4. Learning objectives
At the end of the lectures student should able to
know-
1. Definition of peptic ulcer
2. Causes of peptic ulcer.
3. Mechanism of secretion of gastric acid
4. Goals of antiulcer drug
5. Drugs for peptic ulcer disease
6. pharmacology.
5. 1. Definition of Peptic Ulcer:
A benign lesion of gastric or duodenal mucosa
occurring at a site where the mucosal epithelium
is exposed to acid and pepsin;
1) aggressive factors – HCl, H pylori
2) protective factors – mucus, bicarbonate
6. 2. Causes of peptic ulcer.
1. Helicobacter Pylori (H. pylori)
– Most ulcers are the result of infection with H.
pylori
– Not all of those infected with H. pylori develop
ulcers
– H. pylori MAY result in a weakening of the mucosal
defense systems, allowing for development of
ulcer subsequent to acid/pepsin aggression;
7. 2. NSAIDs
– Long term use of nonsteroidal anti-inflammatory
drugs. NSAIDs block COX enzymes and decrease
prostaglandins (PGs).
3. Gastrinoma (Zollinger-Ellison Syndrome)
– Tumors of the duodenum or pancreas secrete
abnormally high amounts of gastrin which
stimulates gastric acid.
4. Stress ulcers
– Result of physical trauma (i.e., burn patients).
9. 3. Mechanism of secretion of gastric
acid
• Parietal cells in the stomach secrete roughly two liters of acid a day
in the form of hydrochloric acid. Acid in the stomach functions to kill
bacteria, and to aid digestion by solubilizing food. The acid is also
important to establish the optimal pH (between 1.8-3.5) for the
function of the digestive enzyme pepsin.
• A key protein for acid secretion is the H+/K+-ATPase (or proton
pump). This protein, which is expressed on the apical membrane of
parietal cells, uses the energy derived from ATP hydrolysis to pump
hydrogen ions into the lumen in exchange for potassium ions.
10. Stimulation of acid secretion involves the translocation of H+/K+-
ATPases to the apical membrane of the parietal cell. When the cell is
resting (not stimulated), H+/K+-ATPases are located in vesicles inside
the cell. When the cell is stimulated, these vesicles fuse with the
plasma membrane, thereby increasing the surface area of the plasma
membrane and the number of proton pumps in the membrane
11. 4.Goals of antiulcer drug
• Relief from pain
• Promotion of ulcer healing
• Prevention of complication.
• Prevention of relapse.
19. Pharmacokinetic
• Cimetidine is prototype drug.
• Absorption – oral, im, iv infusion.
Bioavailability - 60-80% , Lipid soluble,non ionized form
• Distribution – widely distributed throuhout all the
tissues.It can cross BBB and can cause
headache,dizziness,somnolence.
Volume of distribution 0.8L/kg
• Metabolism – liver .
• t1/2 - 2-3hrs
• Excretion - urine.
20. Pharmacodynamics
Mechanism of action -
H2 blockers blocks H2 receptor (GPCR) present on
parietal cells blocks the action of histamine
released through vagal or gastrin stimmulation.
21. Adverse drug reaction (ADR)
• CNS effects – Headache, dizziness, restlessness,
convulsion, coma sp. in large doses.
• Bolus i.v. dose can release histamine bradycardia ,
arrythmia, cardiac arrest.
• Antiandrogenic action- increases plasma prolactin.
• High dose gynaecomastia in male, loss of libido,
impotence, decrese sperm count.
22. 3) Proton pump inhibitors
• All PPIs are prodrug as their active entity is
sufanelamide cations that formed within
parietal cells.
MOA
• PPIs bind with H+/k+ ATPase enzyme and
block proton pump and shutting off acid
secretion.
• They inhibit gastric mucosal carbonic
anhydrase and reduce bicarbonate secretio
23. Clinical uses
• Duodenal and gastric ulcer.
• GERD
• NSAID induced ulceration.
• Prevention of ulcer recurrence.
• Zollinger –Ellison syndrome.
• H.pylori associated dis.
• Stress induced mucosal bleeding.
(i.v.pantoprazole)
• Prophylaxis of acid aspiration during gen.
anesthesia.
24. Adverse drug reaction
• Diarrhoea, abd. pain, headache rarely.
• Inhibit Vit B12 on prolong use but not show
deficiency(6-8wks).
• Muscle and joint pain-2-5% pt.
• On prolong use atropic gastritis
25. Now answer this question
It is given in the previous slides that the half life
of proton pump inhibitors is 1.5 hours only
and these drugs are generally given once
daily. How this can be justified ?
Answer :
P.P.I - Irreversible inhibitors of H+K+ATPase
(Hit and run drugs)
26. 4) Prostaglandin analogue
• They inhibit acid secretion by inhibiting cAMP
and gastrin release from antral cell.
• Also enhances mucosal blood flow and
stimulates the secretion of mucous and
bicarbonates.
• Dose- Misoprostol 200ug four times a day
used and approved for healing of peptic ulcer
in pt using NSAIDs and person who are chronic
smokers.
27. Adverse effect-
• diarrhoea ,colic pain bcoz it increases water
and electrolyte secretion in intestine.
• GIT- N,V, flatulence.
C/I
• Pregnant lady
28. Now Answer this Question
A patient comes to your clinic at midnight
complaining of heart burn. You want to
relieve his pain immediately. What drug will
you choose?
29. Answer :
Antacids
Explanation :
Antacids neutralise the already
secreted acid in the stomach. All other
drugs act by stopping acid secretion
and so may not relieve symptoms
atleast for 45 min.
30. 2. Drugs which neutralise gastric acid.-Antacids
A. Systemic antacids – sodium bicarbonate
B. Oral antacids - Al.hydroxide, Al.phosphate,
Mg.tricilicate, Mg. hydroxide, ca2+ carbonate.
C. Misc – Alginates, Simethicone.
31. • These are basic substances which neutralize
gastric acid and raise pH of gastric contents.
• They do not decrease acid production; rather
raise the antral pH >4. gastric release
more acid is secreted, specially in pt. with
hyperacidity and duodenal ulcer.
32. Now answer this question
Is it rational to combine aluminium hydroxide and
magnesium hydroxide in antacid preparations ?
33. Answer
Combination provides a relatively fast and
sustained neutralising capacity .
(Magnesium Hydroxide – Rapidly acting
Aluminium Hydroxide - Slowly acting )
Combination preserves normal bowel function.
(Aluminium Hydroxide – constipation
Magnesium hydroxide – diarrhoea )
35. Now answer this question
A pregnant lady (first trimester) comes to
you with peptic ulcer disease. Which drug
will you prescribe for her ?
36. Answer :
Antacids or Sucralfate
Explanation ;
H2 antagonists cross placenta and
are also secreted in breast milk.
Safety of Proton pump inhibitors not
established in pregnancy.
Misoprostol causes abortion .
37. 4. Anti-H pylori drugs
• H.pylori is a gm –ve bacillus, adapted to survival in the
hostile environment of stomach.
• Has high urease activity produces ammonia, which
maintains a neutral microenvironment around bacteria.
• H.pylori infection starts with neutropenic gastritis lasting 7-
10 days
• Used with H2 blockers /PPI
• 2 wk therapy required
39. Triple Therapy
The BEST among all the Triple therapy regimen is
(CAP)
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
42. Therapeutic Strategy for Peptic Ulcer
Disease
• Old Therapeutic Strategy:
– USED TO BE “no acid, no ulcer”.
• Current Therapeutic Strategy:
– Now “no NSAID damage, no Zollinger -Ellison
syndrome, no H. pylori, no ulcer”.
