Management of peptic ulcer Ref books 1.KD Tripathi 2.HL Sharma& KK Sharma 3.Sparsh Gupta 4.S K Shriwastava

1. Management of Peptic Ulcer
Dr Lokendra Sharma
Professor of Pharmacology
SMS Medical College
Jaipur

2. Discovery ?
“for their discovery of the bacterium Helicobacter pylori
and its role in gastritis and peptic ulcer disease”

3. ?

4. ?

5. Etiology ?

6. Imbalance between aggressive & protective
factors in upper gastrointestinal tract
Protective factors
Mucin
NaHCO3
PGE2,PGI2
Somatostatin
Blood flow
Impermeability to
HCL
Aggressive
factors
H.Pylori
NSAID
Hyperacidity
Pepsin activity
gastrin activity
Muscarinic activity
Smoking Alcohal

7. Symptoms ?

8. Difference between duodenal and
gastric ulcer ?

10. Potassium-competitive acid blockers
Potassium-competitive inhibitors are
experimental drugs that reversibly block the
potassium-binding site of the proton pump.
Soraprazan and revaprazan block H+
secretion
much more quickly than classical PPIs (within
a half-hour).
The development of soraprazan, however, was
discontinued in 2000

11. ProglumideACh
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+
+
+

12. Side Effects ?

13. H2 Receptor blockers
Cimitidine Ranitidine Famotidine Nizatid—Roxa-loxa
Absorb% 60 % 50 % 40% 70-100%
Bioavai% 70-80 30-80 ~- 100%
Potency 1 5 6-20 5-8
T 1/2 2 1.5-2 2.4-5 1.5-1.6 =2
Type of
blockage
Competitive+ Competitive
+
Compititive
Noncom
Non Competitive+
H2 antagonist
Placenta
cross
+ + + +
mg 400-800 150 20 150
Duration
of action
6 hr 8 12 8

14. H2 Receptor blockers
Cimitidine Ranitidine Famotidine Nizatidine/Rox/
Loxa
Tubular
Secretion
+ + main route + main >90%
Renal
clearance of
basic drug
No No
PPB 13-25% 15% 20% 30%
Metabolism
25-40% Minimal Minimal <30%
Presyst
Metabolism
Significant Minimal Minimal <7%
Liver d2 dose Dose No -
Androgen ® ++ +/- - -
Nature Cynoquanidine Nonsulfona
mide
Sulfona mide Nonsulfo
Cyt P450 1 0.1 0 0

15. H2 Receptor blockers
Cimitidine Ranitidine Famotidine Nizatidine
Drug
Interaction
Marked Less None
Other effect HR CO HR,IOP&CO
Nizatidine Prokinetic
Loxatidine noncompititive complete block

16. H2 blocker drugs Q
Nonulcerative use of H2 blocker
urticaria,Pre anesthetic medication
Zaltidine new
Nizatidine -prokinetic

17. ? Q
Famotidine is most potent H2 blocker
All H2 blocker except famotidine inhibits the
gastric first pass metabolism of ethanol
Loxatidine is a non–competitive blocker of H2
receptors.
Nizatidine also possess antiAChE activity and can
cause bradycardia and enhanced gastric emptying.
Nizatidine is having negligible first pass
metabolism (~ 100% bioavailability)

18. Endoscopic view of multiple small ulcer in
ZE syndrome at distil duodenum

20. ?

21. ?

22. NSAID induce ulcers

23. Bismuth tongue

24. Paraenteral PPI ?
Pantoprazole also given intravenously

25. Proton Pump Inhibitor
Omeprazole Pantoprazole Lansoprazole Esomepr
azole
Rabeprazole
Nature Benzimidazo
le
Same - S-Isomer
Bioavai 40% 77% 80% 64-89% 52%
Absorb 50% Rapid
T1/2 1 1-1.4 1.3-1.7 1-1.5 3.1
PPB 95% 98% High 97% 96.3%
Dose mg 20 40 30 40/20 20/10
Elimination 80% Renal
20% biliary
80%R Enteric
coated
80%R 90%R
Hepatic dz +No dose
adjust
+ Mild
moder
+No dose
adjust
Renal dz +No dose
adjust
+
Elder +No dose
adjust
+

26. Proton Pump Inhibitor
Omeprazol Pantoprazo Lanso Esome Rabe
Potency 1 1 more 2-10 x
Enzyme 7-8 loop
irrever
5-6 loop of
submit
7-8 loop 5-6 loop cysteine
813/822 partly
rever sible
Onset of
action
30 45 30 5
G Acid
Inhibition
100%
ADR Hypergastri
mia Rash,
headache
levkopenia
= = = less
DI + Less then
omez &
lanso
Less signi less least

28. FAQ : Peptic Ulcer

29. Q: How does Peptic Ulcer arise in
the body?
Peptic ulcer disease arises from:
Imbalance between defensive factors (mucus,
bicarbonate & mucosal blood flow) &
Aggressive factors (acid, pepsin, NSAIDs and
Helicobacter pylori).

30. Q: What three mediators can stimulate acid
secretion from parietal cells?
1. Histamine (H1 receptors)
Acetylcholine (M1 and M3 receptors)
Gastrin (CCK receptors)

31. Q: What are the mechanisms of Vagus
nerve to increase acid secretion ?
Vagus nerve (via ACh) help in increasing acid
by three mechanisms:
Direct stimulation of proton pump
Stimulation of ECL-cells to release histamine
Direct release of gastrin (by action of G-cells)
& inhibition of somatostatin by action on D-
cells (later inhibits release of gastrin)

32. Q: Write The main strategies employed
for the treatment of peptic ulcer disease
and gastritis
1. Neutralize gastric acid by antacids.
2. Decrease secretion of acid in stomach.
3. Increase protective factors like mucus and
bicarbonate.
4. Protect the ulcer by forming a layer over it.
5. Stimulate the healing of ulcer.
6. Kill H. pylori associated with peptic ulcer
disease.

33. Q: Why Proton Pump Inhibitors inhibit
acid secretion for more than 24 Hours
although having short half –life ?
These drugs have short t1/2 but can inhibit
acid secretion for more than 24 hours because
inhibit proton pump irreversibly(hit and run
drugs)

34. Q: Write drug of choice for PPIs
Peptic ulcer disease (PUD) due to any etiology
(even NSAID induced).
Gastroesophageal reflux disease (GERD)
Zollinger Ellison Syndrome (ZES).

35. Q: Name PPIs given by I.V
Pantoprazole
Esomeprazole
Lansoprazole

36. Q: Which PPI is given in patients with
nasoenteric tube?
Immediate release omeprazole (by nasogastric
tube) is currently preferred.

37. Q: Mention side effects of PPIs on
long-term use?
Subnormal vitamin B12 levels (reduced
absorption)
Increase in risk of hip fractures (reduced
Ca2+ absorption)
Increased risk of enteric bacterial infections :
C. difficile infections
Bacterial gastroenteritis
Pneumonia

38. Q: Write name of most potent PPI.
Lanoprazole is most potent PPI

39. Q: Which one is the safest PPI in
pregnancy?
Lansoprazole is safest PPI in pregnancy

40. Q: Which are the microsomal
enzyme inhiibitors?
Omeprazole and Esomeprazole are
microsomal enzyme inhibitors. These
may decrease the metabolism of
diazepam

41. Q: Which PPI is enzyme enhancer?
Lansoprazole enhances the
metabolism of theophylline

42. Q: Mention the name of most
potent H2 blocker.
Famotidine is most potent H2
blacker.

43. Q: Which H2 blocker does not inhibit
the gastric first pass metabolism of
ethanol?
All H2 blockers except Famotidine inhibits the
gastric first pass metabolism of ethanol

44. Q: Name three causes of peptic
ulcer disease (PUD)
1. Helicobacter pylori infection (primary cause)
2. Nonsteroidal anti-inflammatory drugs
(NSAIDs)
3. Extreme physiologic stress (i.e., patients in
the ICU setting being ventilated, burn
patients)

45. Q:What type of patients do
develop acute peptic ulcers ?
Hospitalized patients who are
critically ill (stress ulcers)

46. Q: Name non- competitive
blocker of H2 receptors?
Loxatidine is a non-competitive
blocker of H2 receptors.

47. Q: Which Histamine blocker has anti-AChE
activity and can cause bradycardia and
enhanced gastric emptying?
Nizatidine

48. Q:What is the name of the syndrome that
is characterized by hypersecretion of
gastric acid secondary to a gastrin-
secreting tumor?
Zollinger-Ellison syndrome

49. Q: Which acid suppressing agents
can result in tolerance and
rebound hyperacidity?
PPIs, H2 blockers

50. Q: Most specific drug for treatment and
prevention of NSAID induced peptic
ulcer?
Misoprostol (PGE1 analogue) is the
MOST SPECIFIC drug for treatment and
prevention
of NSAID induced peptic ulcer whereas
drug of choice is proton pump
inhibitor.

51. Q: Why Sucralfate should not be
given with Antacids ?
It should not be given with antacids
because it acts only in acidic medium
(antacids raise the pH by neutralizing
the gastric acid).

52. Q: Write most common side effect
of sucralfate
Constipation.

53. Q: How does Colloidal bismuth
subcitrate act?
It forms an acid resistant coating over
the ulcer.
It also dislodges H. pylori from the
surface of gastric mucosa and kills it

54. Q: Mention adverse effects of
Colloidal bismuth subcitrate.
Adverse effects include blackening of tongue
and bismuth toxicity (osteodystrophy and
encephalopathy).

55. Rebamipide and Ecabet
Q: Name two cytoprotective drugs
act by increasing PG generation
and by scavenging reactive oxygen
species.

56. Q: Mention two salts of Bismuth
and their different uses
Bismuth subcitrate is used for peptic
ulcer
Bismuth subsalicylate used in Traveller’s
diarrhea.

57. Q: Write the name of test which is
used for H. pylori infection
H. pylori infection can be detected by
“urea breath test”

58. Q: Write drugs used for the
treatment of H.pylori infection .
Metronidazole/tinidazole
Amoxicillin
Clarithromycin
Tetracycline
Colloidal bismuth subcitrate
Omeprazole/lansoprazole

59. Q: Which Histamine blocker has
100% bioavailability?
Nizatidine is having negligible
first pass metabolism (~100%
bioavailability)

60. Q:Which are the drug therapy
goals in treating PUD?
Control H. pylori infection; alleviate
symptoms; promote healing; prevent
recurrences; prevent complications
(eg, hemorrhage)

61. Q: What types of medications are
useful for the treatment of PUD?
Antimicrobial agents; H2-receptor
antagonists; PPIs; prostaglandins;
antimuscarinic agents; antacids;
mucosal protective agents; bismuth
salts

62. Q: How might H. pylori play a role
in peptic ulcer development?
Direct mucosal damage;
alterations in inflammatory
response; induced
hypergastrinemia

63. Q: Meals worsen the pain
associated with what type of
ulcer?
Gastric ulcer

64. Duodenal ulcer
Q: Meals relieve the pain associated with
what type of ulcer?

65. Q:What treatment options are
available to eradicate H. pylori?
Triple therapy with a PPI added to two
antimicrobial agents such as metronidazole,
amoxicillin, tetracycline, or clarithromycin;
four-drug regimens consisting of triple therapy
plus bismuth subsalicylate; (must use triple or
quadruple antibiotic therapy to eradicate H.
pylori)

66. Q: What are the possible adverse
effects of antacids?
Belching (sodium bicarbonate and calcium
carbonate); diarrhea (magnesium salts);
constipation (calcium or aluminum salts); acid-base
disturbances;
Bone damage via binding phosphate in the gut
(aluminum salts); worsening of hypertension and
congestive heart failure (CHF) (sodium salts)
 Decreased absorption of medications via pH
alteration or formation of insoluble complexes
(tetracycline, fluoroquinolones, isoniazid [INH],
ferrous sulfate, ketoconazole, PPIs)

67. Q:Which antacid(s) can produce a
metabolic alkalosis?
Sodium bicarbonate; calcium
carbonate

68. Q:What causes the milk-alkali
syndrome?
Ingestion of excessive amounts of calcium and
absorbable alkali such as sodium bicarbonate
or calcium carbonate

69. Q:What is a potential
complication after discontinuing
chronic antacid use?
Acid rebound

70. Q List the names of the H2-
receptor antagonists.
Cimetidine; famotidine; ranitidine;
nizatidine

71. Cimetidine
Q:Which H2-receptor antagonist
inhibits hepatic cytochrome P-450
metabolizing enzymes?

72. Q:Name at least five drugs showing
potential drug interactions with
cimetidine.
1. Warfarin
2. Diazepam
3. Phenytoin
4. Metronidazole
5. Propranolol
6. Lidocaine
7. Calcium channel blockers (CCBs)
8. Theophylline
9. Certain tricyclic antidepressants (TCAs):
chlordiazepoxide

73. Q: Why should you not give
bismuth subsalicylate to children?
May be associated with Reye syndrome

74. Q: What is Reye syndrome?
Acute onset encephalopathy and fatty liver
formation. Symptoms begin with vomiting,
lethargy, and confusion progressing to stupor,
respiratory distress, coma, and seizures. Aspirin
administration is to be avoided in pediatric
patients.

75. Q: How do prostaglandins help to
treat PUD?
Prostaglandins such as PGE2 and PGI2inhibit
gastric acid secretion and stimulate secretion of
bicarbonate and mucus (cytoprotective activity);
used to treat NSAID-induced peptic ulcers

76. Q: Why should misoprostol not be
given to a preterm pregnant
woman?
Induction of premature uterine
contractions (abortifacient
properties)

77. Q: Which H2-receptor antagonist
can cause gynecomastia?
Cimetidine (prolactin-stimulating
activity)

78. Q: What are the common side
effects of PPIs?
Headache; dizziness; nausea; diarrhea;
constipation. Prolonged use can lead to
bacterial overgrowth in the GI tract.
Histamine H2-receptor inhibitors also
increased fracture risk, but not to the extent
as did PPIs.

79. Q: What is the most serious side
effect of cisapride?
Prolongation of the QT interval

80. Q: Cisapride should be avoided in
which type of patients?
Patients with prolonged QT intervals;
patients taking medications that inhibit
cytochrome P-ISO 3A4 (fluconazole,
ketoconazole, itraconazole,
erythromycin,
clarithromycin, ritonavir)

81. Q:Which type of arrhythmia can
be caused by prolongation of the
Q T interval?
Torsades de pointes (a polymorphic ventricular
tachycardia

82. Q: Which drugs increase cisapride blood
levels by inhibiting the cytochrome P-450
3A4 enzymes that metabolize cisapride?
1. Erythromycin
2. Clarithromycin
3. Itraconazole
4. Fluconazole
5. Ketoconazole
6. Indinavir

83. Q: Write Drug of choice for ulcer.
DRUG OF CHOICE
Condition Drug of choice
Peptic ulcer
Gastric ulcer Proton pump inhibitors (PPI)
Duodenal ulcer PPI
Stress ulcer PPI
NSAID-induced ulcer PPI
H. pylori associated Lansoprazole + Amoxycillin +
clarithromycin
Zollinger Ellison syndrome PPI
Gastro Esophageal Refiux Disease PPI