Ulcer Healing Drugs

A. Antacids

Antacids are basic compounds which neutralize hydrochloric acid in the stomach

Management of dyspepsia, Gastro-Oesophageal Reflux Disease (GORD) and peptic ulcer disease

Normally given between meals and at bedtime, the tablets should be chewed

Suspensions are more effective than tablets, but for neutralizing gastric acidity, large doses are required

Treatment should be maintained for 8 weeks to heal up an ulcer

Antacids should not be taken at the same time with other drugs, especially with tetracycline. It may impair their absorption

Antacids may damage enteric coatings designed to prevent dissolution in the stomach

Antacids may cause rebound acid secretion, especially Calcium carbonate

Preparations available

1. Sodium Bicarbonate (Soda Mint) neutralizes HCI rapidly but produces CO2 in the stomach, so belching and distension often follow its use

Sodium can be absorbed and is not suitable for patients with hypertension

Bicarbonates ion can affect the acid-base balance of the body

It is rarely used as antacid

2. Calcium carbonate (Titralac)

neutralizes HCI rapidly but produces CO2 as does sodium bicarbonate, but tends to produce constipation and acid rebound

It is mainly used as calcium supplement for renal failure

3. Magnesium salts (Magnesium Trisilicate and Magnesium Hydroxide) (Mylanta, Triact, Diovol-plus, Maalox-plus, Gelusil-plus etc)

react with HCI producing Magnesium chloride, which cause Osmotic Diarrhoea

Contraindication: renal disease patients. Magnesium can be absorbed causing hyper-magnesaemia, which may cause CNS and Cardiac depression

4. Combination of preparations

Aluminum hydroxide gel has a slow and sustained effect on the stomach and may form a protective coat over the ulcer

The main side effect is constipation, which may be counteracted by combining Aluminum hydroxide with Magnesium salt

Magnesium hydroxide cause diarrhoea. Aluminum hydroxide cause constipation

Simethicone is an oral anti-foaming agent used to reduce bloating, discomfort and pain caused by excess gas in the stomach or intestinal tract

Gasteel is used for flatulence.

Prolong administration of Aluminum is contraindicated to patient with renal impairment, because aluminum can be absorbed causing neurotoxicity

B. Mucosal protectant (Cytoprotectants)

Mucosal protectants are anti-secretory and protective substances used in the prevention and treatment of peptic ulcer diseases

They mimic the effect of endogenous e.g. the postaglandins (PGs), which protect the mucosa by inhibiting gastric acid secretion and by enhancing protective mucus secretion

Preparations available

1. Misoprostol (Cytotec)

is a synthetic analogue of (prostaglandin E2) PGE2

Used of prevention of Non-Steroid Anti-Inflammatory Drug-induced gastric damage

The major side effects of this compound are contraction of GI smooth muscle causing abdominal cramps, diarrhea and uterine contraction

Contraindicated in pregnancy

Sucralfate (Ulsanic)

Stimulates PGE2 production and enhances mucosal protection

In acid environment it binds to the ulcer surface and forms a barrier, which protects the ulcer from further attack by acid and pepsin

Concomitant administration of sucralfate with antacid and anti-secretory agents reduce its efficacy

It should be taken on empty stomach because the presence of food in the stomach will block the bond to the ulcer surface

It is contraindicated to patients with renal impairment due to Aluminum intoxication

2. Bismuth Subcitrate (Denol)

Acts in a similar manner as Sucralfate

Stimulate PG formation

Bismuth Subcitrate + Metronidazole + Tetracycline or Amoxycillin or other Antibiotics, for the eradication of Helicobacter pylori.

Bismuth has a number of toxicities and neurotoxicity, include headache, GI disturbances, blackening of stool and tongue and neurotoxicity

Cannot be given for prolong period

Usually 120mg qid for 28 days with a washout period of 2 months

Concomitant administration with milk, antacid and H2-receptor antagonists increases its toxicities and reduces its efficacy, because bismuth can be absorbed in raised pH to toxicity

Should be taken at least 30 minutes before meals or two hours after

Cannot be given to patients with renal impairment

C. H2-receptor Antagonists

Block histamine receptors (known as H2-receptors) in gastric parietal cells and so inhibit gastric acid secretion

Significant effect in relieving peptic ulcers and reflux oesophagitis

May relapse following cessation of treatment

Maintenance treatment is best given in courses of 4-8 weeks

Preparations available

1. Cimetidine (Tagamet)

Has some anti-androgenic activity with occasional gynaecomastia

Inhibits cytochrome P-450 and prolongs half-life of some drugs, e.g. Warfarin, Theophylline

2. Ranitidine (Zantac)

3. Famotidine (Pepcid, Famox)

4. Nizatidine (Axid) are newer H2-receptor antagonists with minimal side effect

D. Proton-pump Inhibitors

The gastric proton-pump is an enzyme system (H+/K+ ATPase) situated in the secretory membrane of the gastric parietal cell responsible for gastric acid secretion

The proton-pump inhibitors inactivate the proton-pump process by binding selectively and irreversibly to the enzyme system

Effectively inhibit gastric acid secretion

Produce long-lasting and complete achlorhydria (no gastric acid production) in therapeutic doses

1. In patient not respond satisfactorily to other treatment

Erosive oesophagitis

Zollinger-Ellison Syndrome

2. Triple Therapy : Omeprazole (Losec)

+ Klacid + Amoxycillin for the eradication of Helicobacter pylori regimen for 7 days

Long period of achlorhydria may precipitate infection

May cause tumour formation (found in rats)

Also cause liver enzyme changes, headache, skin reactions, diarrhoea, nausea, constipation and GI disturbances

Preparations available

1. Omeprazole (Losec) used for Duodenal ulcer : 20mg qd for 2-4 weeks

2. Pantoloc and Takepron have similar activities and uses as Losec

3. Nexium is a second-generation proton-pump inhibitors claimed to have fewer side effects with higher efficacies

E. Anti-muscarinics (Anti-cholinergics)

Mode of Action

Reduce gastric motility, inhibit gastric acid secretion and therefore reduce pain

Clinical uses

Gastric ulceration

GI spasm

Excessive gastric acid secretion