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Презентация на тему Peptic ulcer diseases: treatment
Содержание
- 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. Скачать презентацию
- 136. Похожие презентации
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
Слайд 2
Introduction
Peptic ulcer disease (PUD) is a common
disorder that affects millions of individuals worldwide
accounting for roughly 10% of medical costs for digestive diseases
Слайд 3
Introduction
Major advances have been made in the
understanding PUD pathophysiology, particularly the role of Helicobacter pylori
infection & NSAIDsThis has led to important changes in diagnostic & treatment strategies, with potential for improving clinical outcome & decreasing health care costs
NSAIDs= nonsteroidal anti-inflammatory drugs
Слайд 4
Definitions
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 5
Definitions
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 7
Gastric Mucosa & Secretions
The inside of the stomach
is bathed in about 2 liters of gastric juice
every dayGastric 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 8
Gastric 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 9
Negative 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 10
Pathophysiology
A peptic ulcer is a mucosal break, 3
mm or greater in size with depth, that can
involve mainly the stomach or duodenum.
Слайд 11
Pathophysiology
Two major variants in peptic ulcers are commonly
encountered in the clinical practice:
Duodenal Ulcer (DU)
Gastric Ulcer (GU)
Слайд 12
Pathophysiology
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 13
Pathophysiology
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 14
Pathophysiology
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 15
Etiology
The two most common causes of PUD
are:
Helicobacter pylori infection ( 70-80%)
Non-steroidal anti-inflammatory drugs (NSAIDS)
Слайд 16
Etiology
Other uncommon causes include:
Gastrinoma (Gastrin secreting tumor)
Stress ulceration
(trauma, burns, critical illness)
Viral infections
Vascular insufficiency
Слайд 18
H.pylori Epidemiology
One half of world’s population has H.pylori
infection, with an estimated prevalence of 80-90 % in
the developing worldThe annual incidence of new H. pylori infections in industrialized countries is 0.5% of the susceptible population compared with ≥ 3% in developing countries
Слайд 21
Pathogenesis 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 22
Pathogenesis of H. pylori infection
The Flagellae make it
motile, allowing it to live deep beneath the mucus
layerIt uses an adhesin molecule to bind to epithelial cells Where the pH there is close to neutral
Слайд 23
Pathogenesis 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 24
Pathogenesis 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 25
Pathogenesis 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 26
Pathogenesis 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 27
Carcinogenic effect of H. pylori
H. pylori
Host
Factors
Other environmental
Factors
Antral gastritis
Pangastritis
DU
GU
Gastritis Cancer
Слайд 28
Carcinogenic 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 29 For 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 31
NSAIDS
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 32
NSAIDS
Inhibits the production of prostaglandins precursor from membrane
fatty acids resulting in:
1. Decrease mucus & HCO3
production2. Decrease mucosal blood flow
3. Reduce cell renewal
The drugs also generate oxygen-free radicals & products of the lipoxygenase pathway that may contribute to ulceration
Слайд 33
NSAIDS
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 34
NSAIDS
Users of NSAIDs are at approximately 3 times
greater relative risk of serious adverse gastrointestinal events than
nonusers
Слайд 35
NSAIDS
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 38 Does 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 39 Does 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 40 Recommendations 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 bothСлайд 41 Recommendations 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 42
Clinical Presentation
Recurrent epigastric pain (the most common symptom)
Burning
Occurs
1-3 hours after meals
Relieved by food ? DU
Precipitated by
food ? GURelieved by antacids
Radiate to back (consider penetration)
Pain may be absent or less characteristic in one-third of patients especially in elderly patients on NSAIDs
Слайд 43
Clinical Presentation
Nausea, Vomiting
Dyspepsia, fatty food intolerance
Chest discomfort
Anorexia, weight
loss especially in GU
Hematemesis or melena resulting from gastrointestinal
bleeding
Слайд 46
Diagnosis of PUD
In most patients routine laboratory
tests are usually unhelpful
Diagnosis of PUD depends mainly
on endoscopic and radiographic confirmation
Слайд 49
Diagnosis 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 50
Diagnosis of H. pylori
Non-invasive
1. C13
or C14 Urea Breath Test
The best test for
the detection of an active infection
Слайд 51
Diagnosis 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 52
Diagnosis of H. pylori
Invasive
Upper GI endoscopy
Highly sensitive test
Patient
needs sedation
Has both diagnostic & therapeutic role
Слайд 53
Diagnosis 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 54
Diagnosis 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 55
Diagnosis of H. pylori
Invasive (endoscopy)
* Histopathology
Done if the
rapid urease test result is negative
* CultureUsed in research studies and is not available routinely for clinical use
Слайд 56
Diagnostic Tests for Helicobacter pylori
Invasive
ABLES A
Z et al. American Family Physician. 2007
Слайд 57
Diagnostic Tests for Helicobacter pylori
Noninvasive
ABLES
A Z et al. American Family Physician. 2007
Слайд 58
Diagnostic Tests for Helicobacter pylori
Noninvasive
ABLES
A Z et al. American Family Physician. 2007
Слайд 59
Diagnostic Tests for Helicobacter pylori
Noninvasive
ABLES
A Z et al. American Family Physician. 2007
Слайд 60
Testing 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 61
Testing 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 62 Diagnosis 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 63
PUD – Complications
Bleeding
Perforation
Gastric outlet or duodenal obstruction
Chronic
anemia
Слайд 66
Treatment 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 67
General 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 68
General 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 69
Drugs Therapy
H2-Receptors antagonists
Proton pump inhibitors
Cyto-protective
agents
Prostaglandin agonists
Antacids
Antibiotics for H. pylori eradication
Слайд 71
Management 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 72
Healing 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 73 Best 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 74
The Astronaut Study
Ranitidine 150 mg twice daily Vs.
Omeprazole 20 or 40 mg daily
Gastroduodenal ulcer healing rates
at 8weeksRanitidine 87% & Omeprazole 20 mg 71%
Слайд 75 Are 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 treatmentСлайд 76 Reducing 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 77 Reducing 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 patientСлайд 78 Reducing 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 79
Preventing 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 80
Drugs Therapy for Treatment of PUD
1- H2-Receptors antagonists
2- H+, K+ ATPase: Proton pump inhibitors (PPIs)
3-
Cyto-protective agent (Sucalfate)4- Prostaglandin agonists
5- Antacids
6- Antibiotics for H. pylori eradication
Слайд 82
Degree 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 83 The 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 84
The 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 85
Drugs 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 86
Drugs 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 87
Drugs Therapy for Treatment of PUD
1- H2-Receptors Antagonists
Agents
Cimetidine
800mg OD or 400mg BID
Ranitidine 300mg OD or 150mg
BIDFamotidine 40mg OD or 20mg BID
Nizatidine 300mg OD or 150mg BID
Should by taken for 6-8 weeks
Слайд 88
Drugs 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 89
Drugs 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 90
Drugs 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 91
Drugs Therapy for Treatment of PUD
1- H2-Receptors Antagonists
Drug
Interactions
Famotidine & Nizatidine has no effect on hepatic drug
metabolismCombining H2 inhibitor with antacid has little rationale although is done. H2 antagonist + PPI inhibits efficacy of PPI
Over the counter H2 blockers now available, labeled for short-term use in heartburn & dyspepsia
Слайд 92
Drugs 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 93
Drugs 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 hr
Mearin & Ponce. Drugs, 2005
Слайд 94
Drugs Therapy for Treatment of PUD
2- Proton Pump
Inhibitors (PPIs)
Agents
Omeprazole
Lansoprazole
Pantoprazole
Rabeprazole
Esomeprazole
1st Generation
2nd Generation
Слайд 95
Drugs Therapy for Treatment of PUD
2- Proton Pump
Inhibitors (PPIs)
Pharmacological Effect
PPIs dose-dependently inhibit basal & food acid
secretionDecreases pepsinogen secretion &, due to the increase in intragastric pH, inhibit the proteolytic activity of pepsin
Mearin & Ponce. Drugs, 2005
Слайд 96
Drugs 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 97
Drugs 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 98
Drugs 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 99
Drugs 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 100
Drugs 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 secretion
Mearin & Ponce. Drugs, 2005
Слайд 101
Drugs 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 102
Drugs Therapy for Treatment of PUD
2- Proton Pump
Inhibitors (PPIs)
Pharmacokinetics
What is Esomeprazoie?
It is the S isomer of
omeprazolePharmacokinetic & pharmacodynamic studies suggest that this isomer undergoes less first-pass metabolism in the liver & has a lower plasma clearance as compared with omeprazole
Mearin & Ponce. Drugs, 2005
Слайд 103
Drugs 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 104
Drugs 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 105
Drugs 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 PPI
Mearin & Ponce. Drugs, 2005
Слайд 106
Drugs 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 107
Drugs 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 agents
Studies 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 108
Drugs Therapy for Treatment of PUD
3- Cyto-Protective Agent
( Sucalfate)
Sucralfate = complex of Aluminum Hydroxide & Sulfated
SucroseBinds 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 109
Drugs 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 110
Drugs Therapy for Treatment of PUD
3- Cyto-Protective Agent
( Sucalfate)
Side Effects
Constipation; black stool & dry mouth
It is
very safe in pregnancy
Слайд 111
Drugs Therapy for Treatment of PUD
4- Prostaglandin Agonists
(PGE1) Misoprostol
Inhibits secretion of HCl & stimulates secretion of
mucus & bicarbonatemisIt is a methyl analog of PGE1
It is approved for prevention of ulcer induced by NSAIDs
Слайд 112
Drugs Therapy for Treatment of PUD
4- Prostaglandin Agonists
(PGE1) Misoprostol
Optimal role in ulcer treatment is difficult to
definePPIs may be as effective as misoprostol for this indication
Routine 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 113
Drugs 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 & cramps
Category X
Слайд 114
Drugs 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 substance
Antacids vary in palatability & price
Слайд 115
Drugs 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 116
Drugs 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 117
Drugs 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 118
Drugs 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 120
Drugs 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 121
To Select Therapy for H. pylori Eradication
Duration
of treatment & adverse effects
should be considered
Слайд 122
Duration of H. Pylori Eradication Therapy
Until recently,
the recommended duration of therapy for H.pylori eradication was
10 -14 daysThere are number of recent studies evaluated one-, five-, & seven-day regimens
Although 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 123
Adverse 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 124
Selected Long-Duration Regimens for H. pylori Eradication
ABLES
A Z et al. American Family Physician. 2007
Слайд 125
Short-Course Therapy for Eradication of Helicobacter pylori
ABLES
A Z et al. American Family Physician. 2007
Слайд 126
Short-Course Therapy for Eradication of Helicobacter pylori
ABLES
A Z et al. American Family Physician. 2007
Слайд 127
Short-Course Therapy for Eradication of Helicobacter pylori
ABLES
A Z et al. American Family Physician. 2007
Слайд 128
Resistance
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 129
Resistance
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 130
Resistance
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 131
Resistance
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 132
Recurrence
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 133
Recurrence
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 infectionHigher urea breath test values
ABLES A Z et al. American Family Physician. 2007
Слайд 134
Recurrence
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
