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.
• 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
• 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
PHYSIOLOGICAL AND PHARMACOLOGICAL REGULATION OF
GASTRIC ACID SECRETION
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
•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.
DOSAGE OF PPIs :
•Omeprazole 20 mg OD
• Esomeprazole 20 - 40 mg OD
• Rabeprazole 20 mg OD
• Lansoprazole 30 mg OD
• Pantoprazole 40 mg OD
• 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
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
• Ranitidine, Famotidine, Roxatidine, Nizatidine.
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
MISOPROSTOL- PGE1 ANALOGUE
•MOA- Binds to EP3 receptor on parietal cells and
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
• Inhibit acid sec.in 30 min.,peaks at 60-90 min.,lasts
for 3 hrs.
• Exacerbations of IBD
• C/I in pregnancy as increases uterine motility 25
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)
• ALUMINIUM HYDROXIDE, MAGNESIUM HYDROXIDE,
MAGNESIUM TRISILICATE, CALIUM CARBONATE,
•MOA-neutralises HCL and form AlCl3 and MgCl2 &
• Fixed combinations of magnesium and aluminum
(Al3+ can relax gastric smooth muscle, producing delayed
gastric emptying and constipation; Mg2+ causes loose
• 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.)
• Aluminium and Magnesium ions form inert complexes-
Tetracyclines, Fluoroquinlones, Itraconazole, Digoxin or
• 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,
• Silicon polymer, reduces flatulence and hiccups
• Surfactant,antifoaming agent, cause proper dispersal
of antacid over gastric surface , coats ulcer base.
• Hydrophilic colloidal carbohydrate derived from
• Used with antacid & H2 antagonist-heart burn &
•Complex sucrose salt - the hydroxyl groups substituted
by aluminum hydroxide and sulfate.
Enhances prostaglandin synthesis,
Stimulates mucus and bicarbonate secretion, and
Enhances mucosal defense and repair. 31
• 1 g four times daily (for active duodenal ulcer)
• 1 g twice daily (for maintenance therapy)
•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.
COLLOIDAL BISMUTH SUBCITRATE &
• 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
Anti H.pylori drugs
• Helicobacter pylori: gram negative bacillus
• Attaches to gastric epithelium:
gastritis, dyspepsia, peptic ulcer, gastric lymphoma, gastric
• 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
• Choice of a particular regimen will be influenced by -
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
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
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
Major SIDE EFFECTS of drugs
•Bismuth : black stools, constipation, or darkening
of the tongue.
• Amoxicillin : nausea, vomiting, skin rash,
allergic reaction , pseudomembranous colitis ,
• Tetracycline : rashes and, very rarely,
hepatotoxicity and anaphylaxis.
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