SEMINAR ON PEPTIC ULCER

DISEASE

PRESENTED BY :

WALID S MOMIN

1ST YEAR M.PHARM

DEPARTMENT OF PHARMACY PRACTICE

Definition :

Peptic ulcers are the areas of degeneration

and Necrosis of gastrointestinal mucosa

exposed to acid-peptic secretions.

The term peptic ulcer describes a condition in

which there is a discontinuity in the entire

thickness of the gastric or duodenal mucosa

that persists in the gastric juice.

Peptic ulcer is usually represented as

Dyspepsia.

CLASSIFICATION OF PEPTIC

ULCERS Acute or stress ulcers : Multiple, Small mucosal

erosions.

Chronic ulcers: Gastric or Duodenal ulcers.

ETIOLOGY

Occurs due to imbalance between the

aggressive and defensive factors.

Etiological factors of Acute ulcers :

A. Psychological stress

B. Physiological stress

Shock

Severe trauma

Drugs and Local irritants

Cushing’s syndrome

Chronic ulcer disease : Multifactoral, the main

contributing factor is the H-Pylori infection.

Acid-pepsin secretions

Mucus secretion

Gastritis

Local Irritants

Dietary factors

Psychological factors

Genetic factors

Hormonal factors

Miscellaneous factors

Viral Infections (cytomegalovirus)

Radiation

Chemotherapy ( e.g. hepatic artery infusions)

Idioathic

Vascular insufficiency

Cigarette smoking

Infection•H-Pylori Infection

Few months•Chronic superficial gastritis

Years•Hyperacidity

Mucosal layer erosion

•Peptic ulcer

MECHANISM OF PEPTIC ACID

SECRETION

PATHOGENESIS

H-Pylori contains enzymes like urease, protease,

catalase, phospholipase which damage the mucosal

barrier.

Basal and Maximal acid output due to various

stimuli.

Vagal stimulation

Gastric Ulcer : Impaired gastric mucosal defenses

against acid-pepsin secretions.

Pathogenesis : serum gastrin levels due to ingested

food leading to hyperacidity.

OTHER SUGGESTED

PATHOGENESIS Acid secretion because of parietal cell mass.

Inhibition of gastric acid secretion.

Hco3- secretion in the duodenum due to H-Pylori

infection causing local release of cytokins and

further damage.

NSAIDS induced peptic ulcer :

NSAIDS

COX

inhibition

Adherence

of

leucocytes

to mucosal

endothelial

cells

Decreased

prostagland

in synthesis

Superficial

erosions

Peptic ulcer

A number of other factors may contribute to the

development of NSAID induced mucosal injury,

neurtophils adherence may damage vascular

endothelium and cause reduced mucosal blood flow or

may release oxygen derived free radicals and

proteases.

Leukotriens have stimulatory effect on neutrophils

adherence.

Topical irritant properties associated with the acidic

properties of NSAID’s e.g. aspirin and their ability to

decrease hydrophobicity of mucosal gel layer

CLINICAL FEATURES Epigastric pain

Upper abdominal pain occurring 1-3 Hrs after meals and

relieved by food or antacids is a classical symptom of

peptic ulcer disease.

Anorexia, weight loss.

A typical nocturnal pain that awakens the patient from

sleep.

Heart burn due to acid regurgitation.

Nausea may accompany the pain.

DIAGNOSIS

Diagnosis of H-Pylori infection .

Non-Invasive techniques:

A. Urea breath test

B. Serological tests

C. Stool test

• Invasive techniques

A. Rapid urease test

B. Culture

C. Histology

13C Urea breath test : used to demonstrate eradication

of organism following treatment.

Serological test : used to detect antibodies

Used in diagnosis and epidemiological studies.

Stool test : Immunoassay using monoclonal antibodies

for qualitative detection of H-Pylori that leads to colour

change that can be detected visually or by

spectrophotometer.

Used in the diagnosis and monitoring efficacy of

eradication therapy.

Culture : Biopsies cultured on a special medium

Enables sensitivity testing to determine optimum

treatment or antibiotic resistance.

Histology : Gastric mucosal staining, helps in the

classification of gastritis.tests for active HP infection.

Biopsies are done to exclude malignancy and

uncommon lesions such as crohn’s disease.

Wireless capsule endoscopy : determines NSAIDS

induced ulceration of small intestine.

Use of gastrograffin meal:

Gastrografin (Diatrizoate Meglumine and Diatrizoate

Sodium Solution) is a iodinated radiopaque contrast

medium for oral or rectal administration only.

Rapid urease test :

Gastric biopsies with urea solution containing phenol

Urea ammonia

PH

Rapid colour change

OTHER DIAGNOSTIC TESTS

Esophagogastroduodenoscpy : permits direct

visualization of superficial erosions and sites of active

bleeding.

Routine single barium contrast techniques :

Fasting serum concentration studies :

TREATMENT AND

MANAGEMENT

Non pharmacological therapy :

I. Reduce psychological stress

II. Reduce physical stress

III. Cessation of cigarette smoking

IV. Stop use of NSAIDS

V. Avoid spicy foods, caffeine, alcohol

VI. Drink plenty of water

VII. Avoid fasting and maintain optimum gap between

meals

Pharmacological Therapy

Classification of Drugs:

1. Proton Pump Inhibitors : e.g. omeprazole,

pantaprazole,Lansoprazole.

2. H2receptor antagonists : e.g. Ranitidine, Famotidine,

cimetidine

3. Sucralfate

4. Bismuth compounds

5. Antacids : systemic e.g. Sodium bicarbonate, Non

Systemic e.g. Magnesium Trisilicate.

6. Prostaglandin Analogs : e.g. misoprostol, Enprostil.

Anti H-Pylori drugs (Antibiotics) e.g. Amoxicillin,

clarythromycin, tetracyclines.

Proton Pump

Inhibitors

Carried in

blood stream to

the parietal

cells

Activation

Cytosol ESCInhibition of H+

K+ ATPase

Inhibit acid

secretion

PPI’s differ in their in their potencies.

Plasma concentration is reached after 2-3 hrs.

T1/2 48 Hrs.

To be taken 30 minutes prior to food.

2. H2receptor antagonists :

Structural analogs of histamine.

pepsinogen pepsin

Used in symptomatic treatment.

Plasma concentration is reached within 1-3Hrs after administration.

Recommended in patients with nocturnal gastric acid secretion and management of dyspepsia symptoms.

( )

Sucralfate : Basic aluminium salt of sulfated sucrose

Polymerizes at pH <

4.0 by cross linking

of molecules

Gel

Adheres to the

ulcer base

Precipitates surface

proteins and acts as

a physical barrier

Antacids are contraindicated when sulfates are

taken

Prostaglandin Analogs :cytoprotective properties

1. Increase mucus and bicarbonate production.

2. Increase mucosal blood flow

3. Inhibit gastrin production

Antacids : ANC--- No of Meq of 1N Hcl that are

brought to pH 3.5 in 15 minutes by unit dose of

antacid preparation. Mgsio3

Cl- salt

Cl- + HCo3-

No acid-base disturbance

COMPLICATIONS OF PEPTIC ULCER

DISEASE BLEEDING PEPTIC ULCER :

Patients with high risk of bleeding are given high dose of

infusion of omeprazole ( 80 mg bolus followed by

8mg/Hr) for 72 Hrs to reduce rebleeding.

LATE COMPLICATIONS OF PEPTIC ULCER:

Reactive hypoglycaemia, diarrhoea, weight loss,

anaemia, flushing, plapitation, sweating tachycardia,

postural hypotension.

Treatment :

Somatostatin analogs for reactive hypoglycaemia.

Antibiotics

metachlopramide

Zollinger-ellison syndrome: use of octreotide, surgical.

Recommendations for Treating and Monitoring

Patients with Helicobacter pylori (HP)-Associated and

Nonsteroidal

Anti-inflammatory Drug (NSAID)-Induced Ulcers

Assess patient allergies

Assess patient use of alcohol or alcohol-containing

products with metronidazole and oral birth control

medications with antibiotics and counsel appropriately.

Inform the patient of change in stool color when bismuth

salicylate is included in an HP eradication regimen.

Assess and monitor patients for potential adverse

effects.

Assess and monitor patients for potential drug

interactions.

Monitor patients for salicylate toxicity.

o Provide education to patients who are receiving HP

eradication therapy, including why antibiotic and antiulcer

combinations are used, when and how to take medications,

adverse effects, alarm symptoms, when to contact their health

care provider, and the importance of compliance to drug

treatment.

NSAID-induced ulcer

Recommend drug treatment

Assess risk factors for NSAID-induced ulcers and ulcer-related

complications, and when indicated recommend appropriate

strategies for reducing ulcer risk.

Assess and monitor patients for potential drug interactions and

adverse effects (especially misoprostol).

FACTORS THAT CONTRIBUTE TO UNSUCCESSFUL

ERADICATION

Poor Patient compliance

Resistant organisms

Increased bacterial load

Missed dose in a 7 day regimen may also contribute

towards failure of eradication.

Tolerability

Preexisting antimicrobial resistance.

ADVERSE DRUG REACTIONS Proton pump inhibitors :

1. Diarrhea

2. Headache

3. Abdominal pain

4. Nausea and vomiting

5. Microscopic colitis

H2receptor antagonists :

1. Anti-androgeniceffects gynaecomastia.

2. Impotence

Bismuth chelate:

1. Neurotoxicity

Sucralfate :

1. Constipation

2. Hypophosphataemia

Prostaglandin analogs :

1. Diarrhea

2. Abdominal cramps

3. Uterine bleeding

4. Abortion

Antacids : alkalosis, increase sodium load.

DRUG INTERACTIONS PPI’s are metabolised by cytochrome p450 isoenzymes,the

affinity of individual proton pump inhibitors for these enzymes influence the incidence of clinically relevant drug interactions.

E.g. omeprazole+warfarin warfarin levels.

benzodiazepines + omeprazole benzodiazepines levels.

PPI’s also alter the absorption of other drugs du to altered pH

E.g. decreased absorption of Ketoconazole

increased absorption of Digoxin

Cimetidine interacts with Thiophylline, Diazepam, Flurazepam, Triazolam.

All acid suppressing drugs decrease absorption of pH dependent control release tablets.

Antacids interact with tetracyclines, ciprofloxacin forming insoluble complexes or chelates.

PATIENT COUNSELING Weight loss

Avoid spicy foods

Avoid hot beverages

Maintain optimum time interval between meals

Reduce psychological stress

Reduce physical stress

Cut off irregular eating habits

Educate the patient about the current principles of therapeutic management

Patient should be warned about the specific side effects to be expected from the regimen and what to do if they experience any of these side effects.

Avoid drugs e.g. TCA’s, CCB’s, Anticholinergics, NSAIDS.

References

Pharmacotherapy by Dipiro

Clinical Pharmacy and Therapeutics by Roger

Walker

Pharmacology by K.D Tripati

Clinical Medicine by Kumar and Clark

Handbook of Pathology By Harsh Mohan