NURSING 3313 Exam 5 Review-pharm Questions and Answers,100% CORRECT

NURSING 3313 Exam 5 Review-pharm Questions and Answers • Hypothalamus and pituitary o Hypothalamus secretes releasing hormones to the 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. ▪ Pharmacokinetics • Octreotide and lanreotide must be administered subcutaneously. Octreotide is rapidly absorbed and widely distributed throughout the body, and it is metabolized in the tissues with about 30% excreted unchanged in the urine. Lanreotide forms a depot in the subcutaneous tissue and is slowly released into circulation with a half-life of 25 to 30 days. It is metabolized in the tissues and excretion is not known. • Bromocriptine is administered orally and 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 and 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. Because there are no adequate studies of effects of octreotide, lanreotide, and pegvisomant in pregnancy and during lactation, use of these drugs should be reserved for situations in which the benefits to the mother clearly outweigh any potential risks to the fetus or neonate. GH antagonists are contraindicated in the presence of any known allergy to the drug to prevent hypersensitivity reactions. They should be used cautiously in the presence of any other endocrine disorder (e.g., diabetes, thyroid dysfunction) that could be exacerbated by the blocking of GH. ▪ 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 and lanreotide have also been associated with the development of acute cholecystitis, cholestatic jaundice, biliary tract obstruction, and pancreatitis. Patients must be assessed for the possible development of any of these problems. Other less common adverse effects include headache, sinus bradycardia or other cardiac arrhythmias, and decreased glucose tolerance. Because octreotide and lanreotide are administered subcutaneously, they can be associated with discomfort and/or inflammation at injection sites. • Lanreotide is associated with changes in blood glucose levels, and glucose should be followed carefully while on the drug. • 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. If this combination is used, the patient should be monitored carefully. • Patients receiving pegvisomant may require higher doses to receive adequate GH suppression if they are also taking opioids. The mechanism of action of this interaction is not understood. Prototype Summary: Bromocriptine Mesylate Indications: Treatment of Parkinson disease, hyperprolactinemia associated with pituitary adenomas, female infertility associated with hyperprolactinemia, and acromegaly; short-term treatment of amenorrhea or galactorrhea. Actions: Acts directly on postsynaptic dopamine receptors in the brain. Adverse Effects: Dizziness, fatigue, light-headedness, nasal congestion, drowsiness, nausea, vomiting, abdominal cramps, constipation, diarrhea, headache. o • Diabetes insipidus o Caused by deficiency in ADH o Characterized by production of large volumes of dilute urine o Desmopressin and vasopressin are used for treatment o Posterior pituitary disorders that are seen clinically involve ADH release and include diabetes insipidus, which results from insufficient secretion of ADH, and syndrome of inappropriate antidiuretic hormone (SIADH), which occurs with excessive secretion of ADH. Both conditions can now be treated pharmacologically. (See the “Critical Thinking Scenario” related to diabetes insipidus and posterior pituitary hormones.) o Diabetes insipidus is characterized by the production of a large amount of dilute urine containing no glucose. Blood becomes concentrated and blood glucose levels are higher than normal, and the patient presents with polyuria (lots of urine), polydipsia (lots of thirst), and dehydration. With this rare metabolic disorder, patients produce large quantities of dilute urine and are constantly thirsty. Diabetes insipidus is caused by a deficiency in the amount of posterior pituitary ADH and may result from pituitary disease or injury (e.g., head trauma, surgery, tumor). The condition can be acute and short in duration, or it can be a chronic, lifelong problem. o SIADH presents with fluid retention, dilution of the blood and all of the blood elements, and serious issues with water balance and fluid volume. This disorder is now treated with drugs that block the ADH or vasopressin receptors so water is no longer retained and urine is produced, helping to restore water balance. Keeping the fluid balance in check can be tricky, and patients receiving these drugs need to be closely monitored in the hospital. • Thyroid gland o Increases basal metabolic rate o Increases body temperature o Necessary for normal growth and development o Affects CV, respiratory, GI, and neuromuscular function o This chapter reviews drugs that are used to affect the function of the thyroid and parathyroid glands. These two glands are closely situated in the middle of the neck, and they do share a common goal of calcium homeostasis. Serum calcium levels need to be maintained within a narrow range to promote effective blood coagulation, as well as nerve and muscle function. In most respects, however, these glands are different in structure and function. o The thyroid gland is located in the middle of the neck, where it surrounds the trachea like a shield (Fig. 37.1). Its name comes from the Greek words thyros (shield) and eidos (gland). It produces two hormones—thyroid hormone and calcitonin. o Structure and Function ▪ The thyroid is a vascular gland with two lobes—one on each side of the trachea —and a small isthmus connecting the lobes. The gland is made up of cells arranged in circular follicles. The center of each follicle is composed of colloid tissue in which the thyroid hormones produced by the gland are stored. Cells found around the follicle of the thyroid gland are called parafollicular cells (see Fig. 37.1). These cells produce another hormone, calcitonin, which affects calcium levels and acts to balance the effects of the parathyroid hormone (PTH), parathormone. Calcitonin will be discussed later in connection with the parathyroid glands. ▪ The thyroid gland produces two slightly different thyroid hormones, using iodine that is found in the diet: thyroxine, or tetraiodothyronine (T4), so named because it contains four iodine atoms, which is given therapeutically in the synthetic form levothyroxine, and triiodothyronine (T3), so named because it contains three iodine atoms, which is given in the synthetic form liothyronine. The thyroid cells remove iodine from the blood, concentrate it, and prepare it for attachment to tyrosine, an amino acid. A person must obtain sufficient amounts of dietary iodine to produce thyroid hormones. Thyroid hormone regulates the rate of metabolism—that is, the rate at which energy is burned—in almost all the cells of the body. The thyroid hormones affect heat production and body temperature; oxygen consumption and cardiac output; blood volume; enzyme system activity; and metabolism of carbohydrates, fats, and proteins. Thyroid hormone is also an important regulator of growth and development, especially within the reproductive and nervous systems. Because the thyroid has such widespread effects throughout the body, any dysfunction of the thyroid gland will have numerous systemic effects. ▪ When thyroid hormone is needed in the body, the stored thyroid hormone molecule is absorbed into the thyroid cells, where the T3 and T4 are broken off and released into circulation. These hormones are carried on plasma proteins, which can be measured as protein-bound iodine levels. The thyroid gland produces more T4 than T3. More T4 is released into circulation, but T3 is approximately four times more active than T4. Most T4 (with a half-life of about 12 hours) is converted to T3 (with a half-life of about 1 week) at the tissue level. o Control ▪ Thyroid hormone production and release are regulated by the anterior pituitary hormone called thyroid-stimulating hormone (TSH). The secretion of TSH is regulated by thyrotropin-releasing hormone (TRH), a hypothalamic regulating factor. A delicate balance exists among the thyroid, the pituitary, and the hypothalamus in regulating the levels of thyroid hormone. See Chapter 36 for a review of the negative feedback system and the hypothalamic–pituitary axis. The thyroid gland produces increased thyroid hormones in response to increased levels of TSH. The increased levels of thyroid hormones send a negative feedback message to the pituitary to decrease TSH release and, at the same time, to the hypothalamus to decrease TRH release. A drop in TRH levels subsequently results in a drop in TSH levels, which in turn leads to a drop in thyroid hormone levels. In response to low blood serum levels of thyroid • Adrenal gland hormone, the hypothalamus sends TRH to the anterior pituitary, which responds by releasing TSH, which in turn stimulates the thyroid gland to again produce and release thyroid hormone. The rising levels of thyroid hormone are sensed by the hypothalamus, and the cycle begins again. This intricate series of negative feedback mechanisms keeps the level of thyroid hormone within a narrow range of normal o The two adrenal glands are flattened bodies that sit on top of each kidney. Each gland is made up of an inner core called the adrenal medulla and an outer shell called the adrenal cortex. o The adrenal medulla is actually part of the sympathetic nervous system (SNS). It is a ganglion of neurons that releases the neurotransmitters norepinephrine and epinephrine into circulation when the SNS is stimulated. (See Chapter 29 for a review of the SNS.) The secretion of these neurotransmitters directly into the bloodstream allows them to act as hormones, traveling from the adrenal medulla to react with specific receptor sites throughout the body. This is thought to be a backup system for the sympathetic system, adding an extra stimulus to the fight-or-flight response. o The adrenal cortex surrounds the medulla and consists of three layers of cells, each of which synthesizes chemically different types of steroid hormones that exert physiological effects throughout the body. The adrenal cortex produces hormones called corticosteroids. There are three types of corticosteroids: androgens, glucocorticoids, and mineralocorticoids. Androgens are a form of the male sex hormone testosterone; both men and women produce these hormones. They affect electrolytes, stimulate protein production, and decrease protein breakdown. They are used pharmacologically to treat hypogonadism or to increase protein growth and red blood cell production. These hormones are discussed in Chapter 41. • Adrenal excess o Excessive adrenocortical excretion results in a disorder called Cushing disease or Cushing syndrome. This could be the result of an adrenal hyperplasia or tumor, an ACTH- secreting tumor, or an early sign of excessive administration of exogenous steroids. The person with this disorder often presents with a moon-like face, central obesity, hypertension, protein breakdown, and osteoporosis, and females develop hirsutism (Table 36.1). A medication to treat Cushing disease in patients for whom pituitary surgery is not an option is described in Box 36.2. o • Adrenal insufficiency o Some patients experience a shortage of adrenocortical hormones and develop signs of adrenal insufficiency (see Table 36.1). This can occur when a patient does not produce enough ACTH, when the adrenal glands are not able to respond to ACTH, when an adrenal gland is damaged and cannot produce enough hormones (as in Addison disease), or secondary to surgical removal of the glands. o A more common cause of adrenal insufficiency is prolonged use of corticosteroid hormones. When exogenous corticosteroids are used, they act to negate the regular feedback systems (Fig. 36.1). The adrenal glands begin to atrophy because ACTH release is suppressed by the exogenous hormones, so the glands are no longer stimulated to produce or secrete hormones. It takes several weeks to recover from the atrophy caused by this lack of stimulation. To prevent this from happening, patients should receive only short-term steroid therapy and should be weaned slowly from the hormones so that the adrenals have time to recover and start producing hormones again. • Adrenal crisis o Patients who have an adrenal insufficiency may do quite well until they experience a period of extreme stress, such as a motor vehicle accident, a surgical procedure, or a massive infection. Because they are not able to supplement the energy-consuming effects of the sympathetic reaction, they enter an adrenal crisis, which can include physiological exhaustion, hypotension, fluid shift, shock, and even death. Patients in adrenal crisis are treated with massive infusion of replacement steroids, constant monitoring, and life support procedures. • There are two adrenal glands, one on top of each kidney. • Each adrenal gland is composed of the adrenal medulla and the adrenal cortex. • Corticosteroids help the body conserve energy for the fight-or-flight response and help maintain fluid balance. • Prolonged use of corticosteroids suppresses the normal hypothalamic–pituitary axis and leads to adrenal atrophy from lack of stimulation. o Mineralcorticoids ▪ Aldosterone ▪ Regulates plasma volume by promoting Na reabsorption and K excretion by renal tubules ▪ Mineralocorticoids (see Table 36.3) affect electrolyte levels and homeostasis. These steroid hormones directly affect the levels of electrolytes in the system. The classic mineralocorticoid is aldosterone. Aldosterone holds sodium—and with it water—in the body and causes the excretion of potassium by acting on the renal tubule. Aldosterone is no longer available for pharmacological use. Mineralocorticoids that are available include cortisone, fludrocortisone (generic), and hydrocortisone (Cortef). ▪ Therapeutic Actions and Indications • The mineralocorticoids increase sodium reabsorption in renal tubules, leading to sodium and water retention, and increase potassium excretion (see Fig. 36.2). Fludrocortisone is a powerful mineralocorticoid and is preferred for replacement therapy over cortisone and hydrocortisone; it is used in combination with a glucocorticoid. Hydrocortisone and cortisone also exert mineralocorticoid effects at high doses; however, this effect usually is not enough to maintain electrolyte balance in adrenal insufficiency. These drugs are indicated (in combination with a glucocorticoid) for replacement therapy in primary and secondary adrenal insufficiency. They are also indicated for the treatment of salt-wasting adrenogenital syndrome when taken with appropriate glucocorticoids. See Table 36.3 for usual indications for each mineralocorticoid. ▪ Pharmacokinetics • These drugs are absorbed slowly and distributed throughout the body. They undergo hepatic metabolism to inactive forms. They are known to cross the placenta and to enter breast milk. They should be avoided during pregnancy and lactation because of the potential for adverse effects in the fetus or baby. ▪ Contraindications and Cautions • These drugs are contraindicated in the presence of any known allergy to the drug to avoid hypersensitivity reactions; with severe hypertension, heart failure, or cardiac disease because of the resultant increased blood pressure; and with lactation due to potential adverse effects on the baby. Caution should be used in pregnancy because of the potential for adverse effects to the fetus; in the presence of any infection, which will alter adrenal response; and with high sodium intake because severe hypernatremia could occur. ▪ Adverse Effects • Adverse effects commonly associated with the use of mineralocorticoids are related to the increased fluid volume seen with sodium and water retention (e.g., headache, edema, hypertension, heart failure, arrhythmias, weakness) and possible hypokalemia (Fig. 36.3). Allergic reactions, ranging from skin rash to anaphylaxis, have also been reported. ▪ Clinically Important Drug–Drug Interactions • Decreased effectiveness of salicylates, barbiturates, hydantoins, rifampin, and anticholinesterases has been reported when these drugs are combined with mineralocorticoids. Such combinations should be avoided if possible, but if they are necessary, the patient should be monitored closely and the dose increased as needed. Prototype Summary: Fludrocortisone Indications: Partial replacement therapy in cortical insufficiency conditions, treatment of salt- losing adrenogenital syndrome; off-label use: treatment of hypotension Actions: Increases sodium reabsorption in the renal tubules and increases potassium and hydrogen excretion, leading to water and sodium retention Adverse Effects: Frontal and occipital headaches, arthralgia, weakness, increased blood volume, edema, hypertension, heart failure, rash, anaphylaxis ▪ o There are three types of corticosteroids: androgens (discussed in Chapter 14), glucocorticoids, and mineralocorticoids. Not all adrenocortical agents are classified as only glucocorticoids or mineralocorticoids. Hydrocortisone, cortisone, and prednisone have glucocorticoid and some mineralocorticoid activity and affect potassium, sodium, and water levels in the body when present in high levels (Table 36.2). Box 36.3 discusses their use in different age groups. Figure 36.2 displays the sites of action of the glucocorticoids and the mineralocorticoids. Prototype Summary: Prednisone Indications: Replacement therapy in adrenal cortical insufficiency, short-term management of various inflammatory and allergic disorders, hypercalcemia associated with cancer, hematological disorders, ulcerative colitis, acute exacerbations of multiple sclerosis, palliation in some leukemias, trichinosis with systemic involvement Actions: Enters target cells and binds to intracellular corticosteroid receptors, initiating many complex reactions responsible for its antiinflammatory and immunosuppressive effects Adverse Effects: Vertigo, headache, hypotension, shock, sodium and fluid retention, amenorrhea, increased appetite, weight gain, immunosuppression, aggravation or masking of infections, impaired wound healing ▪ GI system and medications (Ch. 56-59) • Digestion o Two parts: alimentary system and accessory organs o GI tract is a long, continuous, hollow tube extending from the mouth to the anus o Accessory organs include: salivary glands, liver, gallbladder, and pancreas o The tube that comprises the GI tract is continuous with the external environment, opening at the mouth and again at the anus. Because of this, the GI tract contains many foreign agents and bacteria that are not found in the rest of the body. These bacteria, the normal flora of the GI tract, have a role in digestion and in protecting the body from other bacteria that might be ingested. The tube begins in the mouth, which has salivary glands that secrete digestive enzymes and lubricants to facilitate swallowing. The mouth leads to the esophagus, which produces mucus to help facilitate movement, which connects to the stomach. The stomach is responsible for mechanical and chemical breakdown of foods into usable nutrients. The stomach empties into the small intestine, where absorption of nutrients occurs. The pancreas deposits digestive enzymes and sodium bicarbonate into the beginning of the small intestine to neutralize the acid from the stomach and to further facilitate digestion. The liver produces bile, which is stored in the gallbladder. Bile is important in the digestion of fats and is deposited into the small intestine when the gallbladder is stimulated to contract by the presence of fats. All of the nutrients absorbed from the small intestine pass into the liver, which is responsible for processing, storing, or clearing them from the system. The small intestine leads to the large intestine, which is responsible for excreting any waste products that are in the GI system. The excretion occurs through the rectum and is an activity that one learns to control. o The peritoneum lines the abdominal wall and also the viscera, with a small “free space” between the two layers. It helps keep the GI tract in place and prevents a buildup of friction with movement. The greater and lesser omenta hang from the stomach over the lower GI tract and are full of lymph nodes, lymphocytes, monocytes, and other components of the immune and inflammatory systems. This barrier provides rapid protection for the rest of the body if any of the bacteria or other foreign agents in the GI tract should be absorbed into the body. • Major activities of the GI system o Secretion: Of enzymes, acid, bicarbonate, and mucus ▪ The GI tract secretes various compounds to aid the movement of the food bolus through the GI tube, to protect the inner layer of the GI tract from injury, and to facilitate the digestion and absorption of nutrients (see Fig. 56.1). Secretions begin in the mouth. Saliva, which contains water and digestive enzymes, is secreted from the salivary glands to begin the digestive process and to facilitate swallowing by making the bolus slippery. ▪ Mucus is also produced in the mouth to protect the epithelial lining and to aid in swallowing. The esophagus produces mucus to protect the inner lining of the GI tract and to further facilitate the movement of the bolus down the tube. ▪ The stomach produces acid and digestive enzymes. In addition, it generates a large amount of mucus to protect the stomach lining from the acid and the enzymes. In the stomach, secretion begins with what is called the cephalic phase of digestion. The sight, smell, or taste of food stimulates the stomach to begin secreting before any food reaches the stomach. Once the bolus of food arrives at the stomach, gastrin is secreted by gastrin cells (G cells), and this is one of the stimulators of acid release. The gastric chief cells will release pepsinogen that can be activated to the enzyme pepsin that breaks down proteins. The parietal cells are responsible for releasing hydrochloric acid. More acid is released with parasympathetic stimulation of the vagal nerve that will secrete acetylcholine. Gastrin from the G cells also stimulates acid release. There are specialized cells called enterochromaffin-like cells (ECL) that secrete gastric histamine. These cells are near the parietal cells, and the histamine that is secreted will diffuse and react with histamine-2 (H2) receptors on the parietal cells, causing the parietal cells to release hydrochloric acid into the lumen of the stomach. Proteins, calcium, alcohol, and caffeine in the stomach increase gastrin secretion. High levels of acid decrease the secretion of gastrin. Epithelial cells are able to secrete mucus to protect the lining of the stomach. Other digestive enzymes are released appropriately in response to proteins and carbohydrates to begin digestion. Peptic ulcers can develop when there is a decrease in the protective mucosal layer or an increase in acid production. ▪ As the now-acidic bolus leaves the stomach and enters the small intestine, secretin is released, which stimulates the pancreas to secrete large amounts of sodium bicarbonate (to neutralize the acid bolus), the pancreatic enzymes chymotrypsin and trypsin (to break down proteins to smaller amino acids), other lipases (to break down fat), and amylases (to break down sugars). These enzymes are delivered to the GI tract through the common bile duct, which is shared with the gallbladder. ▪ If fat is present in the bolus, the gallbladder contracts and releases bile into the small intestine. Bile contains a detergent-like substance that breaks apart fat molecules so that they can be processed and absorbed. The bile in the gallbladder is produced by the liver during normal metabolism. Once delivered to the gallbladder for storage, it is concentrated; water is removed by the walls of the gallbladder. Some people are prone to developing gallstones in the gallbladder when the concentrated bile crystallizes. These stones can move down the duct and cause severe pain or even blockage of the bile duct. ▪ In response to the presence of food, the small and large intestines may secrete various endocrine hormones, including growth hormone, aldosterone, and glucagon. They also secrete large amounts of mucus to facilitate the movement of the bolus through the rest of the GI tract. o Absorption: Of water and almost all of the essential nutrients needed by the body ▪ Absorption is the active process of removing water, nutrients, and other elements from the GI tract and delivering them to the bloodstream for use by the body. The portal system drains all of the lower GI tract, where absorption occurs, and delivers what is absorbed into the venous system directly to the liver. The liver filters, clears, and further processes most of what is absorbed before it is delivered to the body (see Fig. 56.1). Some absorption occurs in the lower end of the stomach, most commonly absorption of water and alcohol. Most absorption occurs in the small intestine. Absorption in the small intestine is about 8,500 mL/d, including nutrients, drugs, and anything that is taken into the GI tract, as well as any secretions. The small intestine mucosal layer is specially designed to facilitate this absorption with long villi on the epithelial layer providing a vast surface area for absorption. The large intestine absorbs approximately 350 mL/d, mostly sodium and water. o Digestion: Of food into usable and absorbable component ▪ Digestion is the process of breaking food into usable, absorbable nutrients. Digestion begins in the mouth, with the enzymes in the saliva starting the process of breaking down sugars and proteins. The stomach continues the digestion process with muscular churning, breaking down some foodstuffs while mixing them thoroughly with hydrochloric acid and enzymes. The acid and enzymes further break down sugars and proteins into building blocks and separate vitamins, electrolytes, minerals, and other nutrients from ingested food for absorption. The beginning of the small intestine introduces bile to the food bolus, which is now called chyme. Bile breaks down fat molecules for processing and absorption into the bloodstream, and the pancreatic enzymes continue the digestion of sugars, proteins, and fats. Digestion is finished at this point, and absorption of the nutrients begins. o Motility: Movement of food and secretions through the system ▪ The GI tract depends on an inherent motility to keep things moving through the system. The nerve plexus maintains a basic electrical rhythm (BER), much like the pacemaker rhythm in the heart. The cells within the plexus are somewhat unstable and leak electrolytes, leading to the regular firing of an action potential. This rhythm maintains the tone of the GI tract muscles and protects the lining of the GI tract from digestive enzymes and other toxins and is affected by local or autonomic stimuli to increase or decrease the rate of firing.g ▪ The basic movement seen in the esophagus is peristalsis, a constant wave of contraction that moves from the top to the bottom of the esophagus. The act of swallowing, a response to a food bolus in the back of the throat, stimulates the peristaltic movement that directs the food bolus into the stomach. The stomach uses its three muscle layers to produce a churning action. This action mixes the digestive enzymes and acid with the food to increase digestion. A contraction of the lower end of the stomach sends the chyme into the small intestine. ▪ The small intestine uses a process of segmentation with an occasional peristaltic wave to clear the segment. Segmentation involves contraction of one segment of the small intestine while the next segment is relaxed. The contracted segment • Peptic ulcer then relaxes, and the relaxed segment contracts. This action exposes the chyme to a vast surface area to increase absorption. The small intestine maintains a BER of 11 contractions per minute. This regular movement is assessed when listening for bowel sounds. ▪ The large intestine uses a process of mass movement with an occasional peristaltic wave. When the beginning segment of the large intestine is stimulated, it contracts and sends a massive peristaltic movement throughout the entire large intestine. The end result of the mass movement is usually excretion of waste products. ▪ Rectal distention after mass movement stimulates a defecation reflex that causes relaxation of the external and internal sphincters. Control of the external sphincter is a learned behavior. The receptors in the external sphincter adapt relatively quickly and will stretch and require more and more distention to stimulate the reflex if the reflex is ignored. o Erosion of the mucosa layer, usually associated with acute inflammation o Lesion located in the stomach or small intestine o Primary cause is Helicobacter pylori (H. pylori) o Erosions in the lining of the stomach and adjacent areas of the GI tract are called peptic ulcers. Ulcer patients present with a predictable description of gnawing, burning pain often occurring a few hours after meals. Many of the drugs that are used to affect GI secretions are designed to prevent, treat, or aid in the healing of these ulcers. The cause of chronic peptic ulcers is not completely understood. For many years, it was believed that ulcers were caused by excessive acid production, and treatment was aimed at neutralizing acid or blocking the parasympathetic system to decrease normal GI activity and secretions. Further research led many to believe that because acid production was often normal in ulcer patients, ulcers were caused by a defect in the mucous lining that coats the inner lumen of the stomach to protect it from digestive enzymes. o The leading cause of peptic ulcers in the United States is the use of NSAIDs. Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit cyclooxygenase receptors, and one of the functions of these sites is the production of the mucous lining in the stomach. A thinner protective coat is more susceptible to the erosive action of acid. Treatment is now aimed at improving the balance between the acid produced and the mucous layer that protects the stomach lining. Currently, it is believed that chronic ulcers may be the result of impaired mucous lining and infection by Helicobacter pylori bacteria. Combination antibiotics have been found to be quite effective in treating some patients with chronic ulcers. o Acute ulcers, or “stress ulcers,” are often seen in situations that involve acute physiological stress, such as trauma, burns, or prolonged illness. The activity of the sympathetic nervous system during stress decreases blood flow to the GI tract, leading to less blood flow to the inner layer of the GI tract and weakening of the mucosal layer of the stomach and erosion by acid in the stomach. Many of the drugs available for treating various peptic ulcers act to alter the acid-producing activities of the stomach to decrease the erosive action. • Proton pump inhibitors (PPIs) o Binds to enzyme that releases acid, thus reducing acid secretion o Used for short term control o Therapy is usually 4 weeks o Ex. Prilosec and Protonix o Should be taken on empty stomach o Do NOT break or chew tablets or capsules o Side effects: HA, nausea, vomiting o Adverse effects: hypersensitivity to the drug o Proton pump inhibitors (see Table 57.1) suppress the secretion of hydrochloric acid into the lumen of the stomach. Six proton pump inhibitors are available: omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), dexlansoprazole (Kapidex), pantoprazole (Protonix), and rabeprazole (Aciphex). o Therapeutic Actions and Indications ▪ The gastric acid pump or proton pump inhibitors suppress gastric acid secretion by specifically inhibiting the hydrogen–potassium adenosine triphosphatase (H+, K+–ATPase) enzyme system on the secretory surface of gastric parietal cells. This action blocks the final step of acid production, lowering the acid levels in the stomach (see Fig. 57.1; Box 57.5). They are recommended for the short-term treatment of active duodenal ulcers, GERD, erosive esophagitis, and benign active gastric ulcer; for the long-term treatment of pathological hypersecretory conditions; as maintenance therapy for healing of erosive esophagitis and ulcers; and in combination with amoxicillin and clarithromycin for the treatment of Helicobacter pylori infection. See Table 57.1 for usual indications for each of these agents. o Pharmacokinetics ▪ Esomeprazole, lansoprazole, and pantoprazole are available in delayed-release oral forms and as IV preparations. Rabeprazole, dexlansoprazole, and omeprazole are available only in delayed-release oral forms. ▪ These drugs are acid-labile and are rapidly absorbed from the GI tract, reaching peak levels in 3 to 5 hours. They undergo extensive metabolism in the liver and are excreted in the urine. Omeprazole is faster acting and more quickly excreted than the other proton pump inhibitors. It has a half-life of 30 to 60 minutes. Esomeprazole is a longer-acting drug; it has a half-life of 60 to 90 minutes and a duration of 17 hours. It is not broken down as rapidly in the liver as the parent drug omeprazole. Lansoprazole has a half-life of 2 hours and a duration of 12 hours. ▪ Pantoprazole and rabeprazole have half-lives of 90 minutes and durations of 12 to 14 hours. Dexlansoprazole is available in a delayed capsule that offers two releases, having peak effects in 1 to 2 hours and then 4 to 5 hours, offering longer protection throughout the day. There are no adequate studies about whether these drugs cross the placenta or enter breast milk. o Contraindications and Cautions ▪ These drugs are contraindicated in the presence of known allergy to either the drug or the drug components to prevent hypersensitivity reactions. Caution should be used in pregnant or lactating women because of the potential for adverse effects on the fetus or neonate. The safety and efficacy of these drugs have not been established for patients younger than 18 years of age, except for lansoprazole, which is the proton pump inhibitor of choice if one is needed for a child. o Adverse Effects ▪ The adverse effects associated with these drugs are related to their effects on the H+, K+–ATPase pump on the parietal and other cells. CNS effects of dizziness and headache are commonly seen; asthenia (loss of strength), vertigo, insomnia, apathy, and dream abnormalities may also be observed. GI effects can include diarrhea, abdominal pain, nausea, vomiting, dry mouth, and tongue atrophy. Upper respiratory tract symptoms, including cough, stuffy nose, hoarseness, and epistaxis, are frequently seen (Fig. 57.2). Other less common adverse effects include rash, alopecia, pruritus, dry skin, back pain, and fever. In preclinical studies, long-term effects of proton pump inhibitors included the development of gastric cancer. Recent studies show an increase in bone loss and decreased calcium levels, decreased magnesium levels leading to hypertension, and increased incidence of Clostridium difficile diarrhea and pneumonia in patients using these drugs long term. These effects are thought to be related to changing the normal acidity in the stomach that changes the environment for absorbing calcium or magnesium and the environment of normal flora bacteria, which can lead to infection from those previously friendly bacteria. o Clinically Important Drug–Drug Interactions ▪ There is a risk of increased serum levels and increased toxicity of benzodiazepines, phenytoin, and warfarin if these are combined with these drugs; patients should be monitored closely. Decreased levels of ketoconazole and theophylline have been reported when combined with these drugs, leading to loss of effectiveness. Sucralfate is not absorbed well in the presence of these drugs, and doses should be spaced at least 30 minutes apart if this combination is used. There has been some evidence of increased risk of CV events if proton pump inhibitors are combined with clopidogrel due to possible interference with the effectiveness of clopidogrel’s antiplatelet mechanism of action. Therefore, the combination of these medications should be avoided when possible o • H2 receptor antagonists o Suppress parietal cell acid secretion o H2 antagonists (Table 57.1) block the release of hydrochloric acid in response to gastrin. These drugs include cimetidine (Tagamet HB), ranitidine (Zantac), famotidine (Pepcid), and nizatidine (Axid). o Available OTC o Ex. Zantac (ranitidine) ▪ Side effects are minimal ▪ Contraindicated with hypersensitivity ▪ B12 deficiency may occur with long term use o Therapeutic Actions and Indications ▪ The H2 antagonists selectively block H2 receptors located on the parietal cells. Blocking these receptors prevents about 70% of the hydrochloric acid release from the parietal cells. This action also decreases pepsin production by the chief cells. H2 receptor sites are also found in the heart, and high levels of these drugs can produce cardiac arrhythmias (see “Adverse Effects”). ▪ These drugs are used in the following conditions: • Short-term treatment of active duodenal ulcer or benign gastric ulcer (reduction in the overall acid level can promote healing and decrease discomfort) • Treatment of pathological hypersecretory conditions such as Zollinger- Ellison syndrome (blocking the overproduction of hydrochloric acid that is associated with these conditions) • Prophylaxis of stress-induced ulcers and acute upper GI bleeding in critical patients (blocking the production of acid protects the stomach lining, which is at risk because of decreased mucus production associated with extreme stress) • Treatment of erosive gastroesophageal reflux (decreasing the acid being regurgitated into the esophagus will promote healing and decrease pain) • Relief of symptoms of heartburn, acid indigestion, and sour stomach (OTC preparations) o Pharmacokinetics ▪ Cimetidine, ranitidine, and famotidine are available in oral and parenteral forms. Nizatidine is available only in oral form. Cimetidine was the first drug in this class to be developed. It has been associated with antiandrogenic effects, including gynecomastia and galactorrhea. It reaches peak levels in 1 to 1.5 hours and is metabolized mainly in the liver; it can slow the metabolism of many other drugs that use the same metabolizing enzyme system. It is excreted in the urine. It has a half-life of 2 hours and is known to cross the placenta and enter breast milk. ▪ Ranitidine, which is longer-acting and more potent than cimetidine, is not as associated with the antiandrogenic adverse effects or the marked slowing of metabolism in the liver as cimetidine is. It reaches peak levels in 5 to 15 minutes when given parenterally and 1 to 3 hours when given orally. It has a duration of 8 to 12 hours and a half-life of 2 to 3 hours. Ranitidine is metabolized by the liver and excreted in urine. It crosses the placenta and enters breast milk. ▪ Famotidine is similar to ranitidine, but it is much more potent than either cimetidine or ranitidine. It reaches peak effects in 1 to 3 hours and has a duration of 6 to 15 hours. Famotidine is metabolized in the liver and excreted in the urine with a half-life of 2.5 to 3.5 hours. Famotidine crosses the placenta and enters breast milk. Famotidine is approved for use in children aged 1 to 16 years old. ▪ Nizatidine, the newest drug in this class, is similar to ranitidine in its effectiveness and adverse effects. It differs from the other three drugs in that it is eliminated by the kidneys with no first-pass metabolism in the liver. It is the drug of choice for patients with liver dysfunction and for those who are taking other drugs whose metabolism is slowed by the hepatic activity of the other three H2 antagonists. It reaches peak effects in 0.5 to 3 hours and has a half-life of 1 to 2 hours. Like the other three drugs, it crosses the placenta and enters the breast milk. o Contraindications and Cautions ▪ The H2 antagonists should not be used with known allergy to any drugs of this class to prevent hypersensitivity reactions. Caution should be used during pregnancy or lactation because of the potential for adverse effects on the fetus or nursing baby and with hepatic or renal dysfunction, which could interfere with drug metabolism and excretion. (Hepatic dysfunction is not as much of a problem with nizatidine.) Care should also be taken if prolonged or continual use of these drugs is necessary because they may be masking serious underlying conditions. o Adverse Effects ▪ The adverse effects most commonly associated with H2 antagonists include GI effects of diarrhea or constipation; CNS effects of dizziness, headache, somnolence, confusion, or even hallucinations (thought to be related to possible H2 receptor effects in the CNS); cardiac arrhythmias and hypotension (related to H2 cardiac receptor blocking, more commonly seen with IV or IM administration or with prolonged use); and gynecomastia (more common with long-term use of cimetidine) and impotence. o Clinically Important Drug–Drug Interactions ▪ Cimetidine, famotidine, and ranitidine can slow the metabolism of the following drugs, leading to increased serum levels and possible toxic reactions: warfarin anticoagulants, phenytoin, beta-adrenergic blockers, alcohol, quinidine, lidocaine, theophylline, chloroquine, benzodiazepines, nifedipine, pentoxifylline, tricyclic antidepressants (TCAs), procainamide, and carbamazepine. There is a risk of increased salicylate levels if nizatidine is taken with aspirin. o • Antacids o Alkaline, nonorganic compounds of aluminum, magnesium, sodium, or calcium o Do not promote healing of the ulcer o Available OTC in liquid or chewable form o Ex. Tums, Milk of Magnesia, Alka-Seltzer o Adverse effects: nausea, vomiting, constipation, flatulence, distention o Contraindication: suspected bowel obstruction o Antacids (see Table 57.1) are a group of inorganic chemicals that neutralize stomach acid. Antacids are available OTC, and many patients use them to self-treat a variety of GI symptoms. There is no one perfect antacid (see “Adverse Effects”). The choice of an antacid depends on adverse effects and absorption factors. Available agents are sodium bicarbonate (Bell-ans), calcium carbonate (Oystercal, Tums, and others), magnesium salts (Milk of Magnesia and others), and aluminum salts (Amphojel and others). o Therapeutic Actions and Indications ▪ Antacids neutralize stomach acid by direct chemical reaction (see Fig. 57.1). They are recommended for the symptomatic relief of upset stomach associated with hyperacidity, as well as the hyperacidity associated with peptic ulcer, gastritis, peptic esophagitis, gastric hyperacidity, and hiatal hernia. See Table 57.1 for usual indications for each antacid. o Pharmacokinetics ▪ Sodium bicarbonate, the oldest drug in this group, is readily available in many preparations, including baking soda powder, tablets, solutions, and as an injectable for treating systemic acidosis. This drug is widely distributed when absorbed orally, reaching peak levels in 1 to 3 hours, crossing the placenta, and entering breast milk. It is excreted in the urine and can cause serious electrolyte imbalance in people with renal impairment. ▪ Calcium carbonate is actually precipitated chalk and is available in tablet and powder forms. The main drawbacks to this agent are constipation and acid rebound. It has an onset of action in about 3 to 5 minutes. It can be absorbed systemically and cause calcium imbalance. When absorbed, it is metabolized in the liver and excreted in the urine and feces with a half-life of 1 to 3 hours. Calcium carbonate is known to cross the placenta and enter breast milk. ▪ Magnesium salts are effective in buffering acid in the stomach but have been known to cause diarrhea; they are sometimes used as laxatives. They are available as tablets, chewable tablets, capsules, and liquid forms. Although these agents are not generally absorbed systemically and are excreted in the feces, magnesium can lead to nerve damage and even coma if absorbed; it is excreted in the urine. ▪ Aluminum salts, available as tablets, capsules, suspensions, and liquid form, do not cause acid rebound but are not very effective in neutralizing acid. They are bound in the feces for excretion. They have been related to severe constipation. Aluminum binds dietary phosphates and causes hypophosphatemia, which can then cause calcium imbalance throughout the system. ▪ Many of these antacids are available in combination forms to take advantage of the acid-neutralizing effect and block adverse effects. For example, a combination of calcium and aluminum salts (Maalox) buffers acid and produces neither constipation nor diarrhea. o Contraindications and Cautions ▪ Antacids are contraindicated in the presence of any known allergy to antacid products or any component of the drug to prevent hypersensitivity reactions. Caution should be used in the following instances: any condition that can be exacerbated by electrolyte or acid–base imbalance to prevent exacerbations and serious adverse effects; any electrolyte imbalance, which could be exacerbated by the electrolyte-changing effects of