PUD (2).pptx

Peptic Ulcer Disease (PUD) Justin Kirby, PharmD, BCACP, NBC-HWC PHPR 2813: Pharmacotherapy I Objectives • Recall the pathophysiologic mechanisms associated with Peptic Ulcer Disease (PUD). • Identify potential causes of PUD • Compare and contrast treatment options for H. pylori-caused and NSAIDcau...

Peptic Ulcer Disease (PUD) Justin Kirby, PharmD, BCACP, NBC-HWC PHPR 2813: Pharmacotherapy I Objectives • Recall the pathophysiologic mechanisms associated with Peptic Ulcer Disease (PUD). • Identify potential causes of PUD • Compare and contrast treatment options for H. pylori-caused and NSAIDcaused PUD • Discuss potential complications of PUD • Recall the clinical presentation and most common tests used to diagnose PUD. • Develop a patient-specific treatment plan for the eradication of PUD • Identify potential differential diagnoses in the evaluation of a patient with PUD Introduction • Gastric acid is a main culprit of upper GI complications • Peptic Ulcer Disease (PUD) is characterized by large erosions (>5 mm) that extend into the muscularis mucosa • Commonly grouped by their etiology • Helicobacter pylori-positive • Non-steroidal anti-inflammatory drug (NSAID)-induced • Stress-related mucosal damage • Results in impaired quality of life, work loss, and high cost medical care Epidemiology • 0.1-0.3% of the population is affected annually; lifetime prevalence is 5-10% • Prevalence is decreasing in the US • Mortality, hospitalization, am care and ED visits have declined • GI hemorrhage readmission rates related to PUD have increased • Mortality higher in patients >65 and in men Epidemiology • Prevalence varies by region, socioeconomic conditions, ethnicity, and age • The prevalence of H. pylori continues to decline in more developed countries • Black and Hispanic Americans have higher infection rates than nonHispanic white Americans • No difference between genders or smoking status • Gastroduodenal ulcers develop in 30-50% of chronic NSAID users • Low dose aspirin is also a risk factor H.Pylori Etiology • H. pylori increases risk of GI bleeds by 3-7x • No specific link between H. pylori and dyspepsia or GERD • Some patients with dyspepsia may have symptom improvement from H. pylori eradication • H. pylori eradication may worsen GERD symptoms but eradication should be the goal due to known gastric cancer risk NSAID Etiology • Evidence linking NSAID (including low dose aspirin) use to PUD is overwhelming • Dose, duration of use, and and type of NSAID are contributing risk factors • NSAID related dyspepsia does not directly correlate with mucosal injury • Non-relieved, new onset symptoms may suggest ulcer complication • H. pylori + NSAID use seems to have additive effects Other Etiologies • Correlation between smoking and PUD exists • Current and former smokers are 2x more likely to develop PUD than non/never-smokers • Evidence linking psychological stress to PUD is conflicting • Role of stress and PUD is likely multifactorial • Effects of diet on PUD development are uncertain Pathophysiology • Determined by the balance between aggravating (gastric acid and pepsin) and protective factors (mucosal defense and repair) • Endogenous prostaglandins facilitate mucosal integrity and repair • The bacterial enzymes produced by H.pylori, bacterial adherence, and virulence factors cause gastric mucosal injury • Gastric inflammation is caused by H. pylori’s altering of the host inflammatory response Pathophysiology • NSAIDs cause gastric mucosal damage both by local and systemic mechanisms • Local damage is done by the more acidic NSAIDs (aspirin) disrupting the mucous gel layer • Systemic damage is caused by inhibiting endogenous prostaglandins (primary mechanism) • Cyclooxygenase (COX)-the enzyme that converts arachidonic acid to prostaglandin- is inhibited by NSAIDS • COX-1 inhibition causes more damage than COX-2 inhibition Complications • Most serious complications are bleeding, perforation, and obstruction • Mortality is highest in patients with uncontrolled bleeding or in those with a “re-bleeding” event • Incidence of gastric perforation has decreased with the prevalence of PPIs but morbidity and mortality from it remains high • Gastric outlet obstruction can occur with chronic inflammation causing narrowing of the duodenum ⭐️ Treatment • General approach depends on • Ulcer etiology • Initial or recurrent • Complications • Therapy is aimed at • Reliving ulcer pain • Healing the ulcer • Preventing recurrence and complications Treatment • Antimicrobials + acid suppression therapy (PPIs or H2RAs) eradicate H. pylori infection allowing for ulcer healing and relief of symptoms • PPIs provide superior symptom control and ulcer healing compared to H2RAs or sucralfate • PPIs are also preferred for H. pylori negative NSAID-induced ulcers • ALL NSAID THERAPY SHOULD BE DISCONTINUED PERMANENTLY IF POSSIBLE. • Patients requiring continued NSAID use after initial ulcer diagnosis should be swapped to a COX-2 selective NSAID or receive prophylactic co-therapy with a PPI Learn how to draw this out! Nonpharmacological Therapy • Lifestyle Modifications: • Stress reduction • Smoking cessation • No specific dietary recommendations-patients should avoid foods that aggravate ulcer symptoms • Surgery is typically only done in emergent situations (complications) 91% Cost/ lack of data Medication Therapy • Testing for H.pylori should be done in all NSAID induced ulcers to determine their status • H.pylori + First line treatment discussed • H.pylori- NSAID discontinued and started on PPI, H2RA, or sucralfate • NSAID continued: Swap to COX-2 selective and initiate PPI or misoprostol • Maintenance acid suppression therapy should be limited to high risk patients with ulcer complications, those who fail eradication, and those w/ H.pylori- ulcers Medication Therapy • Probiotics • Limit H.pylori colonization • Increase eradication rates compared to placebo • May reduce adverse effects of antibiotic eradication therapy H.pylori Eradication Failure • Initial treatment failures should be referred to a gastroenterologist • Second-line (salvage) therapy should include a regimen with antibiotics differing from the first therapy used and use an extended duration of treatment • Penicillin skin testing may be warranted for patients reporting a penicillin allergy • Medication adherence and pharmacogenomics are important patient factors • Antibiotic resistance is an important H.pylori related factor Medication Therapy • NSAID related ulcers (H.pylori -) typically heal when the NSAID is discontinued and a standard 8 week regimen of a PPI, H2RA, or sucralfate is initiated • PPIs are the drugs of choice • For prevention of NSAID-related PUD, several strategies exist • COX-2 selective NSAID + PPI (greatest protection, followed by…) • COX-2 selective NSAIDs alone • Non-selective NSAIDs w/ PPI (can also use H2RAs-not effective vs. gastric ulcers) • Medical co-therapy with misoprostol (GI side effects limit use) Medication Therapy • Idiopathic ulcers are not commonly diagnosed but may be increasing in prevalence while also having increased morbidity and mortality • Double-check to ensure no history of NSAID usage and H. pylori negative • Treatment follows the NSAID-induced PUD guidelines • Famotidine 40 mg daily and lansoprazole 30 mg daily were seen to be equally effective • Long term maintenance may be required in patients who fail H. pylori eradication, have a history of ulcer-related complications, are heavy smokers or NSAID users • Standard maintenance doses are typically effective Medication Therapy • Sucralfate • Heals peptic ulcers but is no longer widely used • Multiple daily doses necessary, large tablet size, must be separated from meals to prevent interreacting with concomitant medications (fluoroquinolones) • Drug interactions minimized by giving interacting drugs 2 hours before sucralfate • Constipation is the major side effect Medication Therapy • Prostaglandins • Misoprostol is a synthetic PGE1 analogue that moderately inhibits acid secretion and enhances mucosal defense • Antisecretory at 50-200 mcg; cytoprotective at 200 mcg • Diarrhea is seen in 10-30% of patients and is often accompanied by other GI side effects • Contraindicated in pregnancy Medication Therapy • Bismuth Preparations • Bismuth subsalicylate and bismuth subcitrate potassium possibly provide ulcer healing mechanisms by exerting • Antibacterial effects • Local gastroprotective effects • Stimulation of endogenous prostaglandins • Liquid preparations sometimes impart a black color to stool or tongue • Long term use is not recommended due to potential for bismuth toxicity Medication Therapy • Antacids • Neutralize gastric acid, inactivate pepsin, and bind bile salts • Aluminum-containing antacids also suppress H. pylori and enhance mucosal defense • GI adverse effects are most common • Aluminum causes constipation; magnesium causes diarrhea Monitoring • Ulcer pain typically resolves within a few days of discontinuing an NSAID and within 7 days of initiating antiulcer therapy • Patients w/ uncomplicated PUD are typically symptom free after treatment with any of the recommended regimens • Persistent symptoms within 14 days of treatment completion suggest a failure of H. pylori eradication or an alternative diagnosis • Eradication should be confirmed in all individuals by UBT and/or fecal antigen test if endoscopy is not indicated Pearls/Differential Diagnoses • Medication adherence should be assessed in all patients who fail therapy • Advocate for NSAID induced PUD prophylaxis with previously discussed strategies • Related disorders include: • Upper GI Bleeding • Peptic Ulcer-Related Bleeding • Stress-Related Mucosal Bleeding • Zollinger-Ellison Syndrome (ZES): Can be treated w/PPIs and H 2RAs References Love BL. Peptic Ulcer Disease and Related Disorders. 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 05, 2023. https://accesspharmacy.mhmedical.com/content.aspx ?bookid=3097&sectionid=267240133 Peptic Ulcer Disease (PUD) Justin Kirby, PharmD, BCACP, NBC-HWC PHPR 2813: Pharmacotherapy I