Peptic Ulcer Disease (PUD)

Nowras Rahhal

Damascus University – 2014

Clinical and Hospital Pharmacy

What are we going to talk about ?

Definition

Symptoms

Complications

Risk factors

Etiology

Pathophysiology

Diagnostic TestsDrug TherapyHistory

Definition

Peptic ulcer disease is characterized by the development of open sores on the

innerlining of the stomach, duodenum or esophagus.

The combination of increased hydrochloric acid and pepsin and lower GI mucosal defenses allows painful lesions to develop

Types

- Gastric

- Duodenal

- Esophageal

What Causes Ulcers?

No single cause has been found for ulcers. However, it is now clear that an ulcer is the end

result of an imbalance between digestive fluids in the stomach and duodenum. Ulcers can

be caused by :

- H pylori infection

- Drugs (NSAIDs, Clopidogrel, Potassium supplements, Chemotherapy)

- Lifestyle factors (Smoking, Alcohol and Caffeine)

- Severe physiologic stress (Burns, CNS trauma, surgery, and severe medical illness)

- Hypersecretory states (uncommon)

- Genetic factors

H. pylori

• H pylori is most common

cause of PUD

• Secretes urease →convert urea to ammonia

• Produces alkaline environment enabling survival in stomach.

• Estimated 70% of Asians H

pylori (+)

Why NSAIDs

Cause PUD? Risk factors:

previous PUD, Elder, female sex, high doses or

combinations of NSAIDs, long-term NSAID use,

use of anticoagulants.

H pylori and NSAIDs are synergistic.

Ulcers associated with H. pylori : more often in

duodenum, often superficial, less severe GI

bleeding.

Ulcers associated with NSAIDs : more often in

stomach, often deep more severe, GI

bleeding.

• NSAIDs block the function

of COX-1, which is essential for the production of

prostaglandins.

• COX-2 selective anti-

inflammatories )Celecoxib) preferentially inhibit cox-2,

which is less essential in the

gastric mucosa.

What Are the Symptoms and Complications?

An ulcer may or may not have symptoms.

When symptoms occur, they may include:

1. Dyspepsia.

2. Bloating and discomfort.

3. Heartburn.

4. Nausea or vomiting.

5. unexplained weight loss.

In severe cases, symptoms can include:

1. Dark or black stool.

2. Vomiting blood.

3. Severe pain in the mid to upper abdomen.

Complications of peptic ulcer:

1. Gastrointestinal bleeding .

2. Perforation.

3. Perforation and penetration.

4. Gastric outlet obstruction.

5. Cancer.

Gastric Ulcers Duodenal Ulcers Esophageal Ulcers

Pain occurs 1-2 hours

after meals.

Pain occurs 2-4 hours

after meals.

Pain when swallowing

Pain usually does not

wake patient.

Pain wakes up patient. -

Accentuated by

ingestion of food.

Pain relieved by food. -

Risk for malignancy. Very little risk for

malignancy.

-

Pathophysiology

Peptic ulcers are defects in the gastric or duodenal mucosa that extend through the

muscularis mucosa.

Main defense Systems :

1. Mucous layer (First line of defense)

2. Bicarbonate

3. Prostaglandins (PGE)

Additional mechanisms :

1. Ion pumps

2. Mucosal blood flow

3. Healthy cells migrate to the site of injury

PEPTIC ULCER DISEASE

13

IMBALANCE

FACTORS

THAT PROTECT

AGAINST

ACIDITY

FACTORS

THAT INCREASE

ACID

SECRETIO

N

Acid

Pepsin

Bile acids

NSAIDs

H. pylori

Alcohol

Pancreatic enzymes Mucus

bicarbonate layer

Blood flow

cell renewal

Prostaglandins

tight intercellularjunctions

Diagnostic Tests

Laboratory

CBC: Rule out anemia.

Other lap test need (e.g.) Amylase ,Serum gastrin, gastric fluid analysis.

Endoscopy.

Upper GI radiography series (alternative).

Diagnostic test for H. pylori: Noninvasive

Urea breath test (UBT)

Stool antigen test (SAT)

Invasive

Biopsy urease test

Rapid urease test

Primary

treatment Goals

Relieve pain and reduce anxiety.

Relieve dyspepsia and heal the ulcer.

Prevent complications / recurrence.

What are the non-drug treatments?

The following lifestyle modifications can alleviate the symptoms of PUD:

Eat smaller, more frequent meals.

Avoid fatty foods, spicy foods, and coffee.

Reduce stress.

Stop smoking.

Limit alcohol consumption.

Limit NSAID use if possible.

Avoid reclining after meals.

Lose weight.

Drug Therapy

Drugs for reduction of acid secretion:

Proton Pump Inhibitors (PPI): Omeprazole, Lansoprazole, Rabeprazole, Pantoprazole.

• PPIs are pro-drugs that are activated by acid.

• Acid secretion is inhibited by inactivation of the H +/K+ ATPase, or acid pump.

• Used before breakfast

• Side effects included GI disturbances, headache.

H2 receptor antagonists (H2RAs): Cimetidine, Ranitidine, Nizatidine,Famotidine.

• reversibly inhibit gastric acid secretion by competitively binding the histamine

receptor.

• Used in the evening or before sleeping.

• Side effects Diarrhoea , headache, dizziness and rash

Prostaglandin analogues: Misoprostol

• Do Not use with pregnancy or inflammatory bowel disease.

• Side effects: Diarrhoea, abdominal pain, nausea, vomiting, rashes,

dizziness.• Cytoprotective effect.

o Drugs to neutralize gastric acid (antacids): Aluminum + Magnesium. Hydroxide, Calcium carbonate

Sodium bicarbonate Sodium citrate

Sucralfate

o Anti H.pylori drugs:Amoxicillin Clarithromycin Tetracycline, Metronidazole

o Antidiarrheal: (Bismuth subsalicylate) may have antisecretory and antimicrobial

action

Treatment Guideline:

Patients testing positive for H. pylori

should undergo eradication therapy for 10-14 days.

1. First line treatment: Triple therapy of PPI bid, Amoxicillin bid and clarithromycin500mg bid

• If patients are allergic to penicillin then metronidazole 500mg bid is substituted for amoxicillin.

2. Second line treatment (if triple therapy fails): Qyadruple therapy of PPI bid, bismuth subsalicylate bid, tetracycline 500mg qid, and metronidazole 500mg tid.

Patients testing negative for H. pylori

should undergo a 4-8 week antisecretory

trial using a PPI or an H2RA. If the trial fails,

an EGD (Esophagogastroduondonscopy)

is performed.

What if patients had to take NSAIDs?

To prevent NSAID-induced ulcers, pharmacists can make the following treatment

recommendations based on the patient's risk profile:

Low risk (no risk factors): use lowest effective dose of NSAID

Moderate risk (1-2 risk factors): use lowest effective dose of NSAID + Misoprostol, NSAID

+ PPI or H2RA or use a COX2 inhibitor

High risk (multiple risk factors or patients using Concomitant steroids, anticoagulants, or

low-dose aspirin):

Concomitant Steroids: COX-2 inhibitor alone

Concomitant Warfarin: COX-2 inhibitor + misoprostol

Concomitant Aspirin: COX - 2 inhibitor + PPI or misoprostol

History of disease

Helicobacter pylori was rediscovered in 1982 by two Australian scientists, Robin Warren

and Barry J. Marshall as a causative factor for ulcers.

In 2005, Dr. Marshall and Dr. Warren awarded the Nobel Prize in Physiology or Medicine for their discovery of the bacterium Helicobacter pylori and its role in gastritis

and peptic ulcer disease