1. Management of
Peptic ulcer disease
Dr. Bushra Hasan Khan
Junior Resident-1,
Department Of Pharmacology,
JNMC,AMU,Aligarh.
1

2. CONTENTS
 Physiology of Gastric acid secretion
 An introduction to Peptic Ulcer Disease
 Drugs used in PUD
2

3. PHYSIOLOGY OF GASTRIC ACID SECRETION
• Food is broken into macroparticles
• Acid causes hydrolysis,
sterilizes the meal content
& activates pepsinogen to pepsin
• Acid secretion:
• Basal
• Stimulated
3

4. 4
DIAGRAM SHOWING OXYNTIC GASTRIC GLAND

5. GASTRIC PARIETAL CELL UNDERGOING
TRANSFORMATION AFTER SECRETAGOGUE
MEDIATED STIMULATION
5

6. PHASES OF GASTRIC ACID SECRETION AND
THEIR REGULATION
6

7. 7
PATHOPHYSIOLOGY

8. 8
PHYSIOLOGICAL REGULATION OF GASTRIC ACID SECRETION

9. HCL
GASTRIN
HISTAMINE
ACETYLCHOLINE
9
ECL

10. 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
10

11. PEPTIC ULCER DISEASE
Acid
Pepsin
Bile acids
NSAIDs
H. pylori
Alcohol
Pancreatic
enzymes
11
IMBALANCE
FACTORS
THAT
PROTECT
AGAINST
ACIDITY
FACTORS
THAT
INCREASE
ACID
SECRETION
Mucus
bicarbonate layer
Blood flow
cell renewal
Prostaglandins
Tight junction b/w
epithelium

12. 12
CLINICAL PRESENTATION
• Epigastric pain
• Burning, aching, gnawing, hunger pain
 aggravated by food in Gastric ulcer ,
 relieved by food in Duodenal ulcer
• Bloating and nausea
• Loss of appetite and weight loss in Gastric ulcer
• In Severe Cases
- Vomiting blood or coffee ground like material
- Black tarry stools

13. CLASSIFICATION OF ANTI-ULCER DRUGS
1.Drugs for reduction of acid secretion:
 Proton Pump Inhibitors:
Omeprazole , Lansoprozole,
Dexlansoprazole , Pantoprozole ,
Rabeprozole, Esomeprozole
 H2 receptor antagonists:
Ranitidine, Famotidine, Cimetidine ,Roxatidine
 Anticholinergics:
Pirenzepine, Propantheline ,Oxyphenonium
 Prostaglandin analogues:
Misoprostol
13

14. 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
Sodium alginate
14

15. 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
15

16. 16
PHYSIOLOGICAL AND PHARMACOLOGICAL REGULATION OF
GASTRIC ACID SECRETION

17. 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.
17

18. •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 if
they are administered before meal.
18

19. DOSAGE OF PPIs :
•Omeprazole 20 mg OD
• Esomeprazole 20 - 40 mg OD
• Rabeprazole 20 mg OD
• Lansoprazole 30 mg OD
• Pantoprazole 40 mg OD
19

20. PPIs: ADRs
• Nausea, Diarrhea, Abdominal pain, Flatulence.
• Nosocomial pneumonia
• Clostridium difficle diarrhoea
• 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 enz inhibition 
 metabolism of benzodiazepines, warfarin, phenytoin,
diazepam, theophylline etc 20

21. 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.
21

22. Adverse Drug Reactions of H2 antagonists
• Diarrhea, headache, drowsiness, fatigue, muscular
pain, and constipation.
• Confusion, delirium, hallucinations, slurred speech
• REBOUND hyperacidity
• Pancytopenia, neutropenia, anemia, and
thrombocytopenia 22

23. Dose of H2 antagonists
 Ranitidine 300 mg hs
 Famotidine 40 mg hs
 Nizatidine 300 mg hs
23

24. 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. 24

25. 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 25

26. ANTICHOLINERGICS (rarely used now)
SELECTIVE M1 BLOCKERS-PIRENZEPINE,TELENZEPINE
The ACh receptor on the parietal cell is of the M3 subtype.
Suppress neural stimulation of acid production via actions on
M1 receptors of intramural ganglia.
Poor efficacy, significant and undesirable anticholinergic side
effects, and risk of blood disorders (pirenzepine)
26

27. ANTACIDS
• ALUMINIUM HYDROXIDE, MAGNESIUM HYDROXIDE,
MAGNESIUM TRISILICATE, CALIUM CARBONATE,
MAGALDRATE
•MOA-neutralises HCL and form AlCl3 and MgCl2 &
Carbonates
• Fixed combinations of magnesium and aluminum
(Al3+ can relax gastric smooth muscle, producing delayed
gastric emptying and constipation; Mg2+ causes loose
stools). 27

28. • The magnesium-containing preparations :
contraindicated in chronic renal failure patients
because of possible hypermagnesemia.
• Aluminum causes chronic neurotoxicity.
( Calcium Carbonate and Sodium Bicarbonate rarely
used now a days.)
28

29. 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 .
29

30. SIMETHICONE
• Silicon polymer, reduces flatulence and hiccups
• Surfactant,antifoaming agent, cause proper dispersal
of antacid over gastric surface , coats ulcer base.
SODIUM ALGINATE-
• Hydrophilic colloidal carbohydrate derived from
seaweeds
• Used with antacid & H2 antagonist-heart burn &
GERD
30

31. ULCER PROTECTIVES
• SUCRALFATE-
•Complex sucrose salt - the hydroxyl groups substituted
by aluminum hydroxide and sulfate.
•MOA:
Enhances prostaglandin synthesis,
Stimulates mucus and bicarbonate secretion, and
Enhances mucosal defense and repair. 31

32. 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 aluminum-induced neurotoxicity
• The "sticky" nature of the viscous gel - bezoars in
some patients with underlying gastroparesis.
32

33. 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 –antimicrobial activity.
• Dose: 120 mg qid
• Heals ulcer in 4 – 8 wks
• ADRs- blackening of stool,darkening of tongue
• Prolonged use –Neuropathy,osteodystrophy, encephalopathy.33

34. 34

35. 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.
35

36. 36

37. • Choice of a particular regimen will be influenced by -
 Efficacy,
 Patient tolerance,
 Existing antibiotic resistance,
 Cost of the drugs
• Two anti-H. pylori regimens available in prepackaged formulation:
 Prevpac (lansoprazole, clarithromycin, and amoxicillin)
The contents taken twice per day for 14 days
 Helidac (BSS, tetracycline, and metronidazole).
Helidac constituents taken four times per day with an
antisecretory agent (PPI or H2 blocker), also for at least 14 days. 37

38. TRIPLE THERAPY
The BEST among all the Triple therapy regimens is
Omeprazole / Lansoprazole - 20 / 30 mg BD
Clarithromycin - 500 mg BD
Amoxycillin - 1gm BD
Given for 14 days followed by P.P.I for 4 – 6 weeks
38

39. QUADRUPLE THERAPY
GIVEN WHEN TRIPLE THERAPY FAILS
Omeprazole/lansoprazole - 20 / 30 mg OD
Bismuth subsalycilate - 525 mg
Metronidazole - 250 mg QID
Tetracycline - 500 mg QID
39

40. 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
40

41. Major SIDE EFFECTS of drugs
•Bismuth : black stools, constipation, or darkening
of the tongue.
• Amoxicillin : nausea, vomiting, skin rash,
allergic reaction , pseudomembranous colitis ,
antibiotic-associated diarrhea.
• Tetracycline : rashes and, very rarely,
hepatotoxicity and anaphylaxis.
41

42. Treatment of patients infected with
resistant strains of H.pylori
•Regimens considered for second-line therapy include:
• Combi. 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. 42

43. 43
THANK
YOU