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Home-Study Continuing Pharmacy Education MODULES for Nationally Certified Pharmacy Technicians

OCTOBER 2010 VOLUME 15 NUMBER 4

THIS MODULE MUST BE SUCCESSFULLY COMPLETED BY OCTOBER 31, 2012 Pharmacy Tech TopicsTM is provided as a free service TO RECEIVE CPE CREDIT to all Pharmacy Technician Members of the American Society of Health-System Pharmacists. Peptic Ulcer Disease

Pharmacy Tech Topics™ VOLUME 15 ISSUE 4 OCTOBER 2010 PEPTIC ULCER DISEASE

EDITOR: Patricia M. Wegner, PharmD, FASHP DESIGN EDITOR: Barbara J. Yahn

Pharmacy Tech Topics™ (USPS No. 014-766) is published quarterly for $50 per year by the Illinois Council of Health-System Pharmacists, 4055 N. Perryville Road, Loves Park, IL 61111-8653. Phone (815) 227-9292. Periodicals Postage Paid at Rockford, IL and additional mailing offices.

POSTMASTER: Send address changes to: Pharmacy Tech Topics,™ c/o ICHP, 4055 N. Perryville Road, Loves Park, IL 61111-8653 Copyright OCTOBER 2010

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This module is accredited for 2.5 contact hours of continuing pharmacy education and is recognized by the Pharmacy Technician Certification Board (PTCB). LEARNING OBJECTIVES Upon completion of this module, the subscriber will be able to:

1. Describe the pathophysiology of peptic ulcer disease. 2. List the risk factors for developing peptic ulcer disease and the symptoms of peptic ulcer disease. 3. Identify the medications used for the initial therapy and maintenance therapy of peptic ulcer disease. 4. Recognize the appropriate dosage of medications used for peptic ulcer disease. 5. Explain the importance of patient adherence to the treatment plan for peptic ulcer disease.

Accreditation: Pharmacy Tech TopicsTM Modules are accredited for Continuing Pharmacy Education (CPE) credits by the Illinois Council of Health-System Pharmacists. The Illinois Council of Health-System Pharmacists is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. !2010 Illinois Council of Health-System Pharmacists. Pharmacy Tech TopicsTM is a trademark of the Illinois Council of Health-System Pharmacists. The intended audience is pharmacy technicians.

This module will provide 2.5 hours of continuing pharmacy education credit for certified pharmacy technicians. ACPE Universal Activity Number: 121-000-10-004-H01-T Type of Activity: Knowledge Validation Dates: 10/01/10 to 10/31/12

3 PHARMACY TECH TOPICSTM — OCTOBER 2010

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Pharmacy Tech TopicsTM OCTOBER 2010 FACULTY DISCLOSURE

It is the policy of the Illinois Council of Health-System Pharmacists (ICHP) to insure balance and objectivity in all its individually or jointly presented continuing pharmacy education programs. All faculty participating in any ICHP continuing pharmacy education programs are expected to disclose any real or apparent conflict(s) of interest that may have any bearing on the subject matter of the continuing pharmacy education program. Disclosure pertains to relationships with any pharmaceutical companies, biomedical device manufacturers, or other corporations whose products or services are related to the subject matter of the topic.

The intent of disclosure is not to prevent the use of faculty with a potential conflict of interest from authoring a publication but to let the readers know about the relationship prior to participation in the continuing pharmacy education activity. It is intended to identify financial interests and affiliations so that, with full disclosure of the facts, the readers may form their own judgments about the content of the learning activity.

Dr. Sneha Srivastava’s submission has been peer reviewed with consideration and knowledge of these potential conflicts and it has been found to be balanced and objective. The author has no real or apparent conflict(s) of interest that may have any bearing on the subject matter of this continuing pharmacy education program.

NOTICE

Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. The author and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical sciences, neither the author nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they are not responsible for any errors or omissions or for the results obtained from use of such information. Readers are encouraged to confirm the information contained herein with other sources. For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this module is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. This recommendation is of particular importance in connection with new or infrequently used drugs.

4 Peptic Ulcer Disease

Meet the Author Sneha Srivastava, PharmD

Sneha Srivastava, PharmD is an Assistant Professor of Pharmacy Practice at Chicago State University College of Pharmacy. Dr. Srivastava received her Doctor of Pharmacy degree in 2004 from the Ernest Mario School of Pharmacy at Rutgers University. She also completed a Pharmacy Practice Residency and then an Ambulatory Care Specialty Residency at the University of Illinois at Chicago. She served on the faculty of the University of Connecticut School of Pharmacy in Storrs, CT from 2006-2008.

Dr. Srivastava’s clinical interests include diabetes, hypertension, hyperlipidemia, HIV/AIDS, and tobacco dependence, ambulatory and community care, as well as patient education and outreach. Her research interests include medication adherence and health psychology in conjunction with the aforementioned disease states as well as the scholarship of teaching.

PEPTIC ULCER DISEASE

INTRODUCTION Figure 1. Diagram of the Peptic ulcer disease (PUD) is defined as erosions in the secondary to mucosal damage often caused by pepsin and secretion.1 The erosions penetrate the muscularis mucosa and usually occur in the stomach, , , , , and near Meckel’s diverticula; erosions and gastritis usually do not penetrate the mucosa as deep. Helicobacter pylori (H. pylori) associated, nonsteroidal anti-inflammatory drug (NSAID)- induced and stress ulcers are the most common form of peptic ulcers. The stomach and duodenum are the most common places for NSAID-induced and H. pylori ulcers to occur while stress ulcers more often occur in the 2 critically ill patient’s stomach. Peptic ulcer Reprinted with permission from the National Digestive Diseases disease has a 60 to 100% rate of ulcers Information Clearinghouse. reoccurring within one year of initial ulcer. http://digestive.niddk.nih.gov/ddiseases/pubs/pepticulcers_ez/index.htm

5 PHARMACY TECH TOPICSTM — OCTOBER 2010

Epidemiology anatomy and physiology of the alimentary canal, also know as the gastrointestinal (GI) tract, in There are many theories about the etiology particular the parts of the GI tract that may be of peptic ulcers because of the shift in the affected by the ulcers. The GI tract includes the patterns of gastritis. The first description of a mouth, pharynx, esophagus, stomach, small gastric ulcer was made in 1835 and in the intestine, and . The process of beginning, gastric ulcers were found mostly in begins with mastication, where food is young females. In the 1900s, duodenal ulcers chewed and mixed with saliva followed by became more prevalent and the total number of deglutition, the act of swallowing. The food ulcers diagnosed increased as well. Theories passes through the pharynx and esophagus state that environmental factors such as better prior to reaching the stomach, where gastric transportation and refrigeration of food, leading digestion transforms it to chyme, a liquid or to the use of fewer preservatives, especially salt, semiliquid consistency, by way of or caused the shift in patterns. Also, the more muscular contractions. Chyme then travels developed countries have a lower incidence of through the duodenum on its way to the H. pylori because of better hygiene.3 . Simultaneously, the mucous The annual incidence of peptic ulcers is 0.1 membrane of the stomach is secreting gastric to 0.3%, increasing to 1% in patients with juice produced by both the sight of food and H. pylori. The lifetime prevalence is 5 to 10% irritation on the mucous membrane due to the (versus 10 to 20% in patients with H. pylori). In presence of food in the stomach. Gastric juice, a western countries, the occurrence of ulcers is thin colorless liquid with a normal acidity level of similar in both sexes (although duodenal ulcers 0.02%, contains , pepsinogen, were twice as common in men in the past); while rennin, water, ammonium, calcium, potassium, in Asian countries, duodenal ulcers are more and sodium chloride. Pepsin, an enzyme only 3 common in males. Duodenal ulcers tend to present in acidic medium, is made by the occur between 25 and 55 years of age; gastric conversion of pepsinogen in the presence of ulcers are more likely to occur between 40 and hydrochloric acid.4 75 years of age. The estimated mortality The secretion of gastric juice is stimulated by (death) rate is 2.5 per 100,000 individuals. endogenous chemicals, such as acetylcholine, Epidemiologic studies have linked the gastrin, and histamine. Acetylcholine, which is prevalence of peptic ulcers to cigarette smoking, thought to be a neurotransmitter, is released genetic factors, personality profiles, and upon vagal stimulation by acid secretion when H. pylori.3 one sees, smells, tastes, chews, or thinks about Although there have been less physician food. Gastrin is a released by proteins visits, hospitalizations, operations, and deaths in food, vagal stimulation, calcium, magnesium, due to peptic ulcer disease in general, aluminum, and alkalinization of the antrum. hospitalizations and deaths of older adults have Histamine, found in mastlike cells located in increased due to complications of ulcers. This close proximity to parietal cells of the stomach, may be linked to increased use of NSAIDs in the causes acid secretion by acting on receptors older population and because gastric ulcers are on parietal cells much like acetylcholine and more common and associated with a higher gastrin.4 mortality (death) rate.2 As aforementioned, hydrochloric acid and Physiology of the Gastrointestinal pepsin play major roles in peptic ulcer disease. Tract Physiologically, the body has a basal acid output and a maximum acid output. The amount of acid Prior to discussing the pathologic process of secreted while fasting is considered the basal peptic ulcer disease, it is necessary to review the acid output; the amount of acid secreted when

6 Peptic Ulcer Disease injected with histamine is the maximum acid out- stomach, both of which would damage gastric put which reflects the number of parietal cells. mucosa.4 The number of parietal cells functioning under The two most common causes of peptic basal conditions is shown by the ratio of basal ulcers are Helicobacter pylori (H. pylori) infection acid output to maximum acid output. The basal and the use of nonsteroidal anti-inflammatory cell output and ratio increase when there is drugs (NSAIDs).1 Less common causes of an increase in the amount of acetylcholine, ulcers include: cigarette smoking, infection, gastrin, and histamine near the parietal cells, herpes simplex virus, cytomegalovirus, tubercu- causing basal acid hypersecretion. Cholinergic losis, syphilis, medication induced (sirolimus, stimulation mediates not only the secretion of mycophenolate mofetil, potassium chloride, pepsinogen into the gastric lumen but also its chemotherapy), hormonal or mediator-induced, conversion to pepsin under acidic conditions. gastrinoma, systemic mastocytosis, basophilia Endogenous prostaglandins utilize , in myeloproliferative disease, astral G cell bicarbonate, mucosal blood, and cell renewal as hyperfunction, post surgical, antral exclusion, possible defense mechanisms against possible post-gastric bypass, vascular insufficiency, aggressive factors that may cause damage to crack/cocaine use, duodenal obstruction, the mucosa such as, acid, pepsin, , and radiation therapy, infiltrating disease, sarcoido- pancreatic enzymes. The respective roles of sis, and Crohn’s disease.3 In a study comparing these defense mechanisms are to form a smokers to never smokers in Brazil, peptic protective coat over mucosal cells; allow for a pH ulcers were found in 56.9% of smokers versus gradient between the acidic lumen environment 28.3% in never smokers, a statistically signifi- and the mucosal surface; remove acid from the cant difference.5 Although the mechanism is mucosa; and maintain mucosal integrity.4 unclear, other epidemiologic studies have also found positive correlations between smokers Pathophysiology and peptic ulcer disease. This includes higher There is no single factor that explains why rates of PUD in those who smoke more ulcers occur.3 One factor is an abnormality in the cigarettes, higher rates of deaths due to PUD secretion of acid and pepsin. Acid secretion is in smokers, and less healing as well as higher in about 30 to 40% of patients with the reoccurrence of duodenal ulcers in duodenal ulcers, however, it is normal in most smokers.4 Medications, other than NSAIDs, patients with gastric ulcers except those with have conflicting data regarding their contribu- Zollinger-Ellison syndrome. Normal acid tion, or lack thereof, to PUD. In addition, there is secretion rate does not preclude acid and pepsin no evidence that alcohol and caffeine cause as being factors in causing the ulcer. peptic ulcer disease even though they do Additionally, bile and reflux is increase acid production.4 thought to cause damage to the gastric mucosa by altering mucosal epithelial cells and Pathophysiology of disrupting the pH gradient formed, thus allowing H. pylori-induced PUD the mucosa to become permeable to acid and H. pylori is present in almost half of the pepsin. Also, there may be a reduced amount of world’s population.4 Protective roles of H. pylori mucus, mucosal blood flow, and bicarbonate have been speculated including low incidences secretion in patients with ulcers. Although not of gastroesophageal reflux disease (GERD) and clearly proven, emotional stress is thought to childhood diarrhea. H. pylori may be spread due increase gastric acidity while delayed gastric to a contaminated water supply and many emptying is thought to cause gastritis by developing countries have developed a drug refluxing the duodenal contents back into the resistance to local strains of it.6 Although many

7 PHARMACY TECH TOPICSTM — OCTOBER 2010 people harbor H. pylori, approximately 20% will events.7 Meta-analysis studies (studies that develop peptic ulcer disease and less than one statistically analyze several studies that are percent will develop gastric cancer. H. pylori is similar to look for stronger significance of the not a typical bacterial pathogen, it is able to results) have identified certain characteristics survive in the acidic environment of the stomach that place patients in the category of having a and it causes disease not only by releasing high risk of NSAID-related gastrointestinal toxins but also by interaction with its host and complications. These risk factors include: environment. It is also the first bacterial previous gastrointestinal event, age, drug pathogen known to cause cancer.6 interactions, high-dose NSAID therapy, chronic The stomach may be colonized with H. pylori debilitating disorders (especially cardiovascular for years, causing continuous inflammation. This disease), concurrent low-dose aspirin, genetics, 7 bacterial colonization, usually inhibited by and H. pylori infection. peristalsis and gastric acidity, is allowed for Each of the risk factors should be considered by constituents of H. pylori such as urease, in detail. There is a higher risk associated with flagellae, adhesins, vasculating cytotoxin, and complicated and/or more recent gastrointestinal CagA. Urease targets gastric acid by neutraliz- events. Generally, age above 75 years old is ing acidity while flagellae and adhesins target considered a higher risk. There are several gastric peristalsis because of their function of medication interactions that increase the risk of motility and adherence to gastric epithelium, NSAID-induced events. This includes concurrent respectively. Although in vitro (outside of the use of multiple NSAIDs, low dose aspirin, body) studies show that H. pylori is susceptible selective serotonin reuptake inhibitors, to the antibodies formed; H. pylori is able to exist alendronate, corticosteroids, and clopidogrel. in vivo (inside of the body), suggesting that the Additionally, since H. pylori infection was shown gastric mucosa may provide a protective to increase the risk of NSAID-related gastroin- environment against the antibodies formed.4 testinal events, the guidelines also concluded There are several mechanisms of H. pylori that testing for and possibly eradicating H. pylori induced inflammation that are postulated. One may be advantageous in patients that require 7 mechanism is that inflammation occurs because long-term NSAID therapy. of cytokine release secondary to direct contact Aspirin and PUD of H. pylori with gastric epithelial cells. This can be spread by the fecal-oral route, oral-oral route, A study looked at 156 adults with a history of or through iatrogenic ways, such as via an cardiovascular disease who had peptic ulcer endoscopic tube if improperly cleaned.2 bleeding and were treated with endoscopic therapy. These patients were then randomized Pathophysiology of NSAID to either aspirin 80mg daily or placebo for 8 Induced Ulcers weeks. The researchers found that about 10% of the patients assigned to aspirin had a recurrent Mucosal injury to the upper gastrointestinal ulcer bleed within 30 days. Five percent of the tract, leading to peptic ulcer disease and patients in the placebo group had a recurrent possibly upper gastrointestinal hemorrhage and ulcer bleed. Additionally, they found that 10 of 78 perforation, may be caused by NSAID use. It is patients in the placebo group died at 8 weeks estimated that 25% of chronic NSAID users will versus 1 of 78 patients in the aspirin group. The develop PUD with bleeding or perforation in deaths in the placebo group were due to acute about 2 to 4% of cases. The hospital admission coronary syndrome, stroke, heart failure, rate is about 100,000 cases per year and there perforated ulcer and pneumonia. The one death are about 7,000 to 10,000 deaths annually in the aspirin group was due to heart failure. secondary to NSAID-related gastrointestinal Since this was a small study, no absolute

8 Peptic Ulcer Disease conclusions can be made. This study suggests are not indicated for peptic ulcer disease as that continued aspirin use after a peptic ulcer over-the-counter products. Therefore, when bleed increases chances of recurrent bleeding suspecting peptic ulcer disease, patients should and that reduction in death with aspirin use be referred to their physician.9 needs to be further studied.8 Diagnosis Clinical Presentation There are certain conditions that mimic the Symptoms usually occur in two thirds of symptoms of PUD. Therefore, diseases such as patients with ulcers. The most common myocardial infarction, pericarditis, esophagitis, symptoms include dyspepsia (heartburn), cholecystitis, pancreatitis, and irritable bowel usually manifesting as nausea, vomiting, disease should be considered when evaluating a anorexia, fullness, and/or bloating.1 Dyspepsia is patient for a possible ulcer.3 also common in other gastrointestinal diseases, Endoscopy is the most accurate way to 4 so it can not be used alone to diagnose PUD. visualize the ulcer and may also allow for biopsy Patients may also complain of recurrent post- and cytologic study if necessary. Radiography, prandial (after meal) epigastric pain. Typically, although it may miss up to 20% of ulcers, is often pain in the epigastrium is described as burning used to make the initial diagnosis since it is or gnawing comparable to hunger pangs. The cheaper and even patients in fragile condition occurrence of pain is usually episodic with each can usually tolerate it. If bleeding is suspected or episode lasting minutes and occurring in clusters if cost is not an issue, endoscopy is preferred. In lasting from days to weeks or there may be long the case of duodenal ulcers, radiographic periods of no pain. If the pain changes in diagnosis does not warrant a follow up character, it could be due to perforation or endoscopy and reassessment via radiography is penetration. not routinely done after treating the ulcer. On the The aforementioned symptoms require other hand, gastric ulcers usually require further evaluation to diagnose peptic ulcer endoscopy to rule out malignancy or at least a disease. When a patient presents with certain follow-up radiographic assessment to prove alarm symptoms, they should be directed to their healing after 8 to 12 weeks of treatment. health care provider immediately for evaluation Laboratory studies are usually recommend- as these symptoms may suggest complications ed in a certain subset of patients where hyper- of ulcers. Alarm symptoms include: anemia, secretory diseases such as Zollinger-Ellison hematemesis (throwing up blood), melena syndrome are suspected. Serum gastrin should (blood in stool), or heme-positive stool, vomiting, be measured in patients with a family history of anorexia or weight loss, persisting upper PUD, ulcers associated with increase calcium abdominal pain radiating to the back, and levels or diarrhea, and recurrent ulcers requiring severe, spreading upper abdominal pain. surgery, as well as other indications as Patients that are greater than the age of 55 dictated by their healthcare provider. should also be referred to their physician as Additionally, H. pylori should be tested for via 1 soon as possible. biopsy or C-urea breath test.4 In the community setting, a patient may come in with dyspepsia or epigastric pain, ask- Treatment ing for a recommendation on antacids, histamine Medications and surgery are options in the 2 blockers, or proton-pump inhibitors which are treatment of peptic ulcer disease. Usually, available over-the-counter (OTC). Patients may medications are first line in treating ulcers, use these for symptomatic relief; however these however surgery may be indicated in certain should not be recommended for ulcer therapy. It patients with complications. Indications for is very important to note that these medications

9 PHARMACY TECH TOPICSTM — OCTOBER 2010 surgery usually include complications of ulcers The side effect profile for PPIs is generally such as hemorrhage, perforation, or gastric minimal. Clinical studies showed that the most outlet obstruction as well as intractable (untreat- common side effects of headache, abdominal able or resistant) ulcer disease.1 pain, and diarrhea, were found to occur in simi- Duodenal ulcers can be treated with lar frequency to placebo. Additionally, there was a concern of fundic gland polyps; however there histamine-2 receptor antagonists (H2RAs) such as ranitidine 150mg twice daily or 300mg at bed- are no studies that advise stopping PPIs in this time, famotidine 20mg twice daily or 40mg at case. Other concerns associated with PPI use bedtime, or cimetidine 400mg twice daily or include increased incidence of gastric carci- 800mg at bedtime for four to eight weeks. noids, vitamin B12 deficiency, pneumonia, Duodenal and gastric ulcers can be treated with Clostridium difficile infections, and an increase in proton pump inhibitors (PPIs) for eight weeks. hip fractures. The carcinoids and vitamin B12 Typical PPI regimens include once daily deficiency have not been proven to be true; treatment with omeprazole 20mg, lansoprazole concern of pneumonia is difficult to substantiate 15mg, rabeprazole 20mg, or pantoprazole since the study included many patients with 40mg. Additionally, sucralfate is an option to use multiple co-morbidities; and the C. difficile for four weeks at a dose of 1 gram four times correlation was seen in case-control studies but daily.2 the mechanism is not clear. Additionally, the increases in hip fractures have been shown in Proton Pump Inhibitors (PPIs) several studies where other confounders were As of April 2010, six proton pump inhibitors taken into account and therefore, although there are on the United States market for use. are no guidelines that discourage long term use These include dexlansoprazole, lansoprazole, of PPIs in patients, the association between long omeprazole, esomeprazole, pantoprazole, and term PPI use and hip fractures is possible. On rabeprazole. There are several GI-related the other hand, an observational study did not indications for these agents, but we will find any of the aforementioned side effects for concentrate on their use in the treatment of the 11 years that 230 patients were on PPI 10 peptic ulcer disease. These PPIs have similar therapy. efficacy and side effect profiles while differing There are six PPIs on the market currently mainly in doses and dosing schedules. and some are available without a prescription. The mechanism of action of proton pump Each PPI differs in the availability of dosage inhibitors is to suppress gastric acid by inhibiting forms, strength, dosing schedule, and the proton pump in parietal cells. The PPIs FDA-approved indications, which will not be 11 irreversibly bind to the active H+/K+ATPase discussed in this review. pumps leading to the inhibition of hydrogen ions • Dexlansoprazole (Dexilant®) is the flow into the gastric lumen. The basal and meal- newest PPI available. There is no dosing stimulated acid production is inhibited by PPIs. suggested for the treatment of peptic ulcer Initially, there is only a limited amount of acid disease.12 production inhibited by PPIs; however more is • Esomeprazole (Nexium®) is available as inhibited once steady-state is reached after five capsules, oral suspension, and for to seven days of therapy. Dosing PPIs twice intravenous (IV) use. The dosing for daily allows for more pumps to be inhibited, H. pylori eradication is 40mg daily in the leading to more rapid and complete gastric acid triple or quadruple therapy regimen (refer to suppression. Additionally, alkalinization of the section on H. pylori eradication). The gastric pH leads to less pepsinogen conversion dosing for the prevention of NSAID-induced to pepsin.10 ulcers is 20 to 40mg daily for up to six

10 Peptic Ulcer Disease

months and 40mg twice daily (maximum of 20 mg/sodium bicarbonate 1,100 mg 240mg/daily) may be used in pathologic capsules. Since the bicarbonate in each of hypersecretory conditions. The IV dosing is the capsules is the same, two 20mg 80mg twice daily for pathologic capsules is not the same as one 40mg hypersecretory conditions. The maximum capsule. The sodium bicarbonate used in dose of esomeprazole is 20mg daily for this formulation is for the protection of patients with severe hepatic impairment. It omeprazole from the acidic nature of the should be taken one hour before meals and stomach thereby allowing for its absorption. the granules from the capsules can be It is dosed at 20mg daily for four weeks for mixed with applesauce or given through the the treatment of duodenal ulcers and at nasogastric (NG) tube. The suspension can 40mg daily for four to eight weeks for be given through the NG tube as well.11 benign gastric ulcers, taken on an empty • Lansoprazole (Prevacid®) is available over- stomach, one hour prior to meals. The the-counter, prescription, and generic. It is preventive dose for bleeding in critically ill available in 15mg and 30mg strengths as patients is 40mg daily after giving 40mg delayed release granules for suspension, twice daily, spaced by 6 to 8 hours on day delayed release capsules, and delayed one. Unlike the other capsules, the granules release orally disintegrating tablets (ODT). can not be removed; however the powder It is also available in 30mg powder for for suspension can be used via NG tube. injection. The OTC formulation is only On the other hand, omeprazole is available available as a 15mg delayed release tablet. in 10mg, 20mg, and 40mg capsules (can The prescription dosing for the prevention of sprinkle contents into applesauce) and NSAID-induced ulcers is 15mg daily for up 2.5mg and 10mg suspension (can be given to three months and 30 mg daily up to eight through the NG tube); the OTC formulation weeks for the treatment of NSAID induced contains 20mg of omeprazole. The dosing ulcers; the dose should be reduced in for duodenal ulcers is 20mg daily for four patients with hepatic impairment. The weeks (repeat for an additional four weeks if granules from the capsules and the ODT necessary) and 40mg daily for four to eight can be given through an NG tube; however weeks for gastric ulcers. The dosing for unlike esomeprazole, the suspension should pathologic hypersecretion is 60mg daily with 11 not be given this way. Additionally, a maximum of 360mg/day. applesauce, Ensure pudding, cottage • Pantoprazole (Protonix®) is dosed at 40mg cheese, yogurt, strained pears, apple, twice daily or 80mg every 12 hours orange, or tomato juice can be used to mix (maximum of 240mg/day) for pathologic the granules from the capsules just so long hypersecretory conditions. It is available as it is taken immediately.11 generically in 20mg and 40mg tablets, 40mg • Omeprazole is also available OTC, suspension, and 40mg injection. The prescription, and generic. The Zegerid® and suspension should be taken 30 minutes Zegerid® OTC formulations contain prior to meals and may be used via NG 11 omeprazole and sodium bicarbonate; while tube. the Prilosec® formulation contains only • Rabeprazole (Aciphex®) is available in omeprazole. Zegerid® is available only 20mg tablets and dosed at 20mg daily for under the brand name in 20mg and 40mg four to eight weeks to treat duodenal capsules (with 1,100mg of sodium bicarbon- ulcers and 60mg daily for pathologic ate) and powder for suspension (with hypersecretory conditions with a maximum 1,680mg of sodium bicarbonate); the of 120mg/day.11 OTC formulation contains omeprazole

11 PHARMACY TECH TOPICSTM — OCTOBER 2010

Histamine 2 Receptor Antagonist Sucralfate 13 (H2RA) Sucralfate, being viscous in nature and having a negative charge, works by binding to There are four available H2RAs: cimetidine, famotidine, nizatidine, and ranitidine. They are duodenal and gastric ulcers and to gastric indicated for the treatment of active duodenal erosions. It binds to gastric mucosa, creating a and gastric ulcers as well as maintenance barrier from the acid, as well as buffers the acid, therapy for duodenal ulcers. There is a 70 to inhibits pepsin, and adsorbs bile salts.14 The 80% rate of healing in duodenal ulcer after four treatment dose for duodenal or gastric ulcers is weeks and 87 to 94% after eight weeks. Each 1 gram four times daily or 2 grams twice daily and the maintenance dose is 1 to 2 grams H2RA is comparable for the treatment of ulcers and may be taken as one dose at bedtime or twice daily or 1 gram four times daily.2 This divided into multiple doses. Multiple doses is medication is not commonly used anymore, preferred in patients who experience daytime most probably because of the amount and symptoms. Smokers require higher doses and frequency of dosing, as well as the need to be may need to be treated for a longer period of taken on an empty stomach. Side effects time; whereas patients with moderate to severe include constipation, nausea, dry mouth, renal failure should have a dose reduction or an metallic taste in the mouth, as well as rare increased duration between doses. Generally occurrence of seizures and hypophosphatemia. the side effect profile is minimal; however, Sucralfate should be taken two hours central nervous system related side effects after medications such as fluoroquinolones, rarely occur in patients with renal failure due to phenytoin, digoxin, theophylline, amitriptyline, medication accumulation. Another rare side warfarin, and ketoconazole.2 effect implicated in H RA therapy is thrombocy- 2 Bismuth topenia. Of the four H2RAs, cimetidine has the most drug interactions due to its inhibition of Bismuth subsalicylate is thought to heal several CYP450 isoenzymes.2 ulcers by an antibacterial and local gastro- protective effect as well as by stimulating • Cimetidine (Tagamet®) is dosed at 400mg prostaglandins. Adverse effects include black twice daily (or 800mg at bedtime) to a stool or a hairy tongue. This is not considered maximum of 1600mg/day for duodenal to be a first line agent to treat peptic ulcers.16 ulcers and 300mg four times daily for gastric ulcers; the maintenance dose is Antacids 400mg at bedtime.13 The mechanism of action of antacids are to • Famotidine (Pepcid®) is dosed at 40mg at neutralize gastric acid, inhibit pepsin, and bind bedtime for gastric ulcers; 20mg twice daily bile acids. Aluminum containing antacids have for active duodenal ulcers and then once the additional mechanism of increasing mucosal 13 daily for maintenance therapy. defense and suppressing H. pylori. Antacids • Nizatidine (Axid®) is dosed at 300mg at usually contain aluminum or magnesium and bedtime for duodenal ulcers or 150mg twice cause more immediate relief for symptoms of daily for duodenal and gastric ulcers, using dyspepsia. However, they have many drug 150mg at bedtime for the maintenance interactions which may decrease absorption of therapy.13 certain medications. Although they may be used • Ranitidine (Zantac®) is dosed the same as in patients with peptic ulcer disease, they are not nizatidine.13 considered first line therapy.

12 Peptic Ulcer Disease

H. Pylori Eradication therapy is shown to decrease the incidence of gastric cancer.17 However, there was also When a patient with peptic ulcer disease another study that did not show a significant tests positive for H. pylori, first-line eradication decrease in gastric cancer with H. pylori therapy is recommended with a triple therapy eradication in a population that has the second combination of a PPI, clarithromycin, and highest incidence of gastric cancer. This study amoxicillin, or metronidazole.15 The worldwide noted that further studies evaluating early rate of eradication is usually 70 to 85 percent.15 eradication of H. pylori with vigilant follow-up There are several different combinations utilized data are needed.18 to eradicate H. pylori. In general, the duration of each combination is 10 to 14 days. Although Prevention of NSAID-Related Ulcer some of the PPIs or bismuth-based regimens Complications have FDA-approved indications, studies have shown similar efficacy among all of them.15,16 One of the most common causes of ulcers is Amoxicillin is the preferred antibiotic in the use of NSAIDs. Clinical practice guidelines combination with clarithromycin; however in for the prevention of NSAID-related ulcers have patients with penicillin allergies, metronidazole been created to provide recommendations to can be substituted. This substitution is recom- health care providers using scientific data from mended to occur only in patients that can not studies.7 take penicillins because if the metronidazole Prevention of NSAID-related peptic therapy is ineffective, salvage therapy is found ulceration and mucosal injury is commonly also to not be effective. Quadruple therapy using practiced utilizing one of two methods. The first a PPI, bismuth, tetracycline, and metronidazole method is to concurrently prescribe a PPI, for 10 to 14 days is considered to be either an high-dose (double dose) histamine-2-receptor alternative first line therapy or a salvage therapy antagonist (H2RA) or misoprostol. The second to patients failing clarithomycin based therapy.15 method is to use a COX-2 inhibitor. Another salvage therapy option is using Misoprostol is a synthetic prostaglandin E1 levofloxacin in conjunction with a PPI and analog and was the first agent approved for the amoxicillin.15 prevention of NSAID-related ulcers. It works by Table 1 outlines the various combinations inhibiting gastric acid (basal, nocturnal, and stim- available (refer to Table 1 on pages 12-13). uli-induced) as well as by increasing bicarbonate Some of these combinations may also be and mucus production.19 Meta-analysis studies available in prepackaged brand name have shown that misoprostol is statistically more formulations. It is important to note that Helidac® likely to prevent NSAID-induced ulcers than and Pylera® do not contain the PPI and placebo or H2RA and similarly to lansoprazole. therefore would require a separate prescription Additionally, misoprostol 200mcg four times daily for proper eradication. Since there are several was evaluated in a large, randomized, placebo combinations available to eradicate H. pylori, controlled study and it showed a 40% decrease choosing a regimen should take the following in serious upper GI complications. The FDA- factors into consideration: eradication rate approved dose is 200mcg four times daily with (>80% is preferred), cost, insurance, formulary, food, however, doses of 400-600mcg/day have dosing schedule, and side effects.16 also shown a significant decrease in ulceration There is evidence linking H. pylori as a cause compared to placebo.20 Although it is gastroin- of gastric cancer, one of the most common testinal protective, the main limitation of miso- cancers worldwide. It is important to note that the prostol is the occurrence of side effects. The incidence varies greatly by geographic region. main side effects of misoprostol include diarrhea, Eradication of H. pylori with antibiotics and PPI abdominal pain, nausea, bloating, and fullness.19 _continued on page 14.

13 PHARMACY TECH TOPICSPHARMACYTECH Table 1: Combination Medications for the Eradication of H. Pylori11,13,16 14 PHARMACY TECH TOPICSPHARMACYTECH

Combination Omeprazole Esomeprazole Lansoprazole Pantoprazole Rabeprazole Clarithromycin Amoxicillin Metronidazole Tetracycline Bismuth Subsalicylate Tinidazole Rifampin Levofloxacin

10 to 14 days 40mg 500mg 1000mg FDA -approved daily BID BID

14 days 20mg 500mg 500mg BID or BID BID

40mg daily TM TM — OCTOBER 2010 OCTOBER — — OCTOBER 2010 OCTOBER — 10-14 days 30mg BID 500mg 1000mg FDA –approved BID BID Available as PrevPac®

14 days 30mg BID 500mg BID 500mg BID

10 days 20mg BID 500mg BID 1000mg FDA -approved BID

14 days 20mg BID 500mg BID 500mg BID

14 days 40mg BID 500mg BID 1000mg BID

14 days 40mg BID 500mg BID 500mg BID

14 days 20mg BID 500mg BID 1000mg BID

14 days 20mg BID 500mg BID 500mg BID

10 to 14 days Esomeprazole 20mg BID OR 40mg daily OR 250mg 500mg 525mg Bismuth/ Metronidazole/ Lansoprazole 30mg BID OR Omeprazole 20mg BID OR four times four times four times Tetracycline available Pantoprazole 40mg BID OR Rabeprazole 20mg BID daily daily daily as Helidac®

Peptic Ulcer Disease Levofloxacin

500mg BID days 6 to 10 500mg daily Rifampin

500mg BID days 6 to 10 150mg BID Tinidazole

500mg BID days 6 to 10

Subsalicylate Bismuth Bismuth

525mg four times daily 140mg- 3 capsules four times daily Tetracycline

500mg four times daily 125mg- 3 capsules four times daily Metronidazole

250mg four times daily 125mg- 3 capsules four times daily Amoxicillin

1000mg BID days 1 to 5 1000mg three daily times 1000mg BID 1000mg BID Clarithromycin

CONTINUED

500mg BID days 6 to 10 500mg three times daily for 14 days 11,13,16 11,13,16 Rabeprazole

20mg BID

H. Pylori Pantoprazole Lansoprazole

30mg three times daily

Esomeprazole Omeprazole Famotidine 40mg daily OR Nizatidine 300mg daily OR Ranitidine 150mg twice daily (Ranitidine is FDA-approved in this combination) 20mg BID 40mg daily for 14 days; then 20mg daily for 14 days Esomeprazole 20mg BID OR Lansoprazole 30mg BID OR Omeprazole 20mg BID OR Pantoprazole 40mg BID OR Rabeprazole 20mg BID Esomeprazole 20mg BID OR Lansoprazole 30mg BID OR Omeprazole 20mg BID OR Pantoprazole 40mg BID OR Rabeprazole 20mg BID Combination RA and RA 2 10 to 14 days with a H Bismuth/ Metronidazole/ available Tetracycline as Helidac® 10 days; not considered 1st line therapy 14 days; if a patient is allergic to clarithromycin 10 days; Bismuth/ Metronidazole/ available as Tetracycline Pylera® –approved FDA 14-28 days FDA-Approved but eradication rates are less than 80% 10 to 14 days when patients have failed 2 different first line therapies 10 days when patients fail first line therapies Table 1: Combination Medications Table for the Eradication of

PEPTIC ULCER DISEASE 15 PHARMACY TECH TOPICSTM — OCTOBER 2010

Table 2: Pregnancy Risk Factor Definition22 Risk Factor Definition A Controlled studies in women fail to show a risk to the fetus B 1) Animal-reproduction studies fail to show a fetal risk but no controlled studies in women are available 2) An adverse effect seen in animal reproduction studies but not confirmed in controlled studies in women C 1) Animal-reproduction studies show an adverse effect on the fetus and no controlled studies in women are available 2) There are no studies in animals or women D • Evidence exists of human fetal risk • Benefit of medication may outweigh risk X • Evidence exists of fetal risk in studies of animals or humans and/or human experience • Benefit of medication does not outweigh risk • Use in pregnancy is contraindicated

done to evaluate the role of PPIs in preventing Table 3: Pregnancy Risk Categorization of NSAID-induced peptic ulcers. Two of the major Medications for PUD19, 23 clinical trials compared omeprazole to placebo, Drug Category misoprostol, and ranitidine in patients with ulcers Cimetidine B or erosions. The results showed a significant Famotidine B decrease in NSAID-related ulcers in the Lansoprazole B omeprazole group when compared to ranitidine. In comparison to misoprostol, omeprazole had a Misoprostol X higher prevention rate of duodenal ulcers but Nizatidine B the same prevention rate of gastric ulcers.7 Omeprazole C Pantoprazole B High-dose H2RA Rabeprazole B Single-dose H2RAs do not provide a Ranitidine B reduction in the risk of NSAID-induced gastric Sucralfate B ulcers. On the other hand, double-dose H2RAs are effective in reducing the risk and may be a more cost-effective alternative for some patients. The incidence of diarrhea is between 14 to 40% Prescribing an H RA in all patients with a low to 19 2 and 13 to 20% experience abdominal pain. average risk of developing ulcers while on Additionally, spotting, cramps, hypermenorrhea, NSAID therapy was a strategy suggested by an menstrual disorder, and dysmenorrhea occurred economic analysis study.7 in women. Misoprostol is pregnancy category X and therefore is contraindicated in pregnant COX-2 Inhibitors women (refer to tables 2 and 3).19 Medications such as celecoxib (Celebrex®) PPI and rofecoxib (Vioxx®) were developed to decrease inflammation in musculoskeletal tissue Several randomized clinical trials have been without causing gastrointestinal mucosal

16 Peptic Ulcer Disease damage by selectively inhibiting COX-2. Three means no risk factors, moderate risk means 1 to studies, CLASS, VIGOR, and TARGET com- 2 risk factors, and high risk means either history pared various COX-2 inhibitors to traditional or a previous complication ulcer or more than 2 NSAIDs in patients with arthritis.10 In the first risk factors. The next step is to consider the study, results showed a significant decrease in cardiovascular risk since NSAIDs have been ulcer complications in the celecoxib group at six associated with an increased incidence of months only after the data was adjusted to cardiovascular (CV) events. Risk factors for CV exclude patients taking aspirin. At one year in disease include prior history of CV event, this study, results indicated no difference diabetes, hypertension, hyperlipidemia, and between any of the groups. In the second study, obesity. After determining the risk factors for naproxen was compared to rofecoxib (which has gastrointestinal and CV events, the guidelines since been voluntarily taken off the market) and have recommended a prevention strategy for a significant decrease in ulcers was noted in the each of the groups. In patients with a low rofecoxib group. The third study looked at gastrointestinal risk and low CV risk, NSAIDs at lumiracoxib (a COX-2 inhibitor that was never lowest effective dose should be prescribed. In approved in the United States and taken off patients with moderate gastrointestinal risk and the approved list in other countries because low CV risk, use an NSAID with either a PPI or of hepatotoxicity) which showed a decrease in misoprostol. Patients with a high gastrointestinal gastric complications. The Cochrane database risk should either be given alternative therapy or also reviewed COX-2 inhibitors and concluded a COX-2 inhibitor with a PPI or misoprostol. In that patients taking COX-2 inhibitors have patients with high CV risk but low or moderate GI significantly less gastroduodenal ulcers, risk, naproxen with a PPI or misoprostol is complications, and withdrawals to therapy recommended. Patients with high GI and CV because of gastrointestinal symptoms.7 risk, NSAIDs and COX-2 inhibitors should be 7 In summary, full dose misoprostol, PPIs, and avoided. the use of COX-2 inhibitors instead of traditional PPI Use in Pregnancy21 NSAIDs are effective in preventing ulcers and ulcer complications in patients taking NSAIDs. The first PPI, omeprazole, has several High-dose H2RAs are effective compared to studies that evaluated its safety during placebo but not as effective as PPIs. In choosing pregnancy. In one study, 113 women exposed to a preventive therapy, it is important to consider omeprazole during pregnancy were compared to the limitations with each of these preventive two control groups. One control was a disease- strategies. The main limitation of using miso- paired group using histamine 2 blockers and prostol is its GI side effects. Cost of the PPIs and the other group was healthy women given celecoxib may be a consideration for some nonteratogenic (medications not causing birth patients. Another limitation with celecoxib is that defects) medications. The authors found that patients concurrently taking low dose aspirin, there was no significant difference in the who do not get the benefit of the decrease in occurrence of major malformations, sponta- gastrointestinal events, are at risk of cardiovas- neous abortions, pre-term deliveries, caesarean cular events. In general, the lowest doses of section, and neonatal health problems. Another NSAIDs should be utilized.7 study, also conducted by Motherisk, showed that the use of omeprazole in 534 women that The clinical practice guidelines recommend showed no increase in the risk of malformations. risk stratification by counting the number of risk Additionally, the Swedish Medical Birth factors a patient has of developing NSAID- Registry found that rates of birth weight, induced gastrointestinal injury. In this example of congenital malformations, perinatal death, and risk stratification, the guidelines state low risk low Apgar scores of 955 infants exposed to

17 PHARMACY TECH TOPICSTM — OCTOBER 2010 omeprazole while the mothers were pregnant CONCLUSION (including a majority that were exposed during Peptic ulcer disease is a fairly common their first trimester), were comparable to the disease inflicting both men and women. It may general Swedish population. be treated in the outpatient setting; however, Pantoprazole and lansoprazole, in addition to there is the possibility of complications and even omeprazole, were also compared to a control death if the disease progresses without group in another prospective study (a study that recognition and treatment. The main causes are follows patients forward in time). In this study, the H. pylori and non-steroidal anti-inflammatory omeprazole group had 295 pregnant women, the drug use. In the case of H. pylori, medications lansoprazole group had 62, and the pantopra- aimed at healing the ulcer and eradicating the zole group had 53. The rate of major congenital infection are used in combination while in the malformations was not significantly different in case of NSAIDs, medications are give to heal any of the three PPI groups when compared to the ulcer and the offending agent is usually the control group (3.6% in the omeprazole group, discontinued. Patients should be closely 3.8% in the pantoprazole group, 3.9% in the monitored for the healing of the ulcer and the lansoprazole group, and 3.8% in the control prevention of reoccurrences. ■ group). In general, PPIs may be used in pregnancy, however, should only be done so under doctor’s orders. Complications2 Hemorrhage, perforation, and gastric outlet obstruction are complications that may occur with peptic ulcer disease. It occurs in about 25% of patients with peptic ulcer disease with upper gastrointestinal bleeding and is the most common cause of death because of the disease. Symptoms of upper gastrointestinal bleeding include bright red or coffee ground blood in the stool, melena, fatigue, anemia, orthostatic hypotension, and syncope; however, many patients do not have any symptoms of the ulcer. Another complication is perforation of the duodenum wall or antral wall which may lead to peritonitis. Symptoms of perforation include extreme pain in the abdomen with fever and hypotension if the patient becomes septic. It requires emergency surgery and the mortality (death) rate in older patients is 30 to 50%. Lastly, gastric obstruction resulting from pyloric stenosis may present as vomiting, fullness, weight loss, dehydration, or metabolic alkalosis and usually requires surgery.

18 Peptic Ulcer Disease

REFERENCES 14. Nagashima R. Mechanism of action of sucralfate. J Clin Gastroenterol. 1. Ramakrishnan K, Salinas RC. Peptic ulcer 1981;3(Suppl 2):117-27. disease. Am Fam Physician [Internet]. 2007 Oct 1;76(7):1005-12. 15. Chey WD, Wong B. American College of Gastroenterology Guideline on the Management 2. Berardi RR, Welage LS. Peptic ulcer disease. In: of Helicobacter pylori Infection. Pharmacotherapy: A Pathophysiologic Approach, Am J Gastroenterol 2007;102:1808-1825. Dipiro J (Ed). 16. H. pylori treatment regimens. Pharmacist’s 3. Soll A. Overview of peptic ulcer: epidemiology Letter/Prescriber’s Letter 2007;23(11):231113. and major causes. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2009. 17. Konturek PC, Konturek SJ, Brzozowski T. Helicobacter pylori infection in gastric 4. Halter F. Pathophysiology of peptic ulcer cancerogenesis. J Physiol Pharmacol. disease. In: Hollander D, Tytgat GNJ, editors. 2009 Sep;60(3):3-21 Sucralfate: From Basic Science to the Bedside. NY: Plenum Press;1995. 18. Mabe K, Takahashi M, Oizumi H, Tsukuma H, Shibata A, Fukase K, Matsuda T, Takeda H, 5. Pizzo de Castro MR, Matsuo T, Varges Nunes Kawata S. Does Helicobacter pylori eradication SO. Clinical characteristics and quality of life of therapy for peptic ulcer prevent gastric cancer? smokers at a referral center for smoking World J Gastroenterol. 2009;15(34):4290-4297 cessation. J Bras Pneumol. 2010;36(1):67-74. Available from: URL: 6. Dorer MS, Talarico S, Salama NR. Helicobacter http://www.wjgnet.com/1007-9327/15/4290.asp pylori‘s unconventional role in health and DOI:http://dx.doi.org/10.3748/wjg.15.4290. disease. PLoS Pathogens [serial online] 2009. [accessed March 1, 2010]. Available from URL: 19. Cytotec [package insert]. New York, NY: Pfizer; http://www.ploscollections.org/article/ 2009. info%3Adoi%2F10.1371%2Fjournal.ppat.1000544 [accessed March 1, 2010]. 20. Park SH, Cho CS, Lee OY, Jun JB, et al. Comparison of prevention of NSAID-induced 7. Lanza FL, Chan FKL, Quigley EM, et al. gastrointestinal complications by rebamipide and Guidelines for prevention of NSAID-related ulcer misoprostol: a randomized multicenter, complications. Am J Gastroenterol. controlled trial-STORM study. J. Clin. Biochem 2009;104:728-738. Nutr. 2007;40:148-155. 8. Sung J, Lau JY, Ching JC, Wu Y, et al. 21. Nava-Ocampo AA. Velazquez-Armenta EY. Han Continuation of Low-Dose Aspirin Therapy in JY. Koren G. Motherisk Update. Canadian Peptic Ulcer Bleeding. A Randomized Trial. Family Physician. 2006;52:853-854. Ann Intern Med. 2010;152(1-9). 22. “Pregnancy and Medicines” U.S. Department of 9. Pray WS. Nonprescription Products Health and Human Services, Office on Women’s Therapeutics. Binghamton, NY: Pharmaceutical Health http://www.womenshealth.gov/ Products Press, August 2003. faq/pregnancy-medicines.cfm 10. Katz PO, Zavala S. Proton Pump Inhibitors in [accessed September 7, 2010]. the Management of GERD. J Gastrointestinal 23. Vanderhoff BT, Tahboub RM. Proton pump Surge. 2010:14(Suppl 1):S62–S66. inhibitors: an update. Am Fam Physician. 11. Comparison of proton pump inhibitors. 2002 Jul15;66(2):273-281. Pharmacist’s Letter/Prescriber’s Letter 2009;25(3):250304. (Full update January 2010) 12. Dexilant [package insert]. Deerfield, IL: Takeda Pharmaceuticals, Inc; 2010.

13. Histamine H2 blocker oral dose comparison. Pharmacist’s Letter/Prescriber’s Letter 2009;25(8):250801.

19 PHARMACY TECH TOPICSTM — OCTOBER 2010

VOLUME 15 NO. 4 PEPTIC ULCER DISEASE SELF-ASSESSMENT QUESTIONS 1 — 20

1. What is/are the most common cause(s) 5. A patient is currently taking warfarin and of peptic ulcer disease? is to be started on sucralfate. Which of A. H. pylori the following is the BEST counseling B. NSAIDs point for a pharmacist to give to this patient? C. Food A. There is no drug-drug interaction and D. A and B therefore can be taken together at the same time. 2. Which of the following is a medication B. Warfarin and sucralfate can not be that may cause an ulcer? taken together. We will call the doctor to A. Naproxen change one of your medications. B. Acetaminophen C. Sucralfate should be taken 2 hours C. Sucralfate after warfarin D. Omeprazole D. Warfarin should be taken 1 hour after sucralfate. 3. Which of the following has a major role in the pathogenesis of peptic ulcer 6. H. Pylori may cause peptic ulcer disease disease? by inducing: A. Pepsin A. pepsin B. Antihistamine B. hydrochloric acid C. Bicarbonate C. inflammation D. Mucosal blood flow D. viral infections

4. What may increase the risk of 7. Even at low dose, ______is developing peptic ulcer disease? associated with an increased risk of A. Anorexia developing peptic ulcer disease. B. Alcohol A. hydrocodone C. Smoking cigarettes B. aspirin D. Soda C. acetaminophen D. pseudoephedrine

8. Which of the following is a symptom of peptic ulcer disease? A. Nausea B. Epigastric pain C. Vomiting D. All of the above

20 Peptic Ulcer Disease

9. If a patient complains of dyspepsia and 15. Which of the following is an example of adds he/ she may have an ulcer, the an H2RA? patient should be: A. Ranitidine A. referred to the physician B. Sucralfate B. referred to the emergency room C. Omeprazole C. shown to the stomach pain relief aisle D. Azithromycin D. advised to take acetaminophen 16. Which of the following can be given with 10. PPI stands for: an NSAID to prevent ulcers? A. pantoprazole pump inactivator A. Misoprostol B. proton pump inhibitor B. Azithromycin C. proton pump inactivator C. Omeprazole D. prilosec prevacid inhibitor D. A or C

17. Which of the following can be given for 11. The gold standard for diagnosing peptic inflammation instead of an NSAID to ulcer disease is via: reduce the likelihood of getting an ulcer? A. bronchoscopy A. Naproxen B. ultrasound B. Ibuprofen C. endoscopy C. Meloxicam D. surgery D. Celecoxib

12. Rabeprazole is an example of a/an: 18. Which of the following is a complication A. H2RA of an ulcer which may require surgery? B. PPI A. Perforation C. NSAID B. Hemorrhage D. Antacid C. Gastric outlet obstruction D. All of the above 13. Which of the following is superior in treating PUD? 19. What is the consensus of PPI use in pregnancy? A. Rabeprazole A. PPIs are absolutely contraindicated B. Omeprazole B. PPIs may be used freely C. Lansoprazole C. PPIs may be considered if benefit D. All have the same efficacy outweighs risk D. PPIs are teratogenic 14. Triple therapy to treat H. pylori includes: A. antibiotics and H RA 2 20. Which of the following is/are (an) B. antibiotics and PPI option(s) to treat ulcers? C. H2RA and PPI A. Naproxen D. A and B B. Surgery C. Cimetidine D. B or C

21