Gastroenterology Gastroesophageal Reflux Disease Courses in Therapeutics and

Gastroenterology: Gastroesophageal Reflux Disease Courses in Therapeutics and Disease State Management Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Learning Objectives (Slide 1 of 2) • Define GERD and describe the various stages of disease severity • Describe the etiology of GERD and risk factors associated with the disease • Discuss typical symptoms, alarm symptoms, aggravating factors and complications associated with GERD • Describe how GERD is diagnosed and the role of endoscopy • Discuss the various pharmacologic approaches for the treatment of GERD Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Learning Objectives (Slide 2 of 2) • Review the roles of the H 2 -antagonists and proton pump inhibitors in the treatment of GERD and prevention of its recurrence • Describe non-pharmacologic and lifestyle measures that may be beneficial in the reduction of symptoms of reflux disease • Given a GERD patient history, be able to recommend appropriate pharmacologic and nonpharmacologic therapies and explain the rationale behind your decision • Discuss drug adverse effects and monitoring parameters for drugs and GERD Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Required and Recommended Reading May D, Thiman M, Rao SC. Gastroesophageal Reflux Disease. In: Di. Piro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10 e New York, NY: Mc. Graw. Hill; 2017. Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

GERD Definitions • GERD (Gastroesophageal Reflux Disease) – A condition that occurs when refluxed stomach contents lead to troublesome symptoms and/or complications – Episodic pyrosis (heartburn) that is not frequent enough or painful enough to be considered bothersome by the patient is not included in the above consensus GERD definition • Pyrosis frequency of more than 2 times per week is sometimes used as a criteria for GERD • Chronic symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus. • Symptoms of GERD vary in severity, duration, and frequency. • When the esophagus is repeatedly exposed to refluxed material for prolonged periods of time, inflammation of the esophagus (esophagitis) occurs, and in some cases it can progress to erosion of the squamous epithelium of the esophagus (erosive esophagitis) and may lead to other complications. Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Epidemiology (Slide 1 of 2) • Heartburn is the most frequent clinical complaint – Reported to occur at least once daily in 10% – 20% weekly; – 44% monthly of U. S. adults – $5 billion for OTC/Rx per year • Most frequently occurs in adults over 40 years of age • Incidence in similar between men and women Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Epidemiology (Slide 2 of 2) • About 50% of pregnant women will experience GERD • Can also occur in infants • Prevalence depends on geographic region but is highest in Western countries Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Risk Factors • • • Obesity (BMI ≥ 30) Alcohol use Smoking Excessive caffeine intake Respiratory diseases Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Key Factors in the Development of GERD (Slide 1 of 2) • A decrease in lower esophageal sphincter (LES) pressure • Decreased clearance of gastric contents from the esophagus • Decreased mucosal resistance in the esophagus Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Key Factors in the Development of GERD (Slide 2 of 2) • Composition of reflux contents “extra acidic” – Gastric fluid that has a p. H < 4 is extremely caustic to the esophageal mucosa. • Decreased gastric emptying (increased gastric emptying time) • Certain anatomic features – Most commonly a hiatal hernia Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pathophysiology of GERD (Role of the Lower Esophageal Sphincter) • Link: Figure of comparison of esophageal high-resolution manometry • Link: Figure of pathophysiology of esophageal reflux disease (LES, lower esophageal sphincter) Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Hiatal Hernia • A hiatal hernia occurs when a portion of the stomach protrudes through the diaphragm into the chest – Causes a disruption in the normal anatomic barriers between the stomach and the esophagus • Link: Figure of radiographic anatomy of the gastroesophageal junction Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

GERD Symptoms • GERD symptoms are often grouped in 3 categories – Typical or “classic” esophageal symptoms – Alarm or complicated symptoms • May be indicative of GERD complications – Atypical or extraesophageal symptoms Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Typical or “Classic” Symptoms • Pyrosis (heartburn) – Hallmark symptom – A substernal feeling of warmth or burning rising up from the abdomen that may radiate to the neck • Regurgitation/Belching • Acid brash/Hypersalivation • Chest pain (non cardiac in nature) Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Alarm (Complicated) Symptoms • Any of these symptoms warrant immediate referral for testing – Dysphagia – Odynophagia – Bleeding – Unexplained weight loss – Choking – Chest pain (if could be cardiac in nature) Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Extraesophageal Symptoms/Manifestations (Atypical Symptoms) • These symptoms have an association with GERD but causality should only be considered if a concomitant esophageal symptoms are present – Chronic cough – Asthma-like symptoms • About 50% of those with asthma have GERD – Laryngitis/Hoarseness – Recurrent sore throat – Dental enamel erosion Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

GERD • GERD is often described on either esophageal symptoms or esophageal tissue injury – Symptom-based GERD syndromes (with or without esophageal tissue injury) – Tissue injury-based GERD syndromes (with or without esophageal symptoms) • Extraesophageal GERD syndromes may also occur • GERD is also sometimes described in terms of the absence or presence of esophageal erosions – Non-erosive reflux disease (NERD) – Erosive reflux disease (ERD) Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Symptom-Based GERD Syndromes • May or may not have esophageal tissue injury • Have typical or “classic” esophageal symptoms • May have alarm symptoms particularly if GERD complications (see next section) are present Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Tissue-Injury Based GERD Syndromes • Examples of esophageal tissue injury include the presence of any of the following: – Esophagitis (inflammation of the esophagus) – Erosions (erosion of the squamous epithelium of the esophagus) – Strictures – Barrett’s esophagus – Esophageal adenocarcinoma • May present with alarm symptoms particularly if have GERD complications • May or may not have typical or classic symptoms Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Extraesophageal GERD Syndromes • Present with extraesophageal or atypical symptoms • May or may not have typical esophageal symptoms • Extraesophageal symptoms have an association with GERD, but causality should only be considered if a concomitant esophageal GERD syndrome is also present • Extraesophageal manifestations of GERD are being recognized with increasing frequency. • GERD may be either a causative or exacerbating factor in up to 50% of patients who experience these symptoms. Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Aggravating Factors • • • Recumbency Increased intra-abdominal pressure Reduced gastric motility Decreased LES tone or pressure Direct mucosal irritation Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Decrease in LES Pressure • Examples of foods that decrease LES pressure – Fatty foods, peppermint, spearmint, chocolate, coffee, cola, tea, garlic, onions, chili peppers • Examples of medications that decrease LES pressure – Anticholinergics, barbiturates, benzodiazepines, caffeine, dihydropyridine calcium channel blockers, dopamine, estrogen, ethanol, narcotics, nicotine, nitrates, progesterone, theophylline Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Direct Mucosal Irritation • Examples of foods that are direct irritants to the esophageal mucosa – Spicy foods, orange juice, tomato juice, coffee • Examples of medications that are direct irritants to the esophageal mucosa – Oral bisphonates, aspirin, iron, NSAIDs, quinidine, potassium Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Foods and Medications that May Worsen GERD Symptoms Foods/Beverages Medications Decreased Lower Esophageal Sphincter Pressure Fatty meal Anticholinergics Carminatives (peppermint, spearmint) Barbiturates Chocolate Caffeine Coffee, cola, tea Dihydropyridine calcium channel blockers Garlic Dopamine Onions Estrogen Chili peppers Nicotine Alcohol (wine) Nitrates Progesterone Tetracycline Theophylline Direct Irritants to the Esophageal Mucosa Spicy foods Aspirin Orange juice Bisphonates Tomato juice Nonsteroidal antiinflammatory drugs (NSAIDs) Coffee Iron Tobacco Quinidine Potassium chloride Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Complications of GERD • Esophagitis – Link: Figure of EGD demonstrating linear red streaks with a central white streak extended up the esophagus in peptic regurgitant esophagitis • Erosions and ulceration of the esophageal mucosa • Strictures of the esophagus – Secondary to fibrous tissue deposition after long standing erosion • Barrett’s esophagus – Present in about 10% of those with GERD – Most prevalent in white males in Western countries • Esophageal adenocarcinoma Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Barrett’s Esophagus (Slide 1 of 2) • Barrett’s esophagus occurs when the normal squamous cell epithelium in the esophagus converts to a columnar cell epithelium (intestinal-type epithelium) • More common in men than women • Barrett’s esophagus does not cause specific symptoms but the reflux does Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Barrett’s Esophagus (Slide 2 of 2) • Those with Barrett’s esophagus develop adenocarcinoma of the esophagus at a rate of 0. 12% per year – Gender ratio for esophageal adenocarcinoma is 8: 1 (male: female) • Patients must be monitored via endoscopy to evaluate changes in cell type and conversion to adenocarcinoma Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Complications of GERD (Photos) Link: Photos of endoscopic appearance of peptic esophagitis, a peptic stricture, Barrett’s metaplasia, and adenocarcinoma Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

GERD Diagnosis/Diagnostic Tests (Slide 1 of 4) • Clinical History – Patient’s description of typical or classic GERD symptoms such as pyrosis, is often enough to consider GERD as an initial diagnosis (uncomplicated GERD) • Empiric trial of proton pump inhibitor (PPI) therapy – ACG (American College of Gastroenterology) guidelines state that it is reasonable to assume a GERD diagnosis in patients who respond to appropriate therapy Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

GERD Diagnosis/Diagnostic Tests (Slide 2 of 4) • Endoscopy – Endoscopy is the technique of choice to identify complications of GERD such as ulcerations, erosions, Barrett’s esophagus, etc. – Biopsy of the esophageal tissue is needed to identify and diagnose Barrett’s esophagus and esophageal adenocarcinoma – Many patients with GERD (presenting with typical or atypical symptoms) will have normal appearing esophageal mucosa on endoscopy – Usually not part of the work-up except in certain subsets of patients (alarm symptoms, those refractory to treatment, etc. ) Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

GERD Diagnosis/Diagnostic Tests (Slide 3 of 4) • Ambulatory p. H Monitoring – Identifies patients with excessive esophageal acid exposure and helps determine if symptoms are acid related – Useful in patients not responding to acid-suppression therapy • Barium Radiography – Not routinely used to diagnose GERD due to a lack of sensitivity and specificity – Can detect hiatal hernia Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

GERD Diagnosis/Diagnostic Tests (Slide 4 of 4) • Patients presenting with extraesophageal or atypical symptoms should be reviewed on a case-by-case basis to be considered for testing • Alarm symptoms always warrant further testing Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Therapeutic Approach to GERD • The initial treatment used is determined by the patient’s condition: – Frequency of symptoms – Degree of symptoms – Presence and/or degree of esophagitis – Presence of complications Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Goals of Treatment • • Alleviate or eliminate acute symptoms Decrease frequency of recurrence Promote healing if esophageal tissue injury is present Prevent complications Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

General Treatment Approach • Initial therapy in patients who present with typical GERD symptoms should include patient-directed (self-care) therapy (antacids, OTC H 2 -antagonist, or OTC PPIs) and lifestyle modifications • Those who do not respond to patient-directed therapy and lifestyle modifications after 2 weeks should seek medical attention and are usually started on empiric therapy consisting of an acid suppression agent such as a proton pump inhibitor (PPI) • Those who do not respond to empiric acid suppression therapy or have alarm symptoms should undergo testing such as an endoscopy Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Nonpharmacologic Therapies • Lifestyle modifications – Should be incorporated into the management of GERD regardless of the severity of disease – Lifestyle modifications should be tailored to an each individual patient’s needs • Anti-reflux surgery – Used as a last resort option in select patients • When long-term pharmacologic therapy is undesirable • Who have refractory GERD • Have complications • Endoscopic therapies – Results have been disappointing and hence are not usually recommended Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Lifestyle Modifications (Slide 1 of 2) • Weight loss (if the patient is overweight or obese) • Elevation of the head of the bed 6 to 8 inches • Eat smaller, more frequent meals (as opposed to larger meals less frequently) • Include protein-rich meals in diet (increases LES pressure) Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Lifestyle Modifications (Slide 2 of 2) • • Avoid eating 3 hours prior to sleeping or lying down Avoid foods or medications that exacerbate GERD Avoid alcohol Tobacco cessation Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Endoscopic Interventions • Stretta Procedure – Stretta is an endoscopically guided radiofrequency (RF) energy delivery system. The device is guided down the esophagus and RF energy is delivered to tissues via catheters/needles. RF energy is thought to improve GERD symptoms by increasing collagen deposition at the LES, increasing muscle wall thickness and reconstituting the barrier to the reflux of gastric contents. • LINX Reflux Management System (FDA approved March 2012) – A series of titanium beads each with a magnetic core connected together with a wire to form a ring shape. – Implanted in the LES – The force of the magnetic beads provides additional strength to a keep a weak LES closed. Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Therapeutic Interventions in the Management of GERD Link: Figure of therapeutic interventions in the management of gastroesophageal reflux disease Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pharmacologic Agents Used in the Treatment of GERD • • Antacids and alginic acid products H 2 -receptor antagonists (HRA) Proton pump inhibitors (PPIs) Promotility agents Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Antacids (Slide 1 of 2) • MOA – Neutralize hydrochloric acid in the stomach, which results in an increase in gastric p. H • Agents – Magnesium hydroxide – Aluminum hydroxide – Calcium carbonate • Adverse effects – – Diarrhea (magnesium hydroxide) Constipation (aluminum hydroxide and calcium carbonate) Alterations in mineral metabolism Acid-base disturbances Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Antacids (Slide 2 of 2) • Monitoring – Periodic calcium and phosphate levels if on chronic antacid therapy • Patient counseling – Antacids can decrease the levels of numerous other drugs including tetracyclines, digoxin, iron supplements, fluroquinolones, and ketoconazole. • Patients should separate antacids and other medications by at least 2 hours – Patients with renal impairment should not use aluminum or magnesium containing antacids unless directed by their physician – Onset of relief is less than 5 minutes and duration of relief is 20 to 30 minutes Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Composition and Acid Neutralizing Capacities of Popular Antacid Preparations Al(OH)3 a Mg(OH)2 a Ca. CO 3 a SIMETHICONEa ACID NEUTRALIZING CAPACITYb Gelusil 200 0 25 10. 5 Maalox Quick Dissolve 0 0 600 0 12 Mylanta Double Strength 400 0 40 23 Riopan Plus Double Strength Magaldrate, 1080 20 30 PRODUCT Tablets Calcium Rich Rolaids 80 412 0 11 0 0 750 0 15 Maalox TC 600 300 0 0 28 Milk of Magnesia 0 400 0 0 14 Mylanta Maximum Strength 400 0 40 25 Riopan Magaldrate, 540 0 15 Tums EX Liquids a. Contents, milligrams per tablet or per 5 ml. neutralizing capacity, milliequivalents per tablet or per 5 ml. The U. S. marketplace for antacids is fluid. The current trend of "reusing" well-known brand names to introduce new products that contain an active ingredient different from expected is a source of confusion that can present a danger to patients. Medication safety experts encourage clinical practitioners to refer to the active ingredient(s) in conjunction with the proprietary (brand) name when selecting OTC products. b. Acid Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Antacid-Alginic Acid Combination • MOA – The antacid neutralizes stomach acid and the alginic acid is a foaming agent that creates a viscous solution that floats on top of the stomach contents and may be protect the esophagus from refluxed stomach acid • Agents – Aluminum hydroxide/Magnesium carbonate/Alginic acid (Gaviscon) Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

H 2 -Receptor Antagonists (Slide 1 of 2) • MOA – Competitive inhibition of histamine at H 2 receptors of gastric parietal cells which inhibits gastric acid secretion • Agents – Cimetidine (Tagamet) – Famotidine (Pepcid) – Nizatidine (Axid) – Ranitidine (Zantac) Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

H 2 -Receptor Antagonists (Slide 2 of 2) • Adverse effects – Headache, somnolence, fatigue, dizziness, constipation, diarrhea • Monitoring – Monitor for CNS effects (rare) in those over 50 years old or in those with renal or hepatic impairment • Patient counseling – If taking once a day, it is preferable to take the dose at bedtime – Onset of relief is 30 to 45 minutes and duration of relief is 4 to 10 hours Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Proton Pump Inhibitors (PPIs) (Slide 1 of 3) • MOA – Blocks acid secretion by inhibiting gastric H+/K+ adenosine triphosphatase found on the secretory surface of gastric parietal cells – Results in a long-lasting anti-secretory effect that can maintain gastric p. H levels above 4 • Agents – – – – Dexlansoprazole (Dexilant) Esomeprazole (Nexium) Lansoprazole (Prevacid) Omeprazole (Prilosec) Omeprazole/sodium bicarbonate (Zegerid) Pantoprazole (Protonix) Rabeprazole (Aciphex) Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Proton Pump Inhibitors (PPIs) (Slide 2 of 3) • Common adverse effects – Headache, dizziness, somnolence, diarrhea, constipation, flatulence, abdominal pain, nausea • Serious adverse effects – Increased risk of Clostridium difficile infections – Increase risk of community-acquired pneumonia • Long-term adverse effects (> 1 year) – Hypomagnesemia – Bone fractures – Vitamin B 12 deficiency Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Proton Pump Inhibitors (PPIs) (Slide 3 of 3) • Monitoring – Appearance of diarrhea (frequency and type of diarrhea episodes) – Periodic magnesium levels (if long-term therapy) – Routine bone density studies (DXA scans) • If other risk factors for osteoporosis or bone fractures present • Patient counseling – Preferable to take a PPI 30 to 60 minutes before a meal (mainly breakfast) – If a second dose is needed, take prior to the evening meal – Onset of relief is 2 to 3 hours and the duration of relief is 12 to 24 hours Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Evaluate the Risks versus Benefits of Long-Term PPI Use (Slide 1 of 2) • Long-term PPI use has been associated with increased risk of: – Fractures – Infections such as C. Diff and pneumonia (expand) – Hypomagnesemia – Vitamin B 12 deficiency Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Evaluate the Risks versus Benefits of Long-Term PPI Use (Slide 2 of 2) • Long-term PPI use MAY BE associated with increased risk of: – Dementia – Renal disease – Cardiovascular disease Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Promotility Agents • Promotility agents, such as metoclopramide and bethanechol, have been used as adjunct therapy to acid suppression agents such as PPIs in patients who have a known motility defect • However, they are not generally recommended to be used for GERD treatment due to their limited effectiveness and undesirable adverse effect profiles Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pharmacologic Therapy (Slide 1 of 3) • Patient directed therapy (Self-care) is appropriate for intermittent, mild pyrosis and is managed using over-thecounter products such as antacids, OTC H 2 -receptor antagonists, and OTC proton pump inhibitors (PPIs) • Link: Table on Therapeutic Approach to GERD in Adults Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pharmacologic Therapy (Slide 2 of 3) • Symptomatic relief of uncomplicated GERD is treated with prescription H 2 -receptor antagonists or prescription PPIs at the following doses and durations: • Refer to Link: Table on Therapeutic Approach to GERD in Adults Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pharmacologic Treatment (Slide 3 of 3) • Healing of erosive esophagitis or treatment of patients presenting with moderate to severe symptoms or complications • Refer to Link: Table on Therapeutic Approach to GERD in Adults Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

PPIs v. H 2 -Receptor Antagonists • Symptomatic improvement as well as endoscopic healing rates are higher for the PPIs compared to the H 2 -receptor antagonists • PPIs are therefore preferred over H 2 -receptor antagonists in patients with erosive disease, moderate to severe symptoms, or with complications Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Maintenance Therapy (Slide 1 of 2) • What patients should receive maintenance therapy? – Those with symptomatic relapse following discontinuation of the drug or a decrease in dose. • If NERD/uncomplicated GERD, try to manage with on-demand or intermittent PPI therapy or H 2 -receptor antagonists Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Maintenance Therapy (Slide 2 of 2) • What patients should receive maintenance therapy? – Those with a history of complications (e. g. Barrett’s esophagus, strictures, hemorrhage, ulcerations, etc. ) • Long-term maintenance therapy with PPIs at the lowest possible dose – Can consider intermittent or on demand PPI therapy in some circumstances Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

PPIs and Rebound Acid Secretion (Slide 1 of 2) • There have been reports of rebound acid secretion when PPIs are abruptly discontinued. – This can happen when PPIs are used for as little as 2 months (and of course when they are used longer) – These hyperacidity symptoms include dyspepsia and heartburn • Often attributed to a relapse of the disorder (e. g. GERD), but it can even happen in patients who didn’t have these symptoms to start with Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

PPIs and Rebound Acid Secretion (Slide 2 of 2) • Tapering strategies for patients experiencing rebound acid secretion – (1) Taper PPI over 4 to 6 weeks • First lower the dose of the PPI • Then extend the PPI dosing interval to every other day then every 3 rd day • An H 2 -antagonist or antacid can be used for symptoms on “off days” as needed – (2) Suggest a switch to an H 2 -antagonist with antacids used as needed for several weeks then discontinue Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Patients with Extraesophageal (Atypical) GERD (Slide 1 of 2) • GERD can be considered as a potential co-factor in patients with asthma, chronic cough, or laryngitis – Careful evaluation of non-GERD causes should be undertaken in all of these patients • Patients with atypical symptoms may need higher doses of acid suppression therapy with longer treatment duration compared to those patients with typical symptoms Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Patients with Extraesophageal (Atypical) GERD (Slide 2 of 2) • A PPI trial is recommended to treat extraesophageal symptoms in patients who have typical GERD symptoms as well • Reflux monitoring should be considered before a PPI trial in patients with extraesophageal symptoms who do not have typical GERD symptoms Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pediatric Patients (Slide 1 of 2) • A suspected cause of reflux in infants is a developmentally immature LES • Many infants have reflux with little or no clinical consequence – This uncomplicated reflux usually manifests as regurgitation or spitting up – Usually responds to supportive therapy • Chronic vomiting associated with GERD must be carefully evaluated and distinguished from other causes Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pediatric Patients • Careful consideration should be given before a medication is recommended • When a medication is deemed necessary, ranitidine dosed at 2 to 4 mg/kg twice a day is often used • PPIs are increasing being used in children older than 1 year – Lansoprazole, esomeprazole, and omeprazole are indicated for treating symptomatic and erosive GERD in children > 1 year old – See next slide for dosing ranges • Omeprazole has been used off-label in children less than 1 year old at a dose of 1 mg/kg/day Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

PPIs in Children > 1 year of age • Lansoprazole – 15 mg per day is recommended for children weighing < 30 kg – 30 mg per day is recommended for children weighing > 30 kg • Esomeprazole – Dosed 10 to 20 mg a day for children 1 to 11 years old – Dosed at 20 to 40 mg a day for children 12 to 17 years old • Omeprazole – 5 mg daily in children weighing between 5 and 10 kg – 10 mg daily in children weighing between 10 and 20 kg – 20 mg daily in children weighing ≥ 20 kg Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Elderly Patients • Many elderly patients have decreased defense mechanisms such as decreased saliva production • PPI therapy may be warranted for those > 60 years of age with symptomatic GERD – They have superior efficacy and have once a day dosing – Long-term risk of bone fractures is a concern and elderly patients should be monitored appropriately • Elderly are at higher risk of being sensitive to possible CNS effects of H 2 -receptor antagonists Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Patients with Refractory GERD • Refractory GERD should be considered in patients who have not responded to a standard course of twice a day PPI therapy • The majority of patients with refractory symptoms experience nocturnal acid breakthrough • Switching to a different PPI may be effective in some patients • Adding an H 2 -receptor antagonist at bedtime for nocturnal symptoms is reasonable but the effect may decrease over time due to tachyphylaxis with H 2 -receptor antagonists Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

References (Slide 1 of 3) • May D, Thiman M, Rao SC. Gastroesophageal Reflux Disease. In: Di. Piro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10 e New York, NY: Mc. Graw-Hill; 2017. • Mills JC, Stappenbeck TS. Gastrointestinal Disease. In: Hammer GD, Mc. Phee SJ. eds. Pathophysiology of Disease: An Introduction to Clinical Medicine, Seventh Edition. New York, NY: Mc. Graw-Hill; 2013. • Kahrilas PJ, Hirano I. Diseases of the Esophagus. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 19 e. New York, NY: Mc. Graw-Hill; 2015. Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

References (Slide 2 of 3) • Wallace JL, Sharkey KA. Pharmacotherapy of Gastric Acidity, Peptic Ulcers, and Gastroesophageal Reflux Disease. In: Brunton LL, Chabner BA, Knollmann BC. eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 12 e. New York, NY: Mc. Graw-Hill; 2011. • Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol 2013; 108: 308 -328. • Schoenfeld AJ, Grady D. Adverse effects associated with proton pump inhibitors. JAMA Internal Medicine 2016; 176(2): 172 -174. Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

References (Slide 3 of 3) • Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor, MI. Accessed October 15, 2016. • Lexicomp Online®, Lexi-Drugs®, Hudson, Ohio: Lexi. Comp, Inc. Accessed October 15, 2016. Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved