Peptic ulcer disease management

1. Pharmacotherapy
of
Peptic ulcer disease
Dr. Irfan Ahmad Khan
Senior Resident

2. Physiology of Gastric Acid Secretion
• Gastric cells:
• Chief cell: secrete pepsinogen
• Parietal cells: secrete HCl and
intrinsic factor
• Mucus cells
• Enterochromaffin cells: histamine
• G cells: gastrin hormone
• Food is broken into macroparticles,
acid causes hydrolysis, sterilizes the
meal content & activates pepsinogen to
pepsin
• Acid secretion:
• Basal: nocturnal
• Stimulated : cephalic, gastric and
intestinal.

3. PHASES OF GASTRIC ACID SECRETION AND
THEIR REGULATION
3

4. 4
PHYSIOLOGICAL REGULATION OF GASTRIC ACID SECRETION

5. HCl
GASTRIN
HISTAMINE
ACETYLCHOLINE
ECL

6. PEPTIC ULCER DISEASE
• PEPTIC ULCER is defined as disruption of the mucosal
integrity of the stomach and/or duodenum leading to a
local defect or excavation due to active inflammation.
Epidemiology
• Middle-age to older age .
• Peptic ulcers - first portion of the duodenum or in the
stomach, in a ratio of about 4:1.
• Male/female ratio is 3:1

7. • Abdominal pain, dyspepsia, vomiting, blood in vomit
• Complications:
• Gastric cancer, GIT bleeding, perforation

8. PATHOPHYSIOLOGY

9. PEPTIC ULCER DISEASE
IMBALANCE
FACTORS
THAT
PROTECT
AGAINST
ACIDITY
FACTORS
THAT
INCREASE
ACID
SECRETION
Acid
Pepsin
Bile acids
NSAIDs
H. pylori
AlcoholMucus
Bicarbonate layer
Blood flow
Cell renewal
Prostaglandins
Tight junction b/w
epithelium

10. DRUGS FOR PEPTIC ULCER
1. Drugs for reduction of acid secretion:
 Proton Pump Inhibitors:
Omeprazole, Lansoprozole, Dexlansoprazole,
Pantoprozole, Rabeprozole, Esomeprozole
 H2 receptor antagonists:
Ranitidine, Famotidine, Roxatidine
 Anticholinergics:
Pirenzepine, Propantheline, Oxyphenonium
 Prostaglandin analogues:
Misoprostol

11. 2. Drugs to neutralize gastric acid (antacids):
 Nonsystemic:
Aluminium hydroxide, Mag. Hydroxide, Magaldrate,
Mag.trisilicate, Calcium carbonate
 Systemic:
Sodium bicarbonate , Sodium citrate
MISCELLANEOUS ADJUVANTS-
Simethicone

12. 3.Ulcer Protectives:
• Sucralfate,
• Colloidal Bismuth Subcitrate and Bismuth
Subsalicylate
• Ranitidine bismuth citrate
Newer cytoprotectives- Rebamipide, Ecabet
4.Antimicrobial drugs for H. pylori eradication:
• Amoxycillin
• Clarithromycin
• Metronidazole
• Tinidazole
• Tetracycline

13. 13
SITE OF DRUG ACTION

14. PROTON PUMP INHIBITORS
• Diminish daily acid production (basal and stimulated) by 80-95%
• Absorbed from small intestine at a pH of 6
• PPIs are prodrugs - acidic environment needed for activation.
• MECHANISM OF ACTION
• After absorption prodrug gets activated to a tetracyclic
sulfenamide cation .
• Activated form then binds covalently with sulfhydryl groups of
cysteines in the H+, K+-ATPase, irreversibly inactivating the pump
molecule.

15. • Acid labile, so enteric coated tablets
• Maximum acid inhibitory effect between 2 and 6 hours after
administration and duration of inhibition lasting up to 72–96
hours.
• Because the pumps need to be activated for these agents
to be effective, their efficacy is maximized by giving them
before meal.
• Food interferes with absorption, take empty stomach

16. • Peptic ulcer disease:
• 90% healing of DU in 4wks & 85% healing of GU in
6-8 wks
• Along with long term NSAID therapy, prevent & also
for treatment of NSAID induced ulcer

17. DOSAGE OF PPIs
• Omeprazole 20 mg OD
• Esomeprazole 20 - 40 mg OD
• Rabeprazole 20 mg OD
• Lansoprazole 30 mg OD
• Pantoprazole 40 mg OD

18. PPIs: ADRs
• Nausea, Diarrhea, Abdominal pain, Flatulence.
• Nosocomial pneumonia
• Hypergastrinemia, REBOUND hypersecretion of acid
• Arthralgia, headache, skin rashes.
• Drug interactions :
Decreased acidity may decrease the absorption of
Ketoconazole, Ampicillin esters, Iron salts, Digoxin
CYP2C19 and CYP3A4 inhibition 
 metabolism of benzodiazepines, warfarin, phenytoin,
theophylline etc

19. H2 RECEPTOR ANTAGONISTS
• Inhibit acid production by reversibly competing with histamine
for binding to H2 receptors on the basolateral membrane of
parietal cells.
• Suppress acid production by 70%
• Inhibit basal and stimulated acid secretion, which accounts
for their efficacy in suppressing nocturnal acid secretion.
• Ranitidine, Famotidine, Roxatidine, Nizatidine.

20. Adverse Drug Reactions of H2 antagonists
• Diarrhea, headache, drowsiness, fatigue, muscular pain.
• Confusion, delirium, hallucinations, slurred speech
• REBOUND hyperacidity
• Pancytopenia, neutropenia, anemia, and thrombocytopenia

21. Dose of H2 antagonists
 Ranitidine 300 mg hs
 Famotidine 40 mg hs
 Nizatidine 300 mg hs

22. PROSTGLANDIN ANALOGUES
MISOPROSTOL- PGE1 ANALOGUE
• MOA- Binds to EP3 receptor on parietal cells and stimulate
Gi pathway- thereby decreasing intracellular cAMP &
gastric acid secretion.
• Cytoprotective effects
Daily dose –
• The usual recommended dose for ulcer prophylaxis is
200 micrograms four times a day.

23. Pharmacokinetics
• Inhibit acid sec. in 30 min., peaks at 60-90 min., lasts for 3
hrs.
Adverse effects
• Diarrhea
• Exacerbations of IBD
• C/I in pregnancy as increases uterine motility
Therapeutic Use- prophylaxis of NSAIDs induced ulcers

24. ANTICHOLINERGICS (rarely used now)
-SELECTIVE M1 BLOCKERS-
PIRENZEPINE,TELENZEPINE
-Suppress neural stimulation of acid production via actions
on M1 receptors of intramural ganglia.
-The ACh receptor on the parietal cell is of the M3 subtype.
-Poor efficacy, significant and undesirable anticholinergic
side effects, and risk of blood disorders (pirenzepine)

25. ANTACIDS
• ALUMINIUM HYDROXIDE, MAGNESIUM HYDROXIDE,
MAGNESIUM TRISILICATE, CALIUM CARBONATE,
MAGALDRATE
• MOA- neutralizes HCl and form AlCl3 and MgCl2 &
Carbonates
• More common use : combination of magnesium &
aluminium salts;
• Advantages of combination:
• Magnesium is laxative, aluminium constipating
• Magnesium fast acting & aluminium slow acting so
prompt & sustained effect

26. • The magnesium-containing preparations :
contraindicated in chronic renal failure patients because
of possible hypermagnesemia.
• Aluminium causes chronic neurotoxicity.
(Calcium Carbonate and Sodium Bicarbonate rarely
used now a days.)

27. DRUG INTERACTIONS
• Aluminium and Magnesium ions form inert complexes-
Tetracyclines, Fluoroquinlones, Itraconazole, Digoxin or Iron
salts
• Aluminium group of antacids decrease the bioavailability of
Phosphates, Iron salts and Digoxin
• By raising gastric pH and ionization, antacids decrease the
absorption of acidic drugs- Barbiturates, Phenytoin,
NSAIDS .

28. SIMETHICONE
• Silicon polymer, reduces flatulence and hiccups
• Surfactant, antifoaming agent, cause proper dispersal of
antacid over gastric surface, coats ulcer base.

29. ULCER PROTECTIVES
SUCRALFATE-
• Complex sucrose salt - the hydroxyl groups substituted by
aluminium hydroxide and sulfate.
• MOA:
Enhances prostaglandin synthesis,
At pH < 4 : polymerizes to a viscous, sticky gel
• adheres to ulcer crater
• precipitate the surface proteins and form a physical
barrier preventing acid, pepsin contact
• Taken on empty stomach 1 hr. before meals
• Concurrent antacids, H2 antagonist avoided, require acidic
medium for action

30. Dose:
• 1 g four times daily (for active duodenal ulcer)
• 1 g twice daily (for maintenance therapy)
SIDE EFFECTS
• Constipation
• Avoided in pts. with chronic renal insufficiency to prevent
aluminium-induced neurotoxicity
• The "sticky" nature of the viscous gel - bezoars in some
patients with underlying gastroparesis.

31. COLLOIDAL BISMUTH SUBCITRATE &
BISMUTH SUBSALICYLATE
• In acidic media CBS- forms acid resistant protective coating
over ulcer base
• Also stimulates mucosal PGE2 synthesis & HCO3
- secretion
• Dislodges H.PYLORI from gastric mucosa
• Dose: 120 mg qid
• Heals ulcer in 4 – 8 wks
• ADRs- blackening of stool, darkening of tongue
• Prolonged use– Neuropathy, osteodystrophy,
encephalopathy.

32. Anti H.pylori drugs
• Helicobacter pylori: gram negative bacillus
• Attaches to gastric epithelium:
gastritis, dyspepsia, peptic ulcer, gastric lymphoma, gastric
carcinoma.
• No single agent is effective in eradicating the organism.
• Combination therapy for 14 days provides the greatest
efficacy
• The agents used with the greatest frequency include
amoxicillin, metronidazole, tetracycline, clarithromycin, and
bismuth compounds.

33. TRIPLE THERAPY
 The BEST among all the Triple therapy regimens is
Omeprazole / Lansoprazole - 20 / 30 mg BD
Clarithromycin - 500 mg BD
Amoxycillin - 1g BD
Given for 14 days followed by P.P.I for 4 – 6 weeks

34.  Some other Triple Therapy Regimens are
 Bismuth subsalicylate – 120 mg QID
Metronidazole - 250 mg QID
Tetracycline - 500 mg QID
 Ranitidine Bismuth citrate - 400 mg BD
Tetracycline - 500 mg BD
Clarithromycin / Metronidazole - 500 mg BD

35. QUADRUPLE THERAPY
GIVEN WHEN TRIPLE THERAPY FAILS
Omeprazole/lansoprazole - 20 / 30 mg OD
Bismuth subsalycilate - 120 mg QID
Metronidazole - 250 mg QID
Tetracycline - 500 mg QID

36. SEQUENTIAL THERAPY (10 DAYS)
For 1-5 days
• Omeprazole /lansoprazole -20 mg/30mg BD
• Amoxicillin -1 g BD
Followed by 6-10 days
• Omeprazole/lansoprazole -20mg/30mg BD
• Clarithromycin -500 mg BD
• Tinidazole -500 mg BD

37. Treatment of patients infected with
resistant strains of H.pylori
• Regimens considered for second-line therapy include:
• Combination of Pantoprazole, Amoxicillin, and Rifabutin
for 10 days (86% cure rate)
• Levofloxacin-based triple therapy
(Levofloxacin, Amoxicillin, PPI) for 10 days .
• Furazolidone-based triple therapy
(Furazolidone, Amoxicillin, PPI) for 14 days.

38. THANK
YOU