Pharmacology - Drugs Acting on Endocrine System PDF

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Drugs Actingon EndocrineSystemI. INTRODUCTION TO ENDOCRINE SYSTEMEndocrine system - conjunction with the nervous system working to maintain internal homeostasis and to integrate the body’s response to the external environment - provides communication within the body and helps to regulate growth and ...

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Drugs Acting on Endocrine System

I.

INTRODUCTION TO ENDOCRINE SYSTEM

Endocrine system • conjunction with the nervous system working to maintain internal homeostasis and to integrate the body’s response to the external environment • provides communication within the body and helps to regulate growth and development, reproduction, energy use, and electrolyte balance Glands • organized groups of specialized cells that produce and secrete hormones • do not have ducts, secreting hormones directly to the bloodstream Hormones • chemical messengers, directly into the bloodstream to communicate within the body • all hormones are: o Are produced in very small amounts o Are secreted directly into the bloodstream o Travel through the blood to speci c receptor sites throughout the body o Act to increase or decrease the normal metabolic cellular processes when they react with their speci c receptor sites o Are immediately broken down • can react with receptors on the cell membrane to cause an immediate effect on a cell by altering enzyme systems near the cell membrane or they may enter the cell and react with receptor sites on messenger RNA, which then enters the nucleus and alters cell function. Hypothalamus • coordinating center for the nervous and endocrine responses to internal and external stimuli • “master gland” of the neuroendocrine system - regulate the central and autonomic nervous systems and the endocrine system to maintain homeostasis. • hypothalamus has various neurocenters—areas specifically sensitive to certain stimuli— that regulate a number of body functions, including body temperature, thirst, hunger, water retention, blood pressure, respiration, reproduction, and emotional reactions • hypothalamus is able to in uence, and be in uenced by emotions and thoughts • located at an area poorly protected by blood-brain barrier – thus 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

•

maintains internal homeostasis - by sensing blood chemistries and by stimulating or suppressing endocrine, autonomic, and CNS activity

Produce and secretes releasing hormones • this stimulate the pituitary gland which in turns stimulates or inhibits various endocrine glands throughout the body • connected to pituitary gland by two networks o vascular network - carries the hypothalamic releasing factors directly into the anterior pituitary o neurological network - delivers two other hypothalamic hormones—antidiuretic hormone (ADH) and oxytocin—to the posterior pituitary to be stored • releasing hormones include: growth hormone–releasing hormone (GHRH),thyrotropin-releasing hormone (TRH),gonadotropinreleasing hormone (GnRH), corticotropin-releasing hormone (CRH),and prolactin-releasing hormone (PRH) • two inhibiting factors: growth hormone release–inhibiting factor (somatostatin) and prolactin-inhibiting factor (PIF) o According to research, 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 also is blocked and prolactin levels continue to rise, stimulating breast tissue and milk production.

Pituitary gland • located in the skull in the bony sella turcica under a layer of dura mater • three lobes: anterior, posterior and intermediate lobe • was known as the body’s master gland - through feedback mechanisms, regulates the function of many other endocrine glands o 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 pituitary gland. Anterior Pituitary • six major hormones: growth hormone (GH), adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL),and thyroid-stimulating hormone (TSH,also called thyrotropin) • these hormones are released in a rhythmic manner into the bloodstream • diurnal rhythm – secretion varies in time of the day, begins when 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. 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 hormones are: ADH (also known as vasopressin, and oxytocin) Intermediate Lobe • produces endorphins and enkephalins: released in response to severe pain or stress and occupy speci c endorphin-receptor sites in the brainstem to block the perception of pain

Hypothalamic – Pituitary Axis • hypothalamus and the pituitary function closely to maintain endocrine activity along using a series of negative feedback systems • The hypothalamus secretes releasing factors to cause the anterior pituitary to release stimulating hormones, which act with speci c endocrine glands to cause the release of hormones. • negative feedback system: when the hypothalamus senses a need for a particular hormone, for example, thyroid hormone, it secretes the releasing factor thyrotropin-releasing hormone (TRH) directly into the anterior pituitary. In response to the TRH, the anterior pituitary secretes thyrotropin (TSH), which in turn stimulates the thyroid gland to produce thyroid hormone. When the hypothalamus senses the rising levels of thyroid hormone, it stops secreting TRH, resulting in decreased TSH production and subsequent reduced thyroid hormone levels. The hypothalamus, sensing the falling thyroid hormone levels, secretes TRH again. • Growth hormone and prolactin are released by the anterior pituitary and directly in uence cell activity. These hormones are regulated by the release of the hypothalamic inhibiting factors somatostatin and PIF in response to the levels of the pituitary hormones growth hormone and prolactin. Other forms of regulation Releases

In response to

pancreas

insulin, glucagon, and somatostatin

varying blood glucose levels

parathyroid glands

parathyroid hormone or parathormone

local calcium levels

juxtaglomerular cells in the kidney

erythropoietin and renin

decreased pressure or decreased oxygenation of the blood owing into the glomerulus

Areas of GI tract

GI hormones

local stimuli in areas of the GI tract, such as acid, proteins, or calcium

thyroid gland

calcitonin

serum calcium levels

• When administering any drug that affects the endocrine or nervous systems, it is important for the nurse to remember how closely related all of these activities are. Expected or unexpected adverse effects involving areas of the endocrine and nervous systems often occur. II.

HYPOTHALAMIC AND PITUITARY AGENTS

Hypotalamus ➔ uses a number of hormones or factors to either stimulate or inhibit the release of hormones from the anterior pituitary. Drugs Affecting Hypothalamic Hormones Factors that stimulate the release of hormones: ➔ 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: ➔ Somatostatin (growth hormone–inhibiting factor) ➔ Prolactin-inhibiting factor (PIF) Therapeutic Actions and Indications ➔ 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. ➔ Some hypothalamic releasing hormones described here are used for diagnostic 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 disease (a condition characterized by hypersecretion of adrenocortical hormones in response to excessive ACTH release). ➔ Gonadorelin and Goserelin - are analogues of GnRH. Following an initial burst of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) release, both drugs inhibit pituitary gonadotropin secretion, with a resultant drop in the production of the sex hormones. ➔ Sermorelin (GHRH) - stimulates the production of growth hormone (GH) by the anterior pituitary

Antagonists

➔ Leuprolide - occupies pituitary GnRH receptor sites so that they no longer respond to GnRH. ➔ Nafarelin - is used to decrease the production of gonadal hormones through repeated stimulation of their receptor sites. Pharmacokinetics ➔ Drugs are absorbed slowly when given intramuscularly (IM), subcutaneously (SC), or in depot form. (Nafarelin is given in a nasal form) ➔ Half-lives last days to weeks. ➔ Thought to be metabolized by endogenous hormonal pathways. ➔ Cross the placenta and cross into breast milk. ➔ Mostly excreted in the urine.

Contraindication and Cautions ➔ Hypersensitivity to any component of the drug. ➔ During pregnancy and lactation. ➔ Renal impairment. ➔ Peripheral vascular disorders ➔ Rhinitis when using nafarelin Adverse Effects

➔ Dizziness ➔ Headaches ➔ Peripheral edema ➔ Myocardial infarction ➔ Nausea ➔ Vomiting ➔ Anorexia ➔ Constipation ➔ Urinary frequency ➔ Hematuria ➔ Hot flashes ➔ Increased sweating Drugs Affecting Anterior Pituitary Hormones ➔ Agents that affect pituitary function are used mainly to mimic or antagonize the effects of specific pituitary hormones. ➔ Used either as replacement therapy for conditions resulting from a hypoactive pituitary or for diagnostic purposes. ➔ Antagonist are also available that may be used to block the effects of the anterior pituitary hormones Growth Hormone ➔ Most commonly used pharmacologically ➔ Responsible for: ◆ Linear skeletal growth ◆ Growth of internal organs ◆ Protein synthesis, and the stimulation of many other processes that are required for normal growth. Hypopituitarism ➔ The decreased secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain. ➔ Often seen as GH deficiency before any other signs and symptoms occur. ➔ May occur as a result of: ◆ Developmental abnormalities or congenital defects of the pituitary ◆ Circulatory disturbances ◆ Acute or chronic inflammation of the pituitary, and ◆ Pituitary tumors

Therapeutic Actions and Indications ➔ In clinical practice, the agents that are used purely as a replacement for anterior pituitary hormones are those acting as GH—somatropin and somatropin rDNA origin. Both of these drugs are produced with the use of recombinant DNA technology Pharmacokinetics ➔ Somatropin is injected and reaches peak levels within 7 hours. ➔ Widely distributed in the body and localizes in highly perfused tissues, particularly the liver and kidney. ➔ Excreted in the urine and feces. Contraindications and Cautions ➔ Any known allergy to the drug or ingredients. ➔ Presence of closed epiphyses or with underlying cranial lesions. Adverse Effects ➔ Development of antibodies to GH and subsequent signs of inflammation and autoimmune-type reactions, such as swelling and joint pain, and the endocrine reactions of hypothyroidism and insulin resistance. Clinically Important Drug to Drug Interactions ➔ Any drugs using the cytochrome P450 liver enzyme system. ➔ Abdominal surgery and acute illness secondary to complications of open-heart surgery. ➔ Should be used with caution in pregnancy and lactation. Nursing Considerations for Patients Receiving Drugs Affecting Growth Hormone Agonists Assessment ➔ Assess history of allergy to any GH or binder, presence of closed epiphyses or underlying cranial lesions, serious infection following open-heart surgery, abdominal surgery, and pregnancy or lactation status to determine contraindications to the use of the drug. ➔ Assess height, weight, thyroid function tests, glucose tolerance tests, and GH levels to determine baseline status before beginning therapy and for any potential adverse effects. Diagnosis ➔ Imbalanced Nutrition: Less Than Body Requirements related to metabolic changes. ➔ Acute Pain related to need for injections. ➔ Deficient Knowledge regarding drug therapy. Implementation ➔ Reconstitute the drug following manufacturer’s directions because individual products vary; administer intramuscularly or subcutaneously for appropriate delivery of drug. ➔ Monitor response carefully when beginning therapy to allow appropriate dose adjustments as needed. ➔ Monitor thyroid function, glucose tolerance, and GH levels periodically to monitor endocrine changes and to institute treatment as needed. ➔ Provide thorough patient teaching, including measures to take to avoid adverse effects, warning signs of problems, and the need for regular evaluation (including blood tests) to enhance patient knowledge about 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 patient 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 (patient can name drug, dosage, adverse effects to watch for, and specific measures to avoid them; family members can demonstrate proper technique for preparation and administration of the drug). ➔ Monitor the effectiveness of comfort measures and compliance with the regimen. Growth Hormone Antagonists GH hypersecretion ❖ ❖ ❖ ❖

usually caused by pituitary tumors can occur at any time of life. often referred to as hyperpituitarism If it occurs before the epiphyseal plates of the long bones fuse it causes gigantism of 7 to 8 feet in height with fairly normal body proportions. ❖ 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; occurs after puberty. ❖ GH hypersecretion can treated by drug therapy but often mostly by radiation therapy or surgery The drugs include: ● Dopamine agonist (bromocriptine [Parlodel]) ● Somatostatin analogue (octreotide acetate [Sandostatin]) ● 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, it is not desirable as a therapeutic agent. ❖ An analogue of somatostatin, octreotide acetate, is considerably more potent in inhibiting GH release with less of an inhibitory effect on insulin release. it is used instead of somatostatin. ❖ Bromocriptine, is a dopamine agonist frequently used to treat acromegaly. It may be used alone or as an adjunct to irradiation.

❖ Pegvisomant is a GH analogue that was approved in late 2003 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.

Pharmacokinetics Octreotide must be administered subcutaneously. ➢ The drug is rapidly absorbed and widely distributed throughout the body.I ➢ t is metabolized in the tissues with about 30% excreted unchanged in the urine. Bromocriptine is administered orally ➢ 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 ➢ 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 lactation because of effects on the fetus and because it blocks lactation. ● There are no adequate studies of effects of octreotide and pegvisomant in pregnancy and during lactation. Adverse Effects ● Patients with renal dysfunction may accumulate higher levels of octreotide. ● GI complaints (e.g., constipation or diarrhea, flatulence, and nausea) are not uncommon because of the drug’s effects on the GI tract. ● Octreotide has also been associated with the development of acute cholecystitis, cholestatic jaundice, biliary tract obstruction, and pancreatitis. ● Other, less common adverse effects include headache, sinus bradycardia or other cardiac arrhythmias, and decreased glucose tolerance. ● It can be associated with discomfort and/or inflammation at injection sites. ● Bromocriptine is also associated with GI disturbances. ● Because of its dopamine-blocking effects, it may cause drowsiness and postural hypotension. It blocks lactation and should not be used by nursing mothers. ● Pegvisomant may cause pain and inflammation at the injection site (common). Increased incidence of infection, nausea, and diarrhea and changes in liver function may also occur.

Clinically Important Drug–Drug Interactions ❖ Increased serum bromocriptine levels and increased toxicity occur if it is combined with erythromycin. This combination should be avoided. ❖ The effectiveness of bromocriptine may decrease if it is combined with phenothiazines. ❖ Patients receiving pegvisomant may require higher doses to receive adequate GH suppression if they are also taking opioids. Nursing Considerations for Patients Receiving Growth Hormone Antagonists Assessment: History and Examination ❖ Assess for history of allergy to any GH antagonist or binder to prevent hypersensitivity reactions; other endocrine disturbances, which could be exacerbated when blocking GH; and pregnancy and lactation because of the potential for adverse effects to the fetus and the blocking of lactation. ❖ Assess orientation, affect, and reflexes; blood pressure, pulse, and orthostatic blood pressure; abdominal examination; glucose tolerance tests and GH levels, to determine baseline status before beginning therapy and for any potential adverse effects. Nursing Diagnoses Nursing diagnoses related to drug therapy might include the following: ● ● ● ●

Imbalanced Nutrition: More Than Body Requirements related to metabolic changes Acute Pain related to need for injections (octreotide, pegvisomant) Deficient Knowledge regarding drug therapy Implementation With Rationale Reconstitute octreotide and pegvisomant following manufacturer’s directions; administer these drugs subcutaneously and rotate injection sites regularly to prevent skin breakdown and to ensure proper delivery of the drug. ● Monitor thyroid function, glucose tolerance, and GH levels periodically to detect problems and to institute treatment as needed. ● Arrange for baseline and periodic ultrasound evaluation of the gallbladder if using octreotide to detect any gallstone development and to arrange for appropriate treatment. ● Provide thorough patient teaching, including measures to avoid adverse effects, warning signs of problems, and need for regular evaluation (including blood tests), to enhance patient knowledge about drug therapy and promote compliance. Instruct a family member in proper preparation and administration techniques to ensure that there is another responsible person to administer the drug if needed. Evaluation ● Monitor patient response to the drug (return of GH levels to normal, growth and development). ● Monitor for adverse effects (hypothyroidism, glucose intolerance, nutritional imbalance, GI ...