Drugs used in Peptic Ulcer

Drugs may be useful for following purposes:

1. To eradicate H pylori infection
2. To decrease the gastric acid secretion (Anti-secretory drugs)
3. To give mucosal protective effect
4. To help for healing of ulcer
5. To neutralize the gastric hydrochloric acid

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SAQ/LAQ/Viva

Classify the drugs used for peptic ulcer, with examples.

1.  Anti – H. pylori drugs

  (a) Anti-H pylori antibiotics: Amoxicillin, Clarithromycin, Tetracyclines,

Metronidazole, Tinidazole

(b) Non-antibiotic Anti-H pylori Drugs:

         1. Proton pump inhibitors – Pantoprazole, Rabeprazole,

Lansoprazole, Omeprazole

         2. Colloidal bismuth subcitrate (CBS) or Bismuth

              subsalicylate   

2.  Drugs decreasing gastric acid secretion:

  (a) H2 blockers: Ranitidine, Famotidine

  (b) Proton pump inhibitors: Pantoprazole, Rabeprazole, Lansoprazole,

Omeprazole, Esomeprazole

  (c) Anticholinergics: Pirenzepine, propantheline, oxyphenonium

  (d) PGE1 analogues: Misoprostol,enprostil,rioprostil

3.  ULCER PROTECTIVES/Mucosal protective agents:

       Sucralfate (Aluminium salt of Sulfated sucrose), colloidal bismuth

subcitrate (CBS) /Bismuth subsalicylate

4.  ULCER HEALING DRUGS: Carbenoxolone sodium

5.  Drugs which neutralize gastric acid (antacids)

    –Nonsystemic: Aluminium Hydroxide, Magnesium Hydroxide,

Magnesium trisilicate, Calcium Carbonate

    -Systemic: Sodium Bicarbonate

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SAQ/Viva

Mention various therapeutic regimens against H pylori peptic ulcer.

The current trend is to use a therapeutic regimen for 10 to 14 days (2 weeks).

This regimen is to be followed by a proton pump inhibitor or an H2-blocker for further period of 6 to 8 weeks.

The following regimens may be chosen from;

(A) 3-drug regimens with all 3 drugs 2 times a day (Triple regimen / Triple therapy) – 2 weeks

1. Clarithromycin 500 mg + Amoxicillin 1 gram + Pantoprazole 40 mg
2. Clarithromycin 500 mg + Metronidazole 400 mg/Tinidazole 500 mg + Pantoprazole 40 mg
3. Amoxicillin 1 gram + Metronidazole 400 mg/Tinidazole 500 mg + Pantoprazole 40 mg

(Tetracycline 500 mg 4 times a day may be substituted for Amoxicillin or Metronidazole/Tinidazole)

[Any regimen is to be followed by a proton pump inhibitor or an H2-blocker for further period of 6 to 8 weeks].

(B) 4-drug regimen (Quadruple therapy) – 2 weeks

Tetracycline 500 mg 4 times a day  + Bismuth Subsalicylate 525 mg 4 times a day + Metronidazole 400 mg/Tinidazole 500 mg +   Pantoprazole 40 mg

[To be followed by a proton pump inhibitor or an H2-blocker for further period of 6 to 8 weeks].

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SAQ/Viva

Mention the advantages of PPI-based triple/quadruple therapy.

PPI based triple therapies contain –

• 2 Anti-H pylori antibiotics plus –
• 1 Proton Pump Inhibitor

Quadruple therapies contain –

1. 2 Anti-H pylori antibiotics plus-
2. 1 Proton pump inhibitor plus –
3. Bismuth salt

Combination therapy is useful due to following advantages:

1. Faster rate of healing of ulcer

2. Less rate of relapse relapse rate

3. Single drugs used against H pylori are ineffective. Combination therapy eradicates the organism effectively. Chances of development of resistance are minimized to the combination therapy.

4. A PPI raises the pH in the stomach. This helps to potentiate the action of the anti-H pylori medications.

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SAQ/Viva

Mention the antacid combinations. Why antacid combinations are used? / Mention advantages of antacid combinations.

The common antacid combinations are:

1. Magnesium Hydroxide Plus Aluminium Hydroxide.
2. Aluminium Hydroxide Plus Magnesium-Aluminium Silicate Plus Magnesium Hydroxide
3. Aluminium Hydroxide Plus Magnesium Trisilicate
4. Aluminium Hydroxide Plus Magnesium Carbonate

Some of the combinations may in addition contain methyl polysiloxone / carboxymethyl cellulose / simethicone [as antiflatulent and protective], or oxathazaine [a local anesthetic].

Advantages of combinations/Why antacid combinations are used:

1. The combinations are superior to any single agents used as antacids.
2. When two antacids are combined, they produce additive effect.
3. Magnesium / Calcium speed up the gastric emptying, while aluminium delays the gastric emptying.
4. Magnesium salts are fast acting and Aluminium salts are slow acting. So their combinations usually produce prompt (rapid) and long (sustained) action.
5. Because the two antacids are combined, the doses of individual antacids are minimized.
6. Dose-related adverse effects of individual antacids are minimized.

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SAQ/Viva

Explain mechanism of action, uses, and adverse effects of Proton Pump Inhibitors. (PPIs).

Mechanism of action: Proton Pump Inhibitors (PPIs) inhibit the proton pump (the enzyme H+K+ATPase) present in gastric parietal cells.

The enzyme H+K+ATPase causes transport of H+ ions across parietal cells. H+ is exchanged for K+ ions. Hydrogen ions (H+) thus become available for combining with Chloride ions (Cl-). Thus it leads to formation of Hydrochloric acid (HCl).

Proton Pump (H+K+ATPase Enzyme) gets activated by various stimuli, including – Histamine, Protein Kinase, Gastrin, and Acetylcholine. Thus this proton pump acts as a final common pathway for secretion of HCl.

So when we use proton pump inhibitors, they inhibit the final common pathway responsible for gastric Hydrochloric acid secretion.

Examples: Pantoprazole (Least inhibition of microsomal enzyme systems), Lansoprazole, Rabeprazole (Fastest acid suppression), Omeprazole, Esomeprazole

Uses of PPIs:

1. Duodenal ulcer

2. Gastric ulcers

3. Bleeding peptic ulcers

4. Gastroesophageal reflux disease (GERD)

5. Zollinger-Ellison Syndrome

6. Acute erosive gastritis

7. Stress-induced gastric ulcer (Stress ulcers)

8. NSAID induced gastric ulcers

9. For prevention of aspiration pneumonia due to prolonged anesthesia

Adverse Effects of PPIs:

Adverse effects are minimal and mild. PPIs are considered in general to be safe drugs.

1. Prolonged achlorhydria and hypergastrinemia on Long term administration

2. Atrophic gastritis

3. Loose stools, skin rashes

4, Drowsiness, dizziness, headache, joint/muscle pains

5. Rare Hepatic dysfunction

6. Omeprazole – reduced testosterone levels, gynecomastia, erectile dysfunction

7. Reduced calcium absorption and Osteoporotic fractures on long term use, especially in elderly

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