This document discusses drugs used to treat peptic ulcers and gastroesophageal reflux disease (GERD). It describes the mechanisms and uses of various classes of drugs including antacids, H2 receptor antagonists, proton pump inhibitors, mucosal protective drugs, and anti-Helicobacter pylori drugs. The main goals of antiulcer therapy are relief from pain, promotion of ulcer healing, prevention of complications and relapse. Proton pump inhibitors are now the most widely used drugs for peptic ulcers due to their strong acid suppression and excellent safety profile. Eradication of H. pylori infection is also important for ulcer treatment and prevention.

1. Drugs for Peptic Ulcer & GERD
Dr. K.R.Prabhakar
Asst.Professor

2. Introduction
• Peptic ulcer- localized loss of gastric as well as
duodenal mucosa.
• Peptic ulcer- both gastric & duodenal ulcer.
• Imbalance primarily between Aggressive factors and
Defensive factors:
Aggressive factors,
e,g, acid, pepsin,
NSAID, H.Pylori etc
Defensive factors-
mucus, mucosal
blood flow, HCo3-
& PGE2

3. • Ulcers occur 5 times more common in duodenum.
• 95% occur in duodenal bulb or pylorus.
• Benign gastric ulcers- 60% in antrum.
• 25% at the junction of antrum & fundus of lesser
curvature.
• Presents as gnawing dull hunger like pain in
epigastric region.
• Barium meal X-ray- ulcer crater.

4. Physiology of acid secretion

5. Drug treatment of peptic ulcer
Goals of antiulcer therapy
• Relief from pain.
• Promotion of ulcer healing.
• Prevention of complications.
• Prevention of relapse.

6. Drugs which neutralize gastric acid
• Systemic antacids: Sodium bicarbonate
• Non systemic antacids:
1. Buffer type: Aluminium hydroxide,
Magnesium trisilicate, Magaldrate.
2. Non Buffer type: Magnesium hydroxide,
Calcium carbonate.
3. Miscellaneous: Alginates, Simethicone

7. Drugs which reduce Gastric acid secretion
H2 receptor Antagonist
• Cimetidine
• Ranitidine
• Famotidine
• Nizatidine
• Roxatidine
• Loxatidine
PG analogues
• Misoprostol
• Enprostil, Rioprostil
Proton pump inhibitors
• Omeprazole
• Lansoprazole
• Pantoprazole
• Rabeprazole
• Esomeprazole
Anticholinergics
• Propanthaline,
• Oxyphenonium,
• Pirenzipine, Telenzepine

8. Mucosal protective drugs
• Sucralfate
• Colloidal bismuth
subcitrate
• Ranitidine bismuth
citrate
Ulcer healing drugs
• carbenoxolone
Anti-Helicobacter pylori
drugs
• Amoxicillin
• Clarithromycin
• Tetracycline
• Metronidazole
• Ranitidine bismuth
citrate
• Bismuth subsalicylate
• Proton pump inhibitors

9. Antacids
• Antacids are weak bases that neutralize gastric HCl.
• Raises pH of the stomach and ↓ pepsin activity.
• Promotes mucosal defense by stimulation of PGs.
• Forms protective layer over gastric mucosa.
• Administered b/w meals & at bed time.
• Food prolongs neutralizing capacity.
• Potency expressed in terms of its acid neutralizing
capacity.

10. Systemic antacids
• Sodium bicarbonate- acts rapidly, has brief duration
of action, raises gastric pH to about 7.4.
• It has several demerits:
1. Absorbed systemically: large doses will induce
alkalosis
2. Produces Co2 in stomach→ distension, discomfort,
belching, risk of ulcer perforation.
3. Acid rebound occurs, but is usually short lasting.
4. Increases Na+ load: may worsen edema and CHF.

11. Uses:
• Restricted to casual treatment of heartburn provides
quick symptomatic relief
• Other uses are to alkalinize urine and to treat
acidosis.

12. Non systemic antacids
• Poorly absorbed from GI tract.
• Do not disturb systemic acid base balance.
• Do not elevate urinary pH.
Buffer type
• Aluminium hydroxide,
• Magnesium trisilicate,
• Magaldrate

13. • These have slow onset but longer duration of action.
• Raises gastric pH to 3.5-4.
• Rebound acidity is not a problem.
Aluminium hydroxide & Mg.trisilicate

14. • Al(OH)3 causes constipation because of –
1. Formation of aluminium phosphate.
2. SMR action of Al3+
3. Mucosal astringent action of aluminium salts.
• Binds to PO4
3- in intestine & prevents absorption.
• Hypophosphataemia may occur.
• Al(OH)3 can also be used to treat
Hyperphosphataemia & phosphate stones.

15. Magnesium trisilicate
• Does not disturb acid base balance.
• SiO2 forms a gelatinous coating over gastric mucosa.
• MgCl2 & MgCO3 cause diarrhea.
• Mg salts & Al salts are commonly administered
together to minimize effect on bowel movement.
Magaldrate
• Hydrated complex of Al-Mg hydroxide sulfate.
• Reacts with HCl & releases Al(OH)3 & Mg(OH)3.

16. Non Buffer type
Calcium carbonate
• Powerful antacids with fast action.
• Raises gastric pH above 7.
• Causes belching due to release of CO2.
• Excessive doses with milk causes hypercalcemia,
renal insufficiency & metabolic alkalosis called
milk-alkali syndrome.
• Acid rebound is marked as CaCl2 itself is gastrin
stimulant.
• Causes constipation due to Ca stereate.

17. Magnesium hydroxide
• Efficacious, neutralizes HCl promptly.
• Elevates gastric pH up to 7.
• Acid rebound is mild & brief.
• MgCO3 causes diarrhea.
• Belching does not occur as CO2 is not generated.
• Given along with Al(OH)3.

18. Drug interactions
• AL, Ca & Mg salts forms inert complexes and ↓
absorption & BA of
1. Tetracyclines
2. Fluroquinolones
3. Itraconazole
4. Digoxin
5. Iron salts & phosphates.
• ↓ absorption of acidic drugs like barbiturates,
phenytoin & NSAID’s

19. Miscellaneous adjuants to antacids
Simethicone (Dimethyl polysiloxane)
• Silicon polymer with water repellent properties.
• Acts as antifoaming agent & ↓ flatulence.
• Aids proper dispersion of antacid in gastric contents.
• Coats ulcer surface, prevents hiccups.
• Pharmacologically inert, not absorbed from GIT.
• Also used in topical skin preparations to prevent bed
sores.

20. Sodium alginate
• Hydrophilic colloidal carbohydrate derivatives.
• Extracted from brown sea weeds.
• Used along with antacids/H2 blockers.
• Reacts with gastric acid to form a viscous gel (raft).
• Acts a mechanical barrier to ↓ heartburn & GERD.

21. H2- Receptor antagonists
Mechanism of action:
• Competitively inhibit H2 receptors on parietal cells.
• Suppresses basal & food induced acid secretion.
• Specific for H2, don’t inhibit H1 & H3 receptors.
• Blocks the action of histamine released from ECL
through gastric & vagal stimulation.
• Secretory responses to other stimuli (ACh, gastrin,
insulin, alcohol, food) are also attenuated.
• Markedly↓ gastric acid secretion for longer duration
& pepsin for shorter period.

22. • Blocks >90% of nocturnal acid & 60-70% of day time
food stimulated acid secretion.
• Therapeutic doses maintain 50% of inhibition for up
to 10hrs, hence given twice daily.
• Cimetidine is a prototype drug others are-
• Ranitidine
• Famotidine
• Nizatidine
• Roxatidine
• Loxatidine

23. Clinical uses
• GERD (Gastro Esophageal Reflux Disease).
• Peptic ulcer (gastric & duodenal ulcer)disease.
• NSAID’S induced ulcer (PPI are preferred).
• Prevention of stress related gastric bleeding.
• Prevention of ulcer recurrence.
• Zollinger-Ellison syndrome (PPI are preferred).
• Chronic urticaria as they ↑ efficacy of H1 blockers.

24. Definitive treatment
of ZES is surgery

25. Adverse effects
• Extremely safe drugs.
• Headache, fatigue, myalgia & constipation- rarely.
• Cimetidine –
1. Mental status changes may occur with I.V adm.
2. Impotence in males
3. Gynaecomastia in males, galactorrhoea in females.
• ↓ IF but Vit B12 deficiency do not occur.
• Should be avoided in pregnancy & lactation.

26. Drug interactions
• Antacids ↓ absorption of H2 blockers.
• Cimetidine is potent inhibitor of CYP1A2, CYP2C9,
CYP2D6, CYP3A4.
• Hence effects plasma half lives of-
• Warfarin TCA
• Theophylline Benzodiazipines
• Phenytoin CCB
• Quinidine OHA
• Beta-blockers Metronidazole

27. H2 blockers

28. Proton pump inhibitors
• Most widely used drugs for peptic ulcer.
• Safe & efficacious.
• Omeprazole is the prototype.
• Esomeprazole
• Lansoprazole
• Pantoprazole
• Rabeprazole
• All are given orally, pantaprazole I.V also.
• Available as enteric coated formulations.

29. Mechanism of action
• All PPIs are prodrugs. These are weak bases.
• Active entity is sulfenamide cation formed in parietal
cell.
• Enteric coating dissolves in alkaline intestinal lumen.
• Prodrug gets absorbed in the intestine.
• In parietal cell canaliculus they gets trapped due to
acidic pH.
• Undergoes molecular rearrangement to form
sulfenamide cation.

30. • Sulfenamide forms covalent disulfide bond with SH
group of proton pump.
• Inactivates Proton pump irreversibly & shuts off acid
secretion.
• PPIs also inhibit gastric mucosal CA, ↓HCO3
-
• Tenatoprazole: longer half life than other PPIs.
• Inhibits nocturnal acid secretion effectively.
• Potassium competitive acid pump blockers (P-CABs).
• Newer class of drugs under development.

31. Pharmacokinetics
• Food decreases BA significantly.
• Should be taken in empty stomach, followed 1 hour
later by a meal to activate the H+K+ ATPase and
make it more susceptible to the PPI.
• Short t1/2 but longer duration of action up to 24hrs.
• Inhibits proton pump irreversibly.
• There is a biological lag of 3-4 days for full inhibition.
• Produce 80-98% suppression of 24 hour acid output.

32. • Secretion resumes gradually over 3-5 days of
stopping the drug.
• PPI undergoes rapid first pass & metabolized by liver.
• Dose reduction needed only in severe liver
impairment.
• I.V pantaprazole should be given as 24hrs continuous
infusion.
• Compensatory hypergastrinemia has been observed
on long term use.

33. Clinical uses
• PPIs inhibit fasting & food stimulated acid secretion.
• Duodenal & gastric ulcer disease.
• GERD.
• NSAIDs induced ulceration.
• Prevention of ulcer recurrence.
• ZES.
• H.pylori assosiated ulcers. 2antibiotics+ PPI BD. PPI
continued OD for 4-6 wks to promote ulcer healing.
• Aspiration pneumonia.

35. Adverse effects
• These are minimal:
• Nausea, Loose stools, headache, abdominal pain,
muscle & joint pain, dizziness (3-5%).
• Rashes (1.5% incidence)
• leucopenia and hepatic dysfunction are infrequent.
• On prolonged treatment atrophic gastritis has been
reported occasionally.
• Compensatory hypergastrenemia.

36. Drug interactions
• ↓absorption of ketoconazole & digoxin.
• Omeprazole esomeprazole & lansoprazole inhibit
CYP2C19,& CYP3A4 – May enhance the effect of -
warfarin, phenytoin, carbamazepine & BZD.
• Lansoprazole enhance elimination of theophylline.
• Rabeprazole & pantoprazole exhibit no significant
drug interaction.

37. Anticholinergics
• Propantheline & Oxyphenonium are preferred as
they don’t cross BBB.
• Blocks basal secretions more effectively.
• ↑gastric emptying time and prolongs exposure of
ulcer bed to gastric acid. Relaxes LES.
• These disadvantages make them unsuitable for
peptic ulcer & GERD.
• Nonselective retains anticholinergic side effects.

38. Pirenzepine & Telenzepine
• Selective M1 receptor blockers used in Canada &
Europe for Rx of peptic ulcer.
• Effectively heal as well as prevent recurrence.
• At usual doses side effects are low.

39. PG analogues
Misoprostol (PGE1)
• Inhibit gastric acid secretion
• Enhance local production of mucus or bicarbonate
• Help to maintain mucosal blood
• Therapeutic use:
– Prevention of NSAID-induced mucosal injury
(rarely used because it needs frequent
administration – 4 times daily)

40. • Doses: 200 mcg 4 times a day
• ADRs:
– Diarrhoea and abdominal cramps
– Uterine bleeding
– Abortion
– Exacerbation of inflammatory bowel disease.
Contraindications:
1. Inflammatory bowel disease
2. Pregnancy (may cause abortion)

41. Sucralfate – ulcer protective
• Aluminium salt of sulfated sucrose .
• MOA:
– In acidic environment ( pH <4) it polymerises by
cross linking molecules to form sticky viscous gel
that adheres to ulcer crater - acts as acid resistant
physical barrier.
– Dietary proteins get deposited on this layer
forming another coat.
– May stimulate PGE2 synthesis & HCO3- secretion.

42. • Bind epithelial & fibroblast growth factors which
promotes mucosal repair.
• SE: hypophosphataemia may occur.
• Concurrent antacids avoided.
• Uses:
– Prophylaxis of Stress ulcers
– Bile reflux gastritis
– Topically – burn, bedsore ulcers, excoriated skins
• Dose: 1 gm 1 Hr before 3 major meals and at bed
time for 4-8 weeks .

43. Colloidal Bismuth Subcitrate (CBS)
• Mechanism of action
– CBS and mucous form glycoprotein bi complex
which coats ulcer crater
– ↑ secretion of mucous and bicarbonate, through
stimulation of mucosal PGE production
– Detaches H.pylori from surface of mucosa and
directly kills them

44. • Dose: 120 mg 4 times a day
• Adverse effects
– blackening of tongue, stools, dentures
– Prolonged use may cause osteodystrophy and
encephalopathy
– Diarrhoea, headache, dizziness

45. Eradication of H.pylori
No acid
No ulcer
OLD TESTAMENT
No HP No ulcer
NEW TESTAMENT

46. H.Pylori
• Gram (-) rod.
• Associated with gastritis, gastric & duodenal ulcers,
gastric adenocarcinoma, gastric lymphoma.
• Transmission route fecal-oral
• Secretes urease → convert urea to ammonia.
• Produces alkaline environment enabling survival in
stomach.
• Present in 90% of peptic ulcer cases.
• Higher prevalence in Low SES

47. Who are they ?
Barry J Marshall J. Robin Warren
Nobel Laureates of
Medicine – 2005
Discovery of
H. pylori & its role
in peptic ulcer

51. THANK YOU