GERD and PUD: Diagnosis and Treatment

• The presentation provides information on Gastroesophageal Reflux Disease (GERD) and Peptic Ulcer Disease (PUD).
• The author of the presentation has nothing to disclose concerning possible financial or personal relationships with commercial entities that may have a direct interest in the subject matter.

Learning Objectives

• Recognize the pharmacological agents used in the management of GERD and PUD.
• Discuss clinically relevant considerations for therapy selection.
• Develop appropriate treatment regimen for patients with GERD and PUD.
• Determine appropriate management for a patient at high risk for ulcer-related GI complications taking a nonselective NSAID.

Gastroesophageal Reflux Disease (GERD)

• Important factors in diagnosis include clinical history such as presenting symptoms and risk factors, excluding cardiac causes for chest pain, and endoscopy for alarm symptoms or patients at high risk for complications.

GERD Treatment

• Nonpharmacologic interventions for GERD include weight loss for overweight individuals, head of bed elevation, and avoiding meals 2-3 hours before bedtime.
• Over-the-counter or prescription drug therapy options include H2-receptor antagonists (H2RAs) and proton-pump inhibitors (PPIs).

GERD Guideline Recommendations

• An 8-week course of PPI is a therapy of choice for symptom relief and healing of erosive esophagitis.
• Traditional delayed release PPIs should be administered 30-60 minutes before a meal for maximal pH control, with the exception of dexlansoprazole, which is independent of food and may be dosed any time of day.
• PPI therapy should be initiated at once a day dosing, before the first meal of the day.
• Non-responders to PPI should be referred for evaluation.
• For patients with partial response to once daily therapy, tailored therapy with adjustment of dose timing and/or twice daily dosing should be considered for patients with night-time symptoms, variable schedules, and/or sleep disturbance; additionally, increasing the dose to twice daily therapy or switching to a different PPI may provide additional symptom relief.
• There is no role for sucralfate in the non-pregnant GERD patient, but PPIs are safe in pregnant patients if clinically indicated.
• Symptoms after PPI discontinued are a Maintenance PPI therapy.
• Complications including erosive esophagitis and Barrett's esophagus are a symptom after PPI discontinued.
• Administered in the lowest effective dose, including on demand or intermittent therapy PPI.
• A maintenance H2RA therapy is an option in patients without erosive disease if patients experience heartburn relief, and bedtime H2RA therapy can be added to daytime PPI therapy in selected patients with objective evidence of night-time reflux if needed, although it may be associated with the development of tachyphylaxis after several weeks of use.

Drug Therapy

• Agents that reduce intragastric acidity include proton-pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), and antacids.
• Agents that promote mucosal defense include sucralfate, prostaglandin analogs, and bismuth compounds.

Proton-Pump Inhibitors (PPIs)

• PPIs include esomeprazole (Nexium), omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (AcipHex), pantoprazole (Protonix), and dexlansoprazole (Dexilant).
• The Mechanism of Action irreversibly binds to gastric parietal cell H+/K+ ATP pump shuts down the pump → suppresses gastric acid secretion
• Side effects: headache, dizziness, nausea, diarrhea
• Potential risks: fractures, clostridium difficile-associated diarrhea, pneumonia

H2-Receptor Antagonists (H2RAs)

• H2-Receptor Antagonists, also known as H2RAs, include Cimetidine (Tagamet), Famotidine (Pepcid), and Ranitidine (Zantac).
• The mechanism of Action competitively inhibits histamine at gastric parietal H2-receptors → decreases gastric acid secretion.
• Side effects: headache, dizziness, sedation, agitation
• Prolonged use may lead to reduced efficacy and tachyphylaxis.
• Potential risks: dose reduce in renal impairment, confusion in elderly.

Antacids

• Examples include sodium bicarbonate (Alka Seltzer), calcium carbonate (Tums, Os-Cal), and magnesium hydroxide or aluminum hydroxide (MaAlOx).
• Mechanism of action: weak bases that react with gastric hydrochloric acid to neutralize gastric acid (producing salt and water) → increasing gastric pH.
• Side effects: fairly well tolerated; chalky taste, abdominal cramps.
• Al (cause constipation) and Mg (causes diarrhea): opposites → together MaAlOx
• Potential risks: renal dysfunction; affect absorption of other medications; some formulations contain aspirin → increased bleeding risk.

Peptic Ulcer Disease (PUD)

• Dyspepsia Guideline Recommendations
  • In patients under the age of 60 with dyspepsia a non-invasive test for H. Pylori, and eradication therapy if positive.
  • Urea breath test (UBT) or fecal antigen test (FAT)
  • Empirical PPI therapy if they are H. pylori-negative or who remain symptomatic after H. pylori eradication therapy
  • In patients under the age of 60 with dyspepsia, it NOT suggests endoscopy to investigate alarm features to exclude upper Gl neoplasia.
  • Alarm features: weight loss, anemia, dysphagia, persistent vomiting

H. Pylori Infection

• Patients testing positive for H. pylori should be offered eradication therapy with a PPI-based three or four-drug antibiotic regimen.
• Consider testing for H. pylori infection in patients taking long-term, low-dose aspirin (to reduce the risk of ulcer bleeding), beginning chronic NSAID treatment (though the benefit of testing and treating in a patient already taking an NSAID remains unknown), experiencing unexplained iron deficiency anemia despite appropriate evaluation, or with idiopathic thrombocytopenic purpura (ITP).

Evidence-Based First-Line Treatment

• The following are evidence-based first-line treatments with a conditional recommendation and are of low quality of evidence include Clarithromycin triple therapy consisting of a PPI, clarithromycin, and amoxicillin or metronidazole for 14 days.
• Sequential therapy consisting of a PPI and amoxicillin for 5-7 days followed by a PPI, clarithromycin, and a nitroimidazole for 5-7 days
• Hybrid therapy consisting of a PPI and amoxicillin for 7 days followed by a PPI, amoxicillin, clarithromycin and a nitroimidazole for 7 days
• Levofloxacin triple therapy consisting of a PPI, levofloxacin, and amoxicillin for 10–14 days
• Fluoroquinolone sequential therapy consisting of a PPI and amoxicillin for 5-7 days followed by a PPI, fluoroquinolone, and nitroimidazole for 5–7 days
• Bismuth quadruple therapy consisting of a PPI, bismuth, tetracycline, and a nitroimidazole for 10–14 days along with Concomitant therapy consisting of a PPI, clarithromycin, amoxicillin and a nitroimidazole for 10–14.

Salvage Regimens

• Bismuth quadruple therapy for 14 days.
• Levofloxacin triple regimen for 14 days.
• Concomitant therapy for 10–14 days.
• High-dose dual therapy consisting of a PPI and amoxicillin for 14 days.
• Rifabutin triple regimen consisting of a PPI, amoxicillin, and rifabutin for 10 days.
• AVOID: Clarithromycin triple therapy.
• In patients with persistent H. pylori infection, avoid antibiotics that have been previously taken.

NSAID-Induced Ulcers

• NSAIDs include ibuprofen (Advil, Motrin), naproxen (Aleve), meloxicam (Mobic), celecoxib (Celebrex), diclofenac (Cambia), and indomethacin (Indocin).
• Patients at increased risk for NSAID GI toxicity include:
  • High risk: History of a previously complicated ulcer, especially recent, and multiple (>2) risk factors.
  • Moderate risk (1-2 risk factors): Age >65 years, high dose NSAID therapy, a previous history of uncomplicated ulcer, and concurrent use of aspirin (including low dose) corticosteroids or anticoagulants.
  • Low risk: No risk factors.
  • H. pylori is an independent and additive risk factor and needs to be addressed.

PUD Drug Therapy

• PUD Drug Therapy includes (Pepto-Bismol, Maalox, Kao-Pectate).
• Mechanism of action: exhibits antimicrobial directly against bacterial and viral gastrointestinal pathogens.
• Side effects: constipation and darkening feces and tongue.
• Potential risks: toxicity (heavy metal).

Other Clinical Considerations: Drug Interactions

• Drug interactions include PPIs where velpatasvir, may increase levels of warfarin, tacrolimus, voriconazole, and methotrexate; H2RAS, antivirals for HCV and HIV, atazanavir, rilpivirine, ledipasvir, and velpatasvir; and antacids, which interacts with tetracyclines, fluoroquinolones, itraconazole, and iron.

Medication Counseling

• Indication
• Adherence
• Ongoing re-evaluation of symptoms – assess for opportunity to step down
• Taper off therapy to avoid rebound
• Administer 30 – 60 minutes before a meal for maximum efficacy (exception – dexlansoprazole)
• Once daily: prior to breakfast
• Capsules and tablets are delay release and should NOT be crushed or chewed

Prescribing Tips

• Allergy review.
• Insurance / prior authorizations; Duration of therapy.
• Notations on prescriptions - combination products, formulations, branded vs generic options.