Peptic Ulcer Disease (PUD) - Gastro-Intestinal Pharmacology

PEPTIC ULCER DISEASE  MODULE OUTLINE Background Management of PUD Pathophysiology Medications Etiology Role of the Nurse Prognosis Patient Education Clinical Presentation Diagnosis WHAT IS PEPTIC...

PEPTIC ULCER DISEASE  MODULE OUTLINE Background Management of PUD Pathophysiology Medications Etiology Role of the Nurse Prognosis Patient Education Clinical Presentation Diagnosis WHAT IS PEPTIC ULCER DISEASE??  ETIOLOGY Peptic ulcer disease (PUD) may be due to any of the following: H pylori infection Drugs Lifestyle factors Severe physiologic stress Hypersecretory states (uncommon) Genetic factors  NSAID MEDICATIONS Peptic ulcer disease is a well-recognised complication of NSAID use. Inhibition of COX-1 in the gastrointestinal tract leads to a reduction of prostaglandin secretion and its cytoprotective effects in gastric mucosa. This therefore increases the susceptibility to mucosal injury These drugs disrupt the mucosal permeability barrier, rendering the mucosa vulnerable to injury. As many as 30% of adults taking NSAIDs have GI adverse effects. Risk Factors include history of previous peptic ulcer disease advanced age, high doses or combinations of NSAIDs, long-term NSAID use concomitant use of anticoagulants, and severe comorbid illnesses.  OTHER ETIOLOGICAL FACTORS Low-dose aspirin for secondary prevention of cardiovascular Previous history of peptic ulcer disease Current use of NSAIDs, oral steroid agents Tobacco use Stress Depression Anemia Social deprivation Most evidence now supports the assertion that H pylori and NSAIDs are synergistic with respect to the development of peptic ulcer disease.  NSAID GASTROPATHY IN CHILDREN Prevalence in children unknown Seems to be increasing, especially in children with chronic arthritis treated with NSAIDs. Case reports have demonstrated gastric ulceration from low-dose ibuprofen in children, even after just 1 or 2 doses.  CORTICOSTEROIDS AND OTHERS Corticosteroids alone do not increase the risk for PUD; however, they can potentiate ulcer risk in patients who use NSAID drugs concurrently. It is suggested that the mechanisms responsible for peptic ulcer formation induced by corticosteroids include enhanced gastrin and parietal cell hyperplasia with increased acid secretion, diminished gastric mucus synthesis, and suppressed arachidonic acid metabolism and prostaglandin (PG) synthesis  LIFESTYLE FACTORS Evidence that tobacco use is a risk factor for duodenal ulcers is not conclusive. Alcohol is known to cause; gastric mucosal irritation Little evidence suggests that caffeine intake is associated with an increased risk of duodenal ulcers.  SEVERE PHYSIOLOGIC STRESS Stressful conditions that may cause PUD include: Burns central nervous system (CNS) trauma surgery, and severe medical illness. Have you heard of Stress ulcer prophylaxis?  PROGNOSIS Most patients treated successfully with; Eradication of H pylori infection Avoidance of nonsteroidal anti-inflammatory agents (NSAIDs), and The appropriate use of antisecretory therapy Studies have shown eradication of H pylori infection changes the natural history of the disease, and decrease the ulcer recurrence rate from 60- 90% to approximately 10-20%.  DIAGNOSTIC TESTS Test-and-treat strategy for H. pylori is recommended for patients < 55 YEARS with dyspepsia who have no alarm symptoms Endoscopy With Biopsy Stool Monoclonal Antigen Tests Serologic Tests  CLINICAL PRESENTATION Dyspepsia, including; Belching, bloating, distention Fatty food intolerance, fullness, Pain radiating to the back Heartburn Chest discomfort Hematemesis or melena resulting from gastrointestinal bleeding. Melena may be intermittent over several days or multiple episodes in a single day.  OTHER POSSIBLE MANIFESTATIONS Rarely, a briskly bleeding ulcer can present as hematochezia. Symptoms consistent with anemia (e.g, fatigue, dyspnea) Sudden onset of symptoms may indicate perforation. NSAID-induced gastritis or ulcers may be silent, especially in elderly patients. Only 20-25% of patients with symptoms suggestive of peptic ulceration are found on investigation to have a peptic ulcer.  ALARM FEATURES These warrant prompt gastroenterology referral Bleeding or anemia Early satiety Unexplained weight loss Progressive dysphagia or odynophagia Recurrent vomiting Family history of gastrointestinal cancer  PATIENT EDUCATION Patient education should cover the following: nonsteroidal anti-inflammatory drugs (NSAIDs) Aspirin Alcohol Tobacco Caffeine (eg, coffee, tea, cola) Others include Obesity and weight reduction Stress reduction in individual cases  COMPLICATIONS OF PUD Refractory, symptomatic peptic ulcers Intestinal Obstruction Intestinal Perforation Ulcer bleeding - especially in patients with a history of massive hemorrhage and hemodynamic instability Failure of therapeutic endoscopy to control bleeding  TREATMENT OF PEPTIC ULCER DISEASE Goals of Therapy: to eradicate H pylori infection to prevent complications in patients with peptic ulcers  CLASSIFICATION OF DRUGS USED IN PEPTIC ULCER Drugs that inhibit gastric acid secretion Drugs that neutralize gastric acid (Antacids) Ulcer protectives Anti H. pylori drugs  TREATMENT OF PEPTIC ULCER DISEASE General Principles: Pharmacologic management of acute bleeding from PUD Acid suppression using proton pump inhibitors (PPIs). Both classes available in intravenous or oral preparations. Discontinue NSAIDs if clinically feasible. PPI maintenance is recommended to prevent recurrences for patients who must continue with their NSAIDs, even after eradication of H pylori.  TREATMENT OF PEPTIC ULCER DISEASE Principles Cont’d Recommended primary therapy for H pylori infection is proton pump inhibitor (PPI)–based triple therapy Emergency room treatment may include; Antacids or GI cocktail (typically an antacid with an anesthetic such as viscous lidocaine and/or an antispasmodic) for symptomatic therapy High risk patients should be treated with PPIs or H2RAs for 1 year Patients with refractory ulcers may continue receiving once-daily PPI therapy indefinitely  TREATMENT IN THE EMERGENCY DEPARTMENT Antacids or a gastrointestinal (GI) cocktail may be used as symptomatic therapy (typically an antacid with an anesthetic such as viscous lidocaine and/or an antispasmodic) Empiric treatment of H pylori is not recommended WITHOUT confirmation of infection.  BLEEDING PEPTIC ULCERS Endoscopy is indicated for appropriate rapid diagnosis and treatment Endoscopic therapy reduces the likelihood of recurrent bleeding and decreases the need for surgery. Decreases hospital stay  MASSIVE BLEEDING MANAGEMENT Difficult complication to treat. Mainstays of resuscitation include the following: Establishment of adequate intravenous (IV) access, and consider blood transfusion.  MASSIVE BLEEDING MANAGEMENT Nasogastric suction helps to keep the stomach empty and contracted. emergent surgical or endoscopic intervention may be required IV PPI has been shown to reduce: mortality in upper GI bleeds reduce the incidence of rebleeding and the need for surgical intervention; Patients with significant or potentially significant hemorrhage require admission, usually to the intensive care unit.  PROTON PUMP INHIBITER SAFETY AND MONITORING PPIs typically have a very good safety profile Adverse effects: (especially with long-term and/or high-dose therapy) Clostridium difficile infection community-acquired pneumonia hip fracture, and vitamin B12 deficiency decreased absorption of some medications such ketoconazole and iron salt iron deficiency anemia, due to achlorhydria (absence of intragastric acidity) ** ferric form of iron must be converted to the ferrous form by gastric acid**  H PYLORI INFECTION Gram (-) rod Associated with gastritis, gastric & duodenal ulcers, gastric adenocarcinoma Transmission route fecal-oral Secretes urease → convert urea to ammonia Produces alkaline environment enabling survival in stomach  H PYLORI INFECTION Recommended primary therapy for H pylori infection is proton pump inhibitor (PPI)–based triple therapy These regimens result in a cure of infection and ulcer healing in approximately 85-90% of cases. Ulcers can recur in the absence of successful H pylori eradication. Spouses and H pylori –positive family members of H pylori –positive persons should be considered for testing and treatment  PPI-BASED TRIPLE THERAPIES FOR 14-DAY REGIMEN Omeprazole (Prilosec): 20 mg PO bid or Rabeprazole (Aciphex): 20 mg PO bid or Esomeprazole (Nexium): 40 mg PO daily or 20 mg BID Or Pantoprazole 40 mg daily Plus Clarithromycin : 500 mg PO bid and Amoxicillin : 1 g PO bid (Metronidazole for PCN allergic patients)  QUADRUPLE THERAPIES FOR H PYLORI INFECTION Generally reserved for patients in whom the standard course of treatment has failed.  SUMMARY Upper GI endoscopy is the preferred diagnostic test in the evaluation of patients with suspected PUD. Early endoscopy is recommended in patients older than 45-50 years and in patients with associated so-called alarm features. PUD can be treated successfully with; cure of H pylori infection and/or avoidance of nonsteroidal anti-inflammatory drugs (NSAIDs), along with appropriate use of antisecretory therapy. MEDICATIONS  PROTON PUMP INHIBITORS Most effective drugs in antiulcer therapy Prodrugs requiring activation in acid environment Available options: Omeprazole Pantoprazole Lansoprazole Esomeprazole Rabeprazole  PPI PHARMACOKINETICS CONSIDERATION They should be given 30 minutes to 1 hour before food intake