Acid Related Disorders of GIT

2. Introduction
MUP introduces the most
efficient treatment for Acid
Related Disorders
Proton Pump Inhibitor
PANTOLOC
pantoprazole

3. PANTOPRAZOLE
Prof. Dr. Aly Taha

4. PANTOPRAZOLE
PROTON PUMP INHIBITOR PPI
O-CH F2
O C H3 N
H3CO
S N
+
N O Na

5. Main Indications
Acid Related Disorders of
GIT

6. GIT Acid Related Disorders
Dyspepsia
GERD*
Erosive Esophagitis
Barrett’s Esophagus
Gastritis
PUD
Gastric Ulcer
Duodenal Ulcer
* GERD: Gastro-Esophageal Reflux Disease

7. Medical Background
Quick Review

8. General
Anatomy of
the Stomach

9. Detailed Anatomy of the Stomach
Located on the left side of the body, under the diaphragm, the
stomach is a muscular, saclike organ that connects the
esophagus and small intestine through the duodenum. Its main
function is to break down food. Cells in the stomach lining
secrete enzymes, hydrochloric acid, and other chemicals to
continue the digestive process begun in the mouth and produce
mucus to keep these substances from digesting the lining itself.

10. ACID Related Disorders of GIT
Responding to PPI
Treatment
Note : Acid Related Disorders will be abbreviated (ARD)

11. GIT Acid Related Disorders
GERD
Dyspepsia
Gastritis
Gastric Ulcer
Duodenal
Ulcer

12. * Gastro Esophageal
Gastric
Duodenal Reflux Disease
Ulcer Ulcer
Dyspepsia
Peptic
GERD*
Ulcer
ACID
RELATED
DISORDERS
Adeno- Erosive
Carcinoma Esophagitis
Barrett’s
Esophagus

13. Spectrum of Overlapping GIT Symptoms
Ulcer-Like Dysmotility-Like
Epigastric Pain : Early satiety
Nocturnal Postprandial
bloating
Fasting
Nausea /
Relieved by Vomiting
food/antacids
Pain Unrelieved
Bleeding by food or antacids
Nocturnal: Occurring by night
Satiety: a state in which
somebody has had enough or
GERD-Like too much.
Postprandial : after a meal,
Heartburn especially an evening meal
Regurgitation : bring
Bloating : Swollen or Inflated
undigested or partially Regurgitation
digested food up from
stomach to esophagus Chest pain

14. Diseased Conditions & Quality Of Life (QOL)
Psychiatric Patients
Untreated GERD
Population
Untreated Duodenal Ulcer
Angina Pectoris
Mild Heart Failure
Normal Female
Normal Male
60 70 80 90 100 110
Deminas, Scand J Gastroentrol; 1993 Psychological Well Being Index (PGWBI)

15. Acid Related GIT Diseases & QOL
Mean PGWB score
Normal Population
Best 132
100
90
80
70
Worst 22
Esophagitis Gastric Duodenal Negative Gastritis/
ulcer ulcer endoscopy duodenitis
PGWB = Psychological Well Being

16. Dyspepsia

17. Dyspepsia
Dyspepsia is a condition of impaired or
painful digestion resulting from failure of
some phase of the normal digestive
process.
It is a common disorder (up to 25% of
Population) with negative impact on
patient quality of life (QOL)
It can be defined as “persistent or
recurrent abdominal pain or abdominal
discomfort centered in the upper
abdomen”.

18. Possible Causes Of Dyspepsia
The Cause May Be Physical Or Emotional Upset
Among The Physical Causes Are:
Gastritis.
Chronic Peptic Ulceration.
GERD.
Gallbladder Inflammation.
Gastric Cancer.
Drugs.
Symptoms Of Possible Causes Often Overlap,
Which Can Make Initial Diagnosis Difficult.

19. Symptoms Of Dyspepsia
Symptoms May Include
A Heavy Feeling in the Pit of
the Stomach.
Gas and Belching.
Constipation.
Diarrhea.
Nausea.
Heartburn.
Headache or dizziness may
accompany the discomfort.

20. Patients With Dyspepsia May Have
Underlying Organic Lesions
Reflux esophagitis
Normal
23.9%
33.6%
2% Cancer
19.9%
20.8%
Gastritis/duodenitis Peptic ulcer disease

21. Gastritis

22. Gastritis
Acute :
Caused by NSAIDs or Alcohol.
May be associated with mucosal
ulceration.
Chronic :
Often associated with H. pylori
colonization of mucosa.

23. Gastritis
Gastritis is Acute or Chronic inflammation of
the mucosal lining of the stomach
In gastritis the inflammation may be marked
by the erosion of surface cells of the
mucosa, formation of granular nodules,
and hemorrhage.
In chronic gastritis, there is a growth of
fibrous tissue on the lining. Weight loss
and delayed emptying of the contents of
the stomach may accompany the disease.
Gastritis may develop into Gastric Ulcer
specially when H. pylori colonization is present
Psychological stress may also be involved in
the development of gastritis.

24. GERD

25. GERD
Gastro-Esophageal Reflux Disease Is A Common
Condition That Results From The Reflux Of Gastric
Material Through The Lower Esophageal Sphincter
(LES) Into The Esophagus Or Oropharynx, Causing
Symptoms And/Or Injury To Esophageal Tissue.
The Term Encompasses Both Symptoms And
Patho-physiologic Changes To The Esophageal
Mucosa, Which Occur As A Result Of Exposure Of The
Distal Esophagus To Acidic Gastric Contents After
Episodes Of Gastro-esophageal Reflux.
GERD Is Typically Chronic, Generally Non-
progressive, But Some Cases Are Associated With
Complications Of Increasing Severity And
Significance.

26. Clinical Overview of GERD
GERD Is A Dysmotility Problem With A
Broad Clinical Spectrum.
Has High Prevalence Rate.
Greatly Affects Quality of Life (QOL).
Acid Related Complicated Esophageal
Manifestations Are The Real Danger Of
The Disease.
Extra Esophageal Problems Are
Equally Dangerous.

27. GERD
Pathogenesis
Pathophysiology
Clinical Manifestation

28. Esophageal
Non-
Pathologic
Reflux

29. Esophagus
Stomach
Gastric Folds
Lower Esophageal
Sphincter (LES)
Junction of Gastric &
Esophageal Mucosa
Pyloric Sphincter
First Part of Duodenum

30. GERD: A Multi-Factorial Etiology
Acidity
Motility Factors
Factors
Increased
Esophageal
Acid Exposure
Motility Impaired
Dysfunctions Acid Clearance

31. GERD
Main
Etiological
Processes

32. Detailed Etiologic Factors Involved in
GERD
Impaired Esophageal
Impaired Salivary
Acid Clearance
Function
Hiatal Hernia Impaired
Esophageal
Transient, Inappropriate Mucosal
Relaxation of LES Defense
Gastric Acid; Pepsin Secretion:
Normal / Raised
Reduced Resting
Pyloric Tone of LES
Incompetence;
duodenogastric
reflux Delayed Gastric
Emptying
Acidity Related Motility Related

33. Endoscopic
Diagnosis of
GERDs

34. Proportion of Subjects with Esophageal
Motility Abnormalities
50 48
Patients (%)
40
30 26
21
20
9
10
0
Normal Normal Mild Severe
Volunteers Esophagus/ Esophagitis Esophagitis
GERD
Source : Kahrilas, PJ et al : Gastroenterology, 1986; 91:897-904

35. Gastro Esophageal Reflux Mechanisms in Normal &
GERD
1%
100% 5%
Spontaneous
18% Reflux
80% Transient
17%
Increase in
94% Intra-
60%
Abdominal
Pressure
40% 65% Transient
Lower
20% Esophageal
Sphincter
Relaxations
0%
NORMAL Volunteers GERD Patients
Source : Kahrilas, PJ : Cleveland Clin. J Med.,; 70 (Suppl.5) :S4-S17 (Nov.2003)

36. Significance of Acid Reflux in GERD
Prolonged Dwell Time of Acid and
Pepsin in Esophagus.
Normal Gastric And Pepsin Output
in Most Patients.
Daytime Food-stimulated Acid
Reflux May Be an Additive
Factor in Some Patients.
Nocturnal Reflux May Be a Factor
in Severe Esophagitis, Stricture
or Barrett’s Metaplasia.

37. Esophageal pH Monitoring Among Controls &
Patients with Various Grades of GERD
25
Total Time pH <4.0 (%)
21
20 18
15
15
10
7
5 3
0
Controls No Esophagitis Esophagitis Uncomplicated Complicated
Barrett’s Barrett’s
Source : Vaezi,MF et al : Gastroenterology, 1996; 111:1192-1199

38. The Clinical Spectrum of GERD
Physiological Symptomatic Complicated
Esophagitis
Reflux GERD Esophagitis
Typical Atypical Complications
Heartburn Chest pain Ulceration
Regurgitation Dysphagia Erosion
Cough Hemorrhage
Asthma Stricture
Laryngitis Barrett’s Eso.
Adenocarcinoma
Source : Peura DA, et al : Aliment Pharmacol Ther.; 19 Suppl 1: 77-80 (Feb 2004)

39. Atypical and Extra-Esophageal
Manifestations of GERD
Atypical Extra Esophageal
Chest Pain Oral Pulmonary
Epigastric Pain Dental Erosion Chronic Cough
Nausea Asthma
Aspiration
Pulmonary Fibrosis
Pharyngo-laryngeal Recurrent
Pneumonia
Hoarseness
Posterior Laryngitis
Globus Sensation
Sore Throat Other
Vocal Cord Irritation Sleep
Abnormalities
Vocal cord Polyps
Sleep Apnea (?)
Posterior Laryngitis
Angina
Malagelada JR : Aliment Pharmacol Ther 19 Suppl. 1: 43-48. (Feb 2004)

40. Barrett’s Esophagus
Effect of Age Erosive Esophagitis
Heartburn Alone
Patients with GERD (%)
100 6 9 17 17
36 32
80 33
42 28 34
60
39
40 56
61 55
49 49
20
25
13
0
<30 30-39 40-49 50-59 60-69 >70
Age (y)
Proportions of GERD Patients with Heartburn, Erosive
Esophagitis, and Barrett’s Esophagus According to Age Group.
Jankowski J, Sharma P.: Aliment Pharmacol Ther 19 Suppl. 1: 54-9. (Feb 2004)

41. Summary of Symptoms &
Manifestations of GERD
Symptoms Manifestations
Heartburn Esophageal Ulcer
Regurgitation Erosive Esophagitis
Dysphagia Peptic Stricture
Belching Barrett’s Esophagus
Odynophagia Esophageal
Adenocarcinoma
Manifestations of (GERD) are caused directly by contact
between refluxed acidic gastric juice and the esophageal mucosa.
Esophageal erosion & ulcerations result when epithelial cells
succumb to the caustic effects of refluxed acid and pepsin.

42. Percent Prevalence of All GERD Symptoms
HEARTBURN
83%
Regurgitation
70%
4%
Typical 7% odynophagia
Symptoms 8%
10%
Belching
37%
30% 10%
Nausea
Chest Pain
Dysphagia Abdominal Pain
Respiratory
Symptoms
Castell, DO et al : Practical Gastroenterology , Feb 1999: 20-44

43. Hidden Complications of GERD
Chronic, recurrent
heartburn, dysphagia,
hoarseness, etc.
Erosive Esophagitis Reports of frequent episodes
of heartburn, but no other
symptoms
Barrett’s Esophagus
Mild intermittent
heartburn, not seen by
a physician
GERD ICEBERG
Esoph.Adeno-
Carcinoma

44. The Pyramid of Diseases
Associated with GERD
Extra Esophagial
0%
Misc.
Asthma
ENT
Chest Pain
}
Non-Erosive Reflux Dis.
Erosive Esophagitis
100%

45. Peptic Ulcer Diseases (PUD)
PUD

46. What Is A PUD
PUD is a Term Used to Refer to :
Ulcer of Esophagus.
Ulcer of Stomach.
Ulcer of Duodenum.
Definition
It is an Erosion of the Mucosa
True Ulcer Affects Deeper Lesions
Extends Down into Sub-Mucosal Layers
of the Gut Wall.

47. Gastric Mucosa
G Cell : A Gastrine-secreting cell
ECL Cell : (Entero-Chromaffin-Like Cell)
A Histamine-secreting endocrine cell

49. Peptic Ulcer
Esophageal Ulcer Gastric Ulcer Duodenal Ulcer
Esophageal Ulcer
Gastric Ulcer
Duodenal Ulcer

50. ULCER
movie

51. Peptic Ulcer Diseases
Pathogenesis
Increased ACID secretions and digestive
enzymes erode gastric mucosa
Helicobacter pylori plays a role
Complications
Hemorrhage, perforation
peritonitis, scarring

52. Peptic Ulcer Complications
Peptic Ulcers
may lead to
BLEEDING or
PERFORATION
emergency
situations

53. PUD Risk Factors
Social Factors Patho-Physiological Factors
Life Style NSAID Mucosal Damage
Smoking Hypo-Volemia
Alcohol Hyper-secretion of Corticoids
Stress Adrenaline hyper-secretion
hypovolemia - a blood disorder consisting of a decrease in the volume of circulating blood
Aggressive Factors
Hyper Acid Production
Hyper Pepsin Secretion
Helicobacter pylori Colonization

54. PUD Risk Factor H. pylori
H. Pylori Microscopic
H. Pylori Electron Microscopic

55. Epidemiology of H. pylori
World Wide Prevalence

57. Association of Ulcers with H. pylori
Duodenal Ulcer Gastric Ulcer
Pylori-Free
Pylori Positive 25.0%
Pylori Positive Pylori-Free
96.0% 4.0% 75.0%

58. PUD Prevalence
Who May Develop an Ulcer ?
Ulcer can develop at any age, but it is
rare among teenagers and uncommon with
children.
Gastric Ulcers are more likely to develop
in people between 40-60.
Duodenal Ulcers have an earlier peak
incidence between ages of 25-50.
Gastric Ulcers develop more in Women.
Duodenal Ulcers occur more frequently in
Men.

59. What Are The Symptoms Of Peptic Ulcers ?
The Most Common Symptom Is Gnawing Or Burning Pain In
The Abdomen Between The Breast Bone And The Naval Bone.
Stomach Ulcer
Pain Often Occurs After Meals.
It May Last From Few Minutes to Few Hours.
May be Relieved by Taking Antacids.
Duodenal Ulcer
Pain Occurs Between Meals (Hunger Pain).
It Occurs Also by Night and in the Early Morning.
Pain is Relieved by Eating or by Taking Antisecretory.
Stress Ulcer
Is Silent , Asymptomatic Ulcer, But is Life Threatening

60. What Are The Complications Of
Peptic Ulcers ? (1)
Bleeding Due to Deep Ulcer or Erosions.
Minor Bleeding Occurs Rarely, But May
Be Sufficient to Cause Anemia Over a
Period of Time.
Hemorrhage Occurs in The Sub-mucosal
Layer Where a Large Vessel is Eroded.
15-20% of Patients with Peptic Ulcer
Experience an Episode of Hemorrhage.
The Blood May Appear In The Vomits or in
the Stools and Some Patients May be
Shocked.

61. What Are The Complications Of Peptic Ulcers ? (2)
Perforation of the gut wall may occur in 5% of
patients either with peptic ulcer or stress ulcer.
Bacterial infection may occur & is accompanied
by hemorrhage in about 10% of cases.
Acute perforation may lead to 5% mortality rate
mainly in the elderly.
Pyloric stenosis (Gastric outlet obstruction) which
results from fibrous changes, oedema or spasm (or a
combination of all of them).
It may be produced by an ulcer in the region of
pylorus & the obstruct stomach may lead to nausea
and vomiting.
Early symptoms are often sensation of excessive
and long-lasting ”fullness” after a small meal and
continuous vomiting, therefore, it may cause
dehydration.

62. How Can Peptic Ulcers Be Diagnosed ?
Endoscopy
Barium Meal X-Ray
Acid Secretion Test.
H. Pylori Tests.

63. Endoscopy
Large Chronic
Duodenal Ulcer
Gastric Ulcer which
Eroded a Blood Vessel in
Base of Ulcer

64. Therapeutic Approach to PUD : A
Staged Approach
Stage I
Stage II
Stage
Lifestyle
Modification Intensive III
Surgery
+ Therapy :
Endoscopy
Antacids PPI
and/or H2RA
H2RAs PPI

65. Profile & Assessment of ARD
Pharmacotherapy
PANTOLOC MUP RANITOL MUP

66. Medical Therapies for ARD
AGENTS Examples
Mucosal Sucralfate, Sodium
Protectors Alginate
Acid Neutralizers
(Antacids)
Magaldrate, Carbonates
Acid Suppressive Histamine H2 Antagonists,
Agents Proton Pump Inhibitors

67. Medical Therapies for ARD
AGENTS TARGET
Mucosal
Damaged Mucosa
Protectors
Acid Neutralizers Local Raising of
(Antacids) Refluxate pH
Inhibition of Acid
Acid Suppressive
Agents Production in
Parietal Cells

68. Mechanism for Acid Production
Parietal Cell HCl
Proton Pump
(H+ K+ ATPase)
Cl-
K+ H+
Acetylcholine Gastrin
Histamine 2

69. Mechanism for
Acid Inhibition
PPI

70. PPIs : 2004
Omeprazole (OME)
Lansoprazole (LAN)
Pantoprazole (PAN)
Rabeprazole (RAB)
Esomeprazole (ESO)

71. OME
LAN
RAB
PAN
ESO
Source : Maton PN : Cleveland Clinic J Med : 70 (Suppl.5) 851-870 (Jan 2004)

72. PPIs : Chemistry

73. PPIs : Pharmacology
Are substituted benzimidazoles ProDrugs.
They are concentrated & activated in the
parietal cell canalicular lumen by
conversion to sulfenamides in the
presence of acid.
Bind irreversibly to cysteine residues and
inactivate H+, K+ ATPase (proton pump).
Inhibit only active pumps.
A new pump is regenerated in about 24 h
New steady state for acid secretion
occurs in about 3 days.

74. ACTIVATION OF SUBSTITUTED
BENZIMIDAZOLES
Pantoprazole Sulfenic Acid Sulfenamide Inactivated
Enzyme

75. PPIs : Pharmacology (cont.)
Half-life for various PPI’s
reported at 0.5-2.0 hours.
Duration of action is related to
time for regeneration of new pumps
and activation of resting pumps &
not to half-life.
Efficacy allows 24-h acid
suppression with once-daily dosing.

76. Use of PPI’s in GERD
Relieve Symptoms
Heal Esophagitis
Prevent Recurrence
Treat Complications
Chest Pain
Benign Esophageal Stricture
Respiratory Symptoms
Oropharyngeal Symptoms
Barrtett’s Esophagus
Heal Esophagus
Prevent Progression to dysphagia or
adenocarcinoma

77. Clinical Efficiency of PPI’s in GERD
Eliminate Symptoms 90%
Heal Esophageal Lesions 90%
Manage of Prevent Complications 80%
Maintain Remission in Erosive
80%
Esophagitis
Spechler SJ : Am J Med Sci 326:297-84, (Nov 2003)

78. Relation Between Duration of Suppression of Intragastric
Acidity and Esophageal Acid Exposure
Duration Intraesophageal pH<4.0
16 The longer the period of time
14 that the intragastric pH is above
4, the lower the percentage of
(% of Total Time)
12 time that there is contact
between gastric acid and
10 esophageal mucosa
8
6
4
2
0
1 3 5 7 9 11 13 15 17 19 21
Duration Intragastric pH>4.0
Source : Bell et al: Digestion; : 51 (Suppl.) :59 (1992)

79. Healing Rates of Esophagitis During pH Control
% Patients Healed
100
80
60
40 r = 0.87
20
0
2 4 6 8 10 12 14 16 18 20 22
Duration Intragastric pH > 4.0 (hr/24 hr)
Bell, NJV et al Digestion , 51 (Suppl.1) :59-67 (1992)

80. PPI’s versus H2RA’s in Erosive Esophagitis
100
PPI’s
Patients Healed (%)
80
H2RA’s
60
40
Placebo
20
0
Week 0 Week 2 Week 4 Week 6 Week 8 Week 10
Chiba, N. et al Gastroenterology, 112:1798-1810 (1997)

81. PPIs : Are They All The
Same ?
Pharmacologically No
Clinically 80% Yes 20%
No

82. _ +

83. PPIs : Pharmacokinetics
Parameter Bio - Protein Half-
Time to
Avail -
PPI Peak, h Binding Life, h
ability %
Omeprazole 30-40 0.5-3.5 95 0.5-1.0
Esomeprazole N/A 1.6 97 1.2-1.5
Pantoprazole 77 1.1-3.1 98 1.0-1.9
Lansoprazole 80 1.7 97 1.6
Rabeprazole 52 2-5 95-97 0.85-2.0
Source : Vanderhoff BT & Tahbour R: Am Fam Physician ; 66: 273-280 (2002)

84. PPIs : Pharmacodynamics
Parameter Activation Time, min. % Inhibition of
pKa ATPase
PPI At pH 1.2 At pH 5.1 At 10 min. At 45 min.
Omeprazole 4.13 2.8 84 47 83
Esomeprazole 4.13 N/A N/A N/A N/A
Pantoprazole 3.96 4.6 282 83 100
Lansoprazole 4.01 2.0 90 66 100
Rabeprazole 5.0 1.3 7.2 99 100
pKa Influences : Accumulation in Parietal Cells, Acid Stability & Activation Rates
Source : Johnson, S: Alim Pharmacol Ther; 14: 1249-1258 (2000)

85. PPIs : Drug-Drug Interactions
PPI OME ESO PAN LAN RAB
Drug
Cyclosporine
Diazepam
Digoxin
Ketoconazole
Phenytoin
Theophylline
Warfarin
Clinically Significant Clinically Insignificant
Reported but not well documented
Source : Welage L et al : J Am Pharm Assoc; 40: 52-63 (2000)

86. Specific Binding Sites of
PANTOPRAZOLE to Cysteine
Residues 813 & 822

87. Activation After 1 hour (%)
100
50
1
Parietal Cell
3
Lysosome
5
Acid Activation of PPI’s
7
Cytosol
pH

88. Pantoprazole I.V. Injection
PANTOPRAZOLE is more stable
than OMEPRAZOLE or LANSOPRAZOLE,
and particularly much more stable than
RABEPRAZOLE, under neutral
conditions or conditions that are mildly
acidic (pH ~3.5 to pH ~7.4)
PANTOPRAZOLE, therefore, is the
most suitable PPI to produce in
intravenous form.
Source : Maton PN : Cleveland Clinic J Med : 70 (Suppl.5) 851-870 (Jan 2004)

89. Healing of Erosive GERD : 8 Weeks
Treatment with PPI’s
100 90 91 92 91
90 20 mg
80 30 mg
Healing Rate %
70 40 mg
60
20 mg
50
40
30
20
10
0
OME LAN PAN RAB
Source : Caro, JJ et al: Clin Ther; 23: 998-1017 (2001)

90. Lansoprazole
Pantoprazole
Rabeprazole
Esomeprazole
0.5 0.7 1.0 1.5 2.0
Favors Relative Risk Favors
Omeprazole Other PPI
Relative Risk of Endoscopic Healing at 8 Weeks for All
Standard-Dose PPI’s Compated with Omeprazole 20 mg
Source : Maton PN : Cleveland Clinic J Med : 70 (Suppl.5) 851-870 (Jan 2004)

91. Metabolic Pathways of PPIs
5-O-desmethyl 3-hydroxy 2C19 Esomeprazole
3A4
(major)
2C19 3A4 (remaining)
Omeprazole
2C19 3A4 Hydroxy and Sulfone
desmethyl
Sulfone
5-hydroxy Lansoprazole
2C19 3A4
Not Hydroxy Sulfone
Rabeprazole Cytochrome
2C19 mediated
3A4 Pantoprazole
2C19 3A4
Demethylated Thioether
Sulfone
Sulfone
Demethylated

92. Metabolism of PPIs
Metabolized by CYP2C19 & CYP3A
CYP2C19 Exhibits Genetic
Polymorphism
Rabeprazole least affected by polymorphism
as its major metabolic pathway is non-
enzymatic (not Cytochrome Mediated)
Genetic polymorphism is due to deficiency
of CYP2C19 in some populations :
3% Caucasians & Africans; 12-15% Asians.
Stereo-Selective Metabolism

94. Alteration in Metabolism & Clearance With
Repeated Dosing of Esomeprazole
FIRST DOSE REPEATED DOSING
Esomeprazole Esomeprazole
CYP2C19 CYP3A CYP3A
Esomeprazole Esomeprazole
Hydroxy & Sulphone Sulphone
Desmethyl
• The Inhibition of CYP2C19 by the sulphone
metabolite of esomeprazole lasts > 24 h
• This causes progressive inhibition of
clearance of succeding daily doses of
esomeprazole

95. Clinical Limitations of PPIs
NAB & Nocturnal
Heartburn
Achlorohydria & Bacterial
Colonization
Cost

96. 24-Hours Intragastric pH Profile
Placebo Omeprazole Pantoprazole
pH
INTRAGASTRIC ACIDITY (mmol/L)
M Nocturnal Acid 0
M M
Breakthrough
1
80
2
60
3
40
4
20
5
0 6
0800 1200 1600 2000 2400 0400 0800
Time of Day
M Meal
Source : Castell DO: Medscape ; Prog.118: 1-60 (Jan 2004)

97. Elimination of NAB in GERD
Patients with NAB Eliminated (%)
45 41%
40
35
30
25 18% 18%
20
15 9%
10
5
0
PPI bid PPI am PPI +H2RA PPI /8h
Source : Ours TM et al: Am J Gastroenterol ; 98: 545-550 (2003)

98. PANTOLOC
Features and Benefits

99. PANTOLOC Features and Benefits
Efficacy Allows 24-h Acid Suppression With
Once-Daily Dosing
Patient Convenience Ensures Compliance
Assured Cure of Ulcers

100. PANTOLOC Features and Benefits
Efficacy in Controlled Clinical Trials ~90% :
Eliminates Symptoms
Heals Lesions
Manages or Prevents Complications
Maintains Remission
Ensures Achievement of Therapeutic Results
Rapid & Enhanced Cure of Ulcers

101. PANTOLOC Features and Benefits
Dose Linearity in the Range 10-80 mg
Consistency of Repeated Doses
Continuous, Un-Interrupted Daily
Relief of Symptoms
Omeprazole & Esomeprazole exhibit NONLINEAR Dose Response

102. PANTOLOC Features and Benefits
Absolute Bioavailability 77%
High Blood Level Concentration
Maximum Activity Achieved
Omeprazole (30-40%) ; Rabeprazole (52%)

103. PANTOLOC Features and Benefits
pKa 3.96
Rapid Activity Only at pH 1.2
of the Parietal Cell
Selectivity of Action to Proton Pump Only
No Side-Effects at Liposome or Cytosol Sites

104. PANTOLOC Features and Benefits
pKa 3.96
Stable at Blood pH
The ONLY PPI with I.V. Injection
Form

105. PANTOLOC Features and Benefits
Lack of Any Clinically Significant
Drug-Drug Interactions
No Effect on Other Drugs’ Metabolism
Due to Low Interaction with CYP1A
Safe Co-Administration of Other Drugs
Except Ketoconazole, Contrasted with :
Omeprazole and Rabprazole (Many D-D Interactions)
Lansoprazole and Esomeprazole (more D-D Interactions)

106. PANTOLOC Features and Benefits
Specific Binding Sites of Pantoprazole to
Cysteine Residues 813 & 822 of ATPase
Specific Block of Proton Channel
Maximum Efficiency of Proton
Pump Inhibition

107. PANTOLOC Features and Benefits
Has Least Effect On The ECL Cells Than
Other PPI
Does Not Cause Gastric Atrophy or
Metaplasia
Safe on Prolonged Administration

108. PANTOLOC Features and Benefits
Feature Physician Benefit Patient Benefit
PANTOLOC Doctor, this means that you: Your patients...
is dosed can expect will find
once daily in greater patient PANTOLOC easy
all dosage compliance. to take.
forms
Will find Won’t have to
PANTOLOC easy to take their
prescribe. medication to
work.
Cost-effective
therapy.

109. PANTOLOC Features and Benefits
Feature Physician Benefit Patient Benefit
PANTOLOC Doctor, this means that you: Your patients...
Tablets are Can Tailor will Obtain
Available in 20 Dosage to the the Greatest
mg and 40 mg Needs of Your Relief with the
Strengths Patients. least Amount of
Drug.
As 7 Tabs. Have the Ability
or 14 Tabs. to Titrate Up & benefit from
Down for ON-DEMAND
Maximum Therapy
Therapeutic
Accuracy.

110. PANTOLOC Features and Benefits
Available in Various Package Forms
20 mg (7 or 14 TAB), 40 mg (7 or 14 TAB)
Convenient for both Doctors and
Patients

111. PANTOLOC Features and Benefits
Elderly Patients
Patients With Renal Impairment
Patients With Hepatic Dysfunction

112. PANTOLOC Features and Benefits
60
Pantoprazole
92 40mg
83 88
Healing rates (%)
40
Omeprazole
20mg
20
Lansoprazole
0 30mg
8 weeks
Pilotto et al; 1999

113. 2
(heartburn & acid eructation)
Score improvement
1.5 *
1
0.5
(n=120) 0 1 2 3 4 5 6 7 8
* p=0.012
days (median)
Pantoprazole 40mg Omeprazole 20mg
Scholten et al; 2000

114. PANTOLOC Features and Benefits
100 100
97
91
80 85
Symptom relief (%)
80
Pantoprazole
67 40mg
60 60
40
33 Lansoprazole
30mg
20
0
Epigastric Heartburn Acid Vomiting
Pain Regurgitation
Pilotto et al; 1999

115. For Peptic Ulcer Treatment
For Erosive Esophagitis
For H Pylori Eradication
For Heartburn
For Other Symptoms
Associated with GERD
For Maintenance of Healed
Esophagitis and Peptic Ulcer
On-Demand Therapy

120. PANTOLOC Summary
PANTOLOC
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