GASTROESOPHAGEAL REFLUX DISEASE (GERD) CHRISTINA VOSKANIAN, PHARM.D. WEST COAST UNIVERSITY PHARM 744 MARCH 27TH, 2024 RECOMMENDED READING ¡ DiPiro: Pharmacotherapy A Pathophysiologic Approach, 12e | AccessPharmacy | McGraw Hill Medical. accesspharmacy.mhmedical.com. https://accesspharmacy.mhmedical.com/book.aspx?bookID=3097 2 OBJECTIVES • Define gastroesophageal reflux disease (GERD) and its physiological basis. • Describe the factors that contribute to the development of GERD, including anatomical abnormalities and lifestyle habits. • Explain how certain medical conditions and medications can increase the risk of GERD. • Discuss the role of dietary changes and weight management in GERD treatment. • Discuss the appropriate use and potential side effects of various medications for GERD. 3 INTRODUCTION 4 GASTROESOPHAGEAL REFLUX DISEASE (GERD) ¡ Gastroesophageal reflux disease (GERD) is a chronic gastrointestinal disorder ¡ Characterization: ¡ Regurgitation of stomach acid and stomach contents into the esophagus ¡ Reflux may lead to irritation of the esophagus lining resulting in GERD ¡ Sometimes confused with heartburn or acid reflux 5 GASTROESOPHAGEAL REFLUX DISEASE (GERD) ¡ Statistics: ¡ Most commonly occurs in individuals above 50 years old ¡ May lead to reduction of quality of life and economic burden ¡ Prevalence: ¡ ~ 20% of adults in United States suffer from GERD symptoms on a weekly basis ¡ > 50% still have persistent symptoms even with PPI use 6 GASTROESOPHAGEAL REFLUX DISEASE (GERD) Men Erosive esophagitis Barrett's esophagus Women: Esophageal adenocarcinoma Pregnancy Non-Erosive Reflux Disease (NERD) 7 8 PATHOPHYSIOLOGY ¡ Abnormal reflux of gastric contents from stomach to esophagus, oral cavity, or lung ¡ EGJ Barrier: ¡ Lower esophageal sphincter (LES) ¡ Crural diaphragm (CD) ¡ Angle of His ¡ Flap valve 9 LOWER ESOPHAGEAL SPHINCTER (LES) ¡ Smooth muscle ¡ Located at the distal esophagus ¡ Contracted state to prevent gastric material reflux ¡ Relaxes to permit food passing into the stomach ¡ LES pressure may be reduced by various foods, medications, coughing, bending over, patient position, etc. 10 CONTRIBUTING RISK FACTORS Obesity Tobacco smoking 2.5x higher risk 1.26x higher risk Respiratory diseases Genetics Alcohol Medications Laying down after eating Large gastric volume Hiatal hernia Foods 11 CONTRIBUTING RISK FACTORS 12 FOODS THAT MAY WORSEN GERD Decreased Lower Esophageal Sphincter Fatty meal Carminatives (peppermint, spearmint) Chocolate Coffee, cola tea Garlic Onions Chili peppers Alcohol 13 IRRITANTS THAT MAY WORSEN GERD Direct Irritants to Esophageal Mucosa Spicy foods Orange juice Tomato juice Coffee Tobacco Aspirin Bisphosphonates NSAIDs Iron Quinidine Potassium chloride 14 MEDICATIONS THAT MAY WORSEN GERD MEDICATIONS Anticholinergics Barbiturates Caffeine DHP CCBs Dopamine Estrogen Nicotine Nitrates Progesterone Tetracycline Theophylline 15 COMPLICATIONS – TISSUE INJURY Esophagitis Inflammation of esophagus Esophageal Strictures Narrowing of esophageal lumen Barrett’s Esophagus Lining of the esophagus is damaged by stomach acid Esophageal Adenocarcinoma Cancer in the cells lining the lower part of the esophagus ¡ Severity of symptoms ≠ degree of tissue injury ¡ Correlates to duration of reflux 16 17 18 BARRETTE’S ESOPHAGUS ¡ Normal squamous epithelium lining the esophagus is replaced with metaplastic columnar cell ¡ Result of chronic acid exposure from GERD ¡ Complication of GERD ¡ Often asymptomatic ¡ May present as heartburn and acid reflux 19 BARRETTE’S ESOPHAGUS ¡ Screening ¡ Indicated for men with chronic GERD (5+ years duration) or acid regurgitation (1x per week minimum) OR ≥ 2 risk factors ¡ 50+ years old ¡ White ¡ Central obesity (waist circumference >102 cm or waist –hip ration >0.9) ¡ Tobacco use (past or current use) ¡ Family history ¡ Diagnosis ¡ Upper endoscopy (esophagogastroduodenoscopy or EGD) and biopsy 20 CHECK-IN What is the most common symptom of GERD? a. b. c. d. Diarrhea Heartburn Headache Muscle cramps 21 CHECK-IN What happens in GERD that causes discomfort? a. b. c. d. The stomach doesn't produce enough acid. The lower esophageal sphincter (LES) weakens or relaxes inappropriately. The esophagus becomes inflamed. All of the above 22 CHECK-IN A complication of GERD that can damage the lining of the esophagus is: a. b. c. d. Diverticulitis Barrett's esophagus Ulcerative colitis Irritable bowel syndrome (IBS) 23 CLINICAL PRESENTATION 24 CLINICAL PRESENTATION: GERD Common Symptoms Heartburn Regurgitation Chest pain Dysphagia Chronic cough Laryngitis Wheezing Asthma (~50% also have GERD) 25 CLINICAL PRESENTATION: GERD Dysphagia Alarm Symptoms Odynophagia Weight loss GI Bleeding Iron deficiency anemia Persistent Vomiting Epigastric mass 26 DIAGNOSIS Empiric Proton Pump Inhibitor (PPI) Therapy Less expensive Endoscopy Preference in assessing mucosal injury and complications Diagnosis is based on assumption of treatment response 27 DIAGNOSIS ¡ Endoscopy Indications ¡ Persistent or progressive GERD despite appropriate therapy ¡ Dysphagia or odynophagia ¡ Unexplained weight loss > 5% ¡ GI Bleedings and strictures ¡ Screening for Barrett’s esophagus in high-risk patients ¡ Placement of wireless PH monitoring ¡ Prior to endoscopic or surgical ant reflux procedures 28 DIAGNOSIS ¡ Ambulatory Reflux Monitoring ¡ Non-responsive to acid suppression therapy ¡ Atypical/Extraesophageal symptoms ¡ Preoperatively ¡ Assessment of Acid Exposure Time (AET) ¡ Normal: < 4% or < 40 reflux episodes in 24-hour period ¡ Abnormal: > 6 % or > 80 reflux episodes in 24-hour period 29 CHECK-IN Which test can visualize the esophagus and stomach to assess for GERD? a. b. c. d. X-ray Upper endoscopy (EGD) Colonoscopy Ultrasound 30 CHECK-IN Which of the following can worsen GERD symptoms? a. b. c. d. Eating small frequent meals Maintaining a healthy weight Eating spicy foods Elevating your head during sleep 31 CHECK-IN The development of GERD is a risk factor for which type of cancer? a. b. c. d. Skin cancer Lung cancer Esophageal cancer Colon cancer 32 CHECK-IN A 35 yo with GERD experiences chronic cough and hoarseness. This is most likely due to: a. b. c. d. Direct irritation of the vocal cords by stomach acid. Esophageal stricture (narrowing) caused by long-term GERD. Development of asthma triggered by GERD. Side effects of medication used to treat GERD. 33 CHECK-IN Question was adjusted from: What medication is not typically associated with development of GERD? What medication is typically associated with development of GERD? a. b. c. d. Antidepressants Blood pressure medications (calcium channel blockers) Aspirin or other NSAIDs Muscle relaxants 34 TREATMENT 35 GOALS OF TREATMENT Alleviation or elimination of symptoms Decrease frequency of reflux Promote healing of injured mucosa Prevent complications 36 THERAPY FOCUS Decrease acidity of refluxate Decrease gastric volume Improve gastric emptying Increase LES pressure Enhance esophageal clearance Protect esophageal mucosa 37 APPROACH TO TREATMENT Lifestyle changes Patient Directed Therapy (Antiacids, OTC H2RAs or PPI Prescription Strength Pharmacologic Treatment Surgery Endoscopic Therapies 38 NONPHARMACOLOGICAL PHARMACOLOGICAL SURGICAL TREATMENT 39 TREATMENT: NONPHARMACOLOGICAL 40 NON-PHARMACOLOGICAL TREATMENT ¡ Lifestyle Modifications ¡ Weight loss ¡ Elevation of head in bed ¡ Sleep on left side ¡ Avoid food 2 – 3 hours before bed (if nocturnal symptoms) ¡ Eliminate food that trigger GERD ¡ Smoking cessation ¡ Avoid alcohol ¡ Avoid tight fitting clothing 41 42 CHECK-IN Eating late at night is not an option because nocturnal GERD is not universal so that lifestyle modification is not universal to everyone Which of the following lifestyle modifications should you avoid for GERD management? a) b) c) d) Eating late at night Wearing tight-fitting clothing Eating a balanced diet with fruits and vegetables Maintaining a regular exercise routinev 43 TREATMENT: PHARMACOLOGICAL 44 PHARMACOLOGICAL TREATMENT Nonacid Suppression Therapies Acid Suppression Therapy Antiacids Proton Pump Inhibitor (PPI) Histamine Type-2 Receptor Antagonists (H2RA) Baclofen Sucralfate Prokinetics 45 ACID SUPPRESSION THERAPY ¡ Patient Directed Therapy ¡ Treatment of mild, intermittent symptoms ¡ Continuous symptoms lasting 2 weeks – seek medical attention ¡ Should seek further evaluation if ¡ Nocturnal heartburn exceeds 3 months ¡ Symptomatic with prescription strength medication therapy ¡ Presence of alarm symptoms 46 ACID SUPPRESSION THERAPY ¡ Comments: ¡ Periodic monitoring of calcium and phosphate levels in patients on chronic therapy ¡ Caution use with aluminum and calcium containing antiacids in patients with history of renal impairment ¡ Aluminum antiacids may bind to phosphate in gut à lead to bone demineralization 47 ANTIACIDS ¡ Antiacids alter gastric PH ¡ Short duration of action (requires frequent dosing for persistent symptoms) ¡ For temporary relief of mild and intermittent symptoms 48 MAGNESIUM HYDROXIDE/ALUMINUM HYDROXIDE W/ SIMETHICONE ¡ Dose: ¡ 10 – 20 mL as needed or after meals and at bedtime ¡ Side Effects: ¡ Magnesium: Dose related diarrhea ¡ Constipation ¡ Fecal discoloration (white speckles) ¡ Nausea ¡ Vomiting 49 MAGNESIUM HYDROXIDE/ALUMINUM HYDROXIDE W/ SIMETHICONE ¡ Precaution: ¡ Magnesium toxicity ¡ Comments: ¡ Administer 1 hour after meals or between meals. ¡ Suspension: Shake well prior to use. ¡ When used for self-medication do not use: ¡ Kidney disease (may lead to magnesium accumulation) ¡ More than the recommended dose for > 2 weeks 50 ANTACID/ALGINIC ACID ¡ Dose: ¡ 2 – 4 tablets or 10 – 20 mL after meals and at bedtime ¡ Side Effects: ¡ Constipation ¡ Comments: ¡ Alginic acid content varies per product 51 CALCIUM CARBONATE ¡ Dose: ¡ 2 – 4 tablets or 10 – 20 mL after meals and at bedtime ¡ Side Effects: ¡ Constipation ¡ Headache ¡ Belching ¡ Flatulence ¡ Precaution: ¡ Hypercalcemia 52 SODIUM BICARBONATE/ASPIRIN/CITRIC ACID ¡ Dose: ¡ Dissolve 2 tablets in 4 oz of water every 4 hours as needed (8 tablets) ¡ Side Effects: ¡ Abdominal pain ¡ Dyspepsia 53 SODIUM BICARBONATE/ASPIRIN/CITRIC ACID ¡ Precaution: ¡ Avoid in aspirin allergy ¡ Monitor for GI bleed (due to aspirin) ¡ Heavy ethanol use (>3 drinks/day) ¡ Increased bleeding risk ¡ Increase gastric mucosal damage 54 Antacid Oral Dose Side Effects • • Magnesium: Dose related diarrhea • Administer 1 hour after meals or between meals Aluminum: Dose related • Suspension: Shake well prior to use constipation • When used for self-medication do not use Fecal discoloration (white • Kidney disease (may lead to magnesium speckles) accumulation) Nausea • More than the recommended dose for > 2 Vomiting weeks • • GI bleed Constipation • • Magnesium hydroxide/Aluminum hydroxide + Simethicone Antacid/alginic acid 10-20 mL as needed or after meals and at bedtime 2-4 tablets or 10-20 mL after meals and at bedtime Notes • • Content of alginic acid varies greatly among products; the higher the alginic acid the better (at least 500 mg) ANTIACIDS SUMMARY 55 Antacid Oral Dose Calcium carbonate 500 mg, 2-4 tablets as needed Sodium bicarbonate + Aspirin + Citric acid Dissolve 2 tablets in 4 oz of water every 4 hours as needed (8 tablets) Side Effects Headache Eructation Flatulence Abdominal pain Dyspepsia Notes Alka Seltzer Original contains > 500 mg Na which can worsen edema in CHF or liver cirrhosis ANTIACIDS SUMMARY 56 ANTIACID DRUG INTERACTIONS Only for reference Drug Interacting Drug Potential Interaction Result Administration Practices Antacids Itraconazole, ketoconazole, ferrous sulfate, indinavir, atazanavir ↑ gastric pH may decrease disintegration, dissolution, or ionization of drug leading to decreased absorption Separate doses by at least 2 hours Antacids Amphetamines Amphetamines absorption is ↑ Separate doses by at least 2 hours Antacids Enteric-coated medications ↑ gastric pH → premature breakdown of enteric coating Separate doses by at least 2 hours Calcium carbonate, magnesium hydroxide, aluminum hydroxide Levothyroxine Absorption of levothyroxine is delayed or impaired Separate doses by at least 4 hours Calcium carbonate, magnesium hydroxide, aluminum hydroxide Tetracyclines e.g.minocycline, doxycycline Absorption of antibiotic is ↓ Separate doses by at least 4 hours Calcium carbonate, magnesium hydroxide, aluminum hydroxide Fluoroquinolones Absorption of antibiotic is ↓ Take antibiotic 2 hours before or 6 hours after taking antacid Sodium bicarbonate Quinidine Increased urinary pH may ↓ renal excretion of quinidine Avoid concurrent use or monitor response to therapy Sodium bicarbonate Salicylates Increased urinary pH may ↑ renal excretion of salicylates Avoid concurrent use or monitor for decreased response to salicylates 57 ADAPTED FROM PARNA HAGHPARAST, PHARMD LECTURE ANTIACID MONITORING Drug • Magnesium hydroxide/aluminum hydroxide • Antacid/alginic acid • Calcium carbonate Adverse Drug Reaction Monitoring Parameter • Diarrhea or constipation (depending on product) • Alterations in mineral metabolism • Acid–base disturbances Periodic calcium and phosphate levels in patients on chronic therapy 58 HISTAMINE TYPE-2 RECEPTOR ANTAGONISTS (H2RA) ¡ Effective in lowering gastric acid secretion when taken prior to meals ¡ For patient directed therapy ¡ 12 years of age and older ¡ Taken up to two times daily ¡ Can be combined with antiacids ¡ Should seek provider recommendation if used for more than 14 days 59 HISTAMINE TYPE-2 RECEPTOR ANTAGONISTS (H2RA) ¡ Onset: 30 – 45 minutes ¡ Duration of action: 4 – 10 hours ¡ Monitoring: ¡ Altered kidney function ¡ Hepatic impairment (cimetidine) ¡ CNS effects (esp. in elderly) ¡ Dose Reduction: ¡ Renal Impairment (CrCL < 50 mL/min) 60 FAMOTIDINE (PEPCID) ¡ Dose: ¡ GERD: ¡ OTC Labeling (mild-intermittent symptoms): 10 to 20 mg up to twice daily prn (maximum: 40 mg/day) ¡ RX: 20 mg twice daily ¡ Erosive esophagitis due to GERD: ¡ 20 or 40 mg twice daily for up to 12 weeks 61 FAMOTIDINE (PEPCID) ¡ Side Effects: ¡ Adverse Reactions: ¡ Agitation ¡ Delirium ¡ Confusion ¡ Necrotizing enterocolitis in very low birth weight (VLBW) neonates ¡ Thrombocytopenia (rare) ¡ Somnolence ¡ Fatigue ¡ Dizziness ¡ Constipation ¡ Diarrhea ¡ Headache ¡ Monitoring: ¡ Kidney Function ¡ Vitamin B12 deficiency (seen with long duration and high doses) 62 Only for reference FAMOTIDINE (PEPCID) Usual Dose CrCl (mL/minute) 10 mg twice daily 20 mg once daily 20 mg twice daily CrCl 30 to <60 10 mg once daily or 20 mg every other day 10 mg once daily or 20 mg every other day 20 mg once daily or 40 mg every other day CrCl <30 10 mg every other day 10 mg every other day 10 mg once daily or 20 mg every other day 63 NIZATIDINE (AXID) ¡ Dose: ¡ GERD: 150 mg twice daily ¡ Erosive esophagitis due to GERD: 150 mg twice daily for up to 12 weeks ¡ Side Effects: ¡ Headache ¡ Dizziness ¡ Anxiety 64 Only for reference Active treatment: NIZATIDINE (AXID) • CrCl >50 mL/minute: No dosage adjustment necessary. • CrCl 20 to 50 mL/minute: 150 mg once daily • CrCl <20 mL/minute: 150 mg every other day Maintenance treatment: • CrCl >50 mL/minute: No dosage adjustment necessary • CrCl 20 to 50 mL/minute: 150 mg every other day • CrCl <20 mL/minute: 150 mg every 3 days 65 CIMETIDINE (TAGAMET) ¡ Dose: ¡ OTC: ¡ Prevention: 200 mg daily up to 30 minutes prior to eating foods or beverages that cause heartburn (maximum: 400 mg per 24 hours) ¡ Relief of symptoms: 200 mg daily; maximum: 400 mg per 24 hours ¡ Erosive esophagitis due to GERD: ¡ 400 mg 4 times daily or 800 mg twice daily for 12 weeks 66 CIMETIDINE (TAGAMET) ¡ Side Effects: ¡ Headache ¡ Gynecomastia ¡ Dizziness ¡ Drowsiness ¡ Monitoring: ¡ Renal functioning ¡ Severe kidney impairment: 300 mg every 12 hours 67 H2RAs - SUMMARY Drugs Famotidine(Pepcid, Pepcid AC, Pepcid AC Max Strength ®) + Calcium carbonate and magnesium hydroxide (Pepcid Complete) Dosing OTC(mild-mod heartburn): 10-20 mg 1-2 times daily prn Rx: -GERD: 20 mg BID -Mod-severe symptoms or healing of erosions: 20-40 mg BID x 12 weeks Comments ECG changes (Qtcprolongation) with renal dysfunction -Available as tablets, chewable tablets, suspension, injection -Dose reduction when Crcl< 50 ml/min Nizatidine (Axid®) OTC (mild-mod heartburn): 75 mg 1-2 times daily prn Rx: 150 mg QD/BID -GERD: 150 mg BID -Mod-severe symptoms or healing of erosions: 150 mg BID to QID -Available in capsules, oral solution -Dose reduction when Crcl < 50 ml/min -QID dosing is off-label Cimetidine (Tagamet®) OTC: 200 mg 1-2 times daily prn Rx: 400 mg-800 mg QD-QID -GERD/Mod-severe symptoms of healing of erosions:400 mg Q6 hrs ( or 800 mg BID) Avoid entirely due to DDI and ADR -ADR: can increase Scrwithout causing renal impairment. At high doses: gynecomastia, impotence -Dose reduction when Crcl< 30 ml/min -CYP2C19 inhibitor 68 Only for reference H2RAs – DRUG INTERACTIONS Acid Reducer Drug Potential Interaction Management/preventative measures H2RAs Itraconazole, ketoconazole, Increased gastric pH may decrease disintegration, atazanavir, dissolution, or ionization of drug leading to decreased absorption. Avoid concurrent use or monitor response to therapy. H2RAs Delavirdine Combined use for extended treatment duration may result in reduced delavirdine absorption, and serum levels and attenuated delavirdine efficacy as delavirdine is dependent on an acidic gastric pH for absorption Concomitant use not recommended; antacids may be alternative acid suppressive therapy, with antacid and delavirdine doses separated by at least one hour H2RAs Drugs pH dependent for solubility e.g.dasatinib Adjunctive administration for extended duration may result in reduced exposure and serum levels as select medications dependent on acidic gastric pH for solubility and absorption Combined use not recommended; alternative acid suppressive (e.g., antacids) should be administered 2 hours before or 2 hours after pH-dependent medication for optimal efficacy Cimetidine Warfarin, clopidogrel, dofetilide Cimetidine inhibits CYP450 3A4, 2D6, 1A2, and 2C9. Avoid concurrent use (warfarin: monitor therapy and adjust dose accordingly) 69 HTRAs MONITORING PARAMETERS Drug Adverse Drug Reaction Comments Monitoring Parameter • • Cimetidine • Famotidine • Nizatidine Headache, somnolence, fatigue, dizziness, and either constipation or diarrhea Monitor for CNS effects, especially in older patients May see increased CNS effects (rare) in those over 50 years of age or in those with renal or hepatic dysfunction • May be associated with vitamin B12 deficiency with longer duration therapy and in higher doses 70 PROTON PUMP INHIBITOR (PPI) ¡ MOA: Irreversibly binds to the gastric H+/K+ ATPase pump in parietal cells, blocking gastric acid secretion ¡ Onset: 1 – 3 hours ¡ Duration: > 24 hours, takes a few days to feel results ¡ Patient Directed Therapy: If symptoms are unrelieved after 14 days, patient should get medical attention 71 PROTON PUMP INHIBITOR (PPI) ¡ Side Effects: ¡ Most common: ¡ Headache, dizziness, diarrhea, flatulence, abdominal pain, nausea ¡ Other adverse effects: ¡ Enteric infections, community acquired pneumonia ¡ Long term effects: ¡ Hypomagnesemia, bone fractures, Vitamin B12 deficiency, Chronic Kidney Disease 72 PROTON PUMP INHIBITOR (PPI) ¡ Monitor: ¡ Number and type of diarrhea episodes (risk of C. difficile infection) ¡ Magnesium levels when duration of treatment is > 1 year ¡ Bone density scans ¡ Respiratory symptoms within first 30 days of therapy (Risk of community acquired pheumonia) ¡ Vitamin B12 levels with long term use 73 OMEPRAZOLE (PRILOSEC) ¡ Dose: ¡ OTC: 20 mg once daily for 14 days ¡ RX: ¡ Mild/Intermittent disease (<2 episodes/week): 20 mg once daily ¡ Discontinue once asymptomatic for 8 weeks ¡ Severe or frequent: 20 mg once daily or twice daily ¡ Formulations: Tablet, capsule, packet ¡ Comments: Take before meal (time not specified) 74 OMEPRAZOLE/SODIUM BICARBONATE (ZEGERID) ¡ Dose: ¡ OTC (mild-mod heartburn): 20 mg once daily ¡ Rx: ¡ GERD: 20 mg once daily ¡ Moderate/Severe or healing of erosions: 20 - 40 mg once daily ¡ Formulations: Capsule, powder for oral suspension ¡ Comments: ¡ Zegerid: Take 60 min before breakfast ¡ Consider the sodium content when prescribing omeprazole/sodium bicarbonate capsules or oral suspension. ¡ Do not substitute two 20mg for 40 mg due to sodium content 75 LANSOPRAZOLE ¡ Dose: ¡ OTC (mild to moderate heartburn): 15 mg once daily ¡ Rx: ¡ GERD: 15 mg once daily ¡ Moderate/severe or healing of erosions: 30 mg once daily or twice daily ¡ Formulation: Capsule, ODT, Suspension ¡ Comments: ¡ Take before breakfast (time not specified) ¡ Capsule can be opened (not crushed), mixed in applesauce 76 ESOMEPRAZOLE ¡ Dose: ¡ OTC(mild/moderate heartburn): 20 mg once daily ¡ Rx: ¡ GERD: 20 - 40 mg once daily ¡ Moderate/Severe or healing of erosions: 20 mg once daily or twice daily ¡ Formulation: Capsule, injection, packet ¡ Comments: ¡ Capsule can be opened (not crushed) and mixed in applesauce ¡ Take 60 min before breakfast 77 DEXLANSOPRAZOLE ¡ Dose: ¡ Rx: ¡ GERD: 30 mg once daily ¡ Moderate/Severe or healing of erosions: 60 mg once daily ¡ Formulation: Capsule, ODT ¡ Comments: ¡ Capsule can be opened (not crushed), mixed in applesauce ¡ Capsule: without regards to meal (pre-meal if needed for sx) ¡ ODT: Take 30 min before meal ¡ Dual delayed release formulation 78 PANTOPRAZOLE ¡ Dose: ¡ Rx: ¡ GERD: 20 mg once daily ¡ Moderate/Severe or healing of erosions: 40 mg once daily or twice daily ¡ Formulations: Tablet, Injection, packet ¡ Comments: Take 30 min before breakfast 79 RABEPRAZOLE ¡ Dose: ¡ RX: ¡ GERD: 20 mg once daily ¡ Moderate/Severe or healing of erosions: 20 mg once daily or twice daily ¡ Formulation: Tablet, capsule sprinkle, injection ¡ Comments: ¡ Tablet: Without regards to food ¡ Capsule: sprinkle 30 min before meal 80 Trade Name Omeprazole (Prilosec) Omeprazole/sodium bicarb (Zegerid) Lansoprazole (Prevacid) Esomeprazole (Nexium) Dose OTC (mild-mod heartburn): 20 mg QD Rx: GERD: 20 mg QD Mod-severe sx or healing of erosions: 20 mg QD/BID OTC (mild-mod heartburn): 20 mg QD Rx: • GERD: 20 mg QD • Mod-severe sx or healing of erosions: 20 mg40 mg QD OTC (mild-mod heartburn): 15 mg QD Rx: • GERD: 15 mg QD • Mod-severe sx or healing of erosions: 30 mg QD/BID OTC (mild-mod heartburn): 20 mg QD Rx: • GERD: 20 mg-40 mg QD • Mod-severe sx or healing of erosions: 20 mg QD/BID Notes Formulations: Tablet, capsule, packet Comments: Take before meal (time not specified) Formulation: Capsule, powder for oral suspension Comments: Zegerid: Take 60 min before breakfast Consider the sodium content when prescribing omeprazole/sodium bicarbonate capsules or oral suspension. Do not substitute two 20mg for 40 mg due to sodium content Formulation: Capsule, ODT, Suspension Comments: • Take efore breakfast (time not specified) • Capsule can be opened (not crushed), mixed in applesauce Formulation: Capsule, injection, packet Comments: • Capsule can be opened (not crushed) and mixed in applesauce • Take 60 min before breakfast 81 Trade Name Dose Dexlansoprazole (Dexilant) Rx only Rx Only: • GERD: 30 mg QD • Mod-severe sx or healing of erosions: 60 mg QD Pantoprazole (Protonix) Off-label, Rx only Rabeprazole (Aciphex) Rx only Rx Only: • GERD: 20 mg QD • Mod-severe sx or healing of erosions: 40 mg QD/BID Rx Only: • GERD: 20 mg QD • Mod-severe sx or healing of erosions: 20 mg QD/BID Notes Formulation: Capsule, ODT Comments: • Capsule can be opened (not crushed), mixed in applesauce • Capsule: without regards to meal (pre-meal if needed for sx) • ODT: Take 30 min before meal • Dual delayed release formulation Formulations: Tablet, Injection, packet Comments: Take 30 min before breakfast Formulation: Tablet, capsule sprinkle Comments: • Tablet: Without regards to food • Capsule: sprinkle 30 min before meal 82 Drug Adverse Drug Reaction • Most common adverse effects: • • Dexlansoprazole • • Esomeprazole Lansoprazole • Omeprazole Omeprazole/sodium • • Headache, dizziness, diarrhea, flatulence, abdominal pain, and nausea • Other important adverse effects: Enteric infections • • Community acquired pneumonia Long-term adverse effects: bicarbonate • Hypomagnesemia Pantoprazole Rabeprazole • Bone fractures • Vitamin B12 deficiency • Chronic kidney disease 83 PPI – DRUG INTERACTIONS Only for reference Acid Reducer Drug PPIs Itraconazole, ketoconazole, indinavir, atazanavir PPIs Methotrexate Omeprazole, esomeprazole Clopidogrel Potential Interaction/Preventative measure Increased gastric pH may decrease disintegration, dissolution, or ionization of drug leading to decreased absorption. Concurrent use increases risk of toxicity of methotrexate. Inhibition of variants of CYP2C19 reduces conversion of clopidogrel to its active form. 84 CYTOPROTECTIVE AGENTS SUCRALFATE METOCLOPRAMIDE (REGLAN) BACLOFEN • Mucosal coating agent • Forms a protective barrier between esophageal tissue and gastric refluxate • Adherence issues due to QID dosing • Low efficacy as monotherapy • May be used as adjunct in refractory cases • May be used in pregnancy • Promotility agents improve esophageal peristalsis, gastric emptying and reduce the duration and frequency of reflux • Dopamine antagonist • Not as effective; side effects limits long term use • Not routinely recommended, may be used as adjunct to PPI if co-existing gastroparesis in refractory patients • BBW: tardive dyskinesia with long term use • TLESR inhibitors • 5 –20 mg three times a day • GABA(b) agonist • Inhibits transient lower esophageal sphincter relaxation (TLESR) inhibitor • Alternative for refractory GERD patients (may be considered off-label) • Usage is limited by side effects of dizziness, somnolence, and constipation and dosing frequency 85 MAINTENANCE THERAPY ¡ Possible relapse when therapy is discontinued ¡ Long term maintenance therapy may be required ¡ PPI is first line in moderate to severe GERD, erosive disease, or Barrett's esophagus ¡ Patients on long term PPI should be periodically evaluated to assess need for continuing treatment ¡ H2RA is considered for mild symptoms or low dose PPI with alternating days 86 REFRACTORY GERD ¡ Refractory GERD ¡ Considered in patients who have not responded to a standard course of BID PPI therapy over a 12-week period. ¡ Causes of potential PPI refractory GERD: ¡ Abnormal acid reflux despite PPI therapy ¡ Reflux hypersensitivity where physiologic (normal) reflux causes symptoms ¡ Esophageal disorders other than GERD (eg, achalasia) ¡ Extraesophageal disorders (eg, lung disease or heart disease) ¡ Functional heartburn 87 SUMMARY OF PATIENT DIRECTED THERAPY OTC is appropriate for mild to moderate/ infrequent symptoms (typically < 2 weeks) Antacids/alginic acid, OTC H2RA or combination of both OTC PPIs can be used for treating frequent heartburn (occurring ≥2 days per week) or when patients do not respond to OTC H2RAs No more than 14 days at a time for patient-directed therapy 88 SUMMARY OF PATIENT DIRECTED THERAPY During Patient Directed Therapy: ¡ Refer if alarm symptoms, or continuous (> 14 days), or severe symptoms ¡ OTC therapy may be for prn or intermittent use ¡ Patient should be referred to physician if ¡ Alarm symptoms ¡ Age of onset of symptoms ≥ 65 years old ¡ Familial history of GI cancer ¡ History of non-responsiveness to PPI/H2RA ¡ Suffering from severe symptoms for extended period of time 89 MODERATE-SEVERE SYMPTOM RELIEF AND/OR HEALING OF EROSIVE ESOPHAGITIS ¡ For typical symptoms (heartburn and regurgitation), treat empirically with prescription-strength PPI for presumptive diagnosis ¡ Treatment: Lifestyle modification + Rx H2RA or PPI ¡ If symptoms return à maintenance therapy ¡ PPI drug of choice (alternative: H2RAs) ¡ For extraesophageal or alarm symptoms, obtain endoscopy with biopsy to evaluate mucosa ¡ Treatment duration ¡ PPI: 8 weeks ¡ H2RAs: 6-12 weeks 90 PPI DOSING FOR EROSIVE ESOPHAGITIS PPIs (up to twice daily for up to 8 weeks) Dexlansoprazole 60 mg daily Esomeprazole 2040 mg daily Lansoprazole 30 mg once or twice daily Omeprazole 20 mg once or twice daily Rabeprazole 20 mg once or twice daily Pantoprazole 40 mg once or twice daily • For extraesophageal or alarm symptoms, obtain endoscopy with biopsy to evaluate mucosa. • If symptoms are relieved, consider maintenance therapy. • PPIs are the most effective maintenance therapy for patients with extraesophageal symptoms, complications, and erosive disease. • Start with twice daily PPI therapy if reflux chest syndrome is present. Patients not responding to pharmacologic therapy, including those with persistent extraesophageal symptoms, should be evaluated via manometry and/or ambulatory reflux monitoring. 91 H2RA DOSING FOR EROSIVE ESOPHAGITIS High dose H2RAs (for 8-12 weeks) Cimetidine Famotidine Nizatidine 400mg four times daily or 800 mg twice daily 20-40 mg twice daily 150 mg two to four times daily 92 INTERVENTIONAL THERAPY ¡ Ant-reflux surgery ¡ Bariatric surgery ¡ Endoscopic therapies 93 SURGERY ¡ Ant-reflux Surgery: ¡ Used to reestablish the ant-reflux barrier ¡ Position the LES within the abdomen ¡ Close defects in diaphragm ¡ Only for select patients ¡ Indicated: ¡ Long term pharmacologic is not an option ¡ Persistent GERD symptoms ¡ Significant EGJ disruption (hiatal hernia) 94 SUMMARY ¡ Symptoms of GERD include heartburn and regurgitation ¡ Pathophysiology of GERD is multifactorial. the following contributes to symptoms: impaired esophageal defense mechanisms example transient LES relaxation, reduced LES pressure, impaired esophageal clearance, delayed gastric emptying, hiatal hernia, increased volume of refluxate material ¡ Chronic exposure of the esophagus to the refluxate can lead to complications such as erosive esophagitis ¡ GERD can be diagnosed with combination of clinical presentation, response to PPI trial, endoscopy and/or reflux monitoring ¡ Individualized lifestyle modifications that may improve symptoms ¡ GERD treatment includes lifestyle modifications, PPI, H2RA, and antiacids ¡ Mild symptoms: antiacids and H2RA’s ¡ Moderate to severe: PPI ¡ Patient directed therapy is limited to 14 days ¡ For moderate-severe symptoms and healing of erosion, PPIs are used first line for 8 weeks ¡ Maintenance therapy may be required for patients ¡ PPI is the preferred choice ¡ Lowest effective dose for shortest duration possible 95 CHECK-IN What factors go into choosing an appropriate PPI dose? a. b. c. d. The severity of the patient's symptoms. The presence of erosive esophagitis confirmed by endoscopy. The patient's age and potential for drug interactions with other medications. All of the above. 96 CHECK-IN The mechanism of action of an H2RA for GERD treatment is? a. Reducing stomach acid production by directly inhibiting the proton pump. b. Blocking the action of histamine at H2 receptors, leading to decreased acid secretion. c. Neutralizing stomach acid after it has been secreted. d. Strengthening the lower esophageal sphincter (LES) to prevent reflux. 97 CHECK-IN Compared to proton pump inhibitors (PPIs), H2RAs generally: a. Provide faster relief from heartburn symptoms. b. Achieve a more profound and long-lasting reduction in stomach acid. c. Are more effective in healing erosive esophagitis. d. Have a higher risk of drug interactions 99 CHECK-IN The mechanism of action of an PPI for GERD treatment is? a. b. c. d. Neutralizing stomach acid directly. Blocking histamine receptors on gastric parietal cells, reducing acid production. Stimulating mucus production in the esophagus for lubrication. Strengthening the lower esophageal sphincter (LES) to prevent reflux. 100 CHECK-IN This question was badly written and will be disregarded. Long-term PPI use can be associated with? a. Increased risk of osteoarthritis and bone fractures b. Vitamin B12 deficiency, especially in older adults or those with pre-existing malabsorption issues c. Development of new gut bacteria with frequent or prolonged use d. All the above 101 CHECK-IN Maintenance therapy implies that the patient has already completed a empiric course of therapy and requires long term maintenance. Option A is the best candidate due to the relapse after an 8 week course of empiric PPI therapy. Which of the following is the best candidate for maintenance therapy for GERD? a. 40 year-old patient who relapses after an 8-week course of PPI therapy b. 31 year-old patient with intermittent GERD symptoms c. 52 year old patient with scleroderma d. 2 month old baby with intermittent regurgitation of feeds 102 REFERENCES ¡ DiPiro: Pharmacotherapy A Pathophysiologic Approach, 12e | AccessPharmacy | McGraw Hill Medical. accesspharmacy.mhmedical.com. https://accesspharmacy.mhmedical.com/book.aspx?bookID=3097 ¡ Andrews WG, Louie BE. The relationship of hiatal hernia and gastroesophageal reflux symptoms—two-sphincter hypothesis: a review. Annals of Laparoscopic and Endoscopic Surgery. 2021;6:41-41. doi:https://doi.org/10.21037/ales.2020.04.01 ¡ Hiatal Hernia Surgery in Brownsville, TX | Carlos A. Barba, MD. Carlos A. Barba, MD, PLLC. Accessed March 24, 2024. https://carlosabarbamd.com/services/hernia-repair/hiatal-hernia/ ¡ Modiano N, Gerson LB. Barrett’s esophagus: Incidence, etiology, pathophysiology, prevention and treatment. Therapeutics and Clinical Risk Management. 2007;3(6):1035-1145. Accessed December 16, 2022. https://pubmed.ncbi.nlm.nih.gov/18516262/ 103 THANK YOU!! ¡ Questions? ¡ 📧 cvoskanian@westcoastuniversity.edu 104

Gastroesophageal Reflux Disease (GERD)

Related Documents

Recommended Documents

Description

Related Documents

Free up your schedule!

Take 5 seconds to unlock