Ulcer Disease.pptx.pdf

I am professionally pharmacist. These slides provide for pharmacy department students, especially for clinical point of view or subject.

1. Peptic Ulcer Disease
Gastric ulcer
Duodenal ulcer

2. Definition
•Refers to a group of disorders characterized by
lesions of the mucosa of the upper gastrointestinal (GI )
tract.

(particularly the stomach and duodenum)

The lesions occur in regions exposed to gastric
juices.

results in impaired quality of life, work loss, and
high-cost medical care.

3. INTRODUCTION
Gastroesophageal
reflux disease (GERD)
movement of gastric contents f rom the stomach into the esophagus.
May lead to inflammation of the esophagus.
Dyspepsia Persistent/recurrent abdominal pain or abdominal discomfort centered
in the upper abdomen.
Duodenal ulcers develop in the duodenal bulb
( the first few centimeters of the duodenum) .
Gastric ulcers commonly in the antrum or at the antral - fundal junction.
Stress ulcers Results from serious trauma or illness, major burns, from mechanical
ventilation, sepsis.
Zollinger -Ellison
syndrome
severe form of peptic ulcer disease
extreme gastric hyperacidity.
Drug-associated ulcersnonsteroidal anti - inflammatory drugs (NSAIDs) .
Mechanism might involve
delayed gastric emptying
inhibition of pancreatic bicarbonate secretion,
promotion of duodeno-gastricreflux.
reduction in mucosal prostaglandin production.
increases gastric acid secretion.

4. Epidemiology
•most common disorder of the upper GI tract .
•Nearly 80% of peptic ulcers are duodenal ulcer.
•10%-20% of gastric ulcer patients also have a
concurrent duodenal ulcer .
•Hospitalization rates in the United States for peptic
ulcers have been declining.
•The mortality rate for gastric ulcers is 1.1 per
100,000.
•Death from GERD is uncommon.

5. Etiology-Causes
•Develop due to imbalance between factors that protect gastric
mucosa and factors that promote mucosal corrosion.
•NSAID intake.(aspirin, indomethacin,CS,chemotherapy.)
•Helicobacter pylori infection-duodenal ulcer.
•Genetic factors……. in first -degree relatives.
•Smoking…delays ulcer healing and increases the risk of relapse after
the ulcer heals.
•Alcohol…. mucosal irritant.
•Coffee….. contain peptides that stimulate release of gastrin.
•hyperparathyroidism, emphysema, rheumatoid arthritis,
cirrhosis.
•Zollinger-Ellison syndrome (ZES).
•psychologic stress/chronic renal failure/hepatic cirrhosis.

6. Pathophysiology.
Peptic ulcers occur when the balance between
aggressive factors and mucosal defensive mechanisms
are disrupted.
1.Protective factors
2.Corrosive factors.
Exposure to gastric acid and pepsin.
Disrupted mucosal barrier integrity.
3. Physiological defects associated with peptic ulcer
disease.
Duodenal ulcer patients.
Gastric ulcer patients.
4. GERD.

7. Protective
factors
mucosa secretes a thick mucus that serves as a barrier.
intact mucosal barrier prevents back-diffusion of gastric acids into mucosal cells.
Mucosal integrity also promotes cell growth and repair after local trauma.
Corrosive
factors.
inability of the gastric mucosa to resist corrosion by irritants.
Exposure to gastric acid and pepsin is necessary for ulcer development .
Disrupted mucosal barrier allows gastric acids to diffuse from the lumen back into
mucosal cells, where they cause injury.
Duodenal
ulcer
patients have up to twice the normal number of parietal cells (which produce HCl ) .
elevated serum levels of pepsinogen I and a corresponding increase in
pepsin-secreting capacity.
Above-normal gastrin secretion.
Above-normal rate of gastric emptying, resulting in delivery of a greater acid
load to the duodenum.
Gastric
ulcer
Deficient gastric mucosal resistance, direct mucosal injury.
Elevated serum gastrin levels/normal or reduced rates of acid secretion.
Delayed gastric emptying.
Increased reflux of bile and other duodenal contents.
Subnormal mucosal levels of prostaglandins.
GERD Esophagitis develops when noxious substances i .e. , acid, pepsin are in contact with
the esophageal mucosa long enough to cause irritation.

a decrease in lower esophageal sphincter (LES) pressure that is not associated with
swallowing or peristalsis.

8. Clinical presentation(Signs and symptoms)
abdominal discomfort, fullness, cramping, Heartburn, bloating.
Ulcer pain typically occurs during the day but can also awaken the patient from sleep (nocturnal pain).
Duodenal
ulcer pain
Pain(heart burn or a gnawing, burning, aching, or cramp- like pain).
abdominal soreness or hunger sensations.
Pain is restricted to a small , mid-epigastric area near the xiphoid.
Pain may radiate below the costal margins into the back or the right shoulder .
Pain from a duodenal ulcer frequently awakens the patient between midnight and 2 A.M. ;
it is almost never present before breakfast .
Food usually relieves duodenal ulcer pain.
duodenal ulcer patients tend to gain weight.
Pain occurs 90 min to 3 hr after meals.
Nausea and vomiting
Gastric ulcer
pain
Gastric ulcer rarely produces nocturnal pain.
Food may cause gastric ulcer pain.
gastric ulcer patients may lose weight .
pain in gastric ulcer patients is usually present 45-60 min after a meal.
Nausea, vomiting, anorexia, and weight loss.
GERD present with heartburn, belching, regurgitation.
chest pain, hoarseness/ laryngitis, loss of dental enamel , asthma, chronic cough, or
dyspepsia.
Complications of GERD include esophageal ulceration.
Dyspepsia Abdominal pain and discomfort , heartburn, nausea, vomiting,

9. Clinical evaluation(Physical findings
Diagnostic test results
Blood tests hypochromic anemia.
Stool tests occult blood.
Gastric secretion testsHyper-secretion of HCl in duodenal ulcer.
normal or subnormal HCl secretion in gastric ulcer patients.
barium x- ray ulcer crater
Upper GI endoscopy detect ulcers not demonstrable by radiography.
Biopsy determine whether a gastric ulcer is malignant .
Noninvasive. H. pylori status is determined by noninvasive tests.
Breath tests can also be used to detect the organism.
False-negative breath tests may occur in patients receiving proton
pump inhibitors, antibiotics, or bismuth compounds.
Invasive. histological visualization ion of H. pylori

10. Diagnostic tests-H Pylori
Tests H.Pylori---mucosal biopsy for the rapid urease test, histology, or culture.
When possible, antibiotics and bismuth salts should be withheld for 4
weeks and H2RAs and PPIs for 1 to 2 weeks prior to endoscopic testing.
Culture test Permits sensitivity testing to determine antibiotic choice or
resistance.
Urea Breath Test Tests for active H. pylori infection.
Withhold H2RAs and PPIs 1 to 2 weeks prior to testing and antibiotics and
bismuth salts 4 weeks prior to testing to reduce the risk of false negatives.
Serologic Antibody Tests Detects IgG antibodies to H. pylori in serum.
Results not affected by H2RAs, PPIs, antibiotics, or bismuth.
Fecal Antigen Test Identifies H. pylori antigen in stool.
H2RAs, PPIs, antibiotics, and bismuth may cause false-negative results
Fasting serum gastrin
concentrations
Recommended for patients unresponsive to therapy or those suspected
of having a hypersecretory disease.
evaluation of ulcer-related
bleeding
Serum hematocrit (Hct) and hemoglobin (Hgb) and stool hemoccult tests.
upper endoscopy. single-barium contrast.
Fiberoptic upper endoscopy (esophagogastroduodenoscopy [EGD]) is the
gold standard.

11. COMPLICATIONS
Hemorrhage. upper GI bleeding.
vomit fresh blood or a coffee grounds- like substance.
bloody or tarry stools.
Diaphoresis.
hypovolemic shock.
Mortality is high in patients who continue to bleed or who rebleed
after the initial bleeding has stopped.
Perforation. Penetration of a peptic ulcer through the gastric or duodenal wall.
Sudden acute upper abdominal pain, rebound tenderness, and absent or
diminished bowel sounds.
pain is typically sudden, sharp, and severe, beginning initially in the epigastric
area but quickly spreading throughout the upper abdominal area.
Obstruction. Inflammatory edema, spasm.
postprandial vomiting or bloating, appetite and weight loss, and abdominal
distention. Next 2010

12. Treatment objectives/Therapeutic Goals
Therapeutic goals depend on
whether ulcer is related to H. pylori or with a NSAID.
whether the ulcer is initial or recurrent.

cost-effective drug regimen.
–Relieve pain symptoms.
–promote healing.
–Prevent complications.
–Minimize recurrence.
–Eradicate H. pylori.
–Maintain adequate nutrition.
–Educate the patient.

13. Non-pharmacologic Therapy
•D/C NSAIDs (including aspirin) if possible.

•Dietary modifications (e.g., spicy foods, caffeine, and
alcohol).

•Lifestyle modifications (reducing stress and decreasing
or stopping cigarette smoking).

•Probiotics and foodstuffs (e.g., cranberry juice and some
milk proteins).

•Require surgery for bleeding, perforation, or
obstruction.

14. Drug therapy.
Pharmaco-dynamic end point is to maintain the pH in
the esophagus at 4 or more.

Drugs used:
•Antacids.
•histamine2- (H2- ) receptor antagonists.
•proton pump inhibitors.

•other drugs are added as necessary.

15. Antacids.
neutralize gastric acid.
Treat ulcer pain and heal the ulcer .
magnesium, aluminum, calcium mixtures of aluminum hydroxide and magnesium hydroxide.
antacids also inhibit pepsin activity.
they strengthen the gastric mucosal barrier .
When ingested 1 hr after a meal , they have a much more prolonged effect , about 3-4 hr.
they should optimally be taken 1 and 3 hr after meals and before sleep.
Non-systemic
antacids
magnesium or aluminum substances.
they avoid the risk of alkalosis
Liquid antacid forms greater buffering capacity than tablets.

Antacid mixtures aluminum hydroxide with magnesium hydroxide.
sustained action than single-agent antacids.
permit a lower dosage of each compound.
Calcium carbonate avoided because it causes acid rebound.
delay pain relief and ulcer healing, and induces constipation.
Hypercalcemia.
acid-neutralizing capacity (ANC)
number of milliequivalents (mEq) of a 1 N solution of HCl that can be brought to a pH of 3.5 in 15
min. required dosage depends on the ANC of the specific antacid.
Dose details Table 52-1.(CPR)

16. H2 - receptor antagonists.
preferred to other antiulcer agents because of their convenience and lack of effect on GI
motility. effective in treating mild to moderate GERD symptoms.
Cimetidine.first H2 - receptor antagonist approved for clinical use.
Reduces gastric acid secretion by approximately 50%
(at a total daily dosage of 1000 mg) .
orally in a dosage of 300 mg four times daily (with meals and at bedtime) for up to
8 weeks.
duodenal ulcer 400 mg twice daily.
Hospitalized patients 300 mg intravenously every 6 hr.
Ranitidine,more potent drug, causes a 70% reduction in gastric acid secretion (at a total daily
dosage of 300 mg)
dosage of 150 mg BD. Duodenal ulcer 300 mg at bedtime (up to 8 weeks)
Hospitalized patients (IV or IM route (50 mg every 6-8 hr ) .
Famotidinemost potent H2 - receptor antagonist . After a 40-mg dose, mean nocturnal gastric
acid secretion is reduced by 94% for up to 10 hr .
duodenal ulcer patients(oral dosage of 40 mg at bedtime) 8 weeks.
Hospitalized patients(IV injection of 20 mg every 12 hr)
Nizatidine,newest H2 - receptor antagonist , may be used to t reat and prevent
recurrence of duodenal ulcers.
Dose regimen Table 52-2.(CPR)

17. Misc
Suraclfate:
mucosal protectant ,a non-absorbable disacchaide containing sucrose and aluminum.
Duodenal ulcers respond better than gastric ulcers to sucralfate therapy.
oral agent , sucralfate is given in a dosage of 1 g four times daily (1 hr before meals) and at
bedtime.
therapy continues for 4-8 weeks.
Constipation is the most common adverse effect of sucralfate.
GI anticholinergics:
belladonna leaf , atropine, propantheline.
used as adjunctive agents for relief of refractory duodenal ulcer pain.
decrease basal and stimulated gastric acid and pepsin secret ion.
delay gastric emptying, thereby prolonging antacid retention.
They are most effective when taken at night and in large doses.
Prostaglandins:Misoprostol
suppress gastric acid secretion and may guard the gastric mucosa against damage from NSAIDs.
Misoprostol increases bicarbonate and mucus production at doses of 200 Vg and above.
Misoprostol also maintains mucosal blood flow.
Misoprostol has not been shown to prevent duodenal ulcers.
dosage is 200 Vg four times daily with food.
Misoprostol is contraindicated in pregnant women

18. Proton pump inhibitors
PPIs are more potent than H2 -blockers.
Omeprazole ,lansoprazole , rabeprazol , pantoprazole , esomeprazole.
inhibi t > 90% of 24-hr acid secret ion in most patients.
IV forms have been approved by the U.S. Food and Drug Administration (FDA) .
PPIs are more rapidly effective than other approved agents.
PPIs provide effective healing of duodenal ulcers.
provide more rapid symptom relief and more consistent healing than H2 - receptor antagonists.
Esomeprazole and lansoprazole have been approved by the FDA for healing and prevention of NSAID-
induced gastric ulcers.
Omeprazole and lansoprazole have been approved by the FDA for use in infants and children for the short
- term treatment of GERD.
PPIs should optimally be taken in the morning 30-60 min before eating.
omeprazole Erosive esophagitis-20 mg for 8-12 weeks.
GERD-20 mg.
delayed- release capsules and should be taken before eating.
Omeprazole in sodium bicarbonate powder for suspension is the first PPI approved by
the FDA for reduction in the risk of upper GI bleeding.
Esomeprazole40 mg daily provided significantly higher Intra-gastric pH values.
erosive esophagitis-esomeprazole 40 mg every day has been shown to produce
significantly higher healing.
GERD-Esomeprazole 20-40 mg
delayed- release capsules and should be taken before eating

19. lansoprazole GERD-30mg
erosive esophagitis-15 mg,
Duodenal ulcer-15 mg
delayed- release capsules and should be taken before eating
rabeprazole GERD-20mg
erosive esophagitis-20 mg daily
Duodenal ulcer-20 mg once daily( 4weeks).
enteric-coated tablets that should not be crushed or chewed.
pantoprazole 40mg GERD.
erosive esophagitis-40 mg,
Duodenal ulcer-40mg.
enteric-coated tablets that should not be crushed or chewed.
IV pantoprazole is indicated for management of erosive esophagitis
and treatment of Zollinger -Ellison syndrome.
Other therapeutic measures
Modification of dietavoid milk-milk increases gastric acid secret ion.
Avoid coffee, caffeinated beverages, and alcohol .
Smoking Discouraged.
NSAIDs should be avoided by ulcer patients.
Surgery. patient who develops complications may require surgery.

20. Management of PUD

21. H. pylori
•Present in the setting of active chronic gastritis.
•Present in the vast majority of duodenal (> 90%) &
gastric (60%-90%) ulcers.
•Association is strong between gastric cancer and H.
pylori.
•H. pylori eradication can cure peptic ulcers and reduce
ulcer recurrence.
•H. pylori (gram-negative, spiral-shaped bacillus).
•resides between the mucus layer and surface epithelial
cells in the stomach.
•higher prevalence among older individuals.
•Transmission occurs by the fecal–oral route or from
fecal-contaminated water or food.

22. Diagnostic Test (H Pylori)
Gastric Mucosal Biopsy in Patients Undergoing Endoscopy
Rapid
Urease
Test
Withhold H2RAs and PPIs 1 to 2 weeks prior to testing and antibiotics and bismuth salts 4
weeks prior to testing.
In the presence of H.pylori urease, urea is metabolized to ammonia and bicarbonate resulting in
an increase in pH, which changes the color of a pH-sensitive indicator.
Histology“gold standard” for detection of H. pylori infection.
histologic analysis and evaluation of infected tissue.
Cultureto determine antibiotic choice or resistance.
Tests That do not Utilize Gastric Mucosal Biopsy
Urea Breath
Test
Radiolabeled urea with is given orally; urease secreted by H. pylori in the stomach
hydrolyzes radiolabed urea to produceradiolabled CO2, which is exhaled and then
quantified from the expired breath
Withhold H2RAs and PPIs 1 to 2 weeks prior to testing and antibiotics and bismuth salts
4 weeks prior to testing.
Serologic
Antibody Tests
Detects IgG antibodies to H. pylori in serum, whole blood or urine.

Fecal Antigen
Test
Identifies H. pylori antigen in stool.
H2RAs, PPIs, antibiotics, and bismuth may cause false-negative results
Table 26-5 (koda Kimble)

23. H. Pylori (P.T)
•First-line therapy (PPI-based three-drug regimen).
•Second course of treatment PPI-based three-drug regimen
should contain different antibiotics.
•Four-drug regimen with a bismuth salt, metronidazole,
tetracycline, and a PPI.
•conventional antiulcer drug is not recommended.
•amoxicillin is usually preferred initially because it is
associated with little or no bacterial resistance.
•All PPIs except pantoprazole have been approved in various
combinations of antibiotics for the eradication of H. pylori.
•Maintenance therapy (patients with ulcer complications,
those with H. pylori–negative ulcers, and patients with other
concomitant acid-related diseases (e.g., GERD).

24. Oral Drug Regimens(Table 26-6 Koda Kimble)

25. NSAIDs.(Drug Induced Ulcer-Page 26-18 Koda Kimble)


•Aspirin, indomethacin, and other NSAIDs.
•Injure the gastric mucosa by allowing back-diffusion
of hydrogen ions into the mucosa.
•Inhibit the synthesis of prostaglandins.
•Selective cyclooxygenase 2 (COX-2) inhibitors,
celecoxib are associated with fewer ulcers than
nonselective NSAIDs.

26. Therapy Monitoring
•Post-treatment testing(UBT, rapid urease test and
histology).
•abdominal pain???
•Diarrhea???
•Renal function????
•Constipation????
•Heart Rate????
•Male gynecomastia and impotence???
•hematological disorders(Cimetidine)??
•Hepatotoxicity (ranitidine)???
•Upper endoscopy.????

27. Patient Education/Counseling
•Importance of taking his medications as prescribed.
•If the PPI is to be taken OD, it should be taken 30 to
60 minutes prior to breakfast
•If PPI is to be taken BD, the second dose should be
taken 30 to 60 minutes prior to dinner.
•Patient should also be informed of the most
common side-effects associated with his treatment
regimen.
•C. difficile–associated diarrhea, a serious
antibiotic-related complication.