Peptic Ulcer and GERDs Conc.Asmaa.A

H2-Receptor Antagonists (H2-Blockers)

Mechanism of action

• H2-receptor antagonists competitively block H2-receptors on parietal celland inhibit gastric acid production. They are mainly effective in suppressingnocturnal acid secretion. H2-blockers also reduce acid secretion stimulatedby ACh, gastrin, food, etc. They are less potent than PPIs—24 h acidsecretion is suppressed by 60–70%.

• Famotidine: Most of the features are similar to ranitidine. It is more potentthan ranitidine and has a longer duration of action.

Therapeutic uses

1.Peptic ulcer disease

2. Zollinger–Ellison syndrome

3. Gastroesophageal reflux disease

4. H2-blockers are used preoperatively before emergency surgery toreduce the risk of aspiration pneumonia.

Antimuscarinic agents (Anticholinergic agents):

Pirenzepine, telenzepine.

• Marked effect on salivary secretions.

• Dry mouth.

• Pirenzepine & Telenzepine - decrease gastric secretion with lesser sideeffects.

• Selective blockade of presynaptic excitatory muscarinic receptors onvagal nerve endings.

• High ratio of M1to M3 affinity.

• Motility of gut smooth muscles decreases.

• Walls of viscera relaxed.

• Tone and propulsive movements decrease.

• Gastric emptying time – Prolonged

• Diarrhoea due to overdosage of parasympathetic agents – Stopped

• Spasmolytic activity in some synthetic antimuscarinic agents.

Prostaglandin Analogues

Misoprostol, a synthetic PG analogue (PGE1), is effective orally for theprevention and treatment of NSAID-induced gastric and duodenalulcers. It inhibits gastric acid secretion, and increases mucus andbicarbonate secretion; it also increases mucosal blood flow, thusproducing cytoprotective effect.

Its common side effects are diarrhea and abdominal cramps.Misoprostol is contraindicated in pregnancy, as it may cause uterinecontractions. Because of its adverse effects and need for frequentdosing, it is rarely used.

Mucosal protective agents

A. Sucralfate: This complex of Aluminum hydroxide and sulfated sucrosecreate physical barrier that protect ulcer from pepsin and acid, stimulatesecretion of mucus, bicarbonate, PG from gastric mucosa, all this actionscontribute to its mucosa protecting action.

Use : Duodenal ulcer and prevention of stress ulcers.

Drug-Drug interaction:

Sucralfate X theophylline, digoxin,tetracycline

Amitriptyline

B-Bismuth subsalicylate: used as component of quadruple therapy(Bismuth subsalicylate, metronidazole, tetracycline plus PPI) to healpeptic ulcers.

It has antimicrobial actions, also inhibit the activity of pepsin, increasesecretion of mucus to coat and protect ulcer.

Antacids

Antacids are weak bases that neutralize gastric acid and thus raise the gastric pH. They do not affect acid production.

Types of antacids

1. Systemic: Sodium bicarbonate and sodium citrate.

2.Nonsystemic: Magnesium hydroxide, magnesium trisilicate, aluminum hydroxide gel and calcium carbonate.

Systemic antacids

Sodium bicarbonate (NaHCO3): It is very effective and rapidlyneutralizes gastric acid, but the duration of action is short. Sodiumbicarbonate is also used to alkalinize urine and to treat acidosis. It shouldbe avoided in patients with hypertension and congestive cardiac failure,as it causes sodium retention.

Non-systemic antacids

Magnesium hydroxide, Magnesium trisilicate, Magnesium Carbonatealuminium hydroxide, Calcium carbonate, etc. form respective chloridesalts in stomach. When this reaches the intestine, the chloride salt reactswith bicarbonate, so HCO3¯ is not available for absorption, hence, thereis no systemic alkalosis.

Combination of antacids produces various beneficial effects. They are:

1.Aluminum salts cause constipation and magnesium salts causediarrhea; so combination of these two can counteract the adverse effectsof each other.

2. Magnesium hydroxide has a rapid onset of action, but aluminumhydroxide acts slowly—the combined product produces rapid andsustained effect.

3. Dose of individual antacid is reduced; hence systemic toxicity isminimized.

Adverse effects of antacids

1. Magnesium hydroxide may produce diarrhoea.

2.Aluminum hydroxide may produce constipation and phosphatedepletion.

3.Calcium carbonate may produce hypercalcaemia and hypercalciuria.

Drug interactions

All antacids increase the pH of stomach and form insoluble and non-absorbable complexes with many drugs—iron, tetracyclines,fluoroquinolones, ketoconazole, etc.

Thus antacids reduce the absorption of these drugs. There should be agap of 2 h between administration of these drugs and antacids.

Antifoaming Agents

• Methylpolysiloxane (simethicone and dimethicone): They are antifoaming agents, usually present in some antacid preparations. They decrease foaming and relieve flatulence.

• Oxethazaine: It is a potent local anaesthetic and is used to anaesthetize gastric mucosa. It produces symptomatic relief in gastritis and GERD. It is available in combination with antacids.

• Sodium alginate: It forms froth on the contents in the stomach—prevents effects of gastroesophageal reflex

Anti-Helicobacter pylori Agents

Helicobacter pylori, a gram-negative, rod-shaped bacteria, is associatedwith gastritis, duodenal ulcer, gastric ulcer and gastric carcinoma.

The mechanism by which H. pylori causes mucosal inflammation anddamage is not clear. The ammonia produced by urease activity maydirectly damage the cells. Many regimens are available for theeradication of H. pylori. Combination therapy (triple/quadruple) isalways recommended.

The objectives of combination therapy are:

1. To prevent or delay the development of resistant organism.

2. To prevent relapse.

3. To promote rapid ulcer healing.

4. To eradicate H. pylori infection.

The duration of treatment could be for 1 week or 2 weeks, of which 2-weeks’ therapy is more effective.

The antimicrobials used in H. pylori infection are amoxicillin,tetracycline, clarithromycin, metronidazole and tinidazole.

Resistance develops rapidly to metronidazole and clarithromycin, butnot to amoxicillin or tetracycline. Other anti-H. pylori drugs are PPIs,H2-blockers and CBS. Some of the recommended regimens are listedbelow:

Triple therapy × 14 days (2 weeks)

• Lansoprazole 30 mg

• Clarithromycin 500 mg

• Amoxicillin 1 g.

Quadruple therapy × 14 days (2 weeks)

• Lansoprazole 30 mg

• Bismuth subsalicylate 525 mg

• Tetracycline 500 mg

• Metronidazole 500 mg.

After completion of the above regimen, proton pump inhibitor should be continued for six more weeks to enhance ulcer healing.