin. Their half-lives
are longer than that of the natural compound, and depot
formulations are available, allowing for administration once
every 4 weeks.
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Octreotide
• A long acting analogue of somatostatin.
• 45 times more potent.
Uses:
– Useful in acromegaly, some hormone secreting tumors and in bleeding
esophageal varices.
– Treatment of AIDS associated diarrhea, Cushing syndrome and insulinoma.
Adverse effect: abdominal pain, nausea, steatorrhea, gallstones.
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Gallbladder emptying is delayed, and asymptomatic
cholesterol gallstones can occur with long-term
treatment
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Lanreotide
• Long-acting analogue of somatostatin,
• Similar in actions and specificity to octreotide
• Indicated for pharmacotherapy of acromegaly.
Pegvisomant
• (peg-VIH-soe-mant)
• Acromegaly that is refractory to other modes of therapy may
be treated with pegvisomant
• Acts as a GH antagonist , because in presence of Pegvisomant,
GH binds to the GH receptor but does not trigger signal
transduction.
• Approved for treatment of acromegaly due to small pituitary
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Gonadotropin-releasing hormone (GnRH):
• Regulates the secretion of gonadotropins—FSH and LH
• Secreted in a pulsatile manner.
• Continuous administration inhibits gonadotropin secretion, that in
turn, leads to reduced production of gonadal steroid hormones
(androgens and estrogens).
• Gonadorelin is synthetic GnRH, used in diagnostic tests in
hypogonadism.
• Pulsatile administration is used in infertility and delayed puberty.
• Used in prostatic cancers, precocious puberty and some gynecological
conditions like uterine fibroids and endometriosis. Ex- leuprolide,
Goserelin, Nafarelin, Triptorelin,
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Spermatogenesis
In 1–2 weeks or ovulation cease
they cause and testosterone
inhibition of FSH suppression or estradiol levels
desensitization
and down and LH of gonadal fall to castration
regulation of secretion function. levels.
GnRH receptors
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Cont….
• Recovery occurs within 2 months of stopping treatment.
• Used as nasal spray or injected s.c.
• Reversible pharmacological oophorectomy/ orchidectomy is used in precocious
puberty, prostatic carcinoma, endometriosis, premenopausal breast cancer, uterine
leiomyoma, polycystic ovarian disease.
• Used as contraceptive for both males and females.
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GnRH antagonists
• Some extensively substituted GnRH analogues act as GnRH receptor antagonists.
• Inhibit Gn secretion without causing initial stimulation.
• They block the pituitary GnRH receptors and thereby suppress the secretion of LH,
FSH and delay ovulation.
• They are used in in vitro fertilization and are also useful in prostatic cancer and in
reducing uterine fibroids and endometriosis.
• Ex- ganirelix and cetrorelix
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Gonadotropins (Gns)
• The anterior pituitary secretes two Gns viz. FSH and LH.
• FSH:
– In the female induces follicular growth, development of ovum and secretion of
estrogens.
– In the male supports spermatogenesis and has a trophic influence on
seminiferous tubules.
– Ovarian and testicular atrophy occurs in the absence of FSH
• LH:
– Induces ovulation
– In male LH stimulates testosterone secretion.
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these hormones are injected via the IM or subcutaneous
route. Injection of hMG or FSH products over a period of 5
to 12 days causes ovarian follicular growth and maturation,
and with subsequent injection of hCG, ovulation occurs
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Uses
• Gonadotropin deficiency in males.
• Undescended testes.
• Amenorrhea and infertility.
• In vitro fertilization—to time the ovulation
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Prolactin
• Physiological function:
– Prolactin causes growth & development of breast in pregnancy.
– Promotes proliferation of ductal as well as acinar cells in breast
and induces synthesis of milk proteins and lactose.
– After parturition, prolactin induces milk secretion.
• Regulation of secretion:
– Prolactin is under predominant inhibitory control of
hypothalamus through PRIH.
• Dopaminergic agonists (bromocriptine, cabergoline) plasma
prolactin levels.
• Dopaminergic antagonists (chlorpromazine, haloperidol,
metoclopramide) and reserpine cause hyperprolactinemia.
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Cont….
• Prolactin levels in blood are low in childhood, increase in girls at puberty and are higher
in adult females.
• A progressive increase occurs during pregnancy, peaks at term.
• High prolactin secretion is maintained by suckling, falls if breast feeding is
discontinued.
• Stress, exertion and hypoglycemia also stimulate prolactin release.
• Hyperprolactinaemia is responsible for the galactorrhoea– amenorrhea– infertility
syndrome in women.
• In males it causes loss of libido and decreased fertility.
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Prolactin inhibitors
Bromocriptine: Prolactin inhibitor
MOA:
• Decreases prolactin release from pituitary by activating dopaminergic receptors on
lactotrope cells.
• Levodopa like actions in CNS—antiparkinsonian and behavioral effects.
Side Effects
• Nausea and vomiting by stimulating dopaminergic receptors in the CTZ.
• Hypotension—due to central suppression of postural reflexes and weak peripheral
α adrenergic blockade.
• Decreases gastrointestinal motility.
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Uses of Bromocriptine
• Hyperprolactinemia due to microprolactinomas causing galactorrhoea, amenorrhea
and infertility in women; gynaecomastia, impotence and sterility in men.
• Parkinsonism
• Bromocriptine is used to suppress lactation and breast engorgement after delivery
(like in stillbirth) and following abortion.
Cabergoline
• It is a newer D2 agonist; more potent; more D2 selective and longer acting.
• Lower Incidence of nausea and vomiting.
• It is preferred for treatment of hyperprolactinemia and acromegaly
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Hormones of the Posterior Pituitary
Vasopressin and oxytocin
• Not regulated by releasing hormones.
• They are synthesized in the hypothalamus, transported to the posterior pituitary,
and released in response to specific physiologic signals, such as high plasma
osmolarity or parturition.
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Oxytocin
Uses
• Used in obstetrics, to stimulate uterine contraction to induce or reinforce labor.
• Oxytocin causes milk ejection by contracting the myoepithelial cells around the
mammary alveoli.
Adverse effects:
• Toxicities are uncommon when used properly: hypertension, uterine rupture, water
retention, and fetal death have been reported.
Contraindications:
• Contraindicated in abnormal fetal presentation, fetal distress, and premature births.
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Vasopressin(antidiuretic hormone)
• Vasopressin has both antidiuretic and vasopressor effects.
• In the kidney, it binds to V2 receptor to increase water
permeability and reabsorption in the collecting tubules.
Uses:
• Major use of vasopressin is to treat diabetes insipidus, also
used in the management of cardiac arrest and in bleeding
due to esophageal varices.
• Other effects of vasopressin are mediated by the V1 receptor,
which is found in liver, vascular smooth muscle (where it
causes constriction).
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Adverse effects:
• Major toxicities are water intoxication and hyponatremia.
Headache, bronchoconstriction, and tremor can also occur.
Desmopressin
• An analogue of vasopressin,
• Minimal activity at the V1 receptor, making it largely free of pressor effects.
• Longer acting than vasopressin
• Preferred for the treatment of diabetes insipidus and nocturnal enuresis.
• Administered intranasally or orally.
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Nursing Consideration
• Assess for contraindications or cautions (e.g. history of allergy, pregnancy,) to avoid
adverse effects.
• Assess height, weight, and GH levels to determine baseline status before beginning
therapy and for any potential adverse effects.
• Monitor patient response to therapy (return of GH levels to normal, growth and
development).
• Monitor for adverse effects
• Monitor patient compliance to drug therapy
• Evaluate patient understanding on drug therapy by asking patient to name the drug,
its indication, and adverse effects to watch for.
- Subject:- Pharmacology
- Course:- B.pharm (pharmacy),
- Semester:- 5th sem , sem :- 5
