GASTROINTESTINAL DRUGS

Antacid, Ulcer Healing, Ulcer

Protective and Anti- H. Pylori Drugs
Prepared by
Surendra kumar dafgar
Introduction
 The acid-peptic diseases are those disorders in which
gastric acid and pepsin are necessary, but usually not
sufficient, pathogenic factors.
 Acid and pepsin in the stomach normally do not produce
damage or symptoms because of intrinsic defense
mechanisms.
 Barriers to the reflux of gastric contents into the esophagus
comprise the primary esophageal defense.
 If these protective barriers fail and reflux occurs, dyspepsia
and/or erosive esophagitis may result.
 The drugs used to treat gastrointestinal disorders are called
gastrointestinal drugs.
 On the basis of mechanism of action, gastrointestinal drugs are
classified in to four categories:
 Products for altering gastric pH
 Protective for intestinal inflammation
 Adsorbents for intestinal toxins, and
 Cathartic and laxative for constipation
Peptic Ulcer
 Peptic ulceration is a common condition consisting of a distinct
break in the gastrointestinal mucosa, usually of the stomach or
duodenum.
 Although the pathogenesis of peptic ulcer disease is not fully
understood, several major causative factors are recognized:
 Non-steroidal anti-inflammatory drug (NSAID) use,
 Infection with gram-negative H. pylori,
 Increased hydrochloric acid secretion, and
 Inadequate mucosal defense against gastric acid.
 It is one of the common gastrointestinal disorders in clinical
practice.
 Peptic ulcer is observed in different parts of the body, such are:
 Lower and esophagus; known as esophageal ulcer (EU)
 Stomach; known as gastric ulcer (GU)
 Duodenum; known as duodenal ulcer
 Among these three types of ulcer, the duodenal ulcer is most
common types of ulcer, gastric ulcer is less common than
duodenal ulcer and esophageal ulcer is less common than
duodenal ulcer.
 Peptic ulcer disease usually presents as dyspeptic pain, sometimes
associated with nausea, vomiting, anorexia, heartburn, or bloating.
 Patients may develop complications such as bleeding, obstruction,
or perforation.
 The tense individual who contains his emotions tends to have
greater incidence of peptic ulcer than does the person who can
release his tension.
 Most peptic ulcers are chronic.
 Hemorrhage is more common with gastric ulcer than with
duodenal ulcer.
 Certain simple measures , may accelerate ulcer healing such as
 bed rest,
 dietary modification, and
 cessation of smoking,
 But these play an adjuvant role, and the basis of treatment is
pharmacological.
 Treatment is aimed at
 eradicating Helicobacter pylori with antibacterial, and
 neutralizing or inhibiting acid activity with anti-secretory drugs.
 Helicobacter Pylori (H. Pylori)
 H. Pylori are a gram negative bacillus that found in the gastric mucus layer or adherent to
epithelial lining of the stomach.
 H. Pylori cause more than 90% of duodenal ulcer and 80% of gastric ulcer.
Drug Used in treatment of H. Pylori
 Clarithromycin 500mg twice daily + Metronidazole 400mg twice daily + Omeprazole 40mg
daily/Lansoprazole 30mg twice daily for to 14 day
 Amoxicillin 500mg twice daily + Clarithromycin 500mg twice daily + Omeprazole 40mg
daily/Lansoprazole 30mg rwice daily for to 14 day
 Amoxicillin 500mg twice daily + Metronidazole 400mg twice daily + Omeprazole 40mg
daily/Lansoprazole 30mg rwice daily for 14 day
 Tetracycline 500mg four times a day + Metronidazole 200mg three times daily + Bismuth subsalicylate
125mg 8 hourly for to 14 day
 1. ANTACIDS
 Antacids are basic compounds that react chemically to neutralize or buffer
hydrochloric acid in the gastric secretions.
 They are used in the symptomatic management of gastrointestinal disorders associated
with gastric hyperacidity such as:
 Dyspepsia
 Gastro-esophageal reflux disease, and
 Peptic ulcer disease
 It has no direct effect on acid output but will increase pH value from stomach contents
thus providing relief of hyperacidity syndrome.
 Antacids are weak bases that react with gastric hydrochloric acid to form a salt and
water.
 Although their principal mechanism of action is reduction of intragastric acidity, they
may also promote mucosal defense mechanisms through stimulation of mucosal
prostaglandin production.
Classification of Antacid
Systemic Antacid
 Systemic antacids are absorbed through systemic circulation.
 These are water soluble compounds so that they circulate in the systemic
circulation.
 They produce systemic alkalosis.
 The common example of systemic antacid is Sodium bicarbonate.

 Sodium bicarbonate reacts rapidly with HCl to produce carbon dioxide and NaCl.
 Formation of carbon dioxide results in gastric distention and belching.
 Unreacted alkali is readily absorbed, potentially causing metabolic alkalosis when
given in high doses or to patients with renal insufficiency.
 Non- Systemic Antacid
 Non-systemic antacids are those which not absorbed through systemic circulation.
 They are insoluble or sparingly soluble in water.
 Examples include,
 aluminium hydroxide,
 magnesium hydroxide,
 magnesium trisilicate,
 calcium oxide,
 bismuth salts,
 gastric mucin etc.
Sodium Bi-Carbonate (NaHCO3)
 Sodium bi-carbonate is a white, water soluble and completely
absorbable antacid.
Mechanism of Action
 In Stomach, it reacts with gastric acid to form sodium chloride, water
and carbon dioxide.
 One gram of the drug neutralized 12 mEq of acid.

 In the intestine, sodium chloride remain unchanged and is unable to

neutralizes the bicarbonates of the intestinal contents and are
absorbed into the blood which may lead to couses of systemic
alkalosis.
Adverse Effect
 Release of carbon dioxide from the reaction may causes of bleaching, flatulence, feeling of
fullness, nausea and esophageal reflex.
 Systemic alkalosis and possibility of edema due to sodium retention is also occurs.
Therapeutic uses
 An antacid
 Metabolic acidosis
 Alkalinization of urine
 Topical use as an antipuritic lotion, as an eye wash, mouth wash, loosens wax in the ear etc.
Dose
 1 to 5 gram daily divided dose, repeated as required.
 Aluminium Hydroxide [Al(OH)3]
 Aluminium Hydroxide is bland, weak slowly reacting antacid.
 It is a white amorphous powder, practically insoluble in water and dissolves in
dilute mineral acids and in solutions of alkali hydroxides.
Mechanism of Action
 Aluminum Hydroxide reacts with Hydrochloric acid to form aluminium chloride
(salt) and water thus neutralizing acids.
 It has astringent and demulcent properties, by which it forms protective coating over
ulcer.

Indication
 Peptic ulcer
 Hyperacidity, and
 hyperphosphataemia
Contraindication 
 Hypophosphataemia: Aluminium hydroxide binds phosphate in the gastrointestinal tract
to form insoluble complexes and reduces phosphate absorption.
 It interferes with absorption of vitamin and tetracycline so that is not used along with
Vitamin and Tetracycline.

Precaution
 Aluminium hydroxide is astringent and may cause constipation; large doses can cause
intestinal obstruction. (Therefore it is used to combination with magnesium hydroxide
or trisilicate)
 Aluminium-containing antacids should not be used in infants with renal failure because
it may cause osteomalacia or encephalopathy with seizures and dementia.
Dose
 It is given in doses of up to about 1 g or divided dose by mouth, between meals and at
bedtime.
 Magnesium Hydroxide [Mg(OH)2]
 Magnesium hydroxide is a quick acting antacid and has prolonged action.
 It is a fine white amorphous powder, practically insoluble in water and dissolves in dilute acids.
 It is also known as milk of magnesia.
Mechanism of Action
 In the presence of gastric acid, magnesium hydroxide is converted to ions. The anion is consumed by the gastric
acid and form water, which neutralizes the acid.
 The cation (Mg++ ) is binds with Cl- to form insoluble MgCl2 which is responsible for laxative action.
Indication
 It is used as antacid in gastric and duodenal ulcer.
 It also used as laxative action.
 It has been used as a food additive and as a magnesium supplement in deficiency states.

Contraindication and precaution

 Magnesium hydroxide may cause diarrhoea, an effect that is dose-dependent.
 Due to its cathartic action, it is not used as single preparation but used with aluminium
hydroxide.
 Hypermagnesaemia may occur, usually in patients with renal impairment and
commonly in infants.
Dose 
 Same as aluminium hydroxide
 Magnesium Trisilicate [Mg2Si3O8.nH2O]
 Magnesium trisilicate is a compound of magnesium oxide and silicon dioxide with varying
proportions of water.
 It is available as a fine, white, tasteless, odorless powder insoluble in water and in alcohol.  
 It is an antacid with general properties similar to those of magnesium hydroxide.
 Thus it is also given combination with aluminium hydroxide.
Mechanism of Action
 Magnesium trisilicate reacts with HCl in the stomach and neutralizes it and form a gelatinous mass
of colloidal silicon dioxide and silicic acid.
 This gelatinous mass acts as a protective to ulcer and prolongs the action to several hours.
Indication 
 Magnesium trisilicate is also used as a food additive and as a
pharmaceutical excipient.
Precaution
 Magnesium trisilicate is a hydrated magnesium silicate. The formation
of renal calculi containing silica is unusual, but has been reported in a
small number of patients.
 In most of these cases, stone formation was attributed to the prolonged,
and sometimes excessive, intake of magnesium trisilicate.
Dose
 It has been given in doses of up to about 2 to 4 gm by mouth.
 The tablet should be chewed before swallowed because it does not
disintegrate rapidly in the stomach.
 Calcium Carbonate [CaCO3]
 Calcium Carbonate is a fine, white, odorless, microcrystalline powder.
 Practically insoluble in water and alcohol
 its solubility in water is increased by the presence of carbon dioxide or ammonium salts
 dissolves with effervescence in acetic acid, in hydrochloric acid, and in nitric acid.
Mechanism of Action
 In stomach, calcium carbonate reacts with gastric acid to form calcium chloride, carbon dioxide and
water.
 In intestine CaCl2 reacts with bicarbonates to regenerated CaCO3, this is excreted in feces.

2CaCl2 + 2H2CO3 2CaCO3 + 4HCl

Uses and dose

 It is used as an antacid, usually in doses of up to about 1.5 g by mouth.

 It is often given with other antacids, especially magnesium-containing
antacids.
 It is also used as a calcium supplement in deficiency states and as an
adjunct in the management of osteoporosis.
 Calcium carbonate is also used as a food additive.
Adverse Effects
 Calcium carbonate may occasionally cause constipation.
 Flatulence from released carbon dioxide may occur in some
patients.
 High doses or prolonged use may lead to gastric hypersecretion.
Precautions
 Calcium salts should be given cautiously to patients with renal
impairment, or diseases associated with hypercalcaemia.
 Plasma-calcium concentrations should be monitored closely in
patients with renal impairment and during parenteral dosage and if
large doses of vitamin D are used concurrently.
2. Ulcer Healing Drugs

 Ulcer healing drugs are also known as

acid secretion inhibitors used in peptic
ulcer disease.
 These drugs reduce the gastric acidity by
acting as
 Histamin (H2) receptor antagonists
 Proton-pump inhibitors; and/or
 Antimuscarinics
Regulation of gastric acid secretion
H2-Receptor Antagonists
 H2-receptor antagonists (commonly referred to as H2 blockers) were the most
commonly prescribed drugs in the world.
 Before the availability of the H2-receptor antagonists, the standard of care was simply
acid neutralization in the stomach lumen, generally with inadequate results.
 With the recognition of the role of H. pylori in ulcer disease (which may be treated
with appropriate antibacterial therapy) and the advent of proton pump inhibitors, the
use of prescription H2 blockers has declined markedly.
 There is four H2 antagonists' are used clinically.
 cimetidine,
 ranitidine,
 famotidine, and
 nizatidine
 General Mechanism of action of H2 antagonist

 The H2-receptor antagonists inhibit acid production by reversibly competing with

histamine for binding to H2-receptors on the basolateral membrane of parietal cells.
 They suppress the normal secretion of acid by parietal cells and the meal-stimulated
secretion of acid.
Adverse Effects
 Infrequent ADRs include hypotension.
 Rare ADRs include:
 Headache,Tiredness, Dizziness, Confusion,Diarrhoea,Constipation, and
 Rash.
 Additionally, cimetidine may also cause gynecomastia in males.
Precautions
 Before giving cimetidine or other histamine H2-antagonists to patients with gastric
ulcers the possibility of malignancy should be considered since these drugs may
mask symptoms and delay diagnosis.
 They should be given in reduced dosage to patients with renal impairment.
Uses
 H2-receptor antagonists are used in peptic ulcer disease, including
 stress ulceration,
 gastro-oesophageal reflux disease,
 selected cases of persistent dyspepsia, and
 pathological hypersecretory states such as the Zollinger-Ellison Syndrome.
 These drugs may also be used to reduce malabsorption and fluid loss in
patients with the short bowel syndrome.
Zollinger-Ellison syndrome
 It is a rare disorder characterised by the presence of a gastrin-producing
tumour (gastrinoma), which leads to hypersecretion of gastric acid and
consequent peptic ulcer disease (often with complications such as
perforation or bleeding), diarrhoea, or malabsorption.
 Gastrinomas usually occur in the non-beta islet cells of the pancreas or in
the duodenal wall.
 Up to two-thirds are malignant.
 About 20 to 25% of cases are seen in patients with multiple endocrine
neoplastic type 1 (MEN-1) syndrome.
 Doses

Cimetidine
 In gastric and duodenal ulcer: a single daily dose of 800 mg by mouth at for at least 4
weeks. The maintenance dose of 400 mg may then be given once daily at bedtime, or
twice daily in the morning and at night.
Ranitidine and Nizatidine
 In gastric and duodenal ulceration: 300 mg by mouth at bedtime or 150 mg twice for
at least 4 weeks.
Famotidine
 In gastric and duodenal ulceration: 40 mg by mouth at bedtime for 4 to 8 weeks.
Proton Pump Inhibitors
 PPIs are a group of drugs whose main action is a pronounced and long-
lasting reduction of gastric acid production.
 They are the most potent inhibitors of acid secretion available today.
 The following proton pump inhibitors are available for clinically used:
 Omeprazole
 Lansoprazole
 Pentaprazole
 Rabeprazole
 Esomeprazole
 Dexlansoprazole
 Mechanism of action
 PPIs act by irreversibly blocking the hydrogen/potassium adenosine
triphosphatase enzyme system (the H+/K+-ATPase, or, more common, gastric
proton pump) of the gastric parietal cell.
 The proton pump is the terminal stage in gastric acid secretion, being directly
responsible for secreting H+ ions into the gastric lumen, making it an ideal target
for inhibiting acid secretion.
 The lack of the acid in the stomach will aid in the healing of duodenal ulcers,
and reduces the pain from indigestion and heartburn.
Uses
 These drugs are utilized in the treatment of many conditions such as:
 Dyspepsia
 Peptic ulcer disease (PUD)
 Gastro-esophageal reflux disease (GRD/GERD)
 Prevention of stress gastritis
 Gastrinomas and other conditions that cause hyper secretion of acid
 Zolinger-Ellison Syndrome (ZES)

Adverse effects
 Adverse effects are similar for all of the proton pumps inhibitors, though they have been
reported more frequently with omeprazole.
 Common adverse effects include: headache, nausea, diarrhoea, abdominal pain, fatigue,
dizziness.
 Infrequent adverse effects include rash, itching, flatulence, constipation, anxiety (a feeling of
worry, nervousness, or unease), depression.
 Decreased vitamin B12 absorption may occur with long-term use.
Doses
Omeprazole:
 20 mg daily for four week in duodenal ulcer and 8 week in gastric ulcer
Lansoprazole:
 15 or 30 mg once daily, for 2 to 4 weeks for the relief of acid-related dyspepsia.
 30 mg once daily for 4 to 8 weeks in the treatment of gastro-oesophageal reflux disease.
 30 mg once daily for peptic ulcer disease
Pentoprazole:
 20 to 40 mg once daily for 4 weeks, increased to 8 weeks if necessary in the treatment of gastro-
oesophageal reflux disease.
 40 mg daily for 2 to 4 weeks in duodenal ulcer and 4 to 8 weeks in gastric ulcer
Rabeprazole:
 20 to 40 mg once daily for 4 weeks for gastro-oesophageal reflux disease.
 60 mg daily for Zollinger-Ellison syndrome
Esomeprazole:
 20 mg daily for 4 to 8 weeks in the treatment of NSAID-associated ulceration.
 40 mg once daily for 4 weeks, extended for a further 4 weeks if necessary for gastro-oesophageal
reflux disease
Antimuscarinic agents (anticholinergic agents)
 Muscarinic receptor stimulation increases gastrointestinal motility and
secretory activity.
 These drugs are used mainly for their antimuscarinic effects on the
gastrin and pepsine secretion and the gastric motility, in the scope of
relieving pain and promoting ulcer healing.
 Belladona and its alkaloid atropine have been used for this purpose for
many years.
 Now, Pirenzepine and Dicyclomine (Dicycloverine) are selective
antimuscarinic drugs that displays a preferential action on the gastric
mucosa thus causing a reduction in the secretion of gastric acid.
 It also reduces the secretion of pepsin and gastric motility.
Mechanism of Action
 Antimuscarinic drugs inhibit gastric motility and prolong the gastric
emptying time by selectively inhibit the H2-receptor and blocked the
action of M1 muscarinic receptor in the stomach.
 This increases the stay of an antacid in the stomach and increases its
effectiveness;

Indication 
 It has been used in the management of peptic ulcer disease
 It also reduces the secretion of pepsin.
Contraindication
 These drugs are contraindicated in the presence of concurrent reflux esophagitis.
Adverse Effect
 Dry mouth,
 Blurred vision
 Thrombocytopenia,
 Agranulocytosis
 Cardiac arrhythmias,
 Constipation, and
 Urinary retention

Doses
Pirenzepin: 50 mg two or three times daily by mouth for 4 to 6 weeks.
Dicyclomine: Adults, 10 to 20 mg three times daily
Children aged 6 months to 2 years: 5 to 10 mg up to 3 or 4 times daily
Children aged 2 to 12 years: 10 mg three times daily
 3. Ulcer protective Drugs
 These drugs, known as cyto-protective drugs, have several actions that
enhance mucosal protection mechanisms, thereby
 Preventing mucosal injury,
 Reducing inflammation, and
 Healing existing ulcers.
 Mucosal prostaglandins appear to be important in stimulating mucus and
bicarbonate secretion and mucosal blood flow.
 A number of agents that potentiate these mucosal defense mechanisms are
available for the prevention and treatment of ulcer.
 The more common ulcer protecting drugs in markets are of:
 Sucralfate
 Bismuth subsalicylate
Sucralfate
 This drug is a complex of aluminum hydroxide and sulfated sucrose.
 In water or acidic solutions it forms a viscous, tenacious paste that binds selectively to ulcers or
erosions for up to 6 hours.
 By forming complex gels with epithelial cells, sucralfate creates a physical barrier that impairs
diffusion of HCl and prevents degradation of mucus by pepsin and acid.
Mechanism of Action
 A variety of beneficial effects have been attributed to sucralfate, but the precise mechanism of
action is unclear.
 It is believed that the negatively charged sucrose sulfate binds to positively charged proteins in the
base of ulcers or erosion, forming a physical barrier that restricts further caustic damage and
stimulates mucosal prostaglandin and bicarbonate secretion.
Uses
 Sucralfate effectively heals duodenal ulcers and is used in long-term maintenance therapy to prevent
their recurrence.
 It is also used for prevention of stress-related bleeding.
Adverse Effects and Precaution
 Because it is not absorbed, sucralfate is virtually devoid of systemic
adverse effects.
 Constipation occurs in 2% of patients due to the aluminum salt.
 Because a small amount of aluminum is absorbed, it should not be used for
prolonged periods in patients with renal insufficiency.
 Because it requires an acidic pH for activation, sucralfate should not be
administered with H2 antagonists or antacids.

Dose:
 Sucralfate is administered in a dosage of 1 g four times daily on an empty
stomach (at least 1 hour before meals).
 Bismuth subsalicylate
 Bismuth subsalicylate is a non-prescription (OTC) formulation containing bismuth and salicylate.
 It contains not less than 56% and not more than 59.4% of Bi, calculated with reference to the dried substance.
Mechanism of Action
 Like sucralfate, bismuth probably coats ulcers and erosions, creating a protective layer against acid and
pepsin.
 It may also stimulate prostaglandin, mucus, and bicarbonate secretion.
Adverse Effects and Precaution
 Bismuth causes blackening of the stool, which may be confused with gastrointestinal bleeding.
 Liquid formulations may cause harmless darkening of the tongue.
 nausea and vomiting,
 blackening of the faeces, and
 darkening of tongue
Doses:
As weak antacid in doses up to about 4 g daily in divided doses