PHARMACOLOGY

PART 6 Drugs Acting on the Endocrine System

1. Introduction to the Endocrine System

➢ The endocrine system is a regulatory system that communicates through the use of hormones.
➢ Because the endocrine and nervous systems are tightly intertwined in the regulation of body
homeostasis, they are often referred to as the neuroendocrine system.
➢ A hormone is a chemical that is produced within the body, is needed in only small amounts, travels
to specific receptor sites to cause an increase or decrease in cellular activity, and is broken down
immediately.
➢ As the “master gland” of the neuroendocrine system, the hypothalamus helps to regulate the central
and autonomic nervous systems and the endocrine system to maintain homeostasis.
➢ The pituitary is made up of three lobes: anterior, posterior, and intermediate.
o The anterior lobe produces stimulating hormones in response to hypothalamic stimulation.
o The posterior lobe stores two hormones produced by the hypothalamus—ADH and oxytocin.
o The intermediate lobe produces endorphins and enkephalins to modulate pain perception.
➢ The hypothalamus and pituitary operate by a series of negative feedback mechanisms called the HPA.
The hypothalamus secretes releasing factors to cause the anterior pituitary to release stimulating
hormones, which act with specific endocrine glands to cause the release of hormones or, in the case
of GH and PRL, to stimulate cells directly. This stimulation shuts down the production of releasing
factors, which leads to decreased stimulating factors and, subsequently, decreased hormone release.
➢ GH and PRL are released by the anterior pituitary and directly influence cell activity. These hormones
are regulated by the release of hypothalamic inhibiting factors in response to hormone levels or a
cellular mediator.
➢ Some hormones are not influenced by the HPA and are released in response to direct local
stimulation.
➢ When any drug that affects either the endocrine or the nervous system is given, adverse effects may
occur throughout both systems because they are closely interrelated.
 2. Hypothalamic and Pituitary Agents

➢ Hypothalamic releasing factors stimulate the anterior pituitary to release hormones.

➢ The hypothalamic releasing factors are used mostly for diagnostic testing and for treating some forms
of cancer.
➢ Anterior pituitary hormones stimulate endocrine glands or cell metabolism.
➢ GH deficiency can cause dwarfism in children and SDS in adults.
o dwarfism: small stature, resulting from lack of growth hormone in children
➢ GH replacement is done with drugs produced by rDNA processes; these agents are more reliable and
cause fewer problems than drugs used in the past.
➢ GH excess causes gigantism in patients whose epiphyseal plates have not closed and acromegaly in
patients with closed epiphyseal plates.
 o gigantism: response to excess levels of growth hormone before the epiphyseal plates close;
heights of 7 to 8 feet are not uncommon
➢ GH antagonists include octreotide and bromocriptine. Blockage of other endocrine activity may occur
when these drugs are used.
➢ Posterior pituitary hormones are produced in the hypothalamus and stored in the posterior pituitary.
They include oxytocin and ADH.
➢ Lack of ADH produces diabetes insipidus, which is characterized by large amounts of dilute urine and
excessive thirst.
o diabetes insipidus: condition resulting from a lack of antidiuretic hormone, which results in
the production of copious amounts of glucose-free urine
➢ ADH replacement uses desmopressin, an analogue of ADH, which can be administered parenterally
or intranasally.
➢ Vasopressin blockers are used to restore sodium balance in patients with severe hyponatremia.
➢ Fluid balance needs to be monitored when patients are taking drugs that affect ADH.
 3. Adrenocortical Agents

➢ The adrenal medulla is basically a sympathetic nerve ganglion that releases norepinephrine and
epinephrine into the bloodstream in response to sympathetic stimulation.
➢ The adrenal cortex produces three types of corticosteroids: androgens (similar to male sex hormones),
glucocorticoids, and mineralocorticoids.
➢ The corticosteroids are released normally in a diurnal rhythm, with the hypothalamus producing peak
levels of CRH around midnight; peak adrenal response occurs around 9 am. The steroid levels drop
slowly during the day to reach low levels in the evening, when the hypothalamus begins CRH
secretion, with peak levels again occurring around midnight. Corticosteroids are also released as part
of the sympathetic stress reaction to help the body conserve energy for the fight-or-flight response.
➢ Prolonged use of corticosteroids suppresses the normal hypothalamic–pituitary axis and leads to
adrenal atrophy from lack of stimulation. Corticosteroids need to be tapered slowly after prolonged
use to allow the adrenals to resume steroid production.
➢ The glucocorticoids increase glucose production, stimulate fat deposition and protein breakdown, and
inhibit protein formation. They are used clinically to block inflammation and the immune response
and in conjunction with mineralocorticoids to treat adrenal insufficiency.
➢ The mineralocorticoids stimulate retention of sodium and water and excretion of potassium. They are
used therapeutically in conjunction with glucocorticoids to treat adrenal insufficiency.
➢ Adverse effects of corticosteroids are related to exaggeration of the physiological effects; they include
immunosuppression, peptic ulcer formation, fluid retention, and edema.
➢ Corticosteroids are used topically and locally to achieve the desired anti-inflammatory effects at a
particular site without the systemic adverse effects that limit the usefulness of these drugs.
 4. Thyroid and Parathyroid Agents

➢ The thyroid gland uses iodine to produce thyroid hormones. Thyroid hormones control the rate at
which most body cells use energy (metabolism).
➢ Control of the thyroid gland is an intricate among between TRH, released by the hypothalamus; TSH,
released by the anterior pituitary; and circulating levels of thyroid hormone.
➢ Hypothyroidism, or lower-than-normal levels of thyroid hormone, is treated with replacement
thyroid hormone.
➢ Hyperthyroidism, or higher-than-normal levels of thyroid hormone, is treated with thioamides, which
block the thyroid from producing thyroid hormone, or with iodines, which prevent thyroid hormone
production or destroy parts of the gland.
➢ The parathyroid glands are located behind the thyroid gland and produce PTH, which works with
calcitonin, produced by thyroid cells, to maintain the calcium balance in the body.

➢ Hypocalcemia, or low levels of calcium, is treated with vitamin D products and calcium replacement
therapy.
➢ Hypercalcemia and hypercalcemic states include postmenopausal osteoporosis and Paget’s disease,
as well as hypercalcemia related to malignancy.
➢ Hypercalcemia is treated with bisphosphonates or calcitonin. Bisphosphonates slow or block bone
resorption, which lowers serum calcium levels. Calcitonin inhibits bone resorption, lowers serum
calcium levels in children and patients with Paget’s disease, and increases the excretion of phosphate,
calcium, and sodium from the kidney.
 5. Agents to Control Blood Glucose Levels

➢ Glucose is the leading energy source for the human body. Glucose is stored in the body for rapid
release in times of stress. As a result, blood glucose levels can be readily maintained so that the
neurons always receive a constant supply of glucose to function. The body’s control of glucose is
intricately related to fat and protein metabolism, balancing energy conservation with energy
consumption to maintain homeostasis in a variety of situations. Many factors have an impact on this
balance and the body’s ability to adapt and to maintain metabolism.
➢ Diabetes mellitus is the most common metabolic disorder. It is characterized by high blood glucose
levels and alterations in the metabolism of fats, proteins, and glucose.
➢ Glucose control is a complicated process affected by various hormones, enzymes, and receptor sites.
➢ Diabetes mellitus is complicated by many end organ problems. These are related to thickening of
basement membranes and the resultant decrease in blood flow to these areas.
➢ Treatment of diabetes involves control of blood glucose levels using diet and exercise, a combination
of other agents to stimulate insulin release or alter glucose absorption, or the injection of replacement
insulin.
➢ Replacement insulin was once obtained from beef and pork pancreas. Today, replacement insulin is
human, derived from genetically altered bacteria.
➢ The amount and type of insulin given must be regulated daily. Patients taking insulin must learn to
inject the drug, to properly dispose of needles and syringes, to test their blood glucose levels, and to
recognize the signs of hypoglycemia and hyperglycemia.
➢ Insulin is used for type 1 diabetes and for type 2 diabetes in times of stress or when other therapies
have failed.
➢ Other antidiabetic agents include first- and second-generation sulfonylureas, which stimulate the
pancreas to release insulin, and other agents that alter glucose absorption, decrease insulin
resistance, or decrease the formation of glucose. These agents are often used in combination to
achieve effectiveness.
➢ Glucose-elevating agents are used to increase glucose when levels become dangerously low.
Imbalance in glucose levels while taking insulin or oral agents is a common cause of hypoglycemia.
Reference:
Karch, A. M. (2013). Focus on nursing pharmacology. Sixth edition. Philadelphia: Wolters Kluwer.