NURSING 3313 Exam 5 Review-pharm Questions and Answers
• Hypothalamus and pituitary
o Hypothalamus secretes releasing hormones to the
... [Show More] pituitary
o Pituitary hormones go to specific tissues
o For instance:
▪ Hypothalamus secretes thyrotropin-releasing hormone (TRH)…telling the pituitary to secrete thyroid stimulating hormone (TSH)…TSH is secreted and acts on the thyroid to stimulate thyroid hormone secretion
o The hypothalamus is the coordinating center for the nervous and endocrine responses to internal and external stimuli. The hypothalamus constantly monitors the body’s homeostasis by analyzing input from the periphery and the central nervous system (CNS) and coordinating responses through the autonomic, endocrine, and nervous systems. In effect, it is the “master gland” of the neuroendocrine system. This title was once given to the pituitary gland because of its many functions and well-protected location.
o The hypothalamus has various regions or clusters of neurons that are sensitive to certain stimuli. It is responsible for regulating a number of body functions, including body temperature, thirst, hunger, water retention, blood pressure, respiration, reproduction, and emotional reactions. Situated at the base of the forebrain, the hypothalamus receives input from virtually all other areas of the brain, including the limbic system, cerebral cortex, and the special senses that are controlled by the cranial nerves—smell, sight, touch, taste, and hearing. Because of its positioning, the hypothalamus is able to influence and be influenced by emotions and thoughts. The hypothalamus is also located in an area of the brain that is poorly protected by the blood–brain barrier, so it is able to act as a sensor to various electrolytes, chemicals, and hormones that are in circulation and do not affect other areas of the brain.
o The hypothalamus maintains internal homeostasis by sensing blood chemistries and by stimulating or suppressing endocrine, autonomic, and CNS activity. In essence, it can turn the autonomic nervous system and its effects on or off. The hypothalamus also produces and secretes a number of releasing hormones or factors that stimulate the pituitary gland, which in turn stimulates or inhibits various endocrine glands throughout the body (Fig. 34.1). These releasing hormones include growth hormone (GH)-releasing hormone, thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone, corticotropin-releasing hormone, and prolactin-releasing hormone. The hypothalamus also produces two inhibiting factors that act as regulators to shut off the production of hormones when levels become too high: GH release–inhibiting factor (somatostatin) and prolactin (PRL)-inhibiting factor (PIF). Recent research has indicated that PIF may actually be dopamine, a neurotransmitter. Patients who are taking dopamine-blocking drugs often develop galactorrhea (inappropriate milk production) and breast enlargement, theoretically because PIF is also blocked and PRL levels continue to rise, stimulating breast tissue and milk production. Research is ongoing about the chemical structure of several of the releasing factors.
o The hypothalamus is connected to the pituitary gland by two networks: a vascular capillary network carries the hypothalamic-releasing factors directly into the anterior pituitary and a neurological network delivers two other hypothalamic hormones— antidiuretic hormone (ADH) and oxytocin—to the posterior pituitary to be stored. These hormones are released as needed by the body when stimulated by the hypothalamus.
o As the “master gland” of the neuroendocrine system, the hypothalamus helps regulate the central and autonomic nervous systems and the endocrine system to maintain homeostasis.
o The hypothalamus produces stimulating and inhibiting factors that travel to the anterior pituitary through a capillary system to stimulate the release of pituitary hormones or block the production of certain pituitary hormones when levels of target hormones get too high.
o The hypothalamus is connected to the posterior pituitary by a nerve network that delivers the hypothalamic hormones ADH and oxytocin to be stored in the posterior pituitary until the hypothalamus stimulates their release.
o Because of its position in the brain, the hypothalamus is stimulated by many things, such as light, emotion, cerebral cortex activity, and a variety of chemical and hormonal stimuli. Together, the hypothalamus and the pituitary function closely to maintain endocrine activity along what is called the hypothalamic–pituitary axis (HPA) using a series of negative feedback systems.
o It is thought that this feedback system is more complex than once believed. The hypothalamus probably also senses TRH and TSH levels and regulates TRH secretion within a narrow range, even if thyroid hormone is not produced. The anterior pituitary may also be sensitive to TSH levels and thyroid hormone, regulating its own production of TSH. This complex system provides backup controls and regulation if any part of the HPA fails. This system also can create complications, especially when there is a need to override or interact with the total system, as is the case with hormone replacement therapy or the treatment of endocrine disorders. Supplying an exogenous hormone, for example, may increase the hormone levels in the body but then may affect the HPA to stop production of releasing and stimulating hormones, leading to a decrease in the body’s normal production of the hormone.
o Two of the anterior pituitary hormones (i.e., GH and PRL) do not have a target organ to produce hormones and so cannot be regulated by the same type of feedback mechanism. The hypothalamus in this case responds directly to rising levels of GH and PRL. When levels rise, the hypothalamus releases the inhibiting factors somatostatin and PIF directly to inhibit the pituitary’s release of GH and PRL, respectively. The HPA functions through negative feedback loops or the direct use of inhibiting factors to constantly keep these hormones regulated.
o
o The pituitary gland is located in the skull in the bony sella turcica under a layer of dura mater. It is divided into three lobes: an anterior lobe, a posterior lobe, and an
intermediate lobe. Traditionally, the anterior pituitary was known as the body’s master gland because it has so many important functions and through feedback mechanisms, regulates the function of many other endocrine glands. In addition, its unique and protected position in the brain led early scientists to believe that it must be the chief control gland. However, as knowledge of the endocrine system has grown, scientists now designate the hypothalamus as the master gland because it has even greater direct regulatory effects over the neuroendocrine system, including stimulation of the pituitary gland to produce its hormones.
o The anterior pituitary produces six major hormones: GH, adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), PRL, and thyroid- stimulating hormone (TSH, also called thyrotropin) (Table 34.2; see also Fig. 34.1). These hormones are essential for the regulation of growth, reproduction, and some metabolic processes. Deficiency or overproduction of these hormones disrupts this regulation.
▪
o The anterior pituitary hormones are released in a rhythmic manner into the bloodstream. Their secretion varies with time of day (often referred to as diurnal rhythm) or with physiological conditions such as exercise or sleep. Their release is affected by activity in the CNS, by hypothalamic hormones, by hormones of the peripheral endocrine glands, by certain diseases that can alter endocrine functioning, and by a variety of drugs, which can directly or indirectly upset the homeostasis in the body and cause an endocrine response. Normally, diurnal rhythm occurs when the hypothalamus begins secretion of corticotropin-releasing factor (CRF) in the evening, peaking at about midnight; adrenocortical peak response is between 6 and 9 am; levels fall during the day until evening, when the low level is picked up by the hypothalamus and CRF secretion begins again.
o The anterior pituitary also produces melanocyte-stimulating hormone (MSH) and various lipotropins. MSH plays an important role in animals that use skin color changes as an adaptive mechanism. It might also be important for nerve growth and development in humans. Lipotropins stimulate fat mobilization but have not been clearly isolated in humans.
o The posterior pituitary stores two hormones that are produced by the hypothalamus and deposited in the posterior lobe via the nerve axons where they are produced. These
two hormones are ADH, also referred to as vasopressin, and oxytocin. ADH is directly released in response to increased plasma osmolarity or decreased blood volume (which often results in increased osmolarity). The osmoreceptors in the hypothalamus stimulate the release of ADH. ADH acts in the kidneys to increase retention of water in order to decrease the osmolarity of the blood volume. Oxytocin stimulates uterine smooth muscle contraction in late phases of pregnancy and also causes milk release or “let- down” reflex in lactating women. Its release is stimulated by various hormones and neurological stimuli associated with labor and with lactation.
o The intermediate lobe of the pituitary produces endorphins and enkephalins, which are released in response to severe pain or stress and occupy specific endorphin receptor sites in the brainstem to block the perception of pain. These hormones are also produced in peripheral tissues and in other areas of the brain. They are released in response to overactivity of pain nerves, sympathetic stimulation, transcutaneous stimulation, guided imagery, and vigorous exercise.
o The pituitary gland has three lobes:
▪ The anterior lobe produces stimulating hormones in response to hypothalamic stimulation.
▪ The posterior lobe of the pituitary stores ADH and oxytocin, which are two hormones produced by the hypothalamus.
▪ The intermediate lobe of the pituitary produces endorphins and enkephalins to modulate pain perception.
• Common hypothalamic hormones
o Gonadotropin-releasing hormone (GnRH)
o The hypothalamus uses a number of hormones or factors to either stimulate or inhibit the release of hormones from the anterior pituitary. Factors that stimulate the release of hormones are growth hormone–releasing hormone (GHRH), thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH), corticotropin-releasing hormone (CRH), and prolactin-releasing hormone (PRH). Factors that inhibit the release of hormones are somatostatin (growth hormone–inhibiting factor) and prolactin- inhibiting factor (PIF). Not all of these hormones are available for pharmacological use.
o Available hypothalamic-releasing hormones include goserelin (Zoladex) (synthetic GnRH), histrelin (Vantas) (a GnRH used as an antineoplastic agent), leuprolide (Lupron) and nafarelin (Synarel) (potent GnRH agonists that will actually block gonadotropin secretion with continuous use), and tesamorelin (Egrifta) (a GRH analogue used to stimulate the release of growth hormone [GH] from the pituitary). Available antagonists that block the effects of hypothalamic-releasing hormones include cetrorelix (Cetrotide) (GnRH antagonist and fertility drug), degarelix (Firmagon) (blocks GnRH and is used as an antineoplastic agent), and ganirelix acetate (Antagon) (blocks GnRH).
o Therapeutic Actions and Indications
o The hypothalamic hormones are found in such minute quantities that the actual chemical structures of all of these hormones have not been clearly identified. Not all of
the hypothalamic hormones are used as pharmacological agents. A number of the hypothalamic-releasing hormones described here are used for diagnostic purposes only, and others are used primarily as antineoplastic agents. Tesamorelin is used to stimulate GH and its lipolytic effects, helping to decrease the excess abdominal fat in HIV-infected patients with lipodystrophy.
▪ Agonists
• Goserelin, histrelin, leuprolide, and nafarelin are analogues of GnRH.
Following an initial burst of follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH) release, they inhibit pituitary gonadotropin secretion, with a resultant drop in the production of sex hormones. Tesamorelin is an analogue of human GH–releasing factor that stimulates the release of GH from the pituitary. See Table 35.1 for usual indications for each of these agents.
▪ Antagonists
• Cetrorelix, degarelix, and ganirelix acetate are antagonists of GnRH. See
Table 35.1 for usual indications for each of these agents.
o Pharmacokinetics
▪ For the most part, these drugs are absorbed slowly when given intramuscularly (IM), subcutaneously, or in depot form. They tend to have long half-lives of days to weeks. Metabolism is not understood, but it is thought that they are
metabolized 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. Nafarelin is given in a nasal form.
o Contraindications and Cautions
▪ These drugs are contraindicated with known hypersensitivity to any component of the drug because of the risk of hypersensitivity reactions and during pregnancy and lactation 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.
o Adverse Effects
▪ Adverse effects associated with these drugs are related to the stimulation or blocking of regular hormone control. Agonists can lead to increased release of sex hormones, leading to ovarian overstimulation, flushing, increased temperature and appetite, and fluid retention (Fig. 35.2). 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: Leuprolide
Indications: Treatment of advanced prostatic cancer, endometriosis, central precocious puberty, uterine leiomyomata.
Actions: GnRH agonist that occupies pituitary GnRH receptors and desensitizes them; causes an initial increase and then profound decrease in LH and FSH levels.
Adverse Effects: Dizziness, headache, pain, peripheral edema, myocardial infarction, nausea, vomiting, anorexia, constipation, urinary frequency, hematuria, hot flashes, increased sweating.
▪
Prototype Summary: Somatropin
Indications: Long-term treatment of children with growth failure associated with various deficiencies, girls with Turner syndrome, AIDS wasting and cachexia, GH deficiency in adults, and treatment of growth failure in children of small gestational age who do not achieve catch-up growth by 2 years of age.
Actions: Replaces human GH; stimulates skeletal growth, growth of internal organs, and protein synthesis.
Adverse Effects: Development of antibodies to growth hormone, insulin resistance, swelling, joint pain, headache, injection-site pain.
• Growth Hormone Antagonists
o GH hypersecretion is usually caused by pituitary tumors and can occur at any time of life. This is often referred to as hyperpituitarism. If hyperpituitarism occurs before the epiphyseal plates of the long bones fuse, it causes an acceleration in linear skeletal growth, producing gigantism of 7 to 8 ft 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.
o Most conditions of GH hypersecretion are treated by radiation therapy or surgery. Drug therapy for GH excess can be used for those patients who are not candidates for surgery or radiation therapy. The drugs include a dopamine agonist (bromocriptine [Parlodel]), the prototype drug; two somatostatin analogues (octreotide acetate [Sandostatin] and lanreotide [Somatuline Depot]); and a GH analogue (pegvisomant [Somavert]).
▪ Therapeutic Actions and Indications
• Somatostatin is an inhibitory factor released from the hypothalamus. It
is not used to decrease GH levels, though it does do that 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 therapeutic agent. Analogues of somatostatin, octreotide acetate, and lanreotide are considerably more
potent in inhibiting 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 patients 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.
• Lanreotide, which acts like somatostatin, is given as a monthly depot
subcutaneous injection. It also affects insulin growth factor levels and is used long-term for patients with acromegaly who have had no response to or cannot be treated with surgery or radiation.
• Pegvisomant is a GH analogue that was approved for the treatment of
acromegaly in patients who do not respond to other therapies. It binds to GH receptors on cells, inhibiting GH effects. It must be given by daily subcutaneous injections. Table 35.2 shows usual indications for each of these agents. [Show Less]