Pharmacotherapy

of Peptic ulcer

Dr Zareen
Objectives
 Regulation of Gastric acid secretion
 Classification of drugs used in peptic
ulcer
 Mechanism of action, Uses & Adverse
effects, drug interactions of
 H2 Blockers
 Proton pump inhibitors
 Antacids
 Ulcer protectives
 Drugs for eradication of [Link]
Why Peptic ulcer occurs
 Imbalance primarily between Aggressive
factors and Defensive factors
Regulation of gastric acid
secretion
Classification of drugs
used in peptic ulcer
1. Drugs that inhibit gastric
acid secretion
2. Drugs that neutralize
gastric acid (Antacids)
3. Ulcer protectives
4. Anti H. pylori drugs
Classification
 Drugs that inhibit gastric acid
secretion
 H2 receptor blockers: Cimetidine,
Ranitidine, Famotidine
 Proton pump inhibitors: Omeprazole,
Pantoprazole, esomeprazole
 Anticholinergics : Pirenzepine
 Prostaglandin analogues: Misoprostol
Classification
 Drugs that neutralize gastric acid
(Antacids)
 Systemic:
• Sodium bicarbonate, sodium citrate
 Non systemic:
• Magnesium hydroxide, Mag. Trisilicate,
Aluminium hydroxide gel, Magaldrate
Classification
 Ulcer protectives
 Sucralfate
 Colloidal Bismuth Sulfate (CBS)
 Anti H. pylori drugs
 Amoxicillin, Clarithromycin,
Metronidazole, Tinidazole, Tetracycline
H2 ANTAGONISTS
Mechanism of action
 Competitively block H2 receptors on
parietal cell & inhibit gastric acid
production
 Suppress secretion of acid in all phases
but mainly nocturnal acid secretion
 Also reduce acid secretion stimulated by
Ach, gastrin, food, etc.
Pharmacokinetics
 Absorption is not interfered by food
 Can cross placental barrier and reaches milk,
Poor CNS penetration
 The serum half-lives range from 1.1 to 4
hours;
 Cleared by a combination of hepatic
metabolism, glomerular filtration, and renal
tubular secretion.
 Dose reduction needed in moderate to severe
renal insufficiency
 Comparison of H2
antagonists
Cimetidine Ranitidine Famotidine Nizatidine

Bioavailability 80 50 40 >90
Relative Potency 1 5 -10 32 5 -10
Half life (hrs) 1.5 - 2.3 1.6 - 2.4 2.5 - 4 1.1 -1.6
DOA (hrs) 6 8 12 8
Inhibition of 1 0.1 0 0
CYP 450
Dose mg (bd) 400 150 20 150
1. H2 antagonists - Uses
Promote the healing of gastric and duodenal ulcers
 Duodenal ulcer – 70 to 90% at 8 weeks
 Gastric Ulcer – 50 to 75%
 NSAID ulcers induced ulcers
 Stress ulcer and gastritis
 Zollinger-Ellison syndrome
 Prophylaxis of aspiration pneumonia
Adverse effects
 Headache, dizziness, bowel upset, dry
mouth
 CNS: Confusion, restlessness
 Bolus IV – release histamine –
bradycardia, arrhythmia, cardiac arrest
 Cimetidine has antiandrogenic actions
Drug interactions
 Cimetidine inhibits several CYP-450
isoenzymes and reduces hepatic blood
flow, so inhibits metabolism of many
drugs like theophylline, metronidazole,
phenytoin, imipramine etc.
 Antacids reduce the absorption of all H2
blockers
2. Proton Pump Inhibitors
 Most effective drugs in antiulcer therapy
 Prodrugs requiring activation in acid
environment
 Activated forms binds irreversibly to
H+K+ATPase and inhibit it

Omeprazole
Pantoprazole
Lansoprazole
Esomeprazole
Mechanism of Action
 Prodrugs inactive at neutral pH
 At pH < 5 rearranges to two charged cationic
forms (sulfenamide + sulphenic acid) that bind
covalently with SH groups of H⁺K⁺ ATPase and
inactivate it irreversibly
Pharmacokinetics - PPI
 Available as enteric coated tablets
 They should be given 30 minutes to 1 hour
before food intake
 half life is very short and only 1-2 Hrs
 Still the action persists for 24 Hrs to 48 hrs after a
single dose
 Action lasts for 3-4days even after stoppage of
the drug
 PPI
 Therapeutic uses:
1. Gastroesophageal reflux disease (GERD)
2. Peptic Ulcer - Gastric and duodenal ulcers
3. Bleeding peptic Ulcer
4. Zollinger Ellison Syndrome
5. Prevention of recurrence of nonsteroidal
antiinflammatory drug (NSAID) - associated gastric
ulcers in patients who continue NSAID use.
6. Reducing the risk of duodenal ulcer recurrence
associated with H. pylori infections
7. Aspiration Pneumonia
Adverse Effects
 Nausea, loose stools, headache
abdominal pain, constipation,
 Muscle & joint pain, dizziness, rashes
 Rare
 Gynaecomastia, erectile dysfunction
 Leucopenia and hepatic dysfunction
 Osteoporosis in elderly on prolonged use
 Hypergastrinemia
Drug interactions
 Omeprazole inhibits the metabolism
of warfarin, phenytoin, diazepam,
and cyclosporine.
 However, drug interactions are not a
problem with the other PPIs.
PPI – Dosage schedule
 Omeprazole 20 mg o.d.
 Lansoprazole 30 mg o.d.
 Pantoprazole 40 mg o.d.
 Rabeprazole 20 mg o.d.
 Esomeprazole 20-40 mg o.d
Proton Pump Inhibitors
 Lansoprazole :
 Partly reversible, more potent, slightly more
against H pylori, Higher BA, rapid onset.
 Pantoprazole:
 More acid stable, I.V, CYP450 less affinity
 Rabeprazole: claimed to most rapid
 Es-omeprazole
 Better intragastric pH , higher healing rates.
 3. Muscarinic antagonists
 Block the M1 class receptors
 Reduce acid production, Abolish gastrointestinal
spasm
Pirenzepine and Telenzepine
 Reduce meal stimulated HCl secretion by reversible
blockade of muscarinic (M1) receptors on the cell
bodies of the intramural cholinergic ganglia
 Unpopular as a first choice because of high
incidence of anticholinergic side effects (dry mouth
and blurred vision)
4. Prostaglandin
analogues- Misoprostol
 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)
Misoprostol
 Doses: 200 mcg 4 times a day
 ADRs:
 Diarrhoea and abdominal cramps
 Uterine bleeding
 Abortion
 Exacerbation of inflammatory bowel disease and
should be avoided in patients with this disorder
Contraindications:
1. Inflammatory bowel disease
2. Pregnancy (may cause abortion)
[Link]

 Weak bases that neutralize acid

 Also inhibit formation of pepsin
(As pepsinogen converted to pepsin at
acidic pH)
 Acid Neutralizing Capacity:
 Potency of Antacids
Systemic antacids
 Sodium Bicarbonate:
 Potent neutralizing capacity and acts instantly
 DEMERITS:
 Systemic alkalosis
 Distension, discomfort and belching – CO2
 Rebound acidity
 Sodium overload
Non systemic antacids
 Insoluble and poorly absorbed basic
compounds
 React in stomach to form
corresponding chloride salt
 The chloride salt again reacts with
the intestinal HCO3- so that HCO3- is
not spared for absorption
Non systemic Antacids
 Magnesium hydroxide ( 30 mEq)
 Aqueos suspension is called Milk of
magnesia
 Magnesium trisilicate ( 10 mEq)
 Aluminium Hydroxide (1-2.5mEq/g)
(Magaldrate – hydrated hydroxy
magnesium aluminate)
Non systemic antacids
 Duration of action : 30 min when taken in empty
stomach and 2 hrs when taken after a meal
 Adverse effects:
 Aluminium antacids – constipation (As they relax gastric
smooth muscle & delay gastric emptying) – also
hypophosphatemia and osteomalcia
 Mg2+ antacids – Osmotic diarrhoea
 In renal failure Al3+ antacid – Aluminium toxicity
& Encephalopathy
Miscellaneous drugs
 Simethicone: Decrease surface
tension thereby reduce bubble
formation - added to prevent reflux
 Alginates: Form a layer of foam on
top of gastric contents & reduce
reflux
 Oxethazaine: Surface anaesthetic
Chemical reactions of
antacids with HCl in the
stomach
Drug interactions
 By raising gastric pH & forming insoluble
complexes ↓ absorption of many drugs
 Tetracyclines, iron salts, H2 Blockers,
diazepam, phenytoin, isoniazid, ethambutol
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 - more
on duodenal ulcer
 Astringent action and acts as physical barrier
 Dietary proteins get deposited on this layer
forming another coat
 Sucralfate
 Concurrent antacids avoided, (as it needs acid for
activation)
 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
 ADRs: Constipation, hypophosphatemia
 Drug interactions : adsorbs many drugs and
interferes with their absorption
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 [Link] from surface of
mucosa and directly kills them
Colloidal Bismuth
subcitrate
 Dose: 120 mg 4 times a day
 Adverse effects
 blackening of tongue, stools, dentures
 Prolonged use may cause
osteodystrophy and encephalopathy
 Diarrhoea, headache, dizziness
 Eradication of [Link]

No acid No HP No ulcer
No ulcer

OLD TESTAMENT NEW TESTAMENT

 H. pylori

 Gram (-) rod

 Associated with gastritis,
gastric & duodenal ulcers,
gastric adenocarcinoma
 Transmission route fecal-oral
 Secretes urease → convert
urea to ammoni
Who are they ?
Nobel Laureates
of Medicine –
2005

Discovery of
H. pylori & its
role in peptic
ulcer

Barry J Marshall J. Robin Warren

 Triple Therapy
The BEST among all the Triple therapy regimen is:

Omeprazole / Lansoprazole - 20 / 30 mg bd
Clarithromycin - 500 mg bd
Amoxycillin / Metronidazole - 1gm / 500 mg bd

Given for 14 days followed by P.P.I for 4 – 6 weeks

Short regimens for 7 – 10 days not very effective
Other 2 weeks
regimen(mg)
 Amoxicillin 750/ + Tinidazole 500
+omeprazole 20 mg/ lansoprazole 30
mg BD
 clarithromycin 250 + Tinidazole
500/amoxicillin 1000 + lansoprazole
30 mg BD
Thank You