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Peptic Ulcer Diseases: Treatment
Содержание
- 1. Peptic Ulcer Diseases: Treatment
- 2. Introduction Peptic ulcer disease (PUD) is a
- 3. Introduction Major advances have been made in
- 4. DefinitionsUlcer: A lesion on an epithelial surface (skin
- 5. DefinitionsPeptic Ulcer An ulcer of the alimentary tract
- 6. Peptic Ulcer Disease
- 7. Gastric Mucosa & SecretionsThe inside of the
- 8. Gastric Mucosa & SecretionsThe Defensive ForcesBicarbonateMucus layer
- 9. Negative Feedback Regulation of Acid Secretion
- 10. PathophysiologyA peptic ulcer is a mucosal break,
- 11. PathophysiologyTwo major variants in peptic ulcers are
- 12. PathophysiologyDU result from increased acid load to
- 13. PathophysiologyDU result from increased acid load to
- 14. PathophysiologyGU results from the break down of
- 15. Etiology The two most common causes of PUD are:Helicobacter pylori infection ( 70-80%)Non-steroidal anti-inflammatory drugs (NSAIDS)
- 16. EtiologyOther uncommon causes include:Gastrinoma (Gastrin secreting tumor)Stress ulceration (trauma, burns, critical illness)Viral infectionsVascular insufficiency
- 17. 1. Etiology – Helicobacter pylori
- 18. H.pylori EpidemiologyOne half of world’s population has
- 19. H.pylori as a cause of PUD
- 20. H.pylori as a cause of PUD95%85%
- 21. Pathogenesis of H. pylori infection H. pylori
- 22. Pathogenesis of H. pylori infectionThe Flagellae make
- 23. Pathogenesis of H. pylori infectionAny acidity is
- 24. Pathogenesis of H. pylori infectionIn the cellular
- 25. Pathogenesis of H. pylori infectionIn the cellular
- 26. Pathogenesis of H. pylori infection- ↓ Somatostatin
- 27. Carcinogenic effect of H. pylori H. pyloriHost FactorsOther environmental FactorsAntral gastritis Pangastritis DUGUGastritis Cancer
- 28. Carcinogenic effect of H. pyloriEpidemiologic evidence suggests
- 29. For persons at high risk for gastric
- 30. 2. Etiology -Non-Steroidal Anti-inflammatory Drugs (NSAIDS)
- 31. NSAIDSSymptomatic GI ulceration occurs in 2% -
- 32. NSAIDSInhibits the production of prostaglandins precursor from
- 33. NSAIDSGastric acid probably aggravates NSAID-induce mucosal injury
- 34. NSAIDSUsers of NSAIDs are at approximately 3
- 35. NSAIDS Identify risk factors: Age > 65
- 36. Type of NSAID & Risk of Ulcer
- 37. Does H. pylori Influence the Ulcer Risk in NSAID Users?
- 38. Does H. pylori Influence the Ulcer Risk
- 39. Does H. pylori Influence the Ulcer Risk
- 40. Recommendations for H.pylori Testing & Eradication in
- 41. Recommendations for H.pylori Testing & Eradication in
- 42. Clinical PresentationRecurrent epigastric pain (the most common
- 43. Clinical PresentationNausea, VomitingDyspepsia, fatty food intoleranceChest discomfortAnorexia,
- 44. Diagnosis of PUD
- 45. Peptic Ulcer DiseaseDiagnosis:Diagnosis of ulcerDiagnosis of H. pylori
- 46. Diagnosis of PUD In most patients routine
- 47. Doudenal Ulcer on EndoscopyDoudenal UlcerNormal doudenal bulb
- 48. Gastric Ulcer on EndoscopyChronic Gastric Ulcers
- 49. Diagnosis of H. pyloriNon-invasiveC13 or C14 Urea
- 50. Diagnosis of H. pyloriNon-invasive 1.
- 51. Diagnosis of H. pyloriNon-invasive Serology for H
- 52. Diagnosis of H. pyloriInvasiveUpper GI endoscopyHighly sensitive testPatient needs sedationHas both diagnostic & therapeutic role
- 53. Diagnosis of H. pyloriInvasive (endoscopy)Diagnostic:Detect the site
- 54. Diagnosis of H. pyloriInvasive (endoscopy)Rapid urease test
- 55. Diagnosis of H. pyloriInvasive (endoscopy)* HistopathologyDone if
- 56. Diagnostic Tests for Helicobacter pylori Invasive ABLES A Z et al. American Family Physician. 2007
- 57. Diagnostic Tests for Helicobacter pylori Noninvasive ABLES A Z et al. American Family Physician. 2007
- 58. Diagnostic Tests for Helicobacter pylori Noninvasive ABLES A Z et al. American Family Physician. 2007
- 59. Diagnostic Tests for Helicobacter pylori Noninvasive ABLES A Z et al. American Family Physician. 2007
- 60. Testing to Document HP EradicationSince treatment is
- 61. Testing to Document HP EradicationShould be confirmed
- 62. Diagnosis of H. pylori in patients with
- 63. PUD – ComplicationsBleedingPerforationGastric outlet or duodenal obstruction Chronic anemia
- 64. Complications of PUD on Endoscopy Bleeding
- 65. PUD Treatment
- 66. Treatment Goals Rapid relief of symptomsHealing of
- 67. General Strategy Treat complications aggressively if presentDetermine
- 68. General Strategy Smoking cessation should be encouragedIf
- 69. Drugs Therapy H2-Receptors antagonists Proton pump inhibitors Cyto-protective agentsProstaglandin agonistsAntacidsAntibiotics for H. pylori eradication
- 70. Management of NSAIDs Ulcers
- 71. Management of NSAIDs UlcersThis can be considered
- 72. Healing the Established NSAIDs-Associated UlcerIf possible, NSAID
- 73. Best Prevention & Treatment for Upper GI
- 74. The Astronaut StudyRanitidine 150 mg twice daily
- 75. Are Better Results Obtained if Additional Inhibition
- 76. Reducing Risk of NSAIDs Ulcers by Choice
- 77. Reducing Risk of NSAIDs Ulcers by Choice
- 78. Reducing Risk of NSAIDs Ulcers by Choice
- 79. Preventing NSAIDs Ulcers with Co-Prescribed Gastric ProtectantsPatients
- 80. Drugs Therapy for Treatment of PUD1- H2-Receptors
- 81. Peptic Ulcer Disease - Treatment
- 82. Degree of Acid Inhibition to Heal an
- 83. The Purpose of Inhibiting Gastric Acid Secretion
- 84. The Ideal Drug to Achieve Potent Acid
- 85. Drugs Therapy for Treatment of PUD1- H2-Receptors
- 86. Drugs Therapy for Treatment of PUD1- H2-Receptors
- 87. Drugs Therapy for Treatment of PUD1- H2-Receptors
- 88. Drugs Therapy for Treatment of PUD1- H2-Receptors
- 89. Drugs Therapy for Treatment of PUD1- H2-Receptors
- 90. Drugs Therapy for Treatment of PUD1- H2-Receptors
- 91. Drugs Therapy for Treatment of PUD1- H2-Receptors
- 92. Drugs Therapy for Treatment of PUD2- Proton
- 93. Drugs Therapy for Treatment of PUD2- Proton
- 94. Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)AgentsOmeprazole LansoprazolePantoprazoleRabeprazoleEsomeprazole1st Generation2nd Generation
- 95. Drugs Therapy for Treatment of PUD2- Proton
- 96. Drugs Therapy for Treatment of PUD2- Proton
- 97. Drugs Therapy for Treatment of PUD2- Proton
- 98. Drugs Therapy for Treatment of PUD2- Proton
- 99. Drugs Therapy for Treatment of PUD2- Proton
- 100. Drugs Therapy for Treatment of PUD2- Proton
- 101. Drugs Therapy for Treatment of PUD2- Proton
- 102. Drugs Therapy for Treatment of PUD2- Proton
- 103. Drugs Therapy for Treatment of PUD2- Proton
- 104. Drugs Therapy for Treatment of PUD2- Proton
- 105. Drugs Therapy for Treatment of PUD2- Proton
- 106. Drugs Therapy for Treatment of PUD2- Proton
- 107. Drugs Therapy for Treatment of PUD2- Proton
- 108. Drugs Therapy for Treatment of PUD3- Cyto-Protective
- 109. Drugs Therapy for Treatment of PUD3- Cyto-Protective
- 110. Drugs Therapy for Treatment of PUD3- Cyto-Protective
- 111. Drugs Therapy for Treatment of PUD4- Prostaglandin
- 112. Drugs Therapy for Treatment of PUD4- Prostaglandin
- 113. Drugs Therapy for Treatment of PUD4- Prostaglandin
- 114. Drugs Therapy for Treatment of PUD5- AntacidsWeak
- 115. Drugs Therapy for Treatment of PUD5- AntacidsAntacids
- 116. Drugs Therapy for Treatment of PUD5- AntacidsVery
- 117. Drugs Therapy for Treatment of PUD5- AntacidsSide
- 118. Drugs Therapy for Treatment of PUD5- AntacidsSide
- 119. The Mechanism & Side Effects of Various Acid Suppressive Medications
- 120. Drugs Therapy for Treatment of PUD6- Antibiotics
- 121. To Select Therapy for H. pylori Eradication
- 122. Duration of H. Pylori Eradication Therapy Until
- 123. Adverse Effects The most commonly reported adverse
- 124. Selected Long-Duration Regimens for H. pylori Eradication ABLES A Z et al. American Family Physician. 2007
- 125. Short-Course Therapy for Eradication of Helicobacter pylori ABLES A Z et al. American Family Physician. 2007
- 126. Short-Course Therapy for Eradication of Helicobacter pylori ABLES A Z et al. American Family Physician. 2007
- 127. Short-Course Therapy for Eradication of Helicobacter pylori ABLES A Z et al. American Family Physician. 2007
- 128. Resistance Resistant H. pylori has been documented
- 129. Resistance Resistance rate to clarithromycin is currently
- 130. Resistance 70 % of patients failing one
- 131. Resistance A meta-analysis of current literature on
- 132. Recurrence Recurrence of H. pylori infection is
- 133. Recurrence Risk factors for recurrence include:Non-ulcer dyspepsiaPersistence
- 134. Recurrence Recurrence rates worldwide vary but lower
- 135. H. pyloriThank U
- 136. Скачать презентанцию
Introduction Peptic ulcer disease (PUD) is a common disorder that affects millions of individuals worldwide It is accounting for roughly 10% of medical costs for digestive diseases
Слайды и текст этой презентации
Слайд 2Introduction
Peptic ulcer disease (PUD) is a common disorder that
affects millions of individuals worldwide
10% of medical costs for digestive diseases
Слайд 3Introduction
Major advances have been made in the understanding PUD
pathophysiology, particularly the role of Helicobacter pylori infection & NSAIDs
This
has led to important changes in diagnostic & treatment strategies, with potential for improving clinical outcome & decreasing health care costsNSAIDs= nonsteroidal anti-inflammatory drugs
Слайд 4Definitions
Ulcer:
A lesion on an epithelial surface (skin or mucous membrane)
caused by superficial loss of tissue
Erosion:
A lesion on an epithelial
surface (skin or mucous membrane) caused by superficial loss of tissue, limited to the mucosa
Слайд 5Definitions
Peptic Ulcer
An ulcer of the alimentary tract mucosa, usually in
the stomach or duodenum, & rarely in the lower esophagus,
where the mucosa is exposed to the acid gastric secretionIt has to be deep enough to penetrate the muscularis mucosa
Слайд 7Gastric Mucosa & Secretions
The inside of the stomach is bathed
in about 2 liters of gastric juice every day
Gastric juice
is composed of digestive enzymes & concentrated hydrochloric acid, which can readily tear apart the toughest food or microorganism
The gastroduodenal mucosal integrity is determined by protective (defensive) & damaging (aggressive) factors
Слайд 8Gastric Mucosa & Secretions
The Defensive Forces
Bicarbonate
Mucus layer
Mucosal blood flow
Prostaglandins
Growth
factors
The Aggressive Forces
Helicobacter pylori
HCl acid
Pepsins
NSAIDs
Bile acids
Ischemia and hypoxia.
Smoking and
alcohol
When the aggressive factors increase or the defensive factors decrease, mucosal damage will result, leading to erosions & ulcerations
Слайд 9Negative Feedback Regulation of Acid Secretion
Antral distention Protein
content
intragastric PH
Gastrin release
somatostatin
secretion Increased gastric acid secretion
Intragastric PH
CGPR release
CGPR= calcitonin gene related peptide
Слайд 10Pathophysiology
A peptic ulcer is a mucosal break, 3 mm or
greater in size with depth, that can involve mainly the
stomach or duodenum.
Слайд 11Pathophysiology
Two major variants in peptic ulcers are commonly encountered in
the clinical practice:
Duodenal Ulcer (DU)
Gastric Ulcer (GU)
Слайд 12Pathophysiology
DU result from increased acid load to the duodenum due
to:
Increased acid secretion because of:
Increased parietal cell mass
Increased gastrin
secretion (e.g. Zollinger-Ellison syndrome, alcohol & spicy food)Decreased inhibition of acid secretion, possibly by H. pylori damaging somatostatin-producing cells in the antrum
Слайд 13Pathophysiology
DU result from increased acid load to the duodenum due
to:
Smoking impairing gastric mucosal healing
Genetic susceptibility may play a role
(more in blood gp. O)HCO3 secretion is decreased in the duodenum by H. pylori inflammation
Слайд 14Pathophysiology
GU results from the break down of gastric mucosa:
Associated with
gastritis affecting the body & the antrum
The local epithelial damage
occurs because of cytokines released from H. pylori & because of abnormal mucus productionParietal cell damage occur so that acid production is normal or low
Слайд 15Etiology
The two most common causes of PUD are:
Helicobacter pylori
infection ( 70-80%)
Non-steroidal anti-inflammatory drugs (NSAIDS)
Слайд 16Etiology
Other uncommon causes include:
Gastrinoma (Gastrin secreting tumor)
Stress ulceration (trauma, burns,
critical illness)
Viral infections
Vascular insufficiency
Слайд 18H.pylori Epidemiology
One half of world’s population has H.pylori infection, with
an estimated prevalence of 80-90 % in the developing world
The annual incidence of new H. pylori infections in industrialized countries is 0.5% of the susceptible population compared with ≥ 3% in developing countries
Слайд 21Pathogenesis of H. pylori infection
H. pylori is Gram-negative, spiral
& has multiple flagella at one end
Transmitted from person-to-person by
Oro–oral or feco-oral spreadNo reservoir in animal or water supply
Слайд 22Pathogenesis of H. pylori infection
The Flagellae make it motile, allowing
it to live deep beneath the mucus layer
It uses an
adhesin molecule to bind to epithelial cells Where the pH there is close to neutral
Слайд 23Pathogenesis of H. pylori infection
Any acidity is buffered by the
organism's production of the enzyme urease, which catalyzes the production
of ammonia (NH3) from urea & raises the pH thereThe bacterium stimulates chronic gastritis by provoking a local inflammatory response.
Слайд 24Pathogenesis of H. pylori infection
In the cellular level:
H. pylori express
cagA & vacA genes
cagA gene signals to the
epithelial cells involving: - Cell replication, - Apoptosis, & - Morphology
Слайд 25Pathogenesis of H. pylori infection
In the cellular level:
vacA gene
producing a pore-forming protein,
which has many destructing effect to the epithelium like: -↑Cell permeability & efflux of micronutrients, - Induction of apoptosis, & - Suppression of local cell immunity
Слайд 26Pathogenesis of H. pylori infection
- ↓ Somatostatin production from antral
D-cells due to antral gastritis
Low somatostatin will ↑Gastrin release
from G-cell hypergastrinemiaThis will stimulate acid production by the parietal cells leading to further duodenal ulceration.
Effects of H. pylori on gastric Hormones
This effect is exaggerated among smokers!
Слайд 27Carcinogenic effect of H. pylori
H. pylori
Host Factors
Other environmental
Factors
Antral gastritis
Pangastritis
DU
GU
Gastritis Cancer
Слайд 28Carcinogenic effect of H. pylori
Epidemiologic evidence suggests that infection with
HP is associated with >2 fold increase risk of gastric
cancerHowever due to uncertainty regarding the benefit of HP eradication on reducing cancer risk, wide-spread screening for HP in asymptomatic individuals cannot be recommended at this time
Слайд 29For persons at high risk for gastric cancer (e.g., first
degree relatives) screening can be considered on a case by
case basis ABLES A Z et al. American Family Physician. 2007
Слайд 31NSAIDS
Symptomatic GI ulceration occurs in 2% - 4% of patients
treated with NSAIDs for 1 year
In view of the million
of people who take NSAIDs annually, these small percentages translate into a large number of symptomatic ulcersThe effects of aspirin & NSAIDs on the gastric mucosa ranges from mucosal hemorrhages to erosions & acute ulcers
Слайд 32NSAIDS
Inhibits the production of prostaglandins precursor from membrane fatty acids
resulting in:
1. Decrease mucus & HCO3 production
2. Decrease
mucosal blood flow3. Reduce cell renewal
The drugs also generate oxygen-free radicals & products of the lipoxygenase pathway that may contribute to ulceration
Слайд 33NSAIDS
Gastric acid probably aggravates NSAID-induce mucosal injury by
-
Converting superficial injury to deeper mucosal necrosis,
- Interfering with
haemostasis & platelet aggregation- Impairing ulcer healing
Слайд 34NSAIDS
Users of NSAIDs are at approximately 3 times greater relative
risk of serious adverse gastrointestinal events than nonusers
Слайд 35NSAIDS
Identify risk factors:
Age > 65 years (3.5-fold
increased risk)
Smoking
Previous history of GI event (e.g.
ulcer bleeding 4-fold increase risk)Concomitant drug use
Anticoagulants ( eg, warfarin; 3-fold increase)
Corticosteroid ( 2-fold increase)
Low dose aspirin alone ( 2.5-fold increase)
Aspirin + NSAIDS (4-fold increase vs aspirin alone)
Слайд 38Does H. pylori Influence the Ulcer Risk in NSAID Users?
Many
investigators had attempted to address this question using case-control or
observational studiesTo date, there are studies showing that the interaction between H. pylori and NSAIDs in ulcer development is synergistic, additive, independent or antagonistic
Слайд 39Does H. pylori Influence the Ulcer Risk in NSAID Users?
These
conflicting results can be largely accounted for by methodological heterogeneity
and diversified host response to H. pylori infection.
Слайд 40Recommendations for H.pylori Testing & Eradication in NSAID Users
1- Patients
who have a history of ulcer complication should undergo H.
pylori testing. H. pylori should be eradicated in all infected patients because it is not plausible to determine whether the ulcer complications were caused by NSAIDs or both
Слайд 41Recommendations for H.pylori Testing & Eradication in NSAID Users
3- Patients
who are about to start receiving NSAIDs, H. pylori testing
& treatment reduces the ulcer risk at an affordable incremental cost4- Since treatment with PPIs aggravate H. pylori corpus gastritis, it is advisable to test for H. pylori & eradicate if present before starting long term therapy with PPI as prophylaxis against NSAID-induced ulcers
Слайд 42Clinical Presentation
Recurrent epigastric pain (the most common symptom)
Burning
Occurs 1-3 hours
after meals
Relieved by food DU
Precipitated by food GU
Relieved
by antacidsRadiate to back (consider penetration)
Pain may be absent or less characteristic in one-third of patients especially in elderly patients on NSAIDs
Слайд 43Clinical Presentation
Nausea, Vomiting
Dyspepsia, fatty food intolerance
Chest discomfort
Anorexia, weight loss especially
in GU
Hematemesis or melena resulting from gastrointestinal bleeding
Слайд 46Diagnosis of PUD
In most patients routine laboratory tests are
usually unhelpful
Diagnosis of PUD depends mainly on endoscopic and
radiographic confirmation
Слайд 49Diagnosis of H. pylori
Non-invasive
C13 or C14 Urea Breath Test
Stool antigen
test
H. pylori IgG titer (serology)
Invasive
Gastric mucosal biopsy
Rapid Urease test
Слайд 50Diagnosis of H. pylori
Non-invasive
1. C13 or C14
Urea Breath Test
The best test for the detection
of
an active infection 
Слайд 51Diagnosis of H. pylori
Non-invasive
Serology for H pylori
Serum Antibodies (IgG)
to H pylori (Not for active infection)
Fecal antigen testing
(Test for active HP) 
Слайд 52Diagnosis of H. pylori
Invasive
Upper GI endoscopy
Highly sensitive test
Patient needs sedation
Has
both diagnostic & therapeutic role
Слайд 53Diagnosis of H. pylori
Invasive (endoscopy)
Diagnostic:
Detect the site and the size
of the ulcer, even small and superficial ulcer can be
detectedDetect source of bleeding
Biopsies can be taken for rapid urease test, histopathology & culture
Слайд 54Diagnosis of H. pylori
Invasive (endoscopy)
Rapid urease test ( RUT)
Considered the
endoscopic diagnostic test of choice
Gastric biopsy specimens are placed in
the rapid urease test kit. If H pylori are present, bacterial urease converts urea to ammonia, which changes pH and produces a COLOR change
Слайд 55Diagnosis of H. pylori
Invasive (endoscopy)
* Histopathology
Done if the rapid urease
test result is negative
* Culture
Used in
research studies and is not available routinely for clinical use
Слайд 56Diagnostic Tests for Helicobacter pylori
Invasive
ABLES A Z et
al. American Family Physician. 2007
Слайд 57Diagnostic Tests for Helicobacter pylori
Noninvasive
ABLES A Z
et al. American Family Physician. 2007
Слайд 58Diagnostic Tests for Helicobacter pylori
Noninvasive
ABLES A Z
et al. American Family Physician. 2007
Слайд 59Diagnostic Tests for Helicobacter pylori
Noninvasive
ABLES A Z
et al. American Family Physician. 2007
Слайд 60Testing to Document HP Eradication
Since treatment is not effective is
some cases (> 20%), individuals at high risk for HP-associated
complications (e.g., prior bleeding ulcer) should undergo confirmatory testing with either- Stool antigen test or
- Urea breath test to confirm HP cure
(Serology has no role in confirmatory testing)
Слайд 61Testing to Document HP Eradication
Should be confirmed after end of
therapy; noninvasive testing with UBT is preferred, 4-8 weeks after
completion of therapyIf ulcer recurs after eradication therapy, a more careful search for reinfection or eradication failure should be carried out by testing for presence of active infection (e.g. by histologic examination & culture, together with antibiotic-sensitivity test)
Слайд 62Diagnosis of H. pylori in patients with bleeding PU
It is
limited by the decreased sensitivity of standard invasive tests; usually,
both the RUT & histologic testing should be performed & then combined with the UBT testInfection should be considered as present when any test is positive, whereas both the invasive tests & the breath test should be negative to establish the absence of infection
Слайд 66Treatment Goals
Rapid relief of symptoms
Healing of ulcer
Preventing ulcer recurrences
Reducing
ulcer-related complications
Reduce the morbidity (including the need for endoscopic therapy
or surgery)Reduce the mortality
Слайд 67General Strategy
Treat complications aggressively if present
Determine the etiology of
ulcer
Discontinue NSAID use if possible
Eradicate H. pylori infection if present
or strongly suspected, even if other risk factors (e.g., NSAID use) are also present;Use antisecretory therapy to heal the ulcer if H. pylori infection is not present
Слайд 68General Strategy
Smoking cessation should be encouraged
If DU is diagnosed
by endoscopy, RU testing of endoscopically obtained gastric biopsy sample,
with or without histologic examination should establish presence or absence of H. pyloriIf DU is diagnosed by x-ray , then a serologic , UBT, or fecal antigen test to diagnose H. pylori infection is recommended before treating the patient for H. pylori
Слайд 69Drugs Therapy
H2-Receptors antagonists
Proton pump inhibitors
Cyto-protective agents
Prostaglandin agonists
Antacids
Antibiotics
for H. pylori eradication
Слайд 71Management of NSAIDs Ulcers
This can be considered under two headings:
The healing of an ulcer that has developed during NSAID
or COX-2 inhibitor treatment; & Strategies for preventing NSAID ulcers in patients who currently are ulcer free
Слайд 72Healing the Established NSAIDs-Associated Ulcer
If possible, NSAID should be stopped,
as healing with a histamine H2-receptor antagonist (H2-RA) will be
faster than if the NSAID is continuedPPI have been shown in 3 randomized controlled trials to be more effective than ranitidine or misoprostol for healing NSAID ulcers when the NSAID is continued
Слайд 73Best Prevention & Treatment for Upper GI Lesions Induced by
NSAIDs
There is conclusive evidence that PPIs decrease the incidence of
ulcers & erosions, & heal them when they have occurred, even when NSAIDs administration is continuedMearin & Ponce. Drugs, 2005
Слайд 74The Astronaut Study
Ranitidine 150 mg twice daily Vs. Omeprazole 20
or 40 mg daily
Gastroduodenal ulcer healing rates at 8weeks
Ranitidine 87% & Omeprazole 20 mg 71%
Слайд 75Are Better Results Obtained if Additional Inhibition of Gastric Acid
Secretion is Achieved?
The healing rate of H.pylori eradication, peptic
ulcer healing, or the extent of mucosal damage induced by NSAIDs are clearly related to the acid inhibition level achieved with the corresponding treatment
Слайд 76Reducing Risk of NSAIDs Ulcers by Choice of Agent
Choose, where
possible, an NSAID from the less damaging end of the
spectrum,Use it in the lowest dose that is effective
Слайд 77Reducing Risk of NSAIDs Ulcers by Choice of Agent
Use highly
selective COX-2 inhibitors (whether to use them instead of a
largely non-selective NSAID such as diclofenac or ibuprofen requires judgments about cost vs. benefit for the individual patient
Слайд 78Reducing Risk of NSAIDs Ulcers by Choice of Agent
In low-risk
patients such as young - middle age individuals without past
history of ulcer & with no hazard-increasing cotherapies (e.g warfarin or steroids), the risk of using a non-selective NSAID is very small
Слайд 79Preventing NSAIDs Ulcers with Co-Prescribed Gastric Protectants
Patients who continue to
require NSAIDs should receive either a PPI or misoprostol to
prevent ulcer recurrence
Слайд 80Drugs Therapy for Treatment of PUD
1- H2-Receptors antagonists
2- H+,
K+ ATPase: Proton pump inhibitors (PPIs)
3- Cyto-protective agent (Sucalfate)
4-
Prostaglandin agonists5- Antacids
6- Antibiotics for H. pylori eradication
Слайд 82Degree of Acid Inhibition to Heal an Ulcer
It has been
reported that a sustained increase in pH > 3 would
be sufficient to heal an ulcerHowever, one of the risk factors for refractory gastric ulcer appears to be the impossibility of maintaining gastric pH > 4 for a minimum daily period of 16 hr
Mearin & Ponce. Drugs, 2005
Слайд 83The Purpose of Inhibiting Gastric Acid Secretion in cases of
Upper GI Bleeding
In upper GI bleeding, the aim is to
achieve the least acid gastric pH possible in order to prevent acid degradation of the clot & accelerate healing as much as possibleBoth clinical & experimental studies suggest that extremely potent inhibition is required to achieve the intended efficacy
Mearin & Ponce. Drugs, 2005
Слайд 84The Ideal Drug to Achieve Potent Acid inhibition
Ideal drug should
be able to maintain pH > 4 for ≥ 16
hr/daySuch level guarantee a consistent response to treatment, & sufficient for most refractory cases of peptic acid disease
Efficacy of the drug would also have to be consistent, so that such potent acid inhibition levels might be achieved in all patients, regardless of their basal acid secretion, metabolic capacity, or the presence or absence of H. pylori infection
Mearin & Ponce. Drugs, 2005
Слайд 85Drugs Therapy for Treatment of PUD
1- H2-Receptors Antagonists
These agents are
capable of 90% reduction in basal & food-stimulated secretion of
gastric acid after single dose. they are somewhat less effective in reducing nocturnal secretionStudies have demonstrated their effectiveness in promoting the healing of DU & GU, & preventing their recurrence
These meds are equally effective in treating these conditions
Слайд 86Drugs Therapy for Treatment of PUD
1- H2-Receptors Antagonists
Previous recommendations were
to administer these agents at least twice a day, a
single bedtime dose may be just as effective & may elicit better complianceIf administered for 6-8 weeks, can heal DU 75% & 90% respectively
Слайд 87Drugs Therapy for Treatment of PUD
1- H2-Receptors Antagonists
Agents
Cimetidine 800mg OD
or 400mg BID
Ranitidine 300mg OD or 150mg BID
Famotidine 40mg OD
or 20mg BIDNizatidine 300mg OD or 150mg BID
Should by taken for 6-8 weeks
Слайд 88Drugs Therapy for Treatment of PUD
1- H2-Receptors Antagonists
Pharmacokinetics
Rapidly absorbed 1-3
hrs to peak
Ranitidine & Cimetidine hepatically metabolized whereas Famotidine &
Nizatidine are renally excretedDose adjustment is needed in some renal & hepatic failure patients
Слайд 89Drugs Therapy for Treatment of PUD
1- H2-Receptors Antagonists
Side Effects
Usually minor;
include headache, dizziness, diarrhea, & muscular pain
Hallucinations & confusion in
elderly patients; Hepatotoxicity with Ranitidine
Cimetidine elevates serum prolactin & alters estrogen metabolism in men
Gynecomastia, Galactorrhea and reduced sperm count
Слайд 90Drugs Therapy for Treatment of PUD
1- H2-Receptors Antagonists
Drug Interactions
Cimetidine slows
microsomal metabolism of some drugs
Cimetidine causes these in a dose-dependent
but reversible mannerInhibits the metabolism of warfarin, theophylline, diazepam & phenytoin
Ranitidine has less effect on hepatic enzymes
Слайд 91Drugs Therapy for Treatment of PUD
1- H2-Receptors Antagonists
Drug Interactions
Famotidine &
Nizatidine has no effect on hepatic drug metabolism
Combining H2 inhibitor
with antacid has little rationale although is done. H2 antagonist + PPI inhibits efficacy of PPIOver the counter H2 blockers now available, labeled for short-term use in heartburn & dyspepsia
Слайд 92Drugs Therapy for Treatment of PUD
2- Proton Pump Inhibitors (PPIs)
Same
Acid Inhibition as Anti-H2??
No
Among anti-secretory drugs, PPIs can inhibit gastric
acid secretion with a greater efficacy than anti-H2Mearin & Ponce. Drugs, 2005
Слайд 93Drugs Therapy for Treatment of PUD
2- Proton Pump Inhibitors (PPIs)
Same
Acid Inhibition as Anti-H2??
They are potent acid inhibitors
Potent acid
inhibition is arbitrarily defined as inhibition that achieves maintenance of an intragastric pH > 4 for ≥ 16 hr out of 24 hrMearin & Ponce. Drugs, 2005
Слайд 94Drugs Therapy for Treatment of PUD
2- Proton Pump Inhibitors (PPIs)
Agents
Omeprazole
Lansoprazole
Pantoprazole
Rabeprazole
Esomeprazole
1st Generation
2nd Generation
Слайд 95Drugs Therapy for Treatment of PUD
2- Proton Pump Inhibitors (PPIs)
Pharmacological
Effect
PPIs dose-dependently inhibit basal & food acid secretion
Decreases pepsinogen
secretion &, due to the increase in intragastric pH, inhibit the proteolytic activity of pepsinMearin & Ponce. Drugs, 2005
Слайд 96Drugs Therapy for Treatment of PUD
2- Proton Pump Inhibitors (PPIs)
Comparative
Anti-secretory Efficacy of the Different PPIs
Among different PPIs administered at
standard doses, esomeprazole 40 mg/day has a greater anti-secretory potencyRabeprazole 20 mg/day & lansoprazole 30 mg/day show a faster action, & slightly greater acid inhibition capacity than omeprazole 20 mg/day & pantoprazole 40 mg/day
Mearin & Ponce. Drugs, 2005
Слайд 97Drugs Therapy for Treatment of PUD
2- Proton Pump Inhibitors (PPIs)
Side
Effects
No evidence that they cause direct toxic effects.
Most common adverse
reactions include episodes of diarrhea, nausea, abdominal pain, dizziness, headache, or skin rash These manifestations are most often transient & moderate in severity, not requiring reductions in compound dosage
Mearin & Ponce. Drugs, 2005
Слайд 98Drugs Therapy for Treatment of PUD
2- Proton Pump Inhibitors (PPIs)
PPIs
& Vitamin B12 Deficiency
In some patients continuously taking PPIs, a
mild vitamin B12 deficiency has been seen as the result of decreased vitamin absorptionThis is due to impaired release of the vitamin from food, because this is a process enhanced by the presence of an intragastric acid environment
Mearin & Ponce. Drugs, 2005
Слайд 99Drugs Therapy for Treatment of PUD
2- Proton Pump Inhibitors (PPIs)
Time
of Administration
Should by administered while fasting & before a meal
so that at the time the peak plasma concentration is reached, there is also a maximum of proton pumps activated (i.e. secreting acid)For treatment of DU & GU should be used for 4-6 weeks
Mearin & Ponce. Drugs, 2005
Слайд 100Drugs Therapy for Treatment of PUD
2- Proton Pump Inhibitors (PPIs)
Pharmacokinetics
How
can PPIs have a Short Half-life & a Long-lasting Effect?
Despite
their short plasma half-life, PPIs exert a persistent pharmacological action because by irreversibly binding to the proton pump they render necessary the synthesis of new enzymes to re-establish gastric acid secretionMearin & Ponce. Drugs, 2005
Слайд 101Drugs Therapy for Treatment of PUD
2- Proton Pump Inhibitors (PPIs)
Pharmacokinetics
Metabolism
PPIs
undergo extensive first-pass metabolism in the liver, resulting in various
inactive metabolites that are excreted in the urine or bileMetabolized by the cytochrome P450 system (mainly by isoenzymes CYP2C19 & CYP3A4)
Mearin & Ponce. Drugs, 2005
Слайд 102Drugs Therapy for Treatment of PUD
2- Proton Pump Inhibitors (PPIs)
Pharmacokinetics
What
is Esomeprazoie?
It is the S isomer of omeprazole
Pharmacokinetic & pharmacodynamic
studies suggest that this isomer undergoes less first-pass metabolism in the liver & has a lower plasma clearance as compared with omeprazoleMearin & Ponce. Drugs, 2005
Слайд 103Drugs Therapy for Treatment of PUD
2- Proton Pump Inhibitors (PPIs)
Dose
Adjustment in Liver Failure
In patients with severe liver failure, the
area under the plasma curve for PPIs increases 7-9 fold, & their half-life is prolonged to 4-8 hr. A decrease in the usual dose of these drugs is recommended in this group of patientsMearin & Ponce. Drugs, 2005
Слайд 104Drugs Therapy for Treatment of PUD
2- Proton Pump Inhibitors (PPIs)
Drug
Interactions
Theoretically, their influence on phenytoin, carbamazepine, warfarin, & diazepam should
be monitoredHowever, as confirmed by a recent analysis of cases recorded by (FDA), the clinical impact of these interactions is very low (rates lower than 0.1 -0.2 per 1,000,000 prescriptions), with no differences between the different PPIs
Mearin & Ponce. Drugs, 2005
Слайд 105Drugs Therapy for Treatment of PUD
2- Proton Pump Inhibitors (PPIs)
Presence
of H. Pylori influence Degree of Acid inhibition ??
PPIs show
a decreased efficacy in patients not infected by H. pylori. This often requires the use of higher doses of the PPIMearin & Ponce. Drugs, 2005
Слайд 106Drugs Therapy for Treatment of PUD
2- Proton Pump Inhibitors (PPIs)
Do
PPIs Have Direct Action on H.Pylori??
Yes, PPIs inhibit the urease
protecting H. pylori from acid & are effective on this microorganism in vitro, although in vivo they only achieve eradication in 10-15% of casesMearin & Ponce. Drugs, 2005
Слайд 107Drugs Therapy for Treatment of PUD
2- Proton Pump Inhibitors (PPIs)
Do
PPI Promote Actions of Antibiotics in H. Pylori Eradication?
In vitro,
PPIs have additive even synergistic effect with several antimicrobial agentsStudies suggest that high dose omeprazole increase amoxycillin level in gastric juice, & high dose of PPIs improve H.pylori cure rate when given with amoxycillin
Clarithromycin activity against H. pylori is enhanced as gastric pH increases
Mearin & Ponce. Drugs, 2005
Слайд 108Drugs Therapy for Treatment of PUD
3- Cyto-Protective Agent ( Sucalfate)
Sucralfate
= complex of Aluminum Hydroxide & Sulfated Sucrose
Binds to positively
charged groups in proteins, glycoproteins of necrotic tissue (coat ulcerated mucosa)Not absorbed systemically
Require acidic media to dissolve & coates the ulcerative tissue so, it can not be given with H2-antagonist, PPIs, & antacids
Слайд 109Drugs Therapy for Treatment of PUD
3- Cyto-Protective Agent ( Sucalfate)
Administration
Should
not be given with food, give 1hr before or 3hr
after mealDose: 1gm/ 4times daily or 2 gm/ 2times daily
Must be given for 6-8 weeks
Large tablet & difficult to swallow
Слайд 110Drugs Therapy for Treatment of PUD
3- Cyto-Protective Agent ( Sucalfate)
Side
Effects
Constipation; black stool & dry mouth
It is very safe in
pregnancy
Слайд 111Drugs Therapy for Treatment of PUD
4- Prostaglandin Agonists (PGE1) Misoprostol
Inhibits
secretion of HCl & stimulates secretion of mucus & bicarbonatemis
It
is a methyl analog of PGE1It is approved for prevention of ulcer induced by NSAIDs
Слайд 112Drugs Therapy for Treatment of PUD
4- Prostaglandin Agonists (PGE1) Misoprostol
Optimal
role in ulcer treatment is difficult to define
PPIs may be
as effective as misoprostol for this indicationRoutine clinical prophylaxis of NSAIDs-induced ulcers may not be justified
However, in patients with rheumatoid arthritis requiring NSAIDs therapy, prophylaxis with Misoprostol or a PPI may be cost-effective
Слайд 113Drugs Therapy for Treatment of PUD
4- Prostaglandin Agonists (PGE1) Misoprostol
Administration
Should
be given 4 time/ day ( inconvenient)
Side effects
Up to
20% develop diarrhea & crampsCategory X
Слайд 114Drugs Therapy for Treatment of PUD
5- Antacids
Weak bases that react
with gastric acid to form water & salt (Neutralize acid)
Studies
indicate mucosal protection either through stimulation of prostaglandin production or binding of unidentified injurious substanceAntacids vary in palatability & price
Слайд 115Drugs Therapy for Treatment of PUD
5- Antacids
Antacids contain either Sodium-bicarbonate,
Aluminum-hydroxide, magnesium-hydroxide & calcium carbonate
Require large neutralizing capacity (a single
dose of 156 meq antacid given 1 hr after meal effectively neutralize gastric acid for 2 hr, a second dose given 3 hr after eating maintains the effect for over 4 hr after the meal)
Слайд 116Drugs Therapy for Treatment of PUD
5- Antacids
Very inconvenient to administer
Tablet
antacids are generally weak in their neutralizing capability, & a
large number of tablets would be required for this high-dose regimen
Слайд 117Drugs Therapy for Treatment of PUD
5- Antacids
Side Effects
Cation absorption (sodium,
magnesium, aluminum, calcium) leads to systemic alkalosis (concern with renal
impairment)Sodium content an issue with congestive heart failure
Слайд 118Drugs Therapy for Treatment of PUD
5- Antacids
Side Effects
Aluminum hydroxide may
be constipating, Magnesium hydroxide may produce diarrhea so, they used
in combinationCalcium-carbonate containing antacids work rapidly & very effective but large dose may cause calciuria
Слайд 120Drugs Therapy for Treatment of PUD
6- Antibiotics for H. Pylori
Eradication
H. pylori eradication significantly reduce the risk of ulcer
recurrence & re-bleeding & less expensive than chronic antisecretory therapyContinuing antisecretory therapy for > 2 weeks following antibiotic treatment is unnecessary after H.pylori eradication
ABLES A Z et al. American Family Physician. 2007
Слайд 121To Select Therapy for H. pylori Eradication
Duration of treatment
& adverse effects should be
considered
Слайд 122Duration of H. Pylori Eradication Therapy
Until recently, the recommended
duration of therapy for H.pylori eradication was 10 -14 days
There
are number of recent studies evaluated one-, five-, & seven-day regimensAlthough not proven, potential benefits of shorter regimens include better compliance, fewer adverse drug effects, & reduced cost to the patient
ABLES A Z et al. American Family Physician. 2007
Слайд 123Adverse Effects
The most commonly reported adverse events were nausea,
vomiting, & diarrhea
A bitter or metallic taste in the
mouth is associated with eradication regimens containing clarithromycinBismuth subsalicylate may cause a temporary grayish-black discoloration of the stool
ABLES A Z et al. American Family Physician. 2007
Слайд 124Selected Long-Duration Regimens for H. pylori Eradication
ABLES A Z
et al. American Family Physician. 2007
Слайд 125Short-Course Therapy for Eradication of Helicobacter pylori
ABLES A Z
et al. American Family Physician. 2007
Слайд 126Short-Course Therapy for Eradication of Helicobacter pylori
ABLES A Z
et al. American Family Physician. 2007
Слайд 127Short-Course Therapy for Eradication of Helicobacter pylori
ABLES A Z
et al. American Family Physician. 2007
Слайд 128Resistance
Resistant H. pylori has been documented in cases of
failed eradication therapy based on biopsy & culture results &
is of great concern in patients at high risk for complications of H.pylori infection ABLES A Z et al. American Family Physician. 2007
Слайд 129Resistance
Resistance rate to clarithromycin is currently 2-30% & to
metronidazole 15-66%
Primary resistance to clarithromycin is a strong predictive risk
factor for treatment failure, whereas primary resistance to metronidazole does not always lead to treatment failure ABLES A Z et al. American Family Physician. 2007
Слайд 130Resistance
70 % of patients failing one or more regimens
responded well to triple-drug therapy that included:
Pantoprazole, amoxicillin, & levofloxacin for 10 days
ABLES A Z et al. American Family Physician. 2007
Слайд 131Resistance
A meta-analysis of current literature on treatment of resistant
H. pylori showed benefit in using quadruple drug therapy, including:
Clarithromycin
+ ranitidine + bismuth + amoxicillin (1 g twice daily) therapy, as well as a combination of PPIs (standard dosage for 10 days) + bismuth + metronidazole + tetracycline
ABLES A Z et al. American Family Physician. 2007
Слайд 132Recurrence
Recurrence of H. pylori infection is defined by:
A positive result on urea breath or stool antigen
testing six or more months after documented successful ABLES A Z et al. American Family Physician. 2007
Слайд 133Recurrence
Risk factors for recurrence include:
Non-ulcer dyspepsia
Persistence of chronic gastritis
after eradication therapy
Female gender
Intellectual disability
Younger age
High rates of primary infection
Higher
urea breath test values ABLES A Z et al. American Family Physician. 2007
Слайд 134Recurrence
Recurrence rates worldwide vary but lower in developed countries
In
the primary care setting, physicians may choose to treat recurrences
with an alternative eradication regimen, depending on symptoms & risk factors for complications of infectionIt is too early to know whether shorter courses of eradication therapy will be associated with a higher resistance rate
ABLES A Z et al. American Family Physician. 2007
