Pharmacology of Peptic
Ulcer, GERD and related
disorders
Dr. Naser Ashraf
Objectives
1.
2.
3.
4.
5.
Classify drugs used in Peptic ulcer and
related disorders
Discuss the Mechanism of Action of
these drugs
Enumerate their uses and side effects
Describe the Pharmaco-therapeutic
management of APD & GERD
Describe the contraindications and drug
precautions
Regulation of gastric acid
secretion
Classification of drugs used in APD
Reduction of gastric acid secretion
I.

H2 anti histamines: Cimetidine, ranitidine,
famotidine

Proton pump inhibitors: Omeprazole, lansoprazole,
pantoprazole, rabeprazole, esomeprazole.

Anti cholinergics: Pirenzepine

PG analogues: Misoprostol, enprostil, rioprostil.
Neuralisation of gastric acid
II.

Systemic: Sodium bicarbonate, sodium citrate.

Non systemic: Mag. Hydroxide, mag. Trisilicate,
Al. hydroxide, megaldrate, calcium carbonate.
4
Classification of drugs used in APD
III. Ulcer protectives: Sucralfate,
colloidal bismuth subcitrate.
IV. Anti –H. pylori drugs: Amoxicillin,
clarithromycin, metronidazole,
tinidazole, teracycline.
H2 ANTAGONISTS
Mechanism of action

Competitively block H2 receptors on
parietal cell & inhibit gastric acid
production

Supress secretion of acid in all phases but
mainly nocturnal acid secretion

Also reduce acid secretion stimulated by
Ach, gastrin, food, etc.
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

GERD

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 can
cause gynaecomastia
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
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

Also inhibits gastric mucosal carbonic anhydrase
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 – contd.

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
 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.
Proton Pump Inhibitors

Lansoprazole :
 Partly reversible, more potent, slightly more
against H pylori.

Pantoprazole:
 More acid stable, CYP450 less affinity

Rabeprazole: claimed to most rapid acting
Prostaglandin analogues- Misoprostol

Therapeutic use:
 Prevention of NSAID-induced mucosal injury
(rarely used because it needs frequent
administration – 4 times daily)
ADRs:



Diarrhoea and abdominal cramps
Uterine bleeding, Abortion
Contraindications:
1.
Inflammatory bowel disease
2.
Pregnancy (may cause abortion)
Antacids

Weak bases that neutralize acid

Acid Neutralizing Capacity:
 Potency of Antacids
 Expressed in terms of Number of mEq of 1N
HCl that are brought down to pH 3.5 in 15
minutes by unit dose of a preparation (1 gm)
Systemic antacids

Sodium Bicarbonate:
Non systemic antacids

E.g Magnesium hydroxide,
magnesium trisilicate,
aluminium hydroxide

Insoluble and poorly
absorbed basic
compounds

React in stomach to form
corresponding chloride
salt
 Potent neutralizing
capacity and acts
instantly
 ANC: 1 gm = 12 mEq

DEMERITS:
 Systemic alkalosis
 Distension, discomfort
and belching – CO2
 Rebound acidity
 Sodium overload
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
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
 Astringent action and acts as physical barrier



ADRs: Constipation, hypophosphatemia
Drug interactions : adsorbs many drugs and
interferes with their absorption
Concurrent antacids avoided, (as it needs acid for
activation)
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 H.pylori 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 H.pylori
No acid
No ulcer
OLD TESTAMENT
No HP
No ulcer
NEW TESTAMENT
H. pylori






Gram (-) rod
Associated with gastritis,
gastric & duodenal ulcers,
gastric adenocarcinoma
Transmission route fecal-oral
Secretes urease → convert
urea to ammonia
Produces alkaline
environment enabling survival
in stomach
Higher prevalence in Low SES
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