This document discusses drugs used to treat peptic ulcers. It describes several classifications of drugs: gastric acid secretion inhibitors like H2 receptor antagonists and proton pump inhibitors; gastric acid neutralizers or antacids; and ulcer protectives like sucralfate. Specific drugs are discussed within each class, including their mechanisms of action, pharmacokinetics, uses, and side effects. The document also covers factors involved in gastric acid secretion and how different drugs work to inhibit this process to treat ulcers.

1. Drugs used in Peptic Ulcer
Madan Sigdel (M. Pharm.)
Lecturer
Department of Pharmacology
Gandaki Medical College

2. Ulcerated lesion in the mucosa of the stomach or duodenum
Types: Gastric & Duodenal

3. Classification
1. Gastric acid secretion inhibitors
(a) H2 antihistamines: Cimetidine, Ranitidine, Famotidine,
Roxatidine
(b) Proton pump inhibitors: Omeprazole, Esomeprazole,
Lansoprazole, Pantoprazole, S (-) Pantoprazole,
Rabeprazole, Dexrabeprazole.
(c) Anticholinergics: Pirenzepine, Propantheline,
Oxyphenonium
(d) Prostaglandin analogues: Misoprostol
2. Gastric acid neutralizers (Antacids)
(a) Systemic: Sodium bicarbonate, Sod. citrate
(b) Nonsystemic: Magnesium hydroxide, Mag. trisilicate,
Aluminium hydroxide gel, Magaldrate, Calcium carbonate

4. Classification – contd.
3. Ulcer protectives
Sucralfate, Colloidal bismuth subcitrate (CBS)
4. Anti-H. pylori drugs
Amoxicillin, Clarithromycin, Metronidazole,
Tinidazole, Tetracycline

5. Formation of HCL

6. ACh
PGE2
Histamine
Gastrin
Adenyl
cyclase
_
+
ATP cAMP
Protein Kinase
(Activated)
Ca++
+
Ca++
Proton pump
KK+
H+
Gastric acid
Parietal cell
Lumen of stomach
Antacid
Omeprazole
Ranitidine
H2M3
Misoprostol
_
_
_
+
PGE
receptor
+
+
Gastrin
receptor+
+
+

8. H2 ANTAGONISTS
 Cimetidine was the first H2 blocker to be introduced
clinically and is described as the prototype, though other Hz
blockers are more commonly used now.
Pharmacological action:
 H2 blockage: Reversible competitive inhibitors of H2
receptor, block histamine-induced gastric secretion.
 Gastric Secretion: All phases of gastric acid secretion is
supressed. Very effective in inhibiting nocturnal acid
secretion (as it depends largely on Histamine ). Modest
impact on meal stimulated acid secretion (as it depends on
gastrin, acetylcholine and histamine) Volume of pepsin
content and IF are also reduced Volume reduced by 60 –
70% - anti ulcerogenic effect. No effect on motility

9. H2 antagonists
 Kinetics:
 All drugs are absorbed orally adequately
 Bioavailability upto 80 %
 Absorption is not interfered by presence of food
 Can cross placental barrier and reaches milk
 Poor CNS penetration
 2/3rd
of the drugs are excreted unchanged in bile and
urine
 Preparations: available as tablets, injections

10. Cimetidine is well tolerated by most patients:
adverse effects occur in < 5%. These are generally mild.
 Headache, dizziness, bowel upset, dry mouth, rashes.
 CNS effects like confusional state, restlessness,
convulsions and coma have occurred infrequently in elderly
patients, in those with renal impairment, especially with
large doses infused i.v.
 Bolus i.v. injection can release histamine-has caused
bradycardia, arrhythmias and cardiac arrest: it should
always be given by slow infusion.
 Cimetidine (but not other Hz blockers) has antiandrogenic
action (displaces dihydrotestosterone from its cytoplasmic
receptor), increases plasma prolactin and inhibits
degradation of estradiol by liver.
 Transient elevation of plasma aminotransferases but
hepatotoxicity is rare.

11. Ranitidine
 About 5 times more potent than cimetidine.
 longer duration of action with greater 24 hr acid suppression is
obtained clinically because of potency.
 No antiandrogenic action & Lesser permeability into the brain.
 Does not significantly inhibit hepatic metabolism of other drugs.
 Overall incidence of side effects is lower: headache, diarrhoea/
constipation, dizziness have an incidence similar to placebo.

12. Famotidine
 It is 5-8 times more potent than ranitidine and
antiandrogenic action is absent. Because of low affinity
for cytochrome P450 and the low dose, drug metabolism
modifying propensity is minimal.
 Incidence of adverse effect is low: only headache,
dizziness, bowel upset rarely disorientation and rash
have been reported.
 Because of the higher potency and longer duration, it
has been considered more suitabic: for ZE syndrome
and for prevention of asp iration pneumonia.

13. Roxatidine
 The pharmacodynamic, pharmcokinetic and
side effect profile of roxatidine is similar to that of
ranitidine, but it is twice as potent and longer acting. It
has no antiandrogenic or cytochrome P450 inhibitory
action.
H2 antagonists - Uses
 Duodenal ulcer – 70 to 90%
 Gastric Ulcer – 50 to 75% (NSAID ulcers))
 Stress ulcer and gastritis
 GERD
 Zollinger-Ellison syndrome
 Prophylaxis of aspiration pneumonia
 Urticaria

14. Proton pump inhibitors
 Proton pump inhibitors act by irreversibly
blocking the hydrogen / potassium adenosine
triphosphatase enzyme system (the H+/K+ ATPase , or,
more common, gastric proton pump ) of the gastric
parietal cell.
 Prototype: Omeprazole
 Examples:
 Lansoprazole
 Pantoprazole
 Rabeprazole
 Esomeprazole

15. Omeprazole - MOA
 Substituted Benzimidazole derivative
 Its a Prodrug
 Diffuses into G. canaliculi = accumulation
pH < 5 (proton catalyzed )= tetracyclic sulfenamide +
sulphenic acid
 Covalent binding with sulfhydryl cysteines of
H K ATPase⁺ ⁺
 Irreversible inactivation of the pump molecule
(The charged forms cannot diffuse back across the
canaliculi)
 Acid suppressants regardless of stimulating factors
 Also inhibits gastric mucosal carbonic anhydrase

16.  Drug Interaction:
 Inhibits metabolism of Warfarin, Diazepam
 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

17.  Adverse effects
 These are minimal: nausea,loose stools, headache,
abdominal pain, muscle and joint pain, dizziness are
complained by 3-5 %. Rashes (1.5% incidence),
leucopenia and hepatic dysfunction are infrequent. On
prolonged treatment atrophic gastritis has been
reported occasionally.

18. Esomeprazole
 esomeprazole It is the S-enantiomer of omeprazole;
claimed to have higher oral bioavailability and to
produce better control of intragastric pH than
omeprazole in GERD patients because of longer t1/2.
Higher healing rates of erosive esophagitis and better
GERD symptom relief have been reported in
comparative trials with omeprazole.
 Side effect and drug interaction profile is similar to the
recemic drug.

19. Lansoprazole
 Somewhat more potent than omeprazole but similar in
properties. Inhibition of H+ K+ ATPase by lansoprazole
is partly reversible. It has higher oral bioavailability,
faster onset of action and slightly longer t1/2 than
omeprazole.
 Dose should be reduced in liver disease. Side effects are
similar, but drug interations appear to be less significant;
diazepam and phenytoin metabolism may be reduced.

20. Pantoprazole
 It is a newer H+ K+ ATPase inhibitor, similar in potency
and clinical efficacy to omeprazole, but is more acid
stable and has higher oral bioavailability. It is also
available for i. v. administration; particularly employed in
bleeding peptic ulcer and for prophylaxis of acute stress
ulcers. It has lower affinity for cytochrome P450 than
omeprazole or lansoprazole: risk of drug interactions is
minimal.
S-pantoprazole
 It is the active single enantiomer, twice as potent as the
recemate.

21. Rabeprazole
 This newer PPI is claimed to cause fastest acid
suppression (due to higher pKa, it is more rapidly
converted to the active species) and to aid gastric mucin
synthesis. However, potency and efficacy are similar to
omeprazole.

22. Anticholinergics
Atropine:
 Block the M1 class receptors
 Reduce acid production
 Abolish gastrointestinal spasm
Pirenzepine and Telenzepine
Mechanism of action:
• Reduce meal stimulated HCl secretion by reversible
blockade of muscarinic (M1) receptors on the cell
bodies of the intramural cholinergic ganglia
(receptors on parietal cells are M3).

23. Prostaglandin analogues
 Inhibit gastric acid secretion
 Exhibit ‘cytoprotective’ activity
 Enhance local production of mucus or bicarbonate
 Promote local cell regeneration
 Help to maintain mucosal blood

24. Prostaglandin analogues -
Misoprostol
 Actions:
 Inhibit histamine-stimulated gastric acid secretion
 Stimulation of mucin and bicarbonate secretion
 Increase mucosal blood flow
(Reinforcing of mucous layer buffered by HCO3 secretion
from epithelial cells)
 Therapeutic uses:
Prevent ion of NSAID-induced mucosal injury (rarely used
because it needs frequent administration – 4 times daily)

25. Misoprostol
 Doses: 200 mcg 4 times a day (Misoprost)
 ADRs:
 Diarrhoea and abdominal cramps
 Uterine bleeding
 Abortion
 Exacerbations of inflammatory bowel disease and
should be avoided in patients with this disorder
Contraindications:
1. Inflammatory bowel disease
2. Pregnancy (may cause abortion)

26. Antacids
 These are basic substances which neutralize gastric acid and
raise pH of gastric contents.
 Also inhibit formation of pepsin (As pepsinogen converted to
pepsin at acidic pH)
 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)

27. Systemic antacids
 Sodium Bicarbonate:
 Potent neutralizing capacity and acts instantly
 ANC: 1 gm = 12 mEq
 DEMERITS:
 Systemic alkalosis
 Distension, discomfort and belching – CO2
 Rebound acidity
 Sodium overload

28. 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
 Magnesium hydroxide (ANC 30 mEq) low water solubility: its
Aqueous suspension (Milk of magnesia) has low conc. Of OH-
ions and thus low alkalinity.
 Magnesium trisilicate (ANC 10 mEq) has low solubility and
reactivity. About 5 % of aadministered Mg is absorbed
systemically- may cause problem if renal function is
inadequate. All Mg salts have laxative action.
 Aluminium Hydroxide (ANC 1-2.5mEq/g) bland, weak and
slowly reacting antacid. The Al 3+ ions relax smooth muscle.
Thus, it delays gastric emptying. Alum. hydrox. frequently,
causesconstipation due to its smooth muscle relaxant
andmucosal astringent action.

29. Magaldrate
 It is a hydrated complex of hydroxymagnesium
aluminate that initially reacts rapidly with acid and
releases alum. hydrox. which then reacts more slowly.
Its ANC is estimated to be 2 mEq HCL/g.
Calcium carbonate
It is a potent and rapidly acting acid neutralizer (1 g 20
mEq HCl), but ANC of commercial preparations is less
and variable due to differing particle size and crystal
structure. it can cause distention and discomfort bacause
of liberation of CO2 in stomach.
 The greatest drawback of CaC03 as an antacid is that
Ca'• ions diffuse into the gastric mucosa-increase HCl
production directly by parietal cells as well as by
releasing gastrin.

30. Antacid combinations
A combination of two or more antacids is frequently used.
These may be superior to any single agent on the
following accounts:
a) Fast (Mag. hydrox.) and slow (Alum. hydrox.) acting
components yield prompt as well as sustained effect.
b) Mag. salts are laxative, while alum. salts are constipating:
combination may annul each other's action and bowel
movement may be least affected.
c) Gastric emptying is least affected; while alum. salts tend to
delay it, mag. / cal. salts tend to hasten it.
d) Dose of individual components is reduced; systemic
toxicity (dependent on fractional absorption) is minimized.

31. Drug interactions
 By raising gastric pH and by forming complexes, the non-
absorbable antacids decrease the absorption of many drugs,
especially tetracyclines, iron salts, fluoroquinolones, ketoconazole,
H2 blockers, diazepam, phenothiazines, indomethacin, phenytoin,
isoniazid, ethambutol and nitrofurantoin.
Uses
 Antacids are no longer used for healing peptic ulcer because they
are needed in large and frequent doses, are inconvenient, can
cause acid rebound and bowel upset
 Antacids are now employed only for intercurrent pain relief and
acidity, mostly self-prescribed by the patients as over the counter
preparations.
 They continue to be used for non ulcer dyspepsia and minor
episodes of heartburn.
 Gastroesophageal reflux Antacids afford faster symptom relief than
drugs which inhibit acid secretion, but do not provide sustained
benefit.

32. Ulcer protective
Sucralfate
 Salt of sucrose complexed to sulfated aluminium
hydroxide (basic aluminium salt)
 MOA:
 In acidic pH polymerises to viscous gel that adheres to
ulcer crater - more on duodenal ulcer
 Precipitates protein on surface proteins and acts as
physical barrier
 Dietary proteins get deposited on this layer forming
another coat
 Delays gastric emptying and causes gastric PG
synthesis – protective action

33. Sucralfate – contd.
 Taken on empty stomach 1 hr. before meals
 Concurrent antacids, H2 antagonist avoided (as
it needs acid for activation)
 Uses:
 NSAID induced ulcers
 Patients with continued smoking
 ICU
 Topically – burn, bedsore ulcers, excoriated skins
 Dose: 1 gm 1 Hr before meals
 ADRs: Constipation, hypophosphatemia

34. Collidal Bismuth Subcitrate
It is a colloidal bismuth compound; water soluble but
precipitates at pH < 5.Heals 60% ulcers at 4 weeks and 80--
90% at 8 weeks.
The mechanism o f action o f CBS is not clear; probabilities are
 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
Milk and antacid, , not be taken concomitantly.
 Side effects reported are diarrhoea, headache and
dizziness . Prolonged use has the potential to cause
osteodystrophy and encephalopathy due to bismuth toxicity.

35. 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
A number of 2-drug and 3-drug regimens of 1 or2 weeks
duration have been tested reporting 60-96% eradication rates,
but the optimum regimen is difficult to proclaim. Some of the 2
week regimens are:

36. ANTI-HELICOBACTER PYLORI DRUGS

37. 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