Anti peptic ulcer drugs, by Baqir Naqvi.pptx

1. Anti Peptic Ulcer Drugs
(Pharmacology & Therapeutics-1)
Lecture By
Dr. Syed Baqir Raza Naqvi
(BSc, Pharm-D, M. Phil-Pharmacology)
Nazar College of Pharmacy
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2. Peptic Ulcer
“A peptic ulcer is a sore on the lining of stomach, small intestine or
esophagus.”
• It refers to an erosion or ulceration of GIT mucosa or adjacent to acid
bearing area.
• Comprises of three important types;
Gastric ulcer Esophageal ulcer
Duodenal ulcer
A peptic ulcer in the
stomach is called a
gastric ulcer.
A duodenal ulcer is a
peptic ulcer that develops
in the first part of the
small intestine
(duodenum).
An esophageal ulcer
occurs in the lower
part of esophagus.
2

3. Causes
• Hyper secretion of gastric juices.
• Prolonged use of ulcer-genic drugs e.g.
NSAIDS.
• Stress.
• Infection by micro organisms like H.
Pylori.
• Inadequate mucosal defense against
gastric acid.
Symptoms
• Intermittent pain in abdomen.
• May cause bleeding or perforation.
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4. Strategies to overcome peptic ulcer
Possible treatment approaches include;
1). Eradicating the H. pylori infection.
2). Reducing secretion of gastric acid with the use of PPIs or H2-
receptor antagonists.
3). Providing agents that protect the gastric mucosa from damage,
such as misoprostol and sucralfate.
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5. 5

6. Classification of Anti peptic ulcer drugs
Book reference: Lippincott's illustrated review of Pharmacology Page # 401 6

7. 1. ANTI-MICROBIAL AGENTS
 Need of Antibiotics; Patients with peptic ulcer disease who are
infected with H. pylori require antimicrobial treatment.
 Significance; Eradication of H. pylori results in rapid healing of
active ulcers and low recurrence rates.
 Ratio of recovery; Successful eradication of H. pylori (80% to
90%) is possible with various combinations of anti microbial drugs.
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8. Currently, triple therapy and quadruple therapies are in use
for microbial peptic ulcers.
PPI’s
Amoxicillin
Clarithromycin
Bismuth
subsalicylate
Metronidazole
Tetracycline
PPI’s
Triple
therapy
Quadruple
therapy
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9. Necessary Precautions while using Antibiotics
i. Treatment with a single anti microbial drug is much less effective,
results in antimicrobial resistance, and is not recommended.
ii. Quadruple therapy should only be considered in areas with high
resistance to clarithromycin.
iii. This usually results in a 90% or greater eradication rate.
iv. Substitution of antibiotics is also not recommended (that is, do not
substitute ampicillin for amoxicillin or doxycycline for tetracycline).
GERD (heartburn) is not associated with H. pylori infection and does
not respond to antibiotics.
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10. These Includes;
2. H₂ RECEPTOR BLOCKERS
Cimetidine
Ranitidine
Famotidine
Consist of furan ring
Contain imidazole ring
Consist of thiazole ring
Rx: Cimet
Tab. 200 mg & 400 mg
Rx: Ranidin
Tab. 150 mg. Inj. 50mg/2ml
Rx: Polypep
Tab. 20 mg & 40 mg
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11. Mechanism of action
• H2 receptor blockers selectively & reversibly inhibit the gastric acid
secretions induced by histamine, gastrin and acetylcholine.
• Usually 60% - 70% of gastric acid is inhibited by H2 receptor blockers.
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12. Pharmacokinetic profile of H2 receptor blockers
• After oral administration, the H2 antagonists distributed widely
throughout the body (including into breast milk and across the
placenta) and are excreted mainly in urine.
• The half-life of all of these agents may be increased in patients with
renal dysfunction and dosage adjustments are needed.
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13. Therapeutic Uses
1. Peptic Ulcer
• Effective in both gastric and duodenal peptic ulcers.
• Known as nocturnal acid suppressors so can be given at bed time.
• However, recurrence is common if H. pylori is present and the
patient is treated with these agents alone.
2. Acute stress ulcers
• These drugs are given as an intravenous infusion to prevent and
manage acute stress ulcers associated with high-risk patients in
intensive care units (ICU).
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14. 3. Gastro-esophageal reflux disease (GERD)
• Low doses of H2 antagonists, are effective for the
treatment of heartburn (GERD) in only about 50% of
patients.
• As H2-receptor antagonists act by stopping acid
secretion. Therefore, they may not relieve symptoms
for at least 45 minutes.
• Antacids more quickly neutralize stomach acid, but
their action is only temporary. For these reasons, PPIs
are now preferably used in the treatment of GERD,
especially for patients with severe heartburn.
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15. Adverse effects of H2 Receptor blockers
Common Adversities
• Comparatively safe drugs but common
adversities includes NVD, fatigue,
headache, drowsiness. (in 3 % patients).
Major side effects
• CNS: Confusion, Hallucinations, Agitation,
• CVS: Bradycardia, Hypotension,
• Endocrine: In males gynaecomastia &
decreased libido. In females galactorrhea,
• Hepatic: Transient changes in LFT’s.
Drug interactions with cimetidine
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CYP-450 Inhibition

16. Comparison of H2 Receptor blockers
Cimetidine Ranitidine Famotidine
Lipid soluble & absorbed 60-80%. Poorly lipid soluble so poorly
absorbed..
Very poorly lipid soluble.
Blocks H1 & H2 receptors so non
specific in action.
Blocks only H2 receptors so specific
in nature
Also blocks only H2 receptors so
specific in in action.
50 % healing rate of peptic ulcer. 75 % healing rate of peptic ulcer. 90 % healing rate of peptic ulcer.
Duration of action is 4-6 hours. Duration of action is 8-12 hours. Duration of action is 12-24 hours.
Inhibits Cytochrome P450 enzyme,
so associated adversities may appear.
No such effects. No such effect appeared.
Causes confusion because it crosses
BBB.
Does not cause mental confusion. Does not cause mental confusion.
Antacids interfere its absorption. Do not interfere Do not interfered by antacids.
Relative Potency ------- 1-time 5 times more potent than
cimetidine.
20-40 times more potent than
cimetidine.
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17. • PPIs were introduced in late 1980’s & Omeprazole was the first PPI
introduced.
• These are the most potent gastric ulcer inhibitors.
• These Includes;
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3. PROTON PUMP INHIBITORS (PPIs)
Omeprazole Esomeprazole
Rabeprazole Pantoprazole
PPI’s

18. • PPIs are commonly administered as enteric coated tablets or capsules.
• When taken orally they are absorbed in small intestine, from where they
are taken to parietal cells where they enter acidic parietal cells.
• As PPIs are weak bases therefore they get protonated in the acidic media of
parietal cells yielding an activated sulphonamide.
• This Sulphonamide bind to the H+/K+ATPase enzyme system (proton
pump) and suppress the secretion of hydrogen ions into the gastric lumen.
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Book reference: Lippincott's illustrated review of Pharmacology Page # 404
Mechanism of Action

19. 19
Book reference: Lippincott's illustrated review of Pharmacology Page # 403
Mechanism of Action

20. 20

21. 1. R/A: All of these agents are effective orally.
2. Th./E: For maximum effect, PPIs should be taken 30 to 60 minutes
before breakfast or the largest meal of the day.
3. Duration of action: Although the plasma half-life of these agents is
only a few hours, they have a long duration of action due to covalent
bonding with the H+/K+ATPase enzyme.
4. Excretion: Metabolites of these agents are excreted in urine and feces.
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Pharmacokinetics of PPIs

22. Therapeutic Uses of PPI’s
1. Peptic Ulcer
• PPIs shows maximum efficacy & superior/faster gastric acid inhibition.
• Drug of choice in NSAIDs induced peptic ulcers.
• Also effective in peptic ulcer induced by H. Pylori, especially when
given with antibiotics.
• Ulcer bleeding is significantly reduced with the use of PPIs.
2. GERD
• PPIs are most effective agents for the treatment of non erosive & non
erosive reflux diseases and esophageal complications of reflux
diseases.
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23. 3. Non Ulcer dyspepsia
• PPIs have modest efficacy for the treatment of non-ulcer dyspepsia.
4. Stress Gastritis
• Intravenous PPIs are increasingly used in critically ill patients to reduce the
incidence of stress related mucosal bleeding.
5. Zollinger-Ellison Syndrome
• More effectively treat symptoms of Zollinger-Ellison syndrome (A condition in
which more gastrin is produced because of tumor that causes hyper secretion of
HCl) . But the ultimate treatment is surgical removal of tumor.
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24. 24
Adverse effects
Generally lower risk of adverse effects.
Common adverse effects includes;
• Alterations in absorption of vitamins (Vit.
B-12).
• CNS: Headache, dizziness
• GIT: Nausea, diarrhea & sometimes
constipation.
• SKIN: Rashes
Contraindications
• During pregnancy & lactation
• Malignancy (cancer)

25. • Sucralphate is a salt of sucrose complexed to sulphated Al(OH)3.
• It was 1st approved by FDA in 1981.
Mechanism of Action
• When it is given orally it exerts its natural effect by local action on gastric
and duodenal linings.
• Exact molecular mechanism of action is still not known, but it is thought to
act by one of the following four ways;
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3. CYTO-PROTECTIVE AGENTS (Sucralfate)

26. Mechanism of Action (Cont.)
1) It forms a protective coating on the surface of ulcerated lesions. Thus
protected it against injury caused by gastric acid and pepsin.
2) By forming complex gels with epithelial cells, sucralfate creates a physical
barrier that protects the ulcer from pepsin and acid, allowing the ulcer to heal.
3) It binds with bile acid coming via bile duct and protect the upper GIT. Against
their erosive effect.
4) It also increases the prostaglandin production which are known to protect the
stomach injuries as they have role in making of gastric mucosa.
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27. 27
Mechanism
of
Action
(Sucralfate)

28. Clinical Uses:
• In the treatment of peptic ulcer.
• Effective in gastritis & doudenitis
• Even protect the stomach after ulcer healing.
Adverse effects
• It’s a well tolerated drug with lower
incidence of side effects.
• 2% patients reported constipation.
• Headache, insomnia, NVD.
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Drug interactions
Sucralphate may binds to
other medications, impairing
their absorption e.g.
tetracycline, cimetidine,
digoxin etc.

29. 2. Bismuth subsalicylate
• This agent is used as a component of quadruple therapy to heal
peptic ulcers.
• In addition to its antimicrobial actions, it inhibits the activity of
pepsin, increases secretion of mucus, and interacts with glycoproteins
in necrotic mucosal tissue to coat and protect the ulcer.
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Further detail of Bismuth subsalicylate is mentioned in anti diarrheal drugs section

30. • Proglumide is made up of amino acids & its molecular structure is similar to
gastrin. It contains amino acid residue that is polypeptide in nature.
Mode of Action
• Three main contributors for the gastric acid secretions are;
1. Histamine 2. Acetylcholine 3. Gastrin
• The most potent among these is gastrin. All of these binds to their specific
receptor sites located in parietal cells.
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4. ANTI GASTRIN AGENTS (Proglumide)

31. • Gastrin binds with the specific gastrin receptors (G. receptors) which are
located on the surface of parietal cell membrane.
• When it binds with G. receptors, certain intracellular events are mediated.
In the consequence, the release of intracellular Ca⁺⁺ is stimulated, which
then activate the protein kinases.
• These kinases then promote the proton pump (H⁺/K⁺ ATPase) which finally
leads to secretion of H⁺ ion into lumen of stomach.
• Proglumide competitively blocks the G. receptors & thus there is
inhibition of proton pump, because gastrin is not able to show its
physiological effects.
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Mechanism of Action (Cont.)

32. 32
Proglumide
Mechanism of Action (Proglumide)

33. Clinical Uses
• Proglumide is considered to be equipotent to
cimetidine in the treatment of gastric ulcer.
1600 mg of Proglumide is considered to be
equal to 400 mg of cimetidine.
Side effects
• This drug is considered safe.
• Very few side effects are reported.
• Rarely, it leads to skin rashes.
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34. • Prostaglandin E, produced by the gastric mucosa,
inhibits secretion of acid and stimulates secretion of
mucus and bicarbonate (Cyto-protective effect).
• A deficiency of prostaglandins is thought to be involved
in the pathogenesis of peptic ulcers.
• Misoprostol, an analog of prostaglandin E1, is
approved for the prevention of NSAID-induced gastric
ulcers.
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5. PROSTAGLANDINS (Misoprostol)
Misoprostol reduces serious
gastrointestinal (GI) complications in
patients with rheumatoid arthritis
receiving NSAIDs.

35. Therapeutic Uses
• It is Prophylactically used in patients who are taking NSAIDs and are at
moderate to high risk of NSAID-induced ulcers, such as elderly
patients and those with previous ulcers.
Adverse Effects
• Dose-related diarrhea and nausea are the most common adverse
effects and limit the use of this agent. Thus, PPIs are preferred agents
for the prevention of NSAID-induced ulcers.
Contraindication
• Misoprostol is contraindicated in pregnancy, since it can stimulate
uterine contractions and cause miscarriage.
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36. Summary of drugs used in hyperacidity of stomach
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