• GERD affects up to 20–30% of adults in Western countries and around 10–15% in the Middle East and Asia.
• Peptic ulcer disease affects approximately 5–10% of people globally at some point in their life.
• H. pylori infection, a major cause of ulcers, affects over 40% of the global population.
• Chronic acid-related disorders lead to significant healthcare utilization, work absenteeism, and reduced quality of life.
• PPIs are among the most prescribed drug classes worldwide, reflecting their clinical effectiveness and broad therapeutic applications.

1. Acetylcholine (vagal stimulation)
2. Gastrin (hormonal stimulation)
3. Histamine (paracrine stimulation)

• Acid reflux damaging the oesophageal lining (GERD).
• Ulceration of gastric or duodenal mucosa (PUD).
• Erosive gastritis or Barrett’s oesophagus (a precancerous condition).

PPIs block the proton pump irreversibly, achieving near-complete suppression of gastric acid for 24 hours or more, allowing the mucosa to heal and preventing recurrence

• H. pylori infection
• Chronic NSAID or aspirin use
• Smoking and alcohol consumption
• Obesity and dietary triggers
• Hiatal hernia
• Stress and irregular eating patterns
• Genetic predisposition (in Zollinger–Ellison syndrome, gastrinomas)

Symptoms vary depending on the underlying condition but typically include:

• Heartburn and acid regurgitation (GERD)
• Epigastric pain that worsens or improves with meals (PUD)
• Bloating and early satiety Nausea, vomiting, or dyspepsia
• Difficulty swallowing (dysphagia) in severe esophagitis
• Occult or overt gastrointestinal bleeding in complicated ulcers

Chronic symptoms often require endoscopic evaluation to rule out malignancy or complications.

1. Clinical Evaluation

• History of symptoms, frequency, and relation to meals or posture.
• Response to empiric PPI therapy can support GERD diagnosis.

2. Diagnostic Tests

• Upper gastrointestinal endoscopy (EGD): Detects mucosal lesions, ulcers, and esophagitis.
• Helicobacter pylori testing: Urea breath test, stool antigen, or biopsy-based urease test.
• pH monitoring and impedance testing: Confirm acid reflux.
• Gastrin levels: Elevated in Zollinger–Ellison syndrome.
• Histological biopsy: For suspected malignancy or metaplasia (Barrett’s oesophagus).

The therapeutic goal is to suppress acid production, promote mucosal healing, eradicate H. pylori, and prevent recurrence or complications.

1. Lifestyle and Non-Pharmacological Measures:

• Eat smaller, more frequent meals.
• Avoid trigger foods (spicy, fatty, citrus, caffeine, alcohol).
• Maintain healthy body weight.
• Avoid lying down immediately after eating.
• Elevate head during sleep for GERD patients.
• Limit NSAID use or take with protective agents if necessary

2. Pharmacological Therapy

a. Proton Pump Inhibitors (PPIs) – First-Line Therapy

• Mechanism of Action: Irreversible inhibition of the H⁺/K⁺-ATPase pump on parietal cells → profound acid suppression.
• Examples: Omeprazole, Esomeprazole, Pantoprazole, Lansoprazole, Rabeprazole, Dexlansoprazole.
• Duration: Typically 4–8 weeks for ulcer healing; long-term for maintenance in GERD.
• Administration: Best taken 30–60 minutes before meals for optimal effect.

b. Other Acid-Controlling Agents

• H₂-receptor antagonists (H₂RAs): (e.g., Ranitidine, Famotidine) – useful for mild or nocturnal symptoms.
• Antacids: Provide short-term symptomatic relief.
• Mucosal protectants: Sucralfate, misoprostol – used in ulcer prevention, especially with NSAIDs.

3. Combination Therapy for H. pylori Eradication

• PPIs are a vital component of triple or quadruple therapy regimens:
• Triple therapy: PPI + Clarithromycin + Amoxicillin (or Metronidazole).
• Quadruple therapy: PPI + Bismuth + Tetracycline + Metronidazole.
• Duration: 10–14 days.
• Successful eradication promotes ulcer healing and reduces recurrence risk.

4. Complications of Long-Term PPI

While PPIs are generally safe, long-term therapy may carry certain risks:

• Nutrient deficiencies: Vitamin B12, magnesium, calcium, and iron.
• Increased risk of fractures (hip, wrist, spine) with prolonged use.
• Increased susceptibility to infections: Clostridioida difficile, community-acquired pneumonia.
• Rebound acid hypersecretion upon sudden discontinuation.
• Kidney disease (rare): Interstitial nephritis or chronic kidney injury.

Therefore, PPI therapy should be individualized, using the lowest effective dose for the shortest duration necessary, with regular reassessment.

• Oesophageal ulcers and strictures (from chronic GERD).
• Upper gastrointestinal bleeding. Perforation of gastric or duodenal ulcer.
• Barrett’s oesophagus and adenocarcinoma risk.
• Chronic anaemia from occult bleeding.
• Early diagnosis and consistent treatment with PPIs can prevent these complications and promote complete mucosal healing

• Limit NSAID and aspirin use or use gastroprotective agents concurrently.
• Eradicate H. pylori when detected. Avoid excessive alcohol and tobacco.
• Maintain a healthy weight and balanced diet.
• Routine screening and follow-up for high-risk patients (elderly, chronic medication users)

Consult a healthcare professional if you experience:

• Frequent heartburn or acid reflux lasting more than two weeks.
• Unexplained weight loss, vomiting, or black/tarry stools.
• Difficulty swallowing or persistent nausea.
• Chest pain not related to heart disease.
• Long-term NSAID use with digestive symptoms.
• Early evaluation ensures accurate diagnosis, effective treatment, and prevention of complications

• Shin JM, Kim N. Pharmacology of proton pump inhibitors. J Neurogastroenterol Motil. 2013;19(1):25–35.
• Katz PO, Gerson LB, Vela MF. Diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108:308–328
• Moayyedi P, et al. Comparative effectiveness of PPIs. Gastroenterology
• Sachs G, Shin JM. Mechanism of action of PPIs. Aliment Pharmacol Ther. 2001;15(2):15–22