1.
DRUGS USED FOR PEPTIC
ULCERS
Dr. Shujauddin
Department of Pharmacology
JNMC, AMU

2.
PEPTIC ULCER
• DEFINITION
• PATHOPHYSIOLOGY
• CLASSIFICATION OF DRUGS

3.
WHAT IS PEPTIC ULCER?
Peptic ulcer is the
area of
degeneration and
necrosis of
gastrointestinal
mucosa exposed
to acid-peptic
secretions.

4.
CLASSIFICATION
1. Stomach (gastric ulcer)
2. Duodenum (duodenal ulcer)
3. Esophagus (esophageal ulcer)
4. Meckel`s diverticulum

5.
SYMPTOMS AND SIGNS
• Abdominal pain
• Water brash
• Nausea and vomiting
• Loss of appetite and weight loss
• Haematemesis
• Melaena
• Heartburn and gastro esophageal reflux

6.
PATHOPHYSIOLOGY
Mechanism of gastric acid secretion
• H+K+ATPase (proton pump)-secretes H+
ions in the apical canaliculi of parietal cells
• Proton pump is activated by-
- Histamine- H2 receptors
- Ach- M3 receptors
- Gastrin-G receptors

7.
PROTECTIVE BARRIER
• Mucus secreted by mucus secreting cells
• Bicarbonate ions
• Role of prostaglandins
-Reduces acid and pepsin
secretions(PGE2)
-Increases mucus secretion and mucosal
blood flow(PGI2)

8.
CLASSIFICATION OF DRUGS
• REDUCTION OF GASTRIC ACID
SECRETION
• H2-ANTIHISTAMINICS
– Cimetidine, Ranitidine, Famotidine, Roxatidine
• PROTON PUMP INHIBITORS
– Omeprazole, Lansoprazole, Pantaprazole,
Rabeprazole
• ANTICHOLINERGICS
– Pirenzepine, Propantheline, Oxyphenonium
• PROSTAGLANDIN ANALOGUES
– Misoprostol, Enprostil, Rioprostil

9.
• ANTACIDS
• SYSTEMIC
– Sodium bicarbonate, sodium citrate
• NON-SYSTEMIC
– Mg hydroxide, Mg trisilicate, Al hydroxide gel,
magaldrate, Ca carbonate
• ULCER PROTECTIVES
- Sucralfate, colloidal bismuth subcitrate(CBS).
• ULCER HEALING DRUGS
– Carbenoxolone sodium
• ANTI-H.PYLORI DRUGS
– Amoxicillin, clarithromycin, metronidazole,
tinidazole, tetracyclines

10.
H2 ANTAGONISTS
THESE ARE THE FIRST CLASS OF HIGHLY EFFECTIVE
DRUGS FOR ACID – PEPTIC DISEASE
SOME OF THE H2 ANTAGONISTS ARE
 CIMETIDINE
 RANITIDINE
 FAMOTIDINE
 ROXATIDINE
 LOXATIDINE
 NAXITIDINE

11.
VAGUS
ACh

12.
VAGUS
ACh
N M
Ganglion
cells
ACh

13.
VAGUS
ACh
N M
Ganglion
cells
ACh
Histaminocyte
M
G
Gastrin

14.
VAGUS
ACh
N M
Ganglion
cells
ACh
Histaminocyte
M
G
Gastrin
Hist. Hist.

15.
VAGUS
ACh
N M
Ganglion
cells
ACh
Histaminocyte
M
G
Gastrin
Hist. Hist.
H2

16.
VAGUS
ACh
N M
Ganglion
cells
ACh
Histaminocyte
M
G
Gastrin
Hist. Hist.
H2
Ca2+

17.
VAGUS
ACh
N M
Ganglion
cells
ACh
Histaminocyte
M
G
Gastrin
Hist. Hist.
H2
Ca2+
H
K
+
+

18.
VAGUS
ACh
N M
Ganglion
cells
ACh
Histaminocyte
M
G
Gastrin
Hist. Hist.
H2
Ca2+
H
K
+
+ Cl
HCl

19.
VAGUS
ACh
N M
Ganglion
cells
ACh
Histaminocyte
M
G
Gastrin
Hist. Hist.
H2
Ca2+
H
K
+
+
G
Ca2+
HCl
Cl

20.
VAGUS
ACh
N M
Ganglion
cells
ACh
Histaminocyte
M
G
Gastrin
Hist. Hist.
H2
Ca2+
H
K
+
+
G
Ca2+
M
HCl
Cl

21.
VAGUS
ACh
N M
Ganglion
cells
ACh
Histaminocyte
M
G
Gastrin
Hist. Hist.
H2
Ca2+
H
K
+
+
G
Ca2+
M
H2X
HCl
Cl

22.
VAGUS
ACh
N M
Ganglion
cells
ACh
Histaminocyte
M
G
Gastrin
Hist. Hist.
H2
Ca2+
H
K
+
+
G
Ca2+
M
H2X
HCl
Cl

23.
VAGUS
ACh
N M
Ganglion
cells
ACh
Histaminocyte
M
G
Gastrin
Hist. Hist.
H2
Ca2+
H
K
+
+
G
Ca2+
M
H2X

24.
VAGUS
ACh
N M
Ganglion
cells
ACh
Histaminocyte
M
G
Gastrin
Hist. Hist.
H2
Ca2+
H
K
+
+
G
M
H2X

25.
VAGUS
ACh
N M
Ganglion
cells
ACh
Histaminocyte
M
G
Gastrin
Hist. Hist.
H2
H
K
+
+
G
M
H2X

26.
VAGUS
ACh
N M
Ganglion
cells
ACh
Histaminocyte
M
G
Gastrin
Hist. Hist.
H2
G
M
H2X

27.
 CIMETIDINE
H2 ANTAGONISTS EFFECTIVE AT INHIBITING
NOCTURNAL ACID SECRETIONS WHICH
DEPENDS WHOLLY ON HISTAMINE
 MODEST IMPACT ON MEAL STIMULATED ACID
SECRETIONS
 THUS BLOCK > 90% NOCTURNAL ACID AND 60-
80% DAY TIME ACID SECRETIONS

28.
ADVERSE DRUG REACTIONS
 HEADACHE, DIZZINESS, TIREDNESS,
CONFUSION,BOWEL UPSET, ETC
 ANTIANDROGENIC ACTION – INCREASES
PROLACTIN
 HIGH DOSES PRODUCE
GYANAECOMASTIA, LOSS OF LIBIDO ,
IMPOTENCE
 REVERSIBLE ON STOPPING DRUG
 THUS OUTDATED NOWADAYS

29.
USES
 PEPTIC ULCER DISEASE
400mg bd or 800mg ORAL at bedtimes
 STRESS ULCER PROPHYLAXIS :50mg/hr iv
 ZOLLINGER- ELLISON SYNDROME
 GASTRO OESOPHAGEAL REFLUX DISEASE
 PROPHYLAXIS OF ASPIRATION PNEUMONIA
 OTHER USES:ADJUVANT IN URTICARIA
DOSAGE : AVAILABLE AS 200mg ,400mg, 800mg tab

30.
RANITIDINE
 OVER THE COUNTER DRUG,
 PREFFERED DRUG OVER CEMITIDINE.WHY?
 5 TIMES MORE POTENT
 NO ANTIANDROGENIC ACTION
 LESS PERMEABLE INTO BRAIN
 DOES NOT SIGNIFICANTLY AFFECT HEPATIC METABOLISM
 COMBINED WITH BISMUTH SALT TREAT H.PYLORI INFECTION
 SIDE EFFECTS – IRREGULAR HEART BEATS , YELLOWING OF
SKIN AND EYES, DIZZINESS, HEADACHE,ETC

31.
DOSAGE
 GERD- ZANTAC 150mg/10ml SYRUP TWICE DAILY
 ACTIVE DU- ZANTAC 150mg/10ml SYRUP TWICE DAILY OR
300mg ONCE DAILY AT BEDTIME
 ZE SYNDROME-150mg/10ml TWICE DAILY
 PAEDIATRIC – DU AND GU -2-4mg/kg TWICE DAILY MAX
300mg/day
 GERD 5-10mg/kg/day AS TWO DIVIDED DOSES
 WITH IMPAIRED RENAL FUNCTION-
 CREATINE CLEARANCE <50ml/min THEN 150mg/10ml SYRUP
EVERY 24 HRS

32.
OTHERS
 FAMOTIDINE- LONGER DURATION OF ACTION. TRADE
NAME- PEPCID
 5-8 TIMES MORE POTENT THAN RANITIDINE, T1/2 2.5-3.5 HRS
 NO ANTIANDROGENIC EFFECT
 MORE SUITABLE FOR ZE SYNDROME
 PEPCID- 10,20 AND 40mg TABLETS
 ROXATIDINE – TWICE AS POTENT , LONGER ACTING
 NO ANTIANDROGENIC OR CYTOCHROMEP450 INHIBITION
 LOXATIDINE:recent

33.
PROTON PUMP
INHIBITORS
(PPIs)

34.
PROTON PUMP INHIBITORS
• PPIs are the drugs which suppress the
gastric acid secretion by reacting
covalently with H⁺K⁺ATPase enzyme and
thus inactivating them irreversibly .

35.
Examples-
1. Omeprazole
2. Esomeprazole
3. Lansoprazole
4. Pantoprazole
5. Rabeprazole

36.
Mechanism of action of PPIs
(taking omeprazole as a prototype)
From the blood
Parietal cells
At pH<5 it rearranges cationic forms -
sulphenic acid
sulphenamide
React with H⁺K⁺ATPase enzyme and inactivate it
irreversibly

37.
• Acid secretion resumes only when new
H⁺K⁺ATPase molecules are synthesized .
• Bioavailability of all PPIs is reduced by
food , they should be taken in empty
stomach followed by 1 hour later meal to
activate the H⁺K⁺ATPase and make it
more susceptible to the PPI.

38.
USES OF PPIs
1. PEPTIC ULCER
2. BLEEDING PEPTIC ULCER
3. GASTROESOPHAGEAL REFLUX
DISEASE
4. ZOLLINGER ELLISON SYNDROME
5. STRESS ULCERS
6. ASPIRATION PNEUMONIA

39.
ADVERSE EFFECTS
• Nausea , loose stools , abdominal pain,
muscle and joint pain , dizziness .
• Rashes , leucopenia , hepatic dysfunction
.
• Few reports of gynaecomastia and erectile
dysfunction have been reported due to
reduced testosterone levels , on prolonged
use.

40.
INDIVIDUAL PPIs
1. OMEPRAZOLE
• Oral absorption is 50 % .
as the gastric pH rises , higher fractions
may be absorbed .
• Plasma t ½ is 1 hr .

41.
2. ESOMEPRAZOLE-
• higher oral bioavailability .
• longer t ½ .
• Better GERD symptom relief .

42.
3.LANSOPRZOLE –
• More potent ,
• high oral availablity ,
• longer t ½ ,faster onset of action than
omeprazole .

43.
4.PANTOPRAZOLE-
• Newer
• More acid stable
• Available for I.V. administration
• Particularly employed in bleeding peptic
ulcer and prophylaxis of acute stress
ulcers.

44.
5. Rabeprazole
• Fastest acid suppression
• Helps in gastric mucin secretion .

45.
ANTICHOLINERGICS
The anti muscarinic drugs were used mainly to treat
peptic ulcers until the introduction of the H2
receptor blocking agents, but now rarely used.
• PIRENZEPINE – selective M1 anti cholinergic.
• ADVERSE EFFECTS –
– Blurred vision
– Dry mouth
– Urine retention

46.
ANTACIDS
 STOMACH ACID NEUTRALISER
 TREAT DYSPEPSIA OR HEARTBURN
 MECH.-PERFORM NEUTRALISATION REACTION ie BUFFER
GASTRIC ACID RAISING pH >4
 INHIBIT ACTIVITY OF PEPSIN WHICH IS IRRITATING TO
THE STOMACH
 INCREASE L.E.S TONE SO THAT REFLUX
IS REDUCED
 RELIEF OCCURS WITH IN 5-15 min
 DURATION OF RELIEF LAST FOR 1-3 HRS

47.
• SYSTEMIC ANTACIDS
– SODIUM BICARBONATE
• NONSYSTEMIC ANTACIDS
– MAG. HYDROXIDE
– MAG. TRISILICATE
– ALUMINIUM HYDROXIDE
– CALCIUM CARBONATE

48.
ANTACID
COMBINATIONS
 COMBINATIONS OF ANTACIDS FREQUENTLY USED
 SINGLE ANTACID NOT SATISFACTORY
a) FAST (Mg.hydrox.) AND SLOW (Alum.hydrox.) YIELD
PROMPT AND SUSTAINED EFFECT
b) Mag. SALTS (LAXATIVE) AND Alum. SALTS
(CONSTIPATING)- BOWEL MOVEMENT LEAST AFFECTED
d) GASTRIC EMPTYING- Alum. SALTS DELAY IT AND Mag.
OR Cal. SALTS TEND TO HASTEN IT
c) DOSE OF INDIVIDUAL COMPONENT IS
REDUCED.THEREFORE SYSTEMIC TOXICITY IS MINIMISED.

49.
CONTD.
 SOMETIMES COMBINED WITH ANTIFLATULENT
COMP.(DIMETHICONE, SIMETHICONE) OR
ANAESTHESIA
 AVAILABLE COMBINATIONS ARE :
 DIGENE:
Alum.hydrox.300mg.Alum.silicate50mg,Mag.
hydrox.25mg,methyl polysilox 10mg/TAB
 DIGENE GEL:
Mag.hydrox.185mg Alum.hydrox.gel830mg,
Sodium carboxymethyl cellulose100mg
Methylpolysilox.25mg PER 10ml SUSP.

50.
CONTD.
 GELUSIL:Alum.hydrox.gel250
mg, Mag.trisilicate500mg
 GELUSIL GEL:
Mag.trisilicate625mg
Alum.hydrox. Gel 312mg PER
5ml SUSP.
 TRICAINE: Alum.hydrox
gel300mg
Mag.hydrox.150mg
Oxethazine10mg ,
simethicone10mg PER 5ml
SUSP.

51.
H. Pylori
• Gram –ve bacillus
• Has high urease activity, produces
ammonia
• Major factor in pathogenesis of peptic
ulcer
• Almost all duodenal ulcers and 70% of
gastric ulcers show presence of H. pylori
• It also causes chronic
gastritis,dyspepsia, gastric lymphoma
and gastric carcinoma

52.
PREFERRED THERAPIES FOR H.
PYLORI INFECTION
• Twice a day PPI or Ranitidine bismuth citrate
• Triple therapies –
A PPI or 400 mg of ranitidine or bismuth citrate twice
a day
Plus 2 of: Amoxicillin 1g; Clarithromycin 500 mg; or
Metronidazole 500 mg (each twice a day)
• Quadruple therapy –
A PPI twice a day
Tetracycline hydrochloride 500 mg, 4 times/day
Bismuth subcitrate 120 mg, 4 times/day
Metronidazole 500 mg, 3 times/day