5 - Peptic Ulcer Disease

What are protective factors of the stomach and duodenum?

• mucus

• bicarbonate

• prostaglandins

• rapid epithelial cell turnover

What are damaging factors of the stomach and duodenum?

• gastric acid

• pepsin

• decreased blood flow

What causes peptic ulcer disease?

1. increased acid and pepsin production

2. decreased mucosal protection

3. altered prostaglandin balance

4. mucosal damage

5. chronic inflammation

What are the causes of peptic ulcer disease?

• helicobacter pylori infection

• medications (NSAIDs, corticosteroids, bisphosphonates, alcohol)

• zollinger-ellison syndrome

• malignancy

• inflammatory conditions (Crohn’s disease)

• severe physiologic stress

What are the characteristics of helicobacter pylori (h. pylori) and how does it cause peptic ulcer disease?

gram-negative, spiral shaped bacterium that colonizes the gastric mucus layer

• flagella penetrates mucus

• urease converts to ammonia, locally neutralizing acid to create an ideal environment

What can occur if h. pylori goes untreated?

chronic gastritis

What are the precusors of ulcer formation?

chronic inflammation → impaired mucosal defenses → ulcer formation

What is the goal of therapy for h. pylori-induced peptic ulcer disease?

1. eradication

2. heal the ulcer

3. substantially reduce ulcer recurrence

What are the non-invasive testing options for h. pylori?

• urea breath test

• stool antigen

What are the invasive testing options for h. pylori?

• rapid urease test

• histology

• culture

When might you consider invasive testing?

• patient already undergoing EGD

• complicated or refractory PUD

• suspected gastric malignancy

• need to evaluate antibiotic resistance

What medications can cause false-negative h. pylori results?

• PPIs (hold >= 2wk)

• antibiotics/bismuth (hold >= 4wk)

What can be used during PPI washout period while holding for h. pylori testing?

H2-receptor antagonists

How do NSAIDs induce peptic ulcer diseae?

weaken the mucosal defense system via COX-inhibition and direct topical injury

What is the result of NSAIDs inhibiting COX?

decreased:

• prostaglandins

• mucus + bicarbonate secretion

• mucosal blood flow

increased acid susceptibility

What is the result of direct topical injury via NSAIDs?

• directly disrupts gastric epithelial cell membranes

• allows H+ ions to penetrate mucosa

What are risk factors of NSAID-associated peptic ulcer disease?

• older age

• high-dose, long duration, or multiple NSAID therapies

• concurrent anticoagulants, antiplatelets, or corticosteroids

Define zollinger ellison syndrome?

formation of gastrinomas (pancreatic or duodenal neuroendocrine tumor)

What is the result of gastrinomas?

secrete high levels of gastrin in the blood

• trigger parietal cells to release excess gastric acid

• causes cell hyperplasia

lack of negative feedback to stop acid production → severe peptic ulcer disease

What are the components of the “triad of zollinger ellison syndrome”?

1. pancreatic or duodenal tumors

2. gastric hypersecretions

3. peptic ulcers

What population are gastric ulcers more prevalent in and what is the common cause?

• adults > 50yrs

• increasingly driven by NSAID use

What population are duodenal ulcers more prevalent in and what is the common cause?

• 30-50yrs

• highly associated with h. pylori

Which type of peptic ulcer is more common?

duodenal

What are the key features of asymptomatic peptic ulcer disease?

• ~70% of peptic ulcers are asymptomatic

• 43-87% o fpatients with bleeding ulcers may have no initial GI symptoms

What are key features of symptomatic peptic ulcer disease?

• present with epigastric discomfort/fullness/pain described as gnawing or burning

• post-prandial belching

• early satiety

• fatty food intolerance

• symptoms may be food related

What is the key feature of gastric ulcers?

pain occurs during or shortly after meals

What is the key feature of duodenal ulcers?

pain may improve with eating, then recur ~2-3 hours after a meal

What is the typical symptom pattern of peptic ulcer disease?

pain may persist for weeks, followed by symptom-free periods lasting weeks to months

What are alarm symptoms of peptic ulcer disease?

• unintentional weight loss

• hematemesis

• melena

• persistent vomiting

What are the types of “complicated” ulcers?

• bleeding

• gastric outlet obstruction

• penetration and fistulization

• perforation

What is the most common complication of ulcers?

acute upper gastrointestinal hemorrhage (bleeding)

What are the symptoms of bleeding ulcers?

• nausea

• hematemesis

• melena

What cause gastric outlet obstruction?

ulcers can lead to significant inflammation and scarring around pyloric valve → narrows opening and prevents stomach emptying

What are the symptoms of gastric outlet obstruction?

• early satiety

• bloating

• nausea

• vomiting

• epigastric pain

• weight loss

What is the cause of penetration and fistulization?

• ulcer erodes deeply enough to penetrate beyond the GI wall and can form a fistula with an adjacent organ

• abnormal connection allows gastric contents to leak into adjacent organ

What is the cause of perforation from ulcers?

more severe complication where gastric contents leak into peritoneal cavity leading to peritonitis

What is the classic “perforation triad”?

1. severe and diffuse abdominal pain

2. tachycardia

3. abdominal rigidity

Which medication class is preferred as 1st line therapy in peptic ulcer disease?

proton pump inhibitor

What is the MOA of PPIs?

irreversibly inhibits H/K/ATPase and prevents gastric acid secretion by parietal cells

• decreases acid exposure, decreasing mucosal injury

• increases tissue repair, clot stability, and ulcer healing

Why are PPIs preferred in PUD?

provide the most potent and sustained suppression of gastric acid resulting in more reliable ulcer healing

How should PPIs be administered?

• 30-60 minutes before the largest meal(s) of the day

• scheduled, not prn

What agents are PPIs?

• protonix (pantoprazole)

• nexium (esomeprazole)

• prilosec (omeprazole)

• dexilant (dexlansoprazole)

• prevacid (lansoprazole)

• aciphex (rabeprazole)

What are the dose and dosage forms of protonix?

40mg DR tab + IV

What are the dose and dosage form of nexium?

20-40mg DR cap/tab + oral suspension + IV

What are the dose and dosage forms of prilosec?

20-40mg DR cap/tab + oral suspension

What are the doses and dosage forms of dexilant?

30-60mg DR cap

What are the dose and dosage forms of prevacid?

15-30mg DR cap + ODT + oral suspension

What are the dose and dosage forms of aciphex?

20mg DR tab + sprinkle capsule

Which PPI agents are Rx only?

• protonix

• dexilant

• aciphex

Which PPI lower dose agents are OTC?

• nexium

• prilosec

• prevacid

T/F: there is no clinical differences in symptom resolution and ulcer healing between PPIs

true

What indications should be considered for PPI selection?

uncomplicated PUD, h. pylori, NSAID-associated, GI bleed

What is a common drug interaction of PPIs?

omeprazole & esomeprazole inhibit CYP2C19 → reduce clopidogrel activation

What should be considered for patients taking PPIs with hepatic impairment?

dose reduction in omeprazole, esomeprazole, lansoprazole

What is the typical duration and dosing frequency for an uncomplicated duodenal ulcer?

• 4 weeks

• oral PPI daily

What is the typical duration and dosing frequency for an uncomplicated gastric ulcer?

• 4-8 weeks

• oral PPI daily

What is the typical duration and dosing frequency for an NSAID-associated ulcer?

4-8 weeks, oral PPI daily

What is the typical duration and dosing frequency for a complicated bleeding ulcer?

8-12 weeks

• IV BID x72hr

• oral BID x2wk

• oral QD x6-8wk

Define refractory ulcer

incomplete healing after 6-12wks on daily PPI

What is the typical duration and dosing frequency for a refractory ulcer?

additional 6-8wk, oral PPI BID

What can prevent ulcer recurrence?

• NSAID avoidance

• h. pylori eradication

• maintenance antisecretory therapy

Which patients qualify for indefinite maintenance therapy?

• giant (>2cm) peptic ulcer and age > 50yr OR multiple comorbidities

• relapsing h. pylori, NSAID ulcers

• failure to eradicate h. pylori after multiple treatment courses

• >2 documented recurrences/year

• continued NSAID or aspirin use

What should be monitored when taking a PPI?

periodic reassessment to ensure patient remains on lowest effective dose

Which labs may be recommended for some long-term PPI patients?

• serum magnesium

• serum vitamin B12

• bone mineral density

What are possible long-term PPI ADE associations?

• pneumonia, c. diff

• fractures

• dementia

• AKI or CKD

What are adjunctive medications to PPIs?

• carafate (sucralfate)

• antacids

What is the MOA of carafate?

forms a protective barrier against acid and pepsin over the ulcer to promote mucosal defense and healing

When may carafate be considered?

not routinely needed when PPI is being used, but may be considered for persistent symptoms despite adequate acid suppression therapy

What are dosing and administration instructions of carafate?

• 1g oral 4 times daily

• 1hr before meals and at bedtime

• separate from other oral medications by at least 2hrs

What is the MOA of antacids?

neutralize existing gastric acid to provide rapid, short-term relief

How should antacids be used in ulcer therapy?

do not provide sustained acid suppression needed, use PRN for breakthrough symptoms

How should NSAID-associated peptic ulcer disease be managed?

1. stop NSAID if possible

2. PPI for ulcer healing

3. if ulcer required → lowest dose + PPI gastroprotection

4. consider COX-2 selective NSAID based on GI and cardiovascular risk

5. assess aspirin indication

6. assess for possible concomitant h. pylori infection

Which type of NSAID is preferred in prior PUD if necessary and why?

COX-2 selective

• minimal COX-1 inhibition

• lower GI mucosal injury

• reduced ulcer/bleeding risk

What is the first line treatment for h. pylori?

optimized bismuth quadruple therapy

1. PPI

2. bismuth subsalicylate

3. tetracycline

4. metronidazole

What is the role of PPI in optimized bismuth quadruple therapy?

suppresses acid + promotes healing

What is the role of bismuth subsalicylate in optimized bismuth quadruple therapy?

direct antimicrobial + mucosal protection

What is the role of tetracycline in optimized bismuth quadruple therapy?

inhibits bacterial protein synthesis

What is the role of metronidazole in optimized bismuth quadruple therapy?

damages bacterial DNA

What are patient considerations/limitations of optimized bismuth quadruple therapy?

• complex regimen, high pill burden

• strict adherence required

• long duration

• cost/availability

When should optimized bismuth salicylate be avoided?

aspirin allergy

What are the drug doses required for optimized bismuth quadruple therapy?

• standard PPI BID

• bismuth subsalicylate 524mg QID

• tetracycline 500mg QID

• metronidazole 500mg TID-QID

for 14 days

What are the components and dosages of pylera?

• bismuth subcitrate 420mg

• metronidazole 375mg

• tetracycline 375mg

QID for 10 days

+PPI standard dose BID

What is the cost consideration for BQT vs. pylera?

pylera is generally more expensive

What are the alternative treatment regimens for h. pylori?

• rifabutin triple therapy

• vonoprazan dual therapy

What are the considerations of rifabutin triple therapy?

• rifabutin and amoxicillin resistance is very low

• significantly lower rate of GI upset, nausea, dizziness

• can be used as salvage therapy after BQT failure

What are the considerations of vonoprazan dual therapy?

• more potent, faster, durable acid suppression

• minimizes antibiotic exposure

• triple therapy reserved for when clarithromycin susceptibility confirmed

• high cost

What are the drugs and doses of rifabutin triple (talicia)?

• rifabutin 50mg

• omeprazole 40mg

• amoxicillin 1g (4 caps)

TID for 14 days

What are the drugs and doses of vonoprazan-amoxicillin dual (voquezna dual pak)?

• vonoprazan 20mg BID

• amoxicillin 1g TID

for 14 days

What are the drugs and doses of vonoprazan-amoxicillin-clarithromycin triple (voquezna triple pak)?

• vonoprazan 20mg

• amoxicillin 1g

• clarithromycin 500mg

BID for 14 days

What is the MOA of voquezna?

potassium-competitive acid blocker (PCAB)

• reversibly and competitively blocks the K+ binding site in the ATPase pump

• provides rapid, potent and sustained acid suppression through the day and night

What is the indication of voquezna other than h. pylori?

healing of erosive gastritis, maintenance of healed erosive gastritis and non-erosive GERD

What are the ADE of voquezna?

stomach pain, diarrhea, nausea, indigestion, bloating, headaches, hypergastrinemia

What are precautions/interactions of voquezna?

• not recommended for eGFR <30 mL/min or child-pugh class B or C

• CYP2C19 substrates, CYP3A inducers

What should be avoided if macrolide and fluoroquinolone susceptibility testing is unavailable?

treatment regimens containing clarithromycin and levofloxacin should be avoided

Can doxycycline be substituted for tetracycline?

ACG guidelines explicitly recommends against substituting doxycycline and tetracycline (eradication rates feel to 65%-70% vs. 88%)

What should be followed up on for h. pylori patients?

confirmation of eradication

• fecal antigen test, urea breath test, upper endoscopy/biopsy

• at least 4 weeks after treatment completion, at least 2 weeks after stopping PPIs