PEPTIC ULCER
By
Dr. Lamiaa Meghawery Matter
Lecturer of medical pharmacology
Faculty of medicine
Cairo university
PEPTIC ULCER
Break in the
gastric or
duodenal mucosa.
Main causes of peptic ulcer disease are:
➢ HCL ➢ Bicarbonate
➢ Pepsin ➢ Prostaglandins
➢ Bile salts ➢ Mucous
➢ Bl. Supply
➢ Mucosal
regeneration
Main causes of peptic ulcer disease are:
*Infection with gram-negative
Helicobacter pylori.
THE SYMPTOMS
OF AN ULCER:
Epigastric pain
Tenderness
Nausea
Vomiting
APPROACHES INCLUDE:
1) Eradicating the H. pylori infection
2) Reducing secretion of gastric acid
3) Providing agents that protect the gastric
mucosa from damage.
Drug Therapy
A) Antacids (Neutralization
of secreted HCI):
B)Antisecretory Drugs
(Reduction of Acid Secretion)
Drug Therapy
C) Mucosal Protectives
d)Anti • Antimicrobial
H.Pylori
• Sedatives and tranquillizers
e)Others • Tricyclic antidepressants
Antacids
Antacids
Chemistry:
▪ Aluminum hydroxide .
▪ Magnesium hydroxide [Mg(OH)2].
▪ Calcium carbonate [CaCO3].
Antacids
*Therapeutic uses:
▪ Antacids are used for symptomatic relief of
peptic ulcer disease and GERD
They should be administered after meals for
maximum effectiveness.
Antacids
*Adverse effects:
▪ Aluminum hydroxide tends to cause constipation,
whereas magnesium hydroxide tends to produce
diarrhea.
▪ The cations from antacids (Mg2+, Al3+, Ca2+)
accumulation and adverse effects may occur in
patients with renal impairment.
Antisecretory
Drugs
Overview of HCL secretion
1. H2 Blockers
Cimetidine
Ranitidine
Famotidine
Nizatidine
▪Potently inhibit basal, food-stimulated,
and nocturnal secretion of gastric acid.
Pharmacodynamics:
Actions:
*By competitively blocking the
binding of histamine to H2
receptors, these agents reduce
the secretion of gastric acid.
Therapeutic uses of H2 blockers:
a. Peptic ulcers:
b. Acute stress ulcers: (IV infusion)
c. Gastroesophageal reflux disease
(GERD):
But proton pump inhibitors (PPIs) are
more effective than H2 antagonists.
Adverse effects of Cimitidine
1. Hepatic Microsomal Enzyme Inhibitor
(Cytochrome P450):
↓Metabolism of Warfarin&clopidogrel
2.In Males (Anti-Androgen) → Gynecomastia &
↓Spermatic count.
3.In Females →↑ Prolactin → Galactorrhea &
Infertility.
4.In Elderly: Mental Confusion bec. It crosses BBB
5. All H2 antagonists may reduce the efficacy of
drugs that require an acidic environment for
absorption, such as ketoconazole.
2. PROTON PUMP INHIBITORS
• Omeprazole
• Lansoprazole
• Rabeprazole
PHARMACOKINETICS OF PPI:
For maximum effect, PPIs should be taken 30 to 60
minutes before breakfast or the largest meal of
the day.
They have a long duration of action due to
covalent bonding with the H+/K+- ATPase enzyme.
These agents are prodrugs
↓Basal & Stimulated gastric acidity up to 100%.
ThePPIs are superior to the H2 antagonists
in all previous therapeutic uses of H2
Blockers.
Finally,
they are used with antimicrobial
regimens to eradicate H. pylori.
• Omeprazole & esomeprazole may decrease the
effectiveness of clopidogrel because they inhibit
CYP2C19 .
• PPIs may increase the risk of fractures
Prolonged acid suppression may result in low
vitamin B12
Elevated gastric pH may also impair the absorption
of calcium carbonate. Calcium citrate is an
effective option for calcium supplementation in
patients on acid suppressive therapy.
Diarrhea &hypomagnesemia
New drugs for GERD and
peptic ulcer:
Potassium-competitive acid
blockers (P-CABs) are novel
drugs that bind reversibly to
K+ ions and block the H+,
K+ ATPase enzyme, thus
preventing acid production.
Members:
Vonoprazan and Topoprazan
Advantages :
• Superior efficacy compared to PPIs
• They have dose-dependent effects on acid
production.
• They do not depend on acid activation
• They bind to the enzyme directly with a rapid
action onset and better control of acid secretion.
• Less adverse effects
However, they have a shorter duration of action than
the PPIs, but they are readily formulated into an
extended-release tablet for a long duration of action,
or they can be given twice daily to inhibit acid
secretion during the day and night .
Mucosal Protective Agents
Also known as cytoprotective
compounds, these agents have several
actions.
As sucralfate and Bismuth
subsalicylate
Sucralfate:
This complex of aluminum hydroxide and sulfated sucrose
By forming complex gels with epithelial cells, a physical
barrier that protects the ulcer from pepsin and acid,
allowing the ulcer to heal.
Its use is limited due to the need for multiple daily dosing
and drug–drug interactions.
Because it requires an acidic pH for activation, sucralfate
should not be administered with PPIs, H2 antagonists, or
antacids.
Bismuth subsalicylate:
It inhibits the activity of pepsin
Increases secretion of mucus
Anti H. pylori action.
MANAGEMENT OF PEPTIC ULCER
1- General Measures
a- Rest:
Mental diazepam
Physical only in presence of
complications.
b- Diet:
1- Small frequent light meals
2- Milk in reasonable amounts is suitable.
C) Drugs to be AVOIDED:
1- Anti-Inflammatory drugs:
a- NSAID b- SAID e.g. ACTH &.Glucocorticoids
2- Alcohol, Beverages: Caffeine and Theophylline →
Irritation.
3- Cigarette smoking → Irritation and ganglia (NSD).
4- Digestatnts.
5- KCl oral preparation→ Irritation
6- Parasympathomimetics.
7- Histamine releasers.
2- Drug treatment
Scheme of
management
A- Active ulcer with No H pylori infection
Either :
- H2 blockers
OR
- Proton Pump Inhibitor
For 4 weeks in duodenal ulcer and
8 weeks in gastric ulcer.
B- Active ulcer + H pylori infection
Antimicrobials + Antisecretory
1- First Line: PPI-based triple therapies
for H pylori are considered the first-line
therapies for the treatment of H pylori.
Triple therapy
2- SECOND LINE:
Quadruple
therapies
Reserved for
patients who have
failed a course of
treatment and are
administered for
14 days.
Thank you
