This protects the mu- SELECTED REFERENCES cosa of the small intestine from the digestive properties of Guyton order levitra extra dosage 60mg free shipping sleeping pills erectile dysfunction, A order levitra extra dosage 60 mg on-line circumcision causes erectile dysfunction. Pathophysiology: Concepts of altered health cretion of pancreatic juices. Discuss significant drug–drug interactions with disease and gastroesophageal reflux disease. Describe characteristics, uses, and effects of peptic ulcers and acid reflux disorders. Teach clients nonpharmacologic measures to the-counter uses of histamine-2 receptor manage peptic ulcers and gastroesophageal blocking agents. Greenspan, a 26-year-old homemaker, has rheumatoid arthritis that has been treated with aspirin, nonsteroidal anti-inflammatory drugs, and prednisone for the last 10 years. She is dizzy when getting up and has had one episode of syncope (fainting). How symptoms of weakness, dizziness, and syncope are associated with a peptic ulcer. What therapies (drugs and nondrugs) can be used to prevent a recurrence of her ulcer. OVERVIEW intestinal (GI) mucosa that are exposed to gastric acid and pepsin. Gastric and duodenal ulcers are more common then Drugs to prevent or treat peptic ulcer and acid reflux dis- esophageal ulcers. To aid understanding structive mechanisms or decreased protective mechanisms). Gastric acid, a strong acid that can digest the stom- ach wall, is secreted by parietal cells in the mucosa of the PEPTIC ULCER DISEASE stomach antrum, near the pylorus. The parietal cells contain re- ceptors for acetylcholine, gastrin, and histamine, substances Peptic ulcer disease is characterized by ulcer formation that stimulate gastric acid production. Acetylcholine is released in the esophagus, stomach, or duodenum, areas of the gastro- by vagus nerve endings in response to stimuli, such as thinking 867 868 SECTION 10 DRUGS AFFECTING THE DIGESTIVE SYSTEM BOX 60–1 SELECTED UPPER GASTROINTESTINAL DISORDERS Gastritis sis, burns, acute respiratory distress syndrome, major surgical pro- Gastritis, a common disorder, is an acute or chronic inflammatory cedures, or other severe illnesses. Stress ulcers are usually manifested by cers usually also have gastritis. Acute gastritis (also called gas- painless upper gastrointestinal (GI) bleeding. The frequency of oc- tropathy) usually results from irritation of the gastric mucosa by currence has decreased, possibly because of prophylactic use of such substances as alcohol, aspirin or other nonsteroidal anti- antacids and antisecretory drugs and improved management of inflammatory drugs (NSAIDs), and others. Chronic gastritis is sepsis, hypovolemia, and other disorders associated with critical usually caused by H. Acidosis increases severity Nonsteroidal Anti-inflammatory Drug Gastropathy of lesions, and correction of acidosis decreases their formation. In NSAID gastropathy indicates damage to gastroduodenal mucosa addition, lesions do not form if the pH of gastric fluids is kept by aspirin and other NSAIDs. Many people take NSAIDs daily for Zollinger-Ellison Syndrome pain, arthritis, and other conditions. Chronic ingestion of NSAIDs Zollinger-Ellison syndrome is a rare condition characterized by causes local irritation of gastroduodenal mucosa, inhibits the syn- excessive secretion of gastric acid and a high incidence of ulcers. Approximately two thirds of the gastrinomas are and mucus, and maintaining mucosal blood flow), and increases malignant. Symptoms are those of peptic ulcer disease, and diag- the synthesis of leukotrienes and possibly other inflammatory sub- nosis is based on high levels of serum gastrin and gastric acid. Treatment may involve long-term use of a proton pump inhibitor to diminish gastric acid, or surgical excision. Stress Ulcers Stress ulcers indicate gastric mucosal lesions that develop in pa- tients who are critically ill from trauma, shock, hemorrhage, sep- about or ingesting food. Gastrin is a hormone released by cells Cell-protective effects (eg, secretion of mucus and bi- in the stomach and duodenum in response to food ingestion and carbonate, dilution of gastric acid by food and secretions, stretching of the stomach wall. It is secreted into the blood- prevention of diffusion of hydrochloric acid from the stom- stream and eventually circulated to the parietal cells. Histamine ach lumen back into the gastric mucosal lining, the presence is released from cells in the gastric mucosa and diffuses into of prostaglandin E, alkalinization of gastric secretions by nearby parietal cells. An enzyme system (hydrogen–potassium pancreatic juices and bile, and perhaps other mechanisms) adenosine triphosphatase, or H+, K+-ATPase) catalyzes the pro- normally prevent autodigestion of stomach and duodenal duction of gastric acid and acts as a gastric acid (proton) pump tissues and ulcer formation. When Pepsin is a proteolytic enzyme that helps digest protein superficial lesions heal, no defects remain. Pepsin is derived cle heals, however, scar tissue remains and the mucosa that re- from a precursor called pepsinogen, which is secreted by generates to cover the scarred muscle tissue may be defective. Pepsinogen is converted to These defects contribute to repeated episodes of ulceration. Gastric ulcers (which may be mucosa of most clients with chronic gastritis, about 75% of preceded by less severe mucosal defects such as erosions or clients with gastric ulcers, and more than 90% of clients with gastritis) are often associated with stress (eg, major trauma or duodenal ulcers.

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After transplantation discount levitra extra dosage 40mg amex erectile dysfunction desi treatment, it takes 2 to 4 weeks for the prophylactic antibacterials that are effective against Staphy- engrafted bone marrow cells to mature and begin producing lococcus aureus (eg purchase levitra extra dosage 60mg visa best erectile dysfunction pills treatment, nafcillin, vancomycin). During this time, the client has virtually no Oprelvekin may be used to prevent or treat thrombocy- functioning granulocytes and is at high risk for infection. Sargramostim promotes engraftment and function of the transplanted bone marrow, thereby decreasing risks of in- fection. If the graft is successful, the granulocyte count Interferons starts to rise in approximately 2 weeks. Sargramostim also In hairy cell leukemia, interferons normalize WBC counts in is used to treat graft failure. In stem cell transplantation, filgrastim or sargramostim is Drug therapy must be continued indefinitely to avoid relapse, used to stimulate the movement of hematopoietic stem cells which usually develops rapidly after the drug is discontinued. Transplantation of large numbers of stem Nursing Notes: Apply Your Knowledge cells can lead to more rapid engraftment and recovery, with less risk of transplant failure and complications. Last month, the nadir lasted for Use in Children 6 days, during which his neutrophil count was less than 1000/mm3. This month he is given filgrastim (granulocyte colony-stimulat- There has been limited experience with hematopoietic and ing factor [G-CSF]). Why is the G-CSF given, and how will you immunostimulant drugs in children (younger than 18 years of evaluate its effectiveness? Filgrastim and sargramostim have been used pairment may delay elimination of other medications and in- in children with therapeutic and adverse effects similar to crease risks of adverse effects. In clinical trials, filgrastim produced a greater incidence of subclinical spleen enlargement in chil- dren than in adults, but whether this affects growth and Use in Hepatic Impairment development or has other long-term consequences is un- known. Oprelvekin has been given to a few children with In some clients with preexisting hepatic impairment, sar- adverse effects similar to those observed in adults. Val- indicate that tachycardia occurs more often in children and ues declined to baseline levels when the drug was stopped or that larger doses are needed (eg, a dose of 75 to 100 mcg/kg its dosage reduced. Hepatic function tests are recommended in children produces similar plasma levels to a dose of every 2 weeks in clients with preexisting impairment. Long-term effects on growth and de- With aldesleukin, hepatic impairment occurs during ther- velopment are unknown. This impairment may be increased if other hepatotoxic Little information is available about the use of interferons in drugs are taken concomitantly. Interferon alfacon-1 (Infergen) is not recommended patic impairment may delay metabolism and elimination of for use in children. Interfer- ons alfa-2b, alfacon-1, and alfa-n1 are contraindicated in Use in Older Adults clients with decompensated liver disease (ie, signs and symp- toms such as jaundice, ascites, bleeding disorders, or de- In general, hematopoietic and immunostimulant agents have creased serum albumin), autoimmune hepatitis, a history of the same uses and responses in older adults as in younger adults. Worsening of liver disease, with jaundice, hepatic adverse effects, especially if large doses are used. Oprelvekin encephalopathy, hepatic failure, and death, has occurred in should be used with caution in clients with a history of or risk these clients. The drugs should be discontinued in clients with factors for atrial fibrillation or flutter; these arrhythmias oc- signs and symptoms of liver failure. In addition, older adults are more likely to have fluid retention, with resultant symptoms of peripheral edema, dyspnea on ex- Home Care ertion, and dilutional anemia. Darbepoetin alfa (Aranesp), epoetin alfa (Epogen), filgrastim (Neupogen, Neulasta), oprelvekin (Neumega), and the inter- Use in Renal Impairment ferons are often self-administered or given by a caregiver to chronically ill clients. The home care nurse may need to teach Except for darbepoetin alfa and epoetin alfa, which are used to clients or caregivers accurate drug preparation and injection treat anemia in clients with chronic renal failure, little informa- techniques, as well as proper disposal of needles and sy- tion is available about the use of hematopoietic and immuno- ringes. Assistance may also be needed in obtaining appropri- stimulant drugs in clients with renal impairment. Renal function tests For example, epoetin alfa is not effective unless sufficient are recommended every 2 weeks in clients with preexisting iron is present, and most clients need an iron supplement. When an iron preparation is prescribed, the home care nurse With aldesleukin, renal impairment occurs during therapy. With fil- This impairment may be increased if other nephrotoxic drugs grastim, the nurse may need to help the client and family with are taken concomitantly. In addition, drug-induced renal im- techniques to reduce exposure to infection. CHAPTER 44 HEMATOPOIETIC AND IMMUNOSTIMULANT DRUGS 667 NURSING Hematopoietic and Immunostimulant Agents ACTIONS NURSING ACTIONS RATIONALE/EXPLANATION 1. Administer accurately For hospitalized clients, the drugs may be prepared for adminis- tration in a pharmacy. Give darbepoetin alfa intravenously (IV) or subcutaneously Outpatients may be taught self-administration techniques. Give epoetin alfa IV or SC; do not shake the vial; and dis- For clients with chronic renal failure on hemodialysis, epoetin alfa card any remainder of multidose vials 21 d after opening. For patients with- out an IV line or who are ambulatory, the drug is injected SC. Shaking can inactivate the medication; the manufacturer does not ensure sterility or stability of multidose vials after 21 days. With aldesleukin, review institutional protocols or the man- This drug has limited uses and is rarely given.

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Teach clients order levitra extra dosage 60 mg on line erectile dysfunction treatment boston medical group, family members generic 60 mg levitra extra dosage overnight delivery erectile dysfunction utah, or caretakers influence drug therapy of eye disorders. Use correct techniques to administer ophthalmic scribed to protect and preserve eyesight. Assess for ocular effects of systemic drugs and systemic effects of ophthalmic drugs. Critical Thinking Scenario Jean Green, a 40-year-old accountant, has made an appointment to have her eyes examined because she has been having difficulty reading small print. When she arrives at the office, you explain that the examination will include using medications to dilate her eyes and a test for glaucoma. Which drugs are used to dilate the eyes for examination, and how they work. When the conjunctiva is irritated or certain emotions are experienced (eg, sadness), the The eye is the major sensory organ through which the per- lacrimal gland produces more fluid than the drainage son receives information about the external environment. The excess fluid overflows Extensive discussion of vision and ocular anatomy is beyond the eyelids and becomes tears. The sclera is a white, opaque, fibrous tis- • The eyelids and lacrimal system function to protect the sue that covers the posterior five sixths of the eyeball. The eyelid is a covering that acts as a barrier to the The cornea is a transparent, special connective tissue entry of foreign bodies, strong light, dust, and other po- that covers the anterior sixth of the eyeball. The canthi (singular, canthus) are blood vessels and connective tissue, continues forward the angles where the upper and lower eyelids meet. The iris is composed of pigmented The lacrimal system produces a fluid that constantly cells, the opening called the pupil, and muscles that moistens and cleanses the anterior surface of the eye- control the size of the pupil by contracting or dilating ball. The fluid drains through two small openings in the in response to stimuli. The retina is the innermost inner canthus and flows through the nasolacrimal duct layer of the eyeball. The most common type of glaucoma is called primary Light rays do not travel directly to the retina. Its etiology is unknown, but contribut- they are deflected in various directions according to the ing factors may include advanced age, a family history of density of the ocular structures through which they pass. In addition, the inci- is the area of the retina where ophthalmic blood vessels dence of glaucoma in African Americans is about three times and the optic nerve enter the eyeball. Closed-angle glau- • The structure and function of the eyeball are further in- coma is usually an acute situation requiring emergency fluenced by the lens, aqueous humor, and vitreous body. It may occur when pupils are dilated and the outflow The lens is an elastic, transparent structure; its function of aqueous humor is blocked. Darkness and drugs with anti- is to focus light rays to form images on the retina. It is cholinergic effects (eg, atropine, antihistamines, tricyclic anti- located behind the iris and held in place by suspensory depressants) may dilate the pupil, reduce outflow of aqueous ligaments attached to the ciliary body. Most of the fluid flows through the pupil into the anterior chamber (between the cornea and the lens Inflammatory or Infectious Conditions and anterior to the iris). Infections may result from production and drainage of aqueous humor are approx- foreign bodies, contaminated hands, contaminated eye med- imately equal, and normal intraocular pressure (<21 mm ications, or infections in contiguous structures (eg, nose, face, Hg) is maintained. Common inflammatory and infectious disorders causes increased intraocular pressure. The vitreous body include the following: is a transparent, jelly-like mass located in the posterior • Conjunctivitis is a common eye disorder that may be portion of the eyeball. It functions to refract light rays caused by allergens (eg, airborne pollens), bacterial or and maintain the normal shape of the eyeball. Symp- toms include redness, tearing, itching, edema, and burn- ing or gritty sensations. Bacterial conjunctivitis is often DISORDERS OF THE EYE caused by Staphylococcus aureus, Streptococcus pneu- moniae, or Haemophilus influenzae and produces mu- The eye is subject to the development of many disorders that copurulent drainage. Conjunctivitis with a purulent threaten its structure, function, or both. Some disorders in discharge is most often caused by the gonococcus; which ophthalmic drugs play a prominent role are discussed corneal ulcers and scarring may result. A hordeolum (commonly called Refractive Errors a stye) is often associated with blepharitis. Refractive errors include myopia (nearsightedness), hyper- • Keratitis (inflammation of the cornea) may be caused opia (farsightedness), presbyopia, and astigmatism. Ophthalmic drugs are used major symptom is pain, which ranges from mild to se- only in the diagnosis of the conditions; treatment involves vere.

Crossed monau- ral pathways are shown in black; binaural pathways are indicated in gray levitra extra dosage 40mg erectile dysfunction vacuum pump medicare. CN discount 60 mg levitra extra dosage with mastercard erectile dysfunction treatment toronto, cochlear nucleus; DNLL, dorsal nucleus of the lateral lemniscus; IC, inferior colliculus; SOC, superior olivary complex; INLL, inter- mediate nucleus of the lateral lemniscus; VNLLc, ventral nucleus of the lateral lemniscus, columnar divi- sion; VNLLm, ventral nucleus of the lateral lemniscus, multipolar cell division (from Covey, 2001). A great deal is known about the function of brain molecules, especially those involved in neuro- Brain Parts on Multiple Scales 71 transmission and neuromodulation. These classes of molecules include neurotrans- mitters, receptors, second messengers, ion channel subunits, etc. Although perhaps not directly relevant to the theme of this book, replacement of brain molecules through pharmacology, transplantation of cells, or gene therapy is clearly an area in which the strategy of replacement has met with considerable success and is likely to be a major area of research and development for therapeutic treatments in the future. Thus, replacement of a molecule is likely to a¤ect global aspects of brain function as well as specific ones. Here we will consider just two examples of molecules that are distributed rather ubiquitously within the central nervous system but that are es- sential for proper auditory system function on a cellular, circuit, and global level. Inhibitory Neurotransmitters, g-Aminobutyric Acid and Glycine Throughout the central auditory system, a large number of neurons synthesize and release g-aminobutyric acid (GABA). Below the level of the midbrain, there are not only many GABAergic neurons, but also many neurons that synthesize and release glycine (e. Thus, cells in structures up through the auditory midbrain center, the inferior col- liculus (IC), may receive two di¤erent types of inhibitory input, each of which pre- sumably serves a di¤erent function. Moreover, the same neurotransmitter may serve both a specific and a global function at any given neuron. The function of GABA in the IC provides a good example of this principle. The mammalian IC contains a higher density of GABAergic terminals and recep- tors than any other part of the brain except the cerebellum (e. The IC contains both GABAa receptors, which provide rapid, short-acting inhibition, and GABAb receptors, which provide delayed, long- acting inhibition. Activation of these two receptor types by GABA release may be one of the factors that provide a restricted temporal window during which ongoing excitatory input can depolarize a cell to threshold, with GABAa activation limiting the early part of the response and GABAb activation limiting the late part of the re- sponse. The characteristics of the window during which excitation may occur would be expected to vary as a function of the relative proportions of the two receptor types on the cell membrane. There is evidence that individual IC neurons not only possess GABAa and GABAb receptors in di¤erent ratios, but that they also receive varying amounts of glycinergic inhibition. Moreover, electrophysiological studies show that the di¤erent 72 Ellen Covey Figure 4. Studies of IC neurons in which GABAa receptors are blocked by bicuculline show that the magnitude and duration of sound-evoked responses greatly increase, suggesting that long-lasting GABAergic input normally suppresses a long-lasting excitatory input to the cell. In the same neuron, blocking glycinergic input with strychnine typically causes first-spike latency to decrease and total spike count to increase, but the dura- tion of the response remains short (Casseday et al. These findings suggest that glycine acts mainly to suppress responses to the early part of a pro- longed sound-evoked excitatory input, whereas GABA suppresses responses to a large portion of the sound-evoked excitation, especially the later part. These findings Brain Parts on Multiple Scales 73 are consistent with the idea that there is a narrow temporal window within which the cell can respond to a sustained excitatory input. Because di¤erent inputs to the IC neuron have di¤erent thresholds, rate-intensity functions, frequency tuning, spatial tuning, and other properties, the temporal relationship among the multiple excitatory and inhibitory inputs to an IC neuron changes parametrically as a function of physical parameters of the sound, such as its intensity or duration. This variable relationship is important for creating selectiv- ity to behaviorally relevant sound features such as its duration (e. There is a large body of evidence indicating that inhibitory neurotransmitters are involved in the specific processing mechanisms that allow auditory midbrain neurons to select specific types of information for transmission to the thalamocortical system and/or motor systems (e. However, it is likely that the massive amount of inhibition in the IC also serves some more global functions. One of these has to do with slowing the cadence of processing from that of the inputs from lower centers that are time locked to the fine structure of the stimulus to a slower rate that is matched to the rate at which motor actions are performed (Casse- day and Covey, 1996). A second global function has to do with keeping the amount of excitation that reaches the IC in check. In the lower brainstem, the auditory nerve diverges to create a number of di¤erent parallel pathways, all of which then converge at the IC (figure 4. If the outputs of all of these pathways were excitatory, the activity arriving via the auditory nerve would be amplified many times over. It seems reasonable to sup- pose that inhibition helps maintain the amount of neural activity at a relatively con- stant level while allowing the IC to integrate many streams of information processed in parallel. Evidence to support this idea comes from studies of audiogenic seizures, which can occur when there is an abnormally high amount of activity in the IC that is due to a pharmacologically or genetically induced deficit in GABAergic inhibition (e. However, GABA also plays a specific role at each neuron that depends on the precise ratio and timing of GABAergic input rel- ative to other inputs, as well as the adjustment of this ratio and timing according to the physical parameters of the stimulus.

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