PEPTIC ULCER DISEASE (PUD)

Dr/Mahmoud Nour El-Din

ULCER

Erosion of mucosa lining any portion of the GIT

Stomach is more protected than
intestine so the incidences of duodenal
ulcer are more than gastric ulcer.

Gastric ulcer (GU)

 Ulcer occurs in the stomach.
 Some of them may be malignant.

Duodenal ulcer (DU)

Most often seen in first portion of
duodenum (> 95%)
 Normal gastric physiology
GIT are present in a balance between
1) Protective
2) Hostile (Aggressive factors)

Protective factors (↑ in normal) Hostile factors (↑ in ulcer)

1) HCO3 (Neutralizing acids) 1) Gastric acid
2) Prostaglandis (↑ mucus , HCO3 , BF & ↓ Acid) 2) Pepsin
3) Mucus membrane (Effective barrier to acid digestion) 3) H.Pylori
4) High blood flow (wash and dilute H+ & pepsin) 4) NSAIDs
5) Diet and beverages
Incidence
 25% of males & 16.5% (1/6) of females develop PUD sometimes during their life
 5-10% will be symptomatic & require treatment
 ↑ Elderly, > 65 years  80% deaths.
o Peptic ulcer is more common in unskilled labourers and low socioeconomic classes

o Rare in children
 Clinical presentations
 Dyspepsia, epigastria pain/ discomfort (90%)

 Bloating, N & V, Anorexia (especially in GU)

 Excessive belching

 Bleeding (blood in vomiting or in stool (melena), Wt loss

 DU GU (↑ with age)
 Very localized pain & can be pointed (DU)  Less localized pain (Pain more diffused)
 Pain Relived by eating / drinking  Pain ↑after food& Wt loss is more common

 Most common in middle age (30-50 yrs)  Common in late middle age (55 - 65)
 Male : female  4 :1 (↑ Men)  Male: female 2 :1 (No sex difference)

 More common with bld grp O  More common with bl.gp A

 Associated with ↑ serum pepsinogen  Use of NSAIDs 3-4 fold ↑ risk of GU

 Duodenal sites are 4x size as GS  GU have a concomitant DU (10-20% )

 Genetic link : 3x in 1st degree relatives

 H.pylori common (95%)  Less related to H. pylori (80%)

 Smoking is twice as common
 Pathophysiology (as it is most common)  Pathophysiology (less common)
Duodenum defense mechanisms are not highly Have normal or low gastric acid output
developed as those in stomach.
Hypergastrinaemia is the cause of PUD
 DU GU (↑ with age)

Causes Causes
1) ↑ resting acid output Abnormal pyloric function 
Reflux of duodenal contents acid, enzymes, bile
2) Twice No. of parietal cells
salts-into the stomach
3) Prolonged acid secretion
4) Abnormal pyloric function (
5) accelerating GER ↑acid environment in
duodenum
6) 5) ↓ HCO3 output

N.B
Zollinger elision (ZE) syndrome
 Caused by gastrin secreting tumors in duodenum or pancreas (gastrinoma)↑HCL
 Severe Slow tumors  50% are malignant (metastases to the liver)

Symptoms
Medical management
 Multiple ulcers
1) Omeprazole (60-80 mg/day) or other PPls
 Ulcers in distal duodenum / proximal jejunum
2) Analogues octreotide effective but has no clear advantage
 Severe diarrhea (due ↑ lipase enzymes)
over PPls
 A NO of diseases have been associated with peptic ulcer including
1) Liver cirrhosis

2) Chronic pulmonary disease (not lead to each other but associated with each other)
It may be due to bad circulation which cause pulmonary disease and ulcer)

3) Chronic renal failure (due to uremia)

4) Pancreatic insufficiency

5) Aortic aneurism (↓ blood flow to GIT)

 Investigations
1) Gastroscopy (Endoscopy) : detects 90% of DUs & 95% of GUs
Endoscopy Allows a tissue diagnosis to be made
a) Sensitive a) Specific
a) Invasive a) Expensive
2) Upper GI radiography  Barium meal : contrast x-ray
3) Biopsy bacteria & malignancy
4) H.pylori
a) Endoscopy
b) Biopsy special stains
c) Culture  difficult

a) Urease tests  Sensitive (by exhalation or stool)

1) Urea breath test (sensitive 90-100%)
o Used for diagnosis
o Done 4 wk post therapy to confirm eradication
o PPIs can give false- ve for H.pylori with urea breath test or biopsy urease test so stop PPI at least 2
weeks before make lab test.
2) Agar-based biopsy urease testes designed to be read at 24hrs

3) More recent strip based biopsy urease test can be read at 2hr following incubation with biopsy material

5) Faecal occult blood test is neither specific nor sensitive to detect NSAIDs induced gastric
damage

6) Full CBC may give evidence of blood loss from PUD.

 Predisposing factors
1) H.Pylori
2) Smoking (↑incidence & the No. of cigarettes correlates with prevalence of PUD)
3) Alcohol and Caffeine- containing beverages (↑ acid secretion)
4) Psychological Stress (little evidence to support this Stress ↑rate of acid secretion)
5) Genetic
6) Drug therapy
• The role of corticosteroids is less well defined
• NSAIDs ↑ risk of superficial gastric erosions
• ECs may prevent superficial damage, but doesn't reduce ulcer risk.
• COX-2 inhibitors or NO-NSAlDs  may↓PUD & its complications.
• COX-2 inhibitors don't ↓mucosal production of protective PGs to same extent as
those inhibit COX-1. COX-2 inhibitors should ↓ inflammation with minimal ADRs
 Management
Objectives of Management
1) Control symptoms
• Pain may persist during the 1st few days following initiation of therapy
• Pts may require antacid during this period

2) Heal ulcers
Anti ulcer therapy is usually given for 4-12 wks for - healing
• DU respond more rapidly (treatment 4-6 wks)
• GU slower to heal (up to 12 wks)

3) Prevention of recurrence
• DU (85%)  recurrence  within 1 year
• GU (40%) recurrence (Slower rate)  within 2 years
 Non-pharmacological management
A) Avoid

Alcohol. Smoking. Heavy meals. Xanthin beverges.

• Small frequent low caloric meals

• Avoid ulcerating drugs e.g. NSAIDs, corticosteroids, xanthines & parasympathomimetics

Pharmacological treatment

1) Histamine 2 antagonists 2) Proton pump inhibitors (PPls)

3) Cytoprotective agents 3) Anticholinergics
5) Prostaglandins 6) Antacids
General strategy
 H2 antagonists
(Cimetidine, Ranitidine, Famotidine , Nizatidine)
• Safe & relatively free from SEs
• They bind to H2 receptors on parietal cell  prevent stimulations of acid rising from Histamine
o ↓ HCL acid secretion
o ↓ Conversion of pepsinogen to pepsin
o ↑ ulcer healing

• All have t 1/2 of about 3 hr (Except nizatidine)

• Famotidine has the longest duration of action.
• Rantidine  150 or 300 mg, 1-2 times daily & less interacting with P450.

• They are equally effective at suppression day time & nocturnal acid secretion
While they don’t cause total achlorhydria.
Roxatidine (China, Japan, Korea, Germany, I
• All are eliminated via kidney & all require dosage reduction in RF. Netherlands, Greece and South Africa)
• Choice depended on cost & Dls Lafutidine (Japan and India)
• They don’t affect gastrin / cholinergic receptors lavoltidine (discontinued as carcinogen)
niperotidine (withdrawn as causing liver da
 PPls
• Inhibit ATPase activated H/K pump in parietal cells potent inhibition of gastric acid output
• 99% ↓ in acid secretion within 24 hr complete achlorohydra

• Healing DUs
50% 2 wks 90% 4 wks
Almost all (6-8 wks)

• Relieve symptoms & heal PUDs faster > H2 antagonists

But continued therapy the healing rates are similar.

• ↑ Gastrin release  rebound hypersecretion & relapse.

• Lansoprazole should be taken AC, as food can ↓its BA.

Omeprazole & Pantoprazole not affected by food & timing not crucial.

• PPIs are metabolized in liver

No dose adjustments necessary  With the exception of severe hepatic dysfunction
Drug interaction
 Omeprazole Cyp450 inhibitors↓ metabolism  Lansoprazole  weak inducer of
of cytochrome p450 ↑ Clearance
 Oral anticoagulants ↑ coagulation time of  Warfarin
warfarin (sp doses > 20 mg/D)

 Antiepileptics (phenytoin)  Phenytoin,

 Theophylline
 Anxiolytics  Oral contraceptive (monitoring)

• Effects of benzodiazepines may be increased by omeprazole but not other PPIs

• Acid-suppressing drugs ↓absorption of nifedipine & quinolones but not clinically significant.

• Warfarin & Omperazole (esomeprazole)

• Clopidogril & Omeprazole (esomeprazole)

 Cytoprotective agents
A) Sucralfate
• In acidic media  sucralfate form gelatinous matrix binds to exposed proteins in ulcerated area
Protects gastric & duodenaI mucosa from acid/pepsin attack
• Protect GI mucosa without affecting gastric acid output
• ↑ Production of PGs mucous, HCO3 & binding Pepsin.
• S.E.  Constipation / Diarrhea, dry mouth, N& V.
• Interacts with other agents (Tetracyclin, Phenytoin) ↓BA (2 hr interval)
• Sucralfate not to be used in renal impairment (AI)

B) Bismuth compound
• It has been included in antacid mixtures for many decades but has neurotoxicity.
• Bismuth is toxic to H. pylori
• Was one of the 1st agents to eradicate M.O & ↓ ulcer recurrence.
• Ranitidine + bismuth (ranitidine bismuth citrate) + 1-2 antibiotics ↑ eradication rate.
ADRs
• Small amounts of bismuth absorbed from bismuth chelate
• urinary bismuth excretion may be raised for several weeks after ttt  accumulate in renal dysfunctions pts
• In recommended & short dose  ↓Risks of intoxication
 Anticholinergic
Pirenzipine, Telenzepine, Atropine, Propantheline, Dicyclomine
 ↓Acid (30-40%) & pepsin output
 Used in combination with H2 blockers to↓incidence of relapse.
 SEs Dry mouth, constipation, blurred vision, glaucoma, prostate hypertrophy, tachycardia

Prostaglandine (Misoprostol)
• Act at prostaglandin (EP3 receptors) on parietal cells & epithelial cells
• They are effective against direct damage produced by alc, aspirin & NSAIDs  Therefore termed
(Cytoprotective)
• ↓ Acid production &↑ defense mechanisms
o ↓ Acid secretion , gastrin release, pepsin secretion
o ↑ Mucus secretion, bicarbonate secretion, mucosal blood flow

Side Effect
• Diarrhea
• Abortion (not be used in pregnant women)
• Exacerbate IBD  Should not be given
 Antacids
• Weak bases neutralize HCI in stomach.

• Don't ↓acid secretion & in some cases ↑secretion (Ca+2)

• Don't suppress nocturnal acid secretion

• Used as Adjunct therapy for PUD

• Effective in healing ulcers (75% healed in 4 wks).

• Relapse the same as H2 blocker

• Should be given at least 4 times/day & 1 hr after meals

• Water insoluble Al-Mg antacids have longer duration > HC03 (remain in stomach longer)

• Liquid forms have superior buffering Capacity > tablets

• Tablets remain longer in stomach & have shown to be effective in promoting healing.
Feature Sodium Calcium Magnesium Aluminum
bicarbonate hydroxide
Onset of action Rapid Intermediate Rapid Slow
Duration of action Short Moderate Moderate Moderate
Systemic alkalosis Yes ? No No
Effect on stool --- Constipating Laxative Constipating
Triple therapy (2wks)
PPls + Clarithromycin + Amoxicillin
 Omeprazole  20 mg PO bid for 14 d or 500 mg PO bid 1 g PO bid
 Lansoprazole  30 mg PO bid for 14 d or for 14 d for 14 d
 Rabeprazole 20 mg PO bid for 14 d or
 Esomeprazole  40 mg PO qd for 14 d

if pt allergic to Penicillin  Can substitute by Flagyl 500 mg PO bid for 14 d

In the setting of an active ulcer additional 2 wks.

Resistant 2 wks PPI + bismuth + tetracycline + metronidazole (Tetrad therapy)

Maintenance Therapy
• About 80% of DU patients treated with H2 blocker, relapse within 1 year.
• Patients for whom maintenance therapy is recommended

1) Rapid relapse after previous treatment. 1) Early onset (< 45 years)

1) Previous history of PUD 1) Family history of PUD
1) Treatment with NSAIDs 1) Smokers

Examples of triple therapy

Omeprazole 20 mg pd Omeprazole 20 mg bd
Amoxicillin 1 mg bd Clarithomycin 250 mg tds
Claritromycin 500 mg bd Amoxicillin 500 mg tds
Omeprazole 20 mg bd Omeprazole 20 mg bd
Metronidazole 400 mg bd Metronidazole 400 mg tds
Claritromycin 500 mg bd Amoxicillin 500 mg tds
Other PPis may be used in place of omeprazole (e.g., lansoprazole 30 mg bd)