Worrying About Ulcers

HEALTH:

Peptic ulcer occurs in that part of the gastrointestinal tract(g.i.t.) which is exposed to gastric acid and pepsin, i.e. the stomach and duodenum.

The etiology of peptic ulcer is not clearly known. It results probably due to imbalance between the aggressive (acid, pepsin, bile and H. pylori) and the defensive (gastric mucus and bicarbonate secretion, prostaglandins, nitric oxide, high mucosal blood flow, innate resistance of the mucosal cells) factors, also the importance of Helico – bacter Pylori infection as a contributor to ulcer formation and recurrence has been recognized.

In gastric ulcer, generally acid secretion is normal or low, while deficient mucosal defense (mostly impaired mucus and bicarbonate secretion) plays a greater role.

In duodenal ulcer, acid secretion is high in about half of the patients but normal in the rest. Notwithstanding whether production of acid is normal or high, it does contribute to ulceration as an aggressive factor, reduction of which is the main approach to ulcer treatment. An understanding of the mechanism and control of gastric acid secretion with elucidate the targets of antisecretory drug action.

Peptic ulcer (especially duodenal) is chronic remitting and relapsing disease lasting several years. The goals of antiulcer therapy are:

• Relief of pain
• Ulcer healing
• Prevention of complications (bleeding, perforation)
• Prevention of relapse

Approaches for the treatment of peptic ulcer are:

1. Reduction of gastric acid secretion

• H₂ antihistamines: Cimetidine, Ranitidine
• Proton pump inhibitors: Omeprazole, Rabeprazole
• Anticholinergic drugs: Pirenzepine, Propantheline
• Prostaglandin analogue: Misoprostol

2. Neutralization of gastric acid (Antacids)

• Systemic: Sodium bicarbonate, Sodium citrate
• Non-systemic: Magnesium hydroxide, Magnesium. trisilicate, Aluminum hydroxide, Calcium carbonate

3. Ulcer protective: Sucralfate, Colloidal bismuth sub citrate (CBS)

4. Anti – H. Pylori drugs: Amoxicillin, Clarithromycin, Metronidazole, Tinidazole, Tetracycline.

Common antiulcer Medicine:

Cimetidine:

These are the first class of highly effective drugs for acid-peptic disease, but have been surpassed by proton pump inhibitors (PPIs). Four H₂ antagonist’s cimetidine, ranitidine, are most common available in market.

Cimetidine was first H₂ blocker to be introduced clinically and is described as the prototype, though other H₂ blocker are more commonly used now.

Adverse effects: Cimetidine is well tolerated by most patients: adverse effects occur in greater 5%. These are generally mild.

• Headache, dizziness, bowel upset, dry mouth, rashes.
• Cimetidine (but not other H₂ blocker) has antiandrogenic action, increase plasma prolactin and inhibit degradation of estradiol by liver. High doses given for long periods have produced gynecomastia, loss of libido, impotence and temporary decrease in sperm count.

Ranitidine

A nonimidazole (has furan ring) H₂ blocker, it has several desirable features compared to cimetidine:

• About 5 times more potent than cimetidine, a longer duration of action with greater 24-hour acid suppression is obtained clinically because of higher potency.
• No antiandrogenic action, does not increase prolactin secretion or spare estradiol from hepatic metabolism-no effect on male sexual function or gynecomastia.
• Lesser permeability into the brain: lower propensity to cause CNS effects. In fact, little effect outside g.i.t. has been observed.
• Less market inhibition of hepatic metabolism of other drugs; drug interactions mostly have no clinical relevance.
• Overall incidence of side effects is lower: headache, diarrhea/constipation, dizziness has an incidence similar to placebo.

Omeprazole

It is the prototype member of substituted benzimidazoles which inhibit the final common step in gastric acid secretion.

The proton pump inhibitors have overtaken H2 blocker for acid-peptic disorders. It is powerful inhibitor of gastric acid: can totally abolish HCL secretion, both resting as well as that stimulated by food or any of the secretagogues, without much effect on pepsin, intrinsic factor, juice volume and gastric motility.

Misoprostol

Prostaglandin (PGE₂ and PGI₂) are produced in gastric mucosa and appear to serve a protective role by inhibiting acid secretion and promoting mucus as well as HCO-_3, secretion and probably have an ill-defined “cytoprotective” action.

Major problems in the use of misoprostol are -diarrhea, abdominal cramps, uterine bleeding, abortion, and need for multiple daily doses. Patient acceptability is poor.

The primary indication of misoprostol is the prevention and treatment of NSAID associated gastrointestinal injury and blood loss. However, it is seldom employed how because PPIs are more effective, more convenient, better tolerated and cheaper.

Magnesium trisilicate

These are basic substances which neutralize gastric acid and raise pH of gastric contents.

About 5% of administered Mg is absorbed systemically-may cause problem if renal function is inadequate. All Mg salts have a laxative action by generating osmotically active MgCl₂ in the stomach and through Mg₂₊ ion induced cholecystokinin release. Soluble Mg salts are used as osmotic purgatives.

Amoxicillin

H. Pylori is a gram-negative bacillus uniquely adapted to survival in hostile environment of stomach.

H. Pylori generally persists for the life of the host. Up to 90% patients of duodenal and gastric ulcer have tested positive for H. pylori.

Antimicrobial that are used clinically against H. pylori are: amoxicillin, clarithromycin, tetracycline and metronidazole /tinidazole. However, any single antibiotics is ineffective. Resistance develops rapidly, especially to metronidazole/tinidazole and clarithromycin, but amoxicillin resistance is infrequent.

In tropical countries, metronidazole resistance is more common than clarithromycin resistance.