Dr.

Badruddeen
Associate Professor &
Member Secretary IAEC,
Integral University, Lucknow (U.P.)

1
 PEPTIC ULCER
DISEASE
• PEPTIC ULCER is defined as disruption of the mucosal
integrity of the stomach and/or duodenum leading to a
local defect due to active inflammation.

• The break can involve the mucosa, muscularis

mucosae, submucosa and in some cases, the
deeper layers of the muscle wall.
• Gastritis is the precursor to peptic ulcer disease
(PUD).
• PUD includes:
 Stomach (called gastric ulcer)
 Duodenum (called duodenal ulcer) 2
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

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 PEPTIC ULCER DISEASE
FACTORS  Acid
THAT
PROTECT  Pepsin
AGAINST  Bile acids
ACIDITY  NSAIDs
 H. pylori
 Mucus  Alcohol
 bicarbonate layer  Pancreatic
 Blood flow enzymes
 cell renewal
FACTORS
 Prostaglandins THAT
 Tight junction b/w IMBALANCE INCREASE
epithelium ACID
SECRETION 1
CAUSES

• Helicobacter pylori
• NSAIDs
• Ethanol
• Tobacco
• Severe physiologic
stress (Burns, CNS trauma,
Surgery, Severe medical illness)
• Steroids
• Cytotoxic drugs/ Anticancer drugs
• Spices
PATHOPHYSIOLOGY

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 CLINICAL PRESENTATION
• Epigastric pain

• Burning, aching, gnawing (persistence stress), 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

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 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
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

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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
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PHYSIOLOGICAL AND PHARMACOLOGICAL REGULATION
OF
GASTRIC ACID SECRETION

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 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.

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• 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.

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 DOSAGE OF
PPIs :
•Omeprazole 20 mg OD

•Esomeprazole 20 - 40 mg OD

•Rabeprazole 20 mg OD

•Lansoprazole 30 mg OD

•Pantoprazole 40 mg OD

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 PPIs:
ADRs
• Nausea, Diarrhea, Abdominal pain, Flatulence.
• Nosocomial pneumonia
• Clostridium difficile diarrhea
• 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 enzyme inhibition 
 metabolism of benzodiazepines, warfarin,
phenytoin, diazepam, theophylline etc
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 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.

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 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
 Dose of antagonis
H2 ts
 Ranitidine 300 mg hs

 Famotidine 40 mg hs

 Nizatidine 300 mg hs

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 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

Adverse effects
• Diarrhea
• Exacerbations of IBD

• C/I in pregnancy as increases uterine motility

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 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)

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 ANTACID
• ALUMINIUM HYDROXIDE, MAGNESIUM HYDROXIDE,
S
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)

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• 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.)

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 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 .
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 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
 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

 Dose:

• 1 g four times daily (for active duodenal ulcer)

• 1 g twice daily (for maintenance therapy)

SIDE EFFECTS

• Constipation

• Avoided in patients with chronic renal insufficiency to

prevent aluminum-induced neurotoxicity

• The "sticky" nature of the viscous gel - bezoars in some

patients with underlying gastroparesis.
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 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

 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.
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33
• 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 da ys.

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 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

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 QUADRUPLE THERAPY

GIVEN WHEN TRIPLE THERAPY

FAILS
Omeprazole/lansoprazole - 20 / 30 mg OD

Bismuth subsalycilate - 525 mg

Metronidazole - 250 mg QID

Tetracyclin - 500 mg QID

e 36
 SEQUENTIAL THERAPY (10
For 1-5 days
DAYS)
• Omeprazole -20 mg/30mg BD
/lansoprazole
• Amoxicillin -1 g BD

Followed by 6-10 days

• Omeprazole/lansoprazole -20mg/30mg BD

• Clarithromycin -500 mg BD

• Tinidazole -500 mg BD
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 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.
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 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.
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THANK
YOU

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