[Web Module] GI System - Drugs for Peptic Ulcer Disease

What is a peptic ulcer?

A break in the gastric mucosa caused by exposure to gastric acid and pepsin in the stomach or duodenum

Is a duodenal or gastric peptic ulcer more common?

Duodenal more common and can heal itself

What are the clinical manifestations of a duodenal peptic ulcer?

More common than a gastric peptic ulcer

Gnawing or burning pain sensation between the breastbone and navel - feels like a heartburn - usually 1 to 3 hours after a meal.

Pain often improves with eating

Can cause GI bleeding if it penetrates deep layers of the mucosa, producing black tarry stools

What are the clinical manifestations of a gastric peptic ulcer?

Less common than a duodenal peptic ulcer

Causes anorexia, weight loss, and vomiting. Gnawing or burning pain sensation which does not improve after eating.

Can cause GI bleeding if it penetrates deep layers of the mucosa, producing black tarry stools and resulting in blood in vomit

What are the differences between a gastric and duodenal peptic ulcer?

Gastric ulcer

-Less common

-Weight loss and vomiting symptoms

-Pain does not improve with eating

-Can cause blood in vomit

-More associated with stress

-Requires long term follow up due to cancer risk

-More common in elderly populations

Duodenal Ulcer

-More common

-Pain improves with eating

-Does not usually require long term follow up

-More associated with smoking

-Can be self healing, although reoccurrence is common without treatment

What are risk factors for a peptic ulcer disease?

Chronic NSAID use

H pylori infection

Stress (Gastric)

Smoking (Duodenal)

Alcohol

What are the 5 destructive factors that can cause a peptic ulcer to form?

Gastric Acid -> can digest stomach and duodenal wall

Pepsin -> can digest stomach and duodenal wall

H.pylori -> causes inflammation

NSAIDS -> inhibit gastric mucous and increase gastric acid

Smoking -> decrease pancreatic bicarbonate

What are the 4 protective factors that can protect against a peptic ulcer?

Pancreatic Juices and Bile

Prostaglandin E production

Mucous and Bicarbonate Synthesis

Food and Secretions

How does gastric acid contribute as a destructive factor for peptic ulcer formation?

Gastric acid is a strong acid, with a pH of 2, that can digest the stomach and duodenal wall. It is secreted by parietal cell in response to histamine, gastrin, and acetylcholine stimulation through parietal cells

How does pepsin contribute as a destructive factor for peptic ulcer formation?

Pepsin is an enzyme that helps digest proteins and can digest the stomach and duodenal wall. Pepsinogen, it's precursor, is secreted by chief cells in the gastric mucosa, and is converted into pepsin in highly acidic environments, (when pH <3) such as in the stomach

How does H.pylori infection contribute as a destructive factor for peptic ulcer formation?

H pylori is a gram negative bacterium and is considered to be the primary cause of peptic ulcers. An H. pylori infection is transmitted through oral-oral or fecal ingestion of the bacteria. The bacteria causes inflammation and ulcer formation on the epithelial cells of the gastric and duodenal mucosa

What is considered to be the primary cause of peptic ulcers?

H. pylori infection

How does NSAID use contribute as a destructive factor for peptic ulcer formation?

NSAIDS block prostaglandin synthesis through inhibition of COX enzymes (specifically COX-1) which causes inhibition of gastric mucous secretion and increased gastric acid production. It is considered to be the second most common cause of peptic ulcers

What is considered to be the second most common cause of peptic ulcers?

Chronic NSAID use

How does smoking contribute as a destructive factor for peptic ulcer formation?

Smoking decreases bicarbonate production, which increases the likelihood that an individual will develop a peptic ulcer, have recurrent ulcers, and increases ulcer-related mortality

Which three neurotransmitters are responsible for stimulating gastric acid production?

Histamine

Acetylcholine

Gastrin

What is the role of histamine, acetylcholine, and gastrin in producing gastric acid?

Histamine, Ach, and gastrin are released in response to food stimulus and bind to receptors on the parietal cell, which increases cAMP function and increases intracellular calcium levels.

An increase in intracellular calcium level boosts H+, K+ ATPase, which transfers a potassium ion from the stomach lumen into the parietal cell in return for secreting an H+ ion from the parietal cell into the stomach lumen - thus producing gastric acid

What is the role of H+, K+ ATPase pump in producing gastric acid?

In response to increased intracellular calcium levels caused by histamine, Ach, and gastrin binding to parietal cells, the ATPase pump cycles a K+ ion into the parietal cell and removes an H+ ion out of the parietal cell - thus producing gastric acid.

What is the role of prostaglandin E in regulating gastric acid production?

Prostaglandin E acts as an antagonist for gastric acid production by inhibiting histamine's action on the parietal cell, thus decreasing gastric acid production and being a protective factor against peptic ulcer formation

What releases histamine for regulating gastric acid production?

Released by cells in the gastric mucosa and diffuses into parietal cells to cause gastric acid production

What releases acetylcholine for regulating gastric acid production?

Released by vagal nerve endings in response to thinking about or ingesting food. It binds to parietal cells to cause gastric acid production

What releases gastrin for regulating gastric acid production?

Released by stomach and duodenal cells in response to ingesting food and stretching of the stomach wall. It circulates in the bloodstream, where it eventually binds to parietal cells to cause gastric acid production

What lifestyle changes are recommended for prevention of peptic ulcer disease?

Avoiding smoking

Avoiding alcohol

Avoiding stress

Can sometimes cause remission of peptic ulcer disease alone without pharmacotherapy

What are the 3 main goals of pharmacotherapy for treating peptic ulcer disease?

Provide Relief of Symptoms (Nausea, Vomiting, Pain)

Provide ulcer healing

Prevent ulcer reoccurrence

Best practice is combination drug therapy -> using multiple drugs to treat the disease

What is the gold standard diagnostic test for detecting peptic ulcer disease?

An upper esophagogastroduodenal endoscopy

Inspection of a peptic ulcer

What is the gold standard diagnostic test for detecting H. pylori infection in peptic ulcer disease?

Histological examination - identifying organisms in tissue

What is the diagnostic process for identifying peptic ulcer disease in patients?

1. An upper esophagogastroduodenal endoscopy is preformed to search for and detect a gastric ulcer

2. Once a peptic ulcer is identified, a mucosal biopsy is taken to determine the cause of the peptic ulcer

2A. To rule out an H.pylori infection, a rapid urease test, histological examination, culturing, serological testing, and urea breath test can be performed

What diagnostic tests can be used to identify an H. pylori infection as the primary cause of a peptic ulcer disease?

Histological examination

->Gold standard test, identify organisms present in the tissue

Rapid urease test

-> H. pylori produces urease, presence = +

Culture

-> Rarely performed to diagnose, usually performed to determine antibiotic susceptibility of the bacteria

Serological Testing

-> Detects presence of H.pylori specific IgG antibiodies in the serum, presence = +

Urea Breath Test

->Patient drinks carbon labelled urea, H.pylori ingests urea and converts it into carbon, presence of carbon in breath = +

What are the 6 different drugs/drug classes used to treat peptic ulcer disease?

1. Antacids -> increase stomach pH

2. Antimicrobials -> kill H.pylori infection

3. Histamine Receptor Antagonists -> lower gastric acid production

4. Proton Pump inhibitors -> lower gastric acid production

5. Sucralfate -> protective barrier between gastric acid and peptic ulcer

6. Misoprostol -> synthetic prostaglandin E

What are antacids? (Use, Mechanism of Action, Dosing, Drug-Drug interactions)

Use

Used to relieve abdominal discomfort and reduce gastric acid damage in peptic ulcer disease

Mechanism of Action

Neutralizes gastric acid and increases the pH, resulting in a decrease in pepsin production in the stomach (requires lower than 3 pH to convert from pepsinogen to pepsin)

Dosing

Should be administered 1 to 2 hours after administering other drugs due to drug-drug interactions

Drug-Drug Interactions

Increases pH of the stomach, thus altering the rate of absorption of other drugs.

What is the use of antacids?

Used to relieve abdominal discomfort and reduce gastric acid damage in peptic ulcer disease

What is the mechanism of action of antacids?

Neutralizes gastric acid and increases the pH, resulting in a decrease in pepsin production in the stomach (requires lower than 3 pH to convert from pepsinogen to pepsin)

What is the dosing of antacids?

Should be administered 1 to 2 hours after administering other drugs due to antacids increasing pH of gastric acid, making it more basic and altering absorption rate of other drugs

What are antimicrobials in peptic ulcer therapy? (Use, Mechanism of Action, Dosing)

Use

Used to eradicate H.pylori infection in peptic ulcer disease

Mechanism of Action

It kills the bacteria

Dosing

Gold standard is to coadministered 2 different antibiotics (to reduce chance of antibiotic resistance) with a proton pump inhibitor (as in an Hp-Pac preparation)

What is the use of antimicrobials in peptic ulcer therapy?

Used to eradicate H.pylori infection in peptic ulcer disease

What is the dosing of antimicrobials in peptic ulcer therapy?

Gold standard is to coadministered 2 different antibiotics (to reduce chance of antibiotic resistance) with a proton pump inhibitor (as in an Hp-Pac preparation)

What are bismuth preparations? (Use, Mechanism of Action)

Use

Used to treat H.pylori caused peptic ulcer diseases

Mechanism of Action

Acts on the bacteria and protects the stomach

-Bacteria

-> Disrupts cell wall, preventing adhesion of bacteria to gastric epithelium

->Inhibits bacterial enzyme activity

-Stomach

->Increases mucous and bicarbonate protection

->Inhibits pepsin

What is the use of bismuth preparations?

Used to treat H.pylori caused peptic ulcer diseases

What is the mechanism of action of bismuth preparations?

Acts on H.pylori bacteria and protects the stomach

-Bacteria

-> Disrupts cell wall, preventing adhesion of bacteria to gastric epithelium

->Inhibits bacterial enzyme activity

-Stomach

->Increases mucous and bicarbonate protection

->Inhibits pepsin

What are Histamine H2 receptor antagonists? (Use, Mechanism of Action, Dosing, Drug-Drug Interactions)

Use

Reduces pain, promotes healing, and reduces risk of reoccurence in peptic ulcer disease

Cheaper alternative to proton pump inhibitors

Mechanism of Action

Acts as a full antagonist at histamine H2 receptors and acts as a partial antagonist at gastrin and acetylcholine receptors - thus having a lower efficacy compared to PPIs

Dosing

Usually dosed for 6-8 weeks for ulcer healing, and then the dose is reduced by 50% for maintenance therapy

Drug-Drug Interactions

Antacids reduce the absorption of Histamine receptor antagonists when they are taken together

What is the use of Histamine H2 receptor antagonists?

Reduces pain, promotes healing, and reduces risk of reoccurence in peptic ulcer disease

What is the mechanism of action of histamine H2 receptor antagonists?

Acts as a full antagonist at histamine H2 receptors and acts as a partial antagonist at gastrin and acetylcholine receptors - thus having a lower efficacy compared to PPIs

What are drug-drug interactions of histamine H2 receptor antagonists?

Antacids reduce the absorption of Histamine receptor antagonists when they are taken together

What are proton pump inhibitors? (Use, Mechanism of Action)

Use

Used to relieve symptoms, heal, and prevent reoccurence of peptic ulcers

They provide faster symptomatic relief and healing time compared to histamine receptor antagonists

Mechanism of Action

Binds irreversibly to the H+, K+ and ATPase proton pump, inhibiting daytime and nocturnal gastric acid secretion, completely blocking gastric acid secretion until the drug's effects are gone

What is the use of proton pump inhibitors?

Used to relieve symptoms, heal, and prevent reoccurence of peptic ulcers

They provide faster symptomatic relief and healing time compared to histamine receptor antagonists

What is the mechanism of action of proton pump inhibitors?

Binds irreversibly to the H+, K+ and ATPase proton pump, inhibiting daytime and nocturnal gastric acid secretion, completely blocking gastric acid secretion until the drug's effects are gone

What is misoprostol? (Use, Mechanism of Action, Adverse Effects, Dosing, Contraindications)

Use

Used to treat NSAID induced peptic ulcer disease

Mechanism of Action

Acts as a synthetic form of prostaglandin E, thus inhibiting gastric acid secretion, increasing mucous and bicarbonate secretion, and enhancing mucosal blood flow and repair

Adverse Effects

Diarrhea

Abdominal Cramping

Dosing

Should be taken with food to reduce abdominal adverse effects

Contraindications

Women in childbearing years

What is the use of misoprostol?

Used to treat NSAID induced peptic ulcer disease

What is the mechanism of action of misoprostol?

Acts as a synthetic form of prostaglandin E, thus inhibiting gastric acid secretion, increasing mucous and bicarbonate secretion, and enhancing mucosal blood flow and repair

What are contraindications of misoprostol?

Women in childbearing years

What is sucralfate? (Use, Mechanism of Action, Drug-Drug Interactions, Dosing)

Use

Used to protect the mucosa in peptic ulcer disease

Mechanism of Action

Creates a protective barrier between gastric acids + pepsin and peptic ulcers

Does not have an effect on H. pylori, thus risk of reoccurence is high if the peptic ulcer was caused by the infection as it is not treated by this medication

Drug-Drug Interaction

Requires acidic pH for activation, thus can not be administered with antacids, proton pump inhibitors, or histamine receptor antagonists

Can bind to other drugs and inhibit their absorption

Dosing

Should be administered 2 hours before or after administering any other medications

What is the use of sucralfate?

Used to protect the mucosa in peptic ulcer disease

What is the mechanism of action of sucralfate?

Creates a protective barrier between gastric acids + pepsin and peptic ulcers

Does not have an effect on H. pylori, thus risk of reoccurence is high if the peptic ulcer was caused by the infection as it is not treated by this medication

What are drug-drug interactions of sucralfate?

Requires acidic pH for activation, thus can not be administered with antacids, proton pump inhibitors, or histamine receptor antagonists

Can bind to other drugs and inhibit their absorption, thus it should be administered 2 hours before or after administering any other medications

What are nursing interventions for peptic ulcer disease?

1. General health measures - education on a well balanced diet, adequate rest, regular exercise, and smoking cessation

2. Avoid gastric irritants - smoking, alcohol, NSAIDS, caffeine

3. Reduce psychological stress

4. Ensure adherence to the drug therapy and regimen

5. Dietary restrictions - avoiding spicy, gas-producing foods

6. Ensure testing for H.pylori infection when peptic ulcer disease occurs

7. Drug and Nutrient absorption - Folate, iron, calcium, and vitamin B12 deficiencies can occur as they are best absorbed in an acidic environment