GERD.pptx

Gastroesophageal Reflux Disease (GERD) Justin Kirby, PharmD, BCACP, NBC-HWC PHPR 2813: Pharmacotherapy I Objectives • Recall the pathophysiologic mechanisms associated with gastroesophageal reflux disease (GERD). • Distinguish between symptom-based (typical or alarm), esophageal tissue-based (esophagitis, strictures, Barrett’s esophagus, or esophageal adenocarcinoma) esophageal GERD syndromes and extraesophageal GERD syndromes (chronic cough, laryngitis, or asthma). • Recall alarm symptoms that mandate further diagnostic evaluation. • List medications or foods that can worsen the symptoms of GERD. • Recall the risk factors that can predispose a patient to GERD. Objectives • Discern which diagnostic test is appropriate based on the patient’s clinical presentation. • Describe the goals of treating a patient with GERD. • Debate the benefits and limitations of lifestyle modifications in the treatment of GERD. • Compare and contrast the differences between patient-directed therapy and medication therapy (with acid suppression agents) • Discuss the benefits of proton pump inhibitors over H2-receptor antagonists in the treatment of moderate-to-severe GERD. Objectives • Evaluate a patient’s medication profile for potential drug–drug or drug–food interactions. • Monitor for potential adverse drug reactions associated with GERD therapies. • Assess the need for maintenance therapy in a patient with GERD. • Describe the potential options available for maintenance therapy of GERD. Introduction • Definition: Symptoms or complications resulting from refluxed stomach contents into the esophagus or beyond, into the oral cavity or lung • Symptoms must adversely affect the patient’s well being and/or quality of life (twice weekly or more) • Does not include episodic heartburn • Can be further classified into symptom-based or tissue injury-based Symptom-based • Symptom-based GERD may exist with or without injury and may include • • • • Heartburn Regurgitation Dysphagia Less commonly odynophagia, belching, bloating, hypersalivation, and water brash • Symptomatic GERD without tissue injury is sometimes termed nonerosive reflux disease (NERD) Tissue Injury-based • Tissue injury-based GERD may exist with or without symptoms • Injury spectrum may include • Esophagitis • Esophageal Strictures • Barrett’s Esophagus • Adenocarcinoma of the esophagus Extraesophageal Reflux Syndromes • Chest pain • Hoarseness • Chronic cough • Asthma Prognosis • Mild GERD typically does not lead to erosive esophagitis • Often managed with lifestyle changes and medications • More severe cases relapse more frequently, require more intensive, long-term treatment with acid suppression and maintenance. • Antireflux surgery is a possibility for select patients • Bariatric surgery is an option for obese patients • Endoscopic therapies are continuing to be evaluated as a less invasive, non-medication option. Epidemiology • Most commonly occurs in people >50 years • Rarely fatal but may have significant quality of life impacts • Difficult to assess true global impact due to several patients not seeking medical care, lack of symptom and disease severity correlation, and lack of standardized diagnostic definition • Prevalence is increasing; 20% of adults in North America suffer from GERD symptoms at least weekly Risk Factors • Gender-related • Symptoms are more prevalent in females, especially when pregnant • Erosive esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma are more common in males • Esophageal adenocarcinoma is more common in patients with chronic GERD symptoms • Family history, smoking, alcohol consumption, certain medications and foods, respiratory disorders, obesity, non-alcoholic fatty liver disease, and major depressive disorder Pathophysiology • Key factor: Abnormal reflux of gastric contents from the stomach into the esophagus, oral cavity, and/or the lung because of an incompetent anti-reflux barrier at the esophagogastric junction (EGJ) • Sometimes this is related to decreased lower esophageal sphincter (LES) tone, which can be caused by • Spontaneous transient LES relaxations • Transient increases in intra-abdominal pressure • An atonic LES Other Pathophysiological Causes • Mucosal malfunctions • Abnormal anatomy • Improper clearance of gastric fluids • Reduced mucosal resistance to acid • Delayed or ineffective gastric emptying • Composition and volume of the reflux Diagnosis • Obtain a clinical history that inquires for presenting symptoms and associated risk factors • A clinical diagnosis of GERD can be assumed in patients who respond to an appropriate, empiric trial of therapy (not appropriate for patients with alarm symptoms) • Other potential tests for diagnosing GERD include endoscopy, ambulatory reflux monitoring, combined impedance-pH monitoring, manometry/high-resolution esophageal pressure topography (HREPT), impedance manometry, and mucosal biopsies • Diagnosis should be proven before long-term acid suppression therapy is considered Treatment • Available treatments are aimed at reversing the various pathophysiological abnormalities • Disease management goals: • Alleviate or eliminate patient symptoms • Decrease the frequency or recurrence and duration of GERD • Promote healing of the injured mucosa • Prevent complications Treatment • Aimed at • Decreasing the acidity of the reflux • Decreasing the gastric volume available to be refluxed • Improve gastric emptying • Increasing LES pressure • Enhancing esophageal acid clearance • Protecting the esophageal mucosa Treatment Recommendations • (Recommendations with at least moderate level of evidence and/or strong strength of evidence) • Lifestyle: Weight loss in overweight GERD patients or in those who have recently gained weight • Acid suppression therapy: Therapy of choice for symptom relief and healing of erosive esophagitis is an 8-week PPI course (similar efficacy among all PPIs) • Should be administered 30-60 minutes before a meal, once daily, and prior to the first meal of each day for maximal pH control • Can be used in patients on clopidogrel without an increased risk of cardiovascular events General Approach to Treatment • Stepwise approach that typically includes • Lifestyle changes and patient directed therapy w/antacids, nonprescription histamine2 receptor antagonists (H2RAs) and/or nonprescription proton pump inhibitors (PPIs) • Pharmacological treatment with prescription strength acid suppression therapy • Surgery • Endoscopic therapies General Approach to Treatment • Patients with typical GERD symptoms should be treated with lifestyle modifications and a trial of empiric acid suppression therapy • Non-responders or patients presenting with alarm symptoms should undergo endoscopy • Patients with mild symptoms can be initiated on an H 2RA • Patients with moderate to severe symptoms can be initiated on a PPI Nonpharmacological Therapy • Lifestyle Modifications: should be patient specific (not all lifestyle modification should be recommended to all people) • Typical interventions include • Weight loss • Elevating the head of the bed for nocturnal symptom control • Eating smaller meals • Not sleeping for 3 hours after eating • Avoiding triggering foods, medications, alcohol, and smoking Patient-Directed Therapy • Patients with mild symptoms may self treat with over the counter medications for up to 2 weeks. • Antacids • May offer symptomatic relief by increasing gastric pH • Documentation in placebo controlled trials is lacking • Several potential drug-drug interactions (tetracycline, iron, sulfonylureas, antibiotics) • Generally taken on an as-needed basis • OTC H2RAs and PPIs may also be used according to package directions Medication Therapy • Patients with moderate but non-alarm symptoms may be prescribed medications if they fail patient-directed treatment • Proton Pump Inhibitors • Provide the greatest symptom relief (83% of patients) and the highest healing rates, especially for patients with erosive disease, moderate-to-severe symptoms, or complications • Include dexlansoprazole (Dexilant©), esomeprazole (Nexium©), lansoprazole (Prevacid©), omeprazole (Prilosec©), omeprazole and sodium bicarbonate (Zegerid©), pantoprazole (Protonix©), and rabeprazole (Aciphex©) Medication Therapy • Proton Pump Inhibitors • Mechanism of action: Block gastric secretion by inhibiting H+/K+-adenosine triphosphate in gastric parietal cells • Maintains extended time with gastric pH >4; correlated with the healing of erosive esophagitis • Similar efficacy among all PPIs • Superior to H2RAs in treating moderate to severe GERD and should be given and trialed in those with troublesome symptoms for at least 8 weeks Medication Therapy • Proton Pump Inhibitors • Should be discontinued in patients with uncomplicated GERD or the dosage should be lowered to the lowest effective dose after the empirical trial • Rebound acid hypersecretion was seen in trials when used for >8 weeks making withdrawal difficult • Data is lacking on a proper tapering protocol • Various approaches may be considered on a case-by-case basis Medication Therapy • Proton Pump Inhibitors • BID dosing in those not responding to a standard once daily course of therapy • Similar efficacy to swapping to an alternative PPI (~20% symptom improvement) • Most common side effects include headache, diarrhea, nausea, and abdominal pain • Increasing concerns with PPI safety have been reported more recently • Community acquired pneumonia has been reported in short term use • Enteric infections, vitamin B12 deficiency, hypomagnesemia, and bone fractures are potential long term adverse effects with renal disease being another concern Medication Therapy • Proton Pump Inhibitors • Drug interactions vary slightly with each agent • All agents decrease absorption of ketoconazole or itraconazole, which require an acidic environment to be absorbed • Omeprazole strongly inhibits CYP2C19, which is the enzyme responsible for the conversion of clopidogrel from prodrug to active ingredient • Dexlansoprazole is uniquely formulated as a dual-delayed release capsule that releases part of the drug 1-2 hours post dose and the rest 4-5 hours post-dose Medication Therapy • Proton Pump Inhibitors • For pediatric patients or patients unable to swallow tablets/capsules, many alternative options exist • Delayed-release (DR) capsules can be mixed in applesauce or OJ • Esomeprazole granules can be dispersed in water • Esomeprazole, omeprazole, and pantoprazole are available in delayed release oral suspension packets • Dexlansoprazole and lansoprazole are available as DR orally disintegrating tablets Medication Therapy • Proton Pump Inhibitors • Rabeprazole is available in a capsule sprinkle that can be opened and placed on food • Esomeprazole and pantoprazole are the only IV formulations available • The omeprazole/Na Bicarbonate combination (Zegerid©) is the only immediate release PPI and should be taken at least an hour before the first meal of the day • The powder formulation offers an alternative option for patients with a nasogastric tube; the capsule formulation should be swallowed whole and never opened Medication Therapy • Proton Pump Inhibitors • Counseling points: patients should take PPIs 30-60 minutes before breakfast or their largest meal of the day to maximize efficacy • Dexlansoprazole can be taken without regard to meals • • Patients with nocturnal symptoms or those on BID dosing should take their evening dose prior to their nightly meal or a snack and at least 10-12 hours after the first dose, respectively Medication Therapy • Histamine2 Receptor Antagonists • Include cimetidine (Tagamet©), famotidine (Pepcid©), and nizatidine • Ranitidine (Zantac©) and the brand name formulation of nizatidine (Axid©) were pulled from the US market in 2020. • Variable effectiveness in treating patients with mild to moderate GERD and often less than desired Medication Therapy • Histamine2 Receptor Antagonists • Disease severity, dosage regimen used, and duration of therapy all affect response • All agents have similar efficacy; agent selection should be patient specific • Cimetidine has many drug interactions and may inhibit the metabolism of warfarin, theophylline, phenytoin, nifedipine, propranolol, and others • Headache, fatigue, dizziness, constipation/diarrhea are the most common adverse effects Medication Therapy • Other agents • The promotility agent metoclopramide, a dopamine antagonist, increases LES pressure in a dose related manner by accelerating gastric emptying. • Does not accelerate esophageal clearance • Provides symptomatic relief for some patients but is not supported by data • Many CNS side effects, including extrapyramidal symptoms and tardive dyskinesia, limit its use • Bethanechol and baclofen are also occasionally used, but side effects also limit their usefulness; Sucralfate, a mucosal protectant, also has limited usefulness in GERD Medication Therapy: Pearls • Data to support the combination of acid suppression therapy with mucosal protection are lacking • The addition of a bedtime dose of an H2RA to PPI therapy may decrease nocturnal symptoms but efficacy can decrease with time • A bedtime dose of the omeprazole/Na bicarbonate immediate release product in addition to a once daily PPI may offer an alternative for nocturnal GERD symptoms • Patients with uncomplicated GERD who respond to short term PPI therapy should be considered for discontinuation or dose de-escalation • Many patients have relapsing symptoms if medication therapy is withdrawn and long term maintenance with a PPI may be required in those patients. Medication Therapy: Pearls • If discontinuation is not possible, ambulatory esophageal reflux pH/impedance monitoring should be performed before committing to lifetime PPI use • Patients using PPIs should be evaluated regularly to ensure the lowest possible effective dose is being used • H2RAs or low dose PPIs may be effective for mild disease • “On demand” PPI use may be reasonable for mild, endoscopic-negative GERD • A trial of PPI therapy is recommended for patients with extraesophageal symptoms with concurrent typical GERD symptoms; ambulatory esophageal reflux monitoring is recommended for patients with extraesophageal symptoms who do not have typical GERD symptoms Medication Therapy: Pearls • Optimal PPI dosing is not well-defined • Maintenance therapy is generally indicated for patients respond to a PPI trial or have endoscopic evidence of reflux • Careful consideration should be taken before prescribing acid suppression therapy to infants as many of them have uncomplicated GERD that resolves by about 12 months • The definition of refractory GERD is not well-developed but should be considered in patients who have not responded to BID PPI therapy for 12 weeks Medication Therapy: Pearls • Proper medication use should be assessed before increasing a dose or changing agents • Antireflux surgery, magnetic sphincter augmentation, and endoscopic therapies may have a role in refractory GERD, depending on patient specific factors • Medication reconciliation is vital in patients with a history of PPI usage References May D, Lavender DL, Rao SC. Gastroesophageal Reflux Disease. In: DiPiro JT, Yee GC, Michael Posey LL, Haines ST, Nolin TD, Ellingrod VL. eds. DiPiro: Pharmacotherapy A Pathophysiologic Approach, 12e. McGraw Hill; 2021. Accessed January 04, 2023. https://accesspharmacy.mhmedical.com/content.aspx ?bookid=3097&sectionid=267287647 Gastroesophageal Reflux Disease (GERD) Justin Kirby, PharmD, BCACP, NBC-HWC PHPR 2813: Pharmacotherapy I

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