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Prescription Practice II – PHAR 422.

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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


13
C UBT Breath Test
(W/Pranactin) - non-radioactive


14
C 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 subsalicylate
c

Metronidazole + an H
2
RA (x 4 wks)
Tetracycline or PPI

c
Chewable
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.