Peptic Ulcer disease …treatment over the years

When I look at health care now I can boldly say that we have come very far. This piece will start with the management of peptic ulcer disease (PUD). When I started hospital practice one of the striking things was the volumes of Mist. Magnesium Trisilicate we had to dispense to a person diagnosed with PUD. There was another mixture for those we wanted to  reduce gastric acid secretion in addition to the antiacid used, that is a liter of Mist. Magnesium Trisilicate with incorporated in it 50ml of Belladonna tincture. The main ingredient, atropine is an anticholinergic which reduces acid secretion and relaxes smooth muscle . There is tablet, Propanthelin, which works in a similar way to Belladonna tincture with less side effects compared to atropine.

At the time, complications from peptic ulcer disease were common and surgery was a key intervention for persons with PUD. For more than a century, the main pathogenic factor for peptic ulcer disease was considered to be the effect of hydrochloric acid on the gastric mucosa, before the mechanism of this secretion was correctly identified. The famous Schwarz paradigm “no acid, no ulcer” dominated the medical approach to peptic ulcer disease for the most of the 20th century until the advent of the infectious etiology of peptic ulcer disease changed this paradigm.

I recall the era of  more effective suppression of acid secretion with the introduction of the first histamine-2 receptor antagonist, Cimetidine (Tagamet). It was a major breakthrough for ulcer therapy. This was followed by the proton pump inhibitors, the first being omeprazole (Losec).

The H2 receptor blockers act by binding to histamine type 2 receptors on the basolateral (antiluminal) surface of gastric parietal cells, interfering with pathways of gastric acid production and secretion.

The selective H2 blockers are less potent in inhibiting acid production than the proton pump inhibitors (which block the common, final step in acid secretion). The selective H2 receptor blockers suppress 24 hour gastric acid secretion by about 70%. The effect of H2 blockers is largely on basal and nocturnal acid secretion, which is important in peptic ulcer healing. 

The first H2 blocker was cimetidine, which was followed by ranitidine, then famotidine and nizatidine. These medications are well tolerated and used widely to treat peptic ulcer disease, heartburn, oesophagitis, and miscellaneous minor upper gastrointestinal symptoms. Their listed indications are for treatment of gastric and duodenal ulcer and oesophageal reflux disease, and to prevent stress ulcers. Side effects are uncommon, usually minor and include diarrhoea, constipation, fatigue, drowsiness, headache and muscle aches. The H2 receptor blockers are metabolized in the liver by the cytochrome P450 system. Among the four agents, cimetidine is distinctive in its potent inhibition of the P450 system (CYP 1A2, 2C9 and 2D6), which can result in significant drug interactions.

The  causes of PUD include  Helicobacter pylori (H. pylori)infection, NSAIDs, medications, Zollinger-Ellison syndrome, malignancy (gastric/lung cancer, lymphomas), stress (acute illness, burns, head injury), viral infection, vascular insufficiency, radiation therapy, chemotherapy and Crohn’s disease.

H. pylori is a gram-negative bacillus that is found within the gastric epithelial cells. This bacterium is responsible for 90% of duodenal ulcers and 70% to 90% of gastric ulcers. H. pylori infection is commonly acquired during childhood. The organism has a wide spectrum of virulence factors allowing it to adhere to and inflame the gastric mucosa (Malik et al. Peptic Ulcer Disease. StatPearls. National Library of Medicine. Update June 11, 2022).

Nonsteroidal anti-inflammatory drugs (NSAIDs),  use is the second most common cause of PUD afterH. pylori infection. The secretion of prostaglandin normally protects the gastric mucosa. NSAIDs block prostaglandin synthesis by inhibiting the COX-1 enzyme, resulting in decreased gastric mucus and bicarbonate production and a decrease in mucosal blood flow.  Examples of NSAIDs are diclofenac, ibuprofen, naproxen. Apart from NSAIDs, corticosteroids, bisphosphonates, potassium chloride, and fluorouracil have been implicated in the etiology of PUD. Smoking also appears to play a role in duodenal ulcers. Alcohol can irritate the gastric mucosa and induce acidity.

Hypersecretory environment occurs in conditions such as Zollinger Ellison syndrome, Systemic mastocytosis, Cystic fibrosis, Hyperparathyroidism, Antral G cell hyperplasia.

Peptic ulcer disease (PUD) is a global problem with a person’s  lifetime risk of  developing Pud ranging from 5% to 10%.  Duodenal ulcers are four times more common than gastric ulcers.

The peptic ulcer disease (PUD) mechanism results from an imbalance between gastric mucosal protective and destructive factors. Once the protective superficial mucosal layer is damaged, the inner layers are susceptible to acidity and the ability of the mucosal cells to secrete bicarbonate is compromised. H. pylori is known to colonize the gastric mucosa and cause inflammation. The H. pylori also impairs the secretion of bicarbonate, promoting the development of acidity and gastric metaplasia.

The diagnosis of PUD requires history taking, physical examination, and invasive/non-invasive medical tests. A careful history is obtained and noted for the presence of any complications. Patient reporting of epigastric abdominal pain, early satiety, and fullness following a meal raise suspicion of PUD. The pain of gastric ulcers increases 2 to 3 hours after a meal and may result in weight loss, whereas the pain of duodenal ulcers decreases with a meal which can result in weight gain. A patient presenting with anaemia, melena (dark tarry stools), haematemesis (vomiting blood), or weight loss is investigated for complications of PUD, such as bleeding, perforation, or cancer.

With investigations, the key tool was the barium meal until the advent of endoscopy. Now, the gold standard is endoscopy- esophagogastroduodenoscopy (EGD) is the most accurate diagnostic test with sensitivity and specificity up to 90% in diagnosing gastric and duodenal ulcers. EGD has become a key element in the diagnosis and treatment of esophageal, gastric, and small-bowel disorders. The many accepted indications for EGD include evaluation of dysphagia (difficulty swallowing), GI bleeding, peptic ulcer disease, medically refractory  gastroesophageal reflux disease (GERD), esophageal strictures, celiac disease, and unexplained diarrhoea. 

H. pylori is responsible for 90% of duodenal ulcers and 70% to 90% of gastric ulcers and the practice now is to test for the presence of the bug through various means such as  the urea breath test, antibodies testing, stool antigen test, endoscopic biopsy.

As earlier related, antisecretory drugs currently used for peptic ulcer disease (PUD) include H2-receptor antagonists and the proton pump inhibitor (PPIs). PPIs have largely replaced H2 receptor blockers due to their superior healing of the ulcer. PPIs block acid production in the stomach, providing relief of symptoms and promote healing. Treatment may be incorporated with calcium supplements as long-term use of the PPIs can increase the risk of bone fractures.

NSAIDs induced PUD can be treated by first stopping  its use,  and starting the person on PPI.  Corticosteroids, bisphosphonates, and anticoagulants should also be discontinued if possible. Prostaglandin analogs (misoprostol), PPIs are  used as prophylaxis for NSAID-induced peptic ulcers.

First-line treatment for H. pylori-induced PUD is a triple regimen comprising two antibiotics and a proton pump inhibitor:  PPI (eg, omeprazole 20 mg BID (twice daily), lansoprazole 30 mg BID (twice daily), esomeprazole 40 mg QD (once daily), pantoprazole  40 mg QD (once daily), rabeprazole  20 mg BID (twice daily) plus Clarithromycin 500 mg BID or metronidazole  500 mg BID(when clarithromycin resistance is increasing)  plus  Amoxicillin 1000 mg BIDor  metronidazole 500 mg BID (if not already selected).

The first line triple therapy  (omeprazole, esomeprazole, . Pantoprazole, clarithromycin, and metronidazole, or amoxicillin) are used for 7 to 14 days.  Antibiotics and PPIs work synergistically to eradicate H. pylori. The antibiotic selected should take into consideration the presence of antibiotic resistance in the environment. If first-line therapy fails, quadruple therapy with bismuth and different antibiotics is used (Buensalido et al. Medscape. Updated August 16, 2022).

Surgical treatment is indicated if the patient is unresponsive to medical treatment, non-compliant, or at high risk of complications. A refractory peptic ulcer is one over 5 mm in diameter that does not heal despite 8-12 weeks of PPI therapy. The common causes are persistent H.pylori infection, continued use of NSAIDs, or significant comorbidities that impair ulcer healing or other conditions like gastrinoma or gastric cancer. If the ulcer persists despite addressing the above risk factors, patients can be candidates for surgical treatment.

Patients with peptic ulcer disease (PUD) should be counseled about potentially injurious agents like nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, alcohol, tobacco, and caffeine.  Obesity has a strong association with PUD, and patients should be counselled about benefit of weight loss.  Stress reduction counseling is also beneficial in the prevention and management of PUDs. Persons with high risk for PUD and need some specific interventions are usually put prophylaxis PPIs.

A strong key is to educate the patient on lifestyle changes, which include discontinuation of smoking, abstaining from alcohol and caffeinated beverages, and using NSAIDs on the advise of  a health professional.




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