Prescription Practice II – PHAR 422.00

Peptic Ulcer Disease

C. Voke Abobo

Professor

Educational Objectives Peptic Ulcer Disease After successfully completing this session, the student should be able to: • Discuss the relationship between H. pylori and duodenal ulcer, gastric ulcer, gastric cancer, and possibly non-ulcer dyspepsia. • Describe the complications of PUD that require referral. • Understand the relative risk associated with the cyclooxygenase isoforms in NSAID-associated gastroduodenopathy. • List the risk factors associated with NSAID-induced gastroduodenopathy. • List the strategies for ameliorating the risk associated with NSAID-induced gastroduodenopathy. • Describe the typical presenting signs and symptoms

associated with PUD.

Educational Objectives (Continued) • Learn the methods used to detect H. pylori and to confirm H. pylori eradication. • List outcomes parameters in the management of PUD. • Design an evidence-based pharmacotherapeutic care plan for treatment directed against H. pylori. • Design an evidence-based pharmacotherapeutic care plan for treatment directed against H. pylori-negative PUD.

PEPTIC ULCER DISEASE Introduction: Demographic Factors Duodenal Ulcer Gastric Ulcer 1. Incidence 6-8% 2-3% 2. Age of Onset 20-35yr 40-50yr 3. Male:Female ratio >2:1 ~same 4. Family History Positive Not relevant

Anatomy of the Stomach a. Fundus b. Body c. Antrum

Acid Secretion a. H+/K+ ATPase (proton pump) b. H2-receptors c. Muscarinic receptors d. Gastrin receptors

Major Causes of Peptic Ulcer Disease Risk Factors Destructive (Aggressive) Protective (Defensive) Acid secretion Bicarbonate secretion Mucosal ischemia Mucus layer Pepsin Mucosal blood flow Bile salts Angiogenesis (growth factors) NSAIDs Cell regeneration H. pylori

Duodenal Ulceration Normal to high acid output H. pylori >90% ZES Duodenal Crohn’s disease Viral infections Penetrating pancreatic cancer NSAIDs Gastric Ulceration Low to normal acid output H. pylori >75% NSAIDS

NSAIDs Gastroduodenopathy Cyclooxygenase COX-1 vs COX-2 nabumetone etodolac oxaproxin diclofenac naproxen meloxicam (mobic)

celecoxib (celebrex) COX-1: constitutive - stomach, intestine, kidneys, platelets COX-2: inducible - joints COX-2:COX-1

Risk Factors for NSAID-Associated Gastropathy Age > 60 yr History of peptic ulcer disease Concurrent corticosteroid use Concurrent selective serotonin reuptake inhibitor (SSRI) use Concurrent anticoagulant use High doses of NSAIDs NSAID use > 1 month Pre-existing coagulopathy (elevated INR, thrombocytopenia)

Gastric Cancer: H. Pylori a definite carcinogen (WHO) prevalence higher in populations at increased risk associated with gastric cancer precursor lesions Mucosa-Associated Lymphoid Tissue (MALT) lymphomas ~ 90% MALTomas associated with H. pylori Eradication of infection associated with regression of early MALTomas

Non-Ulcer Dyspepsia Features of Dyspepsia Pain and discomfort Bloating/Abdominal distention Fullness Early satiety Nausea Vomiting Belching

Clinical Features of Peptic Ulcer Disease Gastric Duodenal Epigastric pain Epigastric pain, frequently nocturnal Pain relieved by antacids Pain relieved by antacids (less consistent) Weight loss common Weight gain common Pain not relieved or worsened Pain relieved by food by food Nausea and vomiting more common Epigastric Pain burning gnawing aching

Diagnosis of Peptic Ulcer Disease Diagnostic Tool Considerations 1. Radiography double contrast 2. Endoscopy esophagus stomach duodenum esophagogastroduodenoscopy (EGD) Alarm Signs and Symptoms Anemia (unexplained) Early satiety Progressive dysphagia Odynophagia Unexplained weight loss Gastrointestinal bleeding Recurrent vomiting New onset of symptoms @ ≥ 45 yr

Non-endoscopic Antibody test Widely available (Serology) Urea Breath Test Identifies active H. pylori infection 13C UBT Breath Test (W/Pranactin) - non-radioactive 14C Pytest - radioactive Fecal Antigen Test Identifies active H. pylori infection

Endoscopic Rapid Urease (eg. CLOtest, Identifies active H. pylori infection HpFast, HUT-test, Pronto Dry, Pyloritek) Histology Identifies active H. pylori infection Culture Identifies active H. pylori infection Allows characterization of antimicrobial sensitivity Polymerase Chain Reaction Identifies active H. pylori infection (PCR) DNA amplification technique; may be useful where organism is not identifiable by other biopsy methods Allows characterization of antimicrobial sensitivity

Limitations of Breath Test 1. Prior antimicrobial and/or antisecretory therapy 2. Premature sampling

Patient Preparation for Breath/Rapid Urease Tests Drugs: Withhold bismuth, antibiotics for at least 28 days prior to tests Withhold PPI for at least 7-14 days prior to tests Withholding H2RAs controversial but many labs recommend 24-48 hrs before tests

Eradication Tests

Urea breath tests

Fecal (Stool) antigen test

Complications of Peptic Ulcer Disease hemorrhage perforation penetration obstruction intractability

Pharmacotherapy of Peptic Ulcer Disease Outcomes relieve pain promote healing prevent recurrences prevent complications prevent antibiotic resistance eliminate maintenance therapy

Agents Antacids H2-receptor antagonists Proton pump inhibitors Cytoprotective agents Antibiotics

ANTACIDS (Obsolete) pH: 3.5-5.5 Acid neutralizing capacity (ANC) Aluminum hydroxide Magnesium hydroxide Calcium carbonate Sodium bicarbonate Dosage regimen: prn

H2-receptor antagonists Agents Cimetidine (Tagamet) Famotidine (Pepcid) Nizatidine (Axid) Ranitidine (Zantac)

Proton Pump Inhibitors Agents Omeprazole (Prilosec) Omeprazole/Sodium bicarbonate (Zegerid) Esomeprazole (Nexium) Lansoprazole (Prevacid ) Rabeprazole (Aciphex) Pantoprazole (Protonix)

Cytoprotectives a. Sucralfate (Carafate): (Active Duodenal Ulcer) adhesive gel formation prostaglandin-mediated mucosal defense pepsin binding bile acid binding Unlabeled Use: Gastric ulcers and prevention of stress ulcers, suspension for topical treatment of chemotherapy-induced stomatitis, and other causes of esophageal and gastric erosions NOTE: Do not give antacids within 30 minutes of administration. Give other potentially interacting drugs (digoxin, phenytoin, warfarin, ketoconazole quinidine, quinolones, tetracycline, theophylline) ≥ 2 hours before sucralfate Adverse drug events - constipation

b. Prostaglandin analogues Misoprostol (E1 analogue; Cytotec): Effective in healing

peptic ulcer disease but is currently approved for the prevention of NSAID-induced gastric mucosal damage:

Warning: Women of child-bearing potential: abortifacient; effective contraception

Therapy of Helicobacter pylori FDA-Approved Options a. Helidac 14-day (Blister Card) Therapy Bismuth subsalicylatec Metronidazole + an H2RA (x 4 wks) Tetracycline or PPI cChewable

b. Pylera capsule Bismuth subcitrate potassium Metronidazole Tetracycline Dose: 3 capsules tid, pc & hs (qid) + omeprazole 20 mg bid (breakfast, dinner) (pc = after breakfast +[ omeprazole], after lunch, after dinner + [omeprazole])

c. Prevpac 10-day Therapy d. 10-day Therapy Lansoprazole Esomeprazole

Amoxicillin Amoxicillin Clarithromycin Clarithromycin Omeprazole Amoxicillin Clarithromycin

e. Lansoprazole 30 mg bid f. 7-day Therapy Amoxicillin 1 g tid This 14-day regimen is restricted Rabeprazole to suspected clarithromycin Amoxicillin resistance, intolerance or allergy. Clarithromycin

Penicillin Allergy g. Standard dose PPI + Clarithromycin + Metronidazole

Clarithromycin/Metronidazole Resistance: 7-day Regimen Esomeprazole 40 mg po daily Moxifloxacin 400 mg po daily Rifabutin 300 mg po daily

Patient Counseling Regarding Some Anti-H. pylori Agents H. pylori failure is usually attributed to: 1. poor compliance 2. antibiotic resistance PPIs: Take the PPIs 30-60 minutes before eating in order to Optimize their effect on gastric acid secretion The most commonly reported side effects are: Headaches Diarrhea Clarithomycin: The most common adverse effects seen with clarithromycin include: GI upset Diarrhea Altered sense of taste Amoxicillin: Common side effects associated with amoxicillin include: GI upset Headache Diarrhea

Patient Counseling Regarding Some Anti-H. pylori Agents Metronidazole: Side effects associated with metronidazole include: Metallic taste Reddish-brown urine Nausea/Diarrhea Disulfiram-like reaction with alcohol use Bismuth: Metallic taste, diarrhea, nausea, headache, discoloration of tongue, grayish-black stool, 8 tabs/day (~ 2 gm salicylate), constipation, ringing in ears Tetracycline: GI upset Photosensitivity Should not be used in children <8 yo because of possible teeth discoloration NOTE Concurrent use of tetracyclines may render oral contraceptives less effective. Patients should be advised to use a different or additional form of contraception. Breakthrough bleeding has been reported.