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Презентация на тему Peptic ulcer diseases: treatment

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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
Peptic Ulcer Diseases: Treatment Prepared by:Dr. Ahmed Y. Mayet Introduction Peptic ulcer disease (PUD) is a common disorder that affects millions Introduction Major advances have been made in the understanding PUD pathophysiology, particularly DefinitionsUlcer:	A lesion on an epithelial surface (skin or mucous membrane) caused by DefinitionsPeptic Ulcer	An ulcer of the alimentary tract mucosa, usually in the stomach Peptic Ulcer Disease Gastric Mucosa & SecretionsThe inside of the stomach is bathed in about Gastric Mucosa & SecretionsThe Defensive ForcesBicarbonateMucus layer Mucosal blood flowProstaglandinsGrowth factorsThe Aggressive Negative Feedback Regulation of Acid Secretion  Antral distention Protein content PathophysiologyA peptic ulcer is a mucosal break, 3 mm or greater in PathophysiologyTwo major variants in peptic ulcers are commonly encountered in the clinical PathophysiologyDU result from increased acid load to the duodenum due to:Increased acid PathophysiologyDU result from increased acid load to the duodenum due to:Smoking impairing PathophysiologyGU results from the break down of gastric mucosa:Associated with gastritis affecting Etiology The two most common causes of PUD are:Helicobacter pylori infection ( 70-80%)Non-steroidal anti-inflammatory drugs (NSAIDS) EtiologyOther uncommon causes include:Gastrinoma (Gastrin secreting tumor)Stress ulceration (trauma, burns, critical illness)Viral infectionsVascular insufficiency 1. Etiology – Helicobacter pylori H.pylori EpidemiologyOne half of world’s population has H.pylori infection, with an estimated H.pylori as a cause of PUD  The majority of PUD patients H.pylori as a cause of PUD95%85% Pathogenesis of H. pylori infection H. pylori is Gram-negative, spiral & has Pathogenesis of H. pylori infectionThe Flagellae make it motile, allowing it to Pathogenesis of H. pylori infectionAny acidity is buffered by the organism's production Pathogenesis of H. pylori infectionIn the cellular level:H. pylori express cagA & Pathogenesis of H. pylori infectionIn the cellular level:vacA gene ? producing Pathogenesis of H. pylori infection- ↓ Somatostatin production from antral D-cells due Carcinogenic effect of H. pylori H. pyloriHost FactorsOther environmental FactorsAntral gastritis Pangastritis DUGUGastritis Cancer Carcinogenic effect of H. pyloriEpidemiologic evidence suggests that infection with HP is For persons at high risk for gastric cancer (e.g., first degree relatives) 2. Etiology -Non-Steroidal Anti-inflammatory Drugs (NSAIDS) NSAIDSSymptomatic GI ulceration occurs in 2% - 4% of patients treated with NSAIDSInhibits the production of prostaglandins precursor from membrane fatty acids resulting in: NSAIDSGastric acid probably aggravates NSAID-induce mucosal injury by - Converting superficial injury NSAIDSUsers of NSAIDs are at approximately 3 times greater relative risk of NSAIDS Identify risk factors: Age > 65 years (3.5-fold increased risk) Smoking Type of NSAID & Risk of Ulcer Does H. pylori Influence the Ulcer Risk in NSAID Users? Does H. pylori Influence the Ulcer Risk in NSAID Users?Many investigators had Does H. pylori Influence the Ulcer Risk in NSAID Users?These conflicting results Recommendations for H.pylori Testing & Eradication in NSAID Users1- Patients who have Recommendations for H.pylori Testing & Eradication in NSAID Users3- Patients who are Clinical PresentationRecurrent epigastric pain (the most common symptom)BurningOccurs 1-3 hours after mealsRelieved Clinical PresentationNausea, VomitingDyspepsia, fatty food intoleranceChest discomfortAnorexia, weight loss especially in GUHematemesis Diagnosis of PUD Peptic Ulcer DiseaseDiagnosis:Diagnosis of ulcerDiagnosis of H. pylori Diagnosis of PUD In most patients routine laboratory tests are usually unhelpful Doudenal Ulcer on EndoscopyDoudenal UlcerNormal doudenal bulb Gastric Ulcer on EndoscopyChronic Gastric Ulcers Diagnosis of H. pyloriNon-invasiveC13 or C14 Urea Breath TestStool antigen testH. pylori Diagnosis of H. pyloriNon-invasive   1. C13 or C14 Urea Breath Diagnosis of H. pyloriNon-invasive Serology for H pyloriSerum Antibodies (IgG) to H Diagnosis of H. pyloriInvasiveUpper GI endoscopyHighly sensitive testPatient needs sedationHas both diagnostic & therapeutic role Diagnosis of H. pyloriInvasive (endoscopy)Diagnostic:Detect the site and the size of the Diagnosis of H. pyloriInvasive (endoscopy)Rapid urease test ( RUT)Considered the endoscopic diagnostic Diagnosis of H. pyloriInvasive (endoscopy)* HistopathologyDone if the rapid urease test result Diagnostic Tests for Helicobacter pylori Invasive ABLES A Z et al. American Family Physician. 2007 Diagnostic Tests for Helicobacter pylori  Noninvasive ABLES A Z et al. American Family Physician. 2007 Diagnostic Tests for Helicobacter pylori  Noninvasive ABLES A Z et al. American Family Physician. 2007 Diagnostic Tests for Helicobacter pylori  Noninvasive ABLES A Z et al. American Family Physician. 2007 Testing to Document HP EradicationSince treatment is not effective is some cases Testing to Document HP EradicationShould be confirmed after end of therapy; noninvasive Diagnosis of H. pylori in patients with bleeding PUIt is limited by PUD – ComplicationsBleedingPerforationGastric outlet or duodenal obstruction Chronic anemia Complications of PUD on Endoscopy  Bleeding DU		 Perforated GU PUD Treatment Treatment Goals Rapid relief of symptomsHealing of ulcerPreventing ulcer recurrencesReducing ulcer-related complicationsReduce General Strategy Treat complications aggressively if presentDetermine the etiology of ulcerDiscontinue NSAID General Strategy Smoking cessation should be encouragedIf DU is diagnosed by endoscopy, Drugs Therapy H2-Receptors antagonists Proton pump inhibitors Cyto-protective agentsProstaglandin agonistsAntacidsAntibiotics for H. pylori eradication Management of NSAIDs Ulcers Management of NSAIDs UlcersThis can be considered under two headings: The healing Healing the Established NSAIDs-Associated UlcerIf possible, NSAID should be stopped, as healing Best Prevention & Treatment for Upper GI Lesions Induced by NSAIDsThere is The Astronaut StudyRanitidine 150 mg twice daily Vs. Omeprazole 20 or 40 Are Better Results Obtained if Additional Inhibition of Gastric Acid Secretion is Reducing Risk of NSAIDs Ulcers by Choice of AgentChoose, where possible, an Reducing Risk of NSAIDs Ulcers by Choice of AgentUse highly selective COX-2 Reducing Risk of NSAIDs Ulcers by Choice of AgentIn low-risk patients such Preventing NSAIDs Ulcers with Co-Prescribed Gastric ProtectantsPatients who continue to require NSAIDs Drugs Therapy for Treatment of PUD1- H2-Receptors antagonists 2- H+, K+ ATPase: Peptic Ulcer Disease - Treatment Degree of Acid Inhibition to Heal an UlcerIt has been reported that The Purpose of Inhibiting Gastric Acid Secretion in cases of Upper GI The Ideal Drug to Achieve Potent Acid inhibitionIdeal drug should be able Drugs Therapy for Treatment of PUD1- H2-Receptors AntagonistsThese agents are capable of Drugs Therapy for Treatment of PUD1- H2-Receptors AntagonistsPrevious recommendations were to administer Drugs Therapy for Treatment of PUD1- H2-Receptors AntagonistsAgentsCimetidine 800mg OD or 400mg Drugs Therapy for Treatment of PUD1- H2-Receptors AntagonistsPharmacokineticsRapidly absorbed 1-3 hrs to Drugs Therapy for Treatment of PUD1- H2-Receptors AntagonistsSide EffectsUsually minor; include headache, Drugs Therapy for Treatment of PUD1- H2-Receptors AntagonistsDrug InteractionsCimetidine slows microsomal metabolism Drugs Therapy for Treatment of PUD1- H2-Receptors AntagonistsDrug InteractionsFamotidine & Nizatidine has Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Same Acid Inhibition Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Same Acid Inhibition Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)AgentsOmeprazole LansoprazolePantoprazoleRabeprazoleEsomeprazole1st Generation2nd Generation Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Pharmacological EffectPPIs dose-dependently Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Comparative Anti-secretory Efficacy Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Side EffectsNo evidence Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)PPIs & Vitamin Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Time of AdministrationShould Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)PharmacokineticsHow can PPIs Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)PharmacokineticsMetabolismPPIs undergo extensive Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)PharmacokineticsWhat is Esomeprazoie?It Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Dose Adjustment in Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Drug InteractionsTheoretically, their Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Presence of H. Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Do PPIs Have Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Do PPI Promote Drugs Therapy for Treatment of PUD3- Cyto-Protective Agent ( Sucalfate)Sucralfate = complex Drugs Therapy for Treatment of PUD3- Cyto-Protective Agent ( Sucalfate)AdministrationShould not be Drugs Therapy for Treatment of PUD3- Cyto-Protective Agent ( Sucalfate)Side EffectsConstipation; black Drugs Therapy for Treatment of PUD4- Prostaglandin Agonists (PGE1) MisoprostolInhibits secretion of Drugs Therapy for Treatment of PUD4- Prostaglandin Agonists (PGE1) MisoprostolOptimal role in Drugs Therapy for Treatment of PUD4- Prostaglandin Agonists (PGE1) MisoprostolAdministrationShould be given Drugs Therapy for Treatment of PUD5- AntacidsWeak bases that react with gastric Drugs Therapy for Treatment of PUD5- AntacidsAntacids contain either Sodium-bicarbonate, Aluminum-hydroxide, magnesium-hydroxide Drugs Therapy for Treatment of PUD5- AntacidsVery inconvenient to administerTablet antacids are Drugs Therapy for Treatment of PUD5- AntacidsSide EffectsCation absorption (sodium, magnesium, aluminum, Drugs Therapy for Treatment of PUD5- AntacidsSide EffectsAluminum hydroxide may be constipating, The Mechanism & Side Effects of Various Acid Suppressive Medications Drugs Therapy for Treatment of PUD6- Antibiotics for H. Pylori Eradication H. To Select Therapy for H. pylori Eradication Duration of treatment & adverse Duration of H. Pylori Eradication Therapy Until recently, the recommended duration of Adverse Effects The most commonly reported adverse events were nausea, vomiting, & Selected Long-Duration Regimens for H. pylori Eradication ABLES A Z et al. American Family Physician. 2007 Short-Course Therapy for Eradication of Helicobacter pylori ABLES A Z et al. American Family Physician. 2007 Short-Course Therapy for Eradication of Helicobacter pylori ABLES A Z et al. American Family Physician. 2007 Short-Course Therapy for Eradication of Helicobacter pylori ABLES A Z et al. American Family Physician. 2007 Resistance Resistant H. pylori has been documented in cases of failed eradication Resistance Resistance rate to clarithromycin is currently 2-30% & to metronidazole 15-66%Primary Resistance 70 % of patients failing one or more regimens responded well Resistance A meta-analysis of current literature on treatment of resistant H. pylori Recurrence Recurrence of H. pylori infection is defined by:   A Recurrence Risk factors for recurrence include:Non-ulcer dyspepsiaPersistence of chronic gastritis after eradication Recurrence Recurrence rates worldwide vary but lower in developed countriesIn the primary H. pyloriThank U ☺
Слайды презентации

Слайд 2 Introduction
Peptic ulcer disease (PUD) is a common

Introduction Peptic ulcer disease (PUD) is a common disorder that affects

disorder that affects millions of individuals worldwide
It is

accounting for roughly 10% of medical costs for digestive diseases

Слайд 3 Introduction
Major advances have been made in the

Introduction Major advances have been made in the understanding PUD pathophysiology,

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 costs

NSAIDs= nonsteroidal anti-inflammatory drugs


Слайд 4 Definitions
Ulcer:
A lesion on an epithelial surface (skin or

DefinitionsUlcer:	A lesion on an epithelial surface (skin or mucous membrane) caused

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,

DefinitionsPeptic Ulcer	An ulcer of the alimentary tract mucosa, usually in the

usually in the stomach or duodenum, & rarely in

the lower esophagus, where the mucosa is exposed to the acid gastric secretion
It has to be deep enough to penetrate the muscularis mucosa

Слайд 6 Peptic Ulcer Disease

Peptic Ulcer Disease

Слайд 7 Gastric Mucosa & Secretions
The inside of the stomach

Gastric Mucosa & SecretionsThe inside of the stomach is bathed in

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 8 Gastric Mucosa & Secretions
The Defensive Forces
Bicarbonate
Mucus layer
Mucosal

Gastric Mucosa & SecretionsThe Defensive ForcesBicarbonateMucus layer Mucosal blood flowProstaglandinsGrowth factorsThe

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

Negative Feedback Regulation of Acid Secretion Antral distention Protein content

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

PathophysiologyA peptic ulcer is a mucosal break, 3 mm or greater

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

PathophysiologyTwo major variants in peptic ulcers are commonly encountered in the

encountered in the clinical practice:
Duodenal Ulcer (DU)
Gastric Ulcer (GU)


Слайд 12 Pathophysiology
DU result from increased acid load to the

PathophysiologyDU result from increased acid load to the duodenum due to:Increased

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

PathophysiologyDU result from increased acid load to the duodenum due to:Smoking

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

PathophysiologyGU results from the break down of gastric mucosa:Associated with gastritis

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 production
Parietal cell damage occur so that acid production is normal or low

Слайд 15 Etiology
The two most common causes of PUD

Etiology The two most common causes of PUD are:Helicobacter pylori infection ( 70-80%)Non-steroidal anti-inflammatory drugs (NSAIDS)

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

EtiologyOther uncommon causes include:Gastrinoma (Gastrin secreting tumor)Stress ulceration (trauma, burns, critical illness)Viral infectionsVascular insufficiency

(trauma, burns, critical illness)
Viral infections
Vascular insufficiency


Слайд 17 1. Etiology – Helicobacter pylori

1. Etiology – Helicobacter pylori

Слайд 18 H.pylori Epidemiology
One half of world’s population has H.pylori

H.pylori EpidemiologyOne half of world’s population has H.pylori infection, with an

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 19 H.pylori as a cause of PUD


The

H.pylori as a cause of PUD The majority of PUD patients

majority of PUD patients are

H. pylori infected


Слайд 20 H.pylori as a cause of PUD
95%
85%

H.pylori as a cause of PUD95%85%

Слайд 21 Pathogenesis of H. pylori infection
H. pylori is

Pathogenesis of H. pylori infection H. pylori is Gram-negative, spiral &

Gram-negative, spiral & has multiple flagella at one end
Transmitted

from person-to-person by Oro–oral or feco-oral spread
No reservoir in animal or water supply

Слайд 22 Pathogenesis of H. pylori infection
The Flagellae make it

Pathogenesis of H. pylori infectionThe Flagellae make it motile, allowing 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 23 Pathogenesis of H. pylori infection
Any acidity is buffered

Pathogenesis of H. pylori infectionAny acidity is buffered by the organism's

by the organism's production of the enzyme urease, which

catalyzes the production of ammonia (NH3) from urea & raises the pH there
The bacterium stimulates chronic gastritis by provoking a local inflammatory response.





Слайд 24 Pathogenesis of H. pylori infection
In the cellular level:
H.

Pathogenesis of H. pylori infectionIn the cellular level:H. pylori express cagA

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

Pathogenesis of H. pylori infectionIn the cellular level:vacA gene ? producing

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

Pathogenesis of H. pylori infection- ↓ Somatostatin production from antral D-cells

from antral D-cells due to antral gastritis
Low somatostatin

will ↑Gastrin release from G-cell ? hypergastrinemia
This 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

Carcinogenic effect of H. pylori H. pyloriHost FactorsOther environmental FactorsAntral gastritis Pangastritis DUGUGastritis Cancer

Factors


Other environmental
Factors
Antral gastritis
Pangastritis
DU
GU
Gastritis Cancer


Слайд 28 Carcinogenic effect of H. pylori
Epidemiologic evidence suggests that

Carcinogenic effect of H. pyloriEpidemiologic evidence suggests that infection with HP

infection with HP is associated with >2 fold increase

risk of gastric cancer
However 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

For persons at high risk for gastric cancer (e.g., first degree

(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 30 2. Etiology -Non-Steroidal Anti-inflammatory Drugs (NSAIDS)

2. Etiology -Non-Steroidal Anti-inflammatory Drugs (NSAIDS)

Слайд 31 NSAIDS
Symptomatic GI ulceration occurs in 2% - 4%

NSAIDSSymptomatic GI ulceration occurs in 2% - 4% of patients treated

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 ulcers
The 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

NSAIDSInhibits the production of prostaglandins precursor from membrane fatty acids resulting

fatty acids resulting in:
1. Decrease mucus & HCO3

production
2. 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

NSAIDSGastric acid probably aggravates NSAID-induce mucosal injury by - Converting superficial


- 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

NSAIDSUsers of NSAIDs are at approximately 3 times greater relative risk

greater relative risk of serious adverse gastrointestinal events than

nonusers

Слайд 35 NSAIDS
Identify risk factors:
Age > 65

NSAIDS Identify risk factors: Age > 65 years (3.5-fold increased risk)

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 36


Type of NSAID & Risk of Ulcer

Type of NSAID & Risk of Ulcer

Слайд 37
Does H. pylori Influence the Ulcer Risk in

Does H. pylori Influence the Ulcer Risk in NSAID Users?

NSAID Users?


Слайд 38 Does H. pylori Influence the Ulcer Risk in

Does H. pylori Influence the Ulcer Risk in NSAID Users?Many investigators

NSAID Users?




Many investigators had attempted to address this question

using case-control or observational studies
To 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

Does H. pylori Influence the Ulcer Risk in NSAID Users?These conflicting

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

Recommendations for H.pylori Testing & Eradication in NSAID Users1- Patients who

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 41 Recommendations for H.pylori Testing & Eradication in NSAID

Recommendations for H.pylori Testing & Eradication in NSAID Users3- Patients who

Users
3- Patients who are about to start receiving NSAIDs,

H. pylori testing & treatment reduces the ulcer risk at an affordable incremental cost
4- 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

Clinical PresentationRecurrent epigastric pain (the most common symptom)BurningOccurs 1-3 hours after

1-3 hours after meals
Relieved by food ? DU
Precipitated by

food ? GU
Relieved 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

Clinical PresentationNausea, VomitingDyspepsia, fatty food intoleranceChest discomfortAnorexia, weight loss especially in

loss especially in GU
Hematemesis or melena resulting from gastrointestinal

bleeding

Слайд 44 Diagnosis of PUD

Diagnosis of PUD

Слайд 45 Peptic Ulcer Disease
Diagnosis:
Diagnosis of ulcer
Diagnosis of H. pylori

Peptic Ulcer DiseaseDiagnosis:Diagnosis of ulcerDiagnosis of H. pylori

Слайд 46 Diagnosis of PUD
In most patients routine laboratory

Diagnosis of PUD In most patients routine laboratory tests are usually

tests are usually unhelpful

Diagnosis of PUD depends mainly

on endoscopic and radiographic confirmation


Слайд 47 Doudenal Ulcer on Endoscopy
Doudenal Ulcer
Normal doudenal bulb

Doudenal Ulcer on EndoscopyDoudenal UlcerNormal doudenal bulb

Слайд 48 Gastric Ulcer on Endoscopy
Chronic Gastric Ulcers

Gastric Ulcer on EndoscopyChronic Gastric Ulcers

Слайд 49 Diagnosis of H. pylori
Non-invasive
C13 or C14 Urea Breath

Diagnosis of H. pyloriNon-invasiveC13 or C14 Urea Breath TestStool antigen testH.

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

Diagnosis of H. pyloriNon-invasive  1. C13 or C14 Urea Breath

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

Diagnosis of H. pyloriNon-invasive Serology for H pyloriSerum Antibodies (IgG) to

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

Diagnosis of H. pyloriInvasiveUpper GI endoscopyHighly sensitive testPatient needs sedationHas both diagnostic & therapeutic role

needs sedation
Has both diagnostic & therapeutic role


Слайд 53 Diagnosis of H. pylori
Invasive (endoscopy)
Diagnostic:
Detect the site and

Diagnosis of H. pyloriInvasive (endoscopy)Diagnostic:Detect the site and the size of

the size of the ulcer, even small and superficial

ulcer can be detected
Detect source of bleeding
Biopsies can be taken for rapid urease test, histopathology & culture

Слайд 54 Diagnosis of H. pylori
Invasive (endoscopy)
Rapid urease test (

Diagnosis of H. pyloriInvasive (endoscopy)Rapid urease test ( RUT)Considered the endoscopic

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

Diagnosis of H. pyloriInvasive (endoscopy)* HistopathologyDone if the rapid urease test

rapid urease test result is negative

* Culture
Used in research studies and is not available routinely for clinical use

Слайд 56 Diagnostic Tests for Helicobacter pylori Invasive
ABLES A

Diagnostic Tests for Helicobacter pylori Invasive ABLES A Z et al. American Family Physician. 2007

Z et al. American Family Physician. 2007


Слайд 57 Diagnostic Tests for Helicobacter pylori Noninvasive
ABLES

Diagnostic Tests for Helicobacter pylori Noninvasive ABLES A Z et al. American Family Physician. 2007

A Z et al. American Family Physician. 2007


Слайд 58 Diagnostic Tests for Helicobacter pylori Noninvasive
ABLES

Diagnostic Tests for Helicobacter pylori Noninvasive ABLES A Z et al. American Family Physician. 2007

A Z et al. American Family Physician. 2007


Слайд 59 Diagnostic Tests for Helicobacter pylori Noninvasive
ABLES

Diagnostic Tests for Helicobacter pylori Noninvasive ABLES A Z et al. American Family Physician. 2007

A Z et al. American Family Physician. 2007


Слайд 60 Testing to Document HP Eradication
Since treatment is not

Testing to Document HP EradicationSince treatment is not effective is some

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

Testing to Document HP EradicationShould be confirmed after end of therapy;

end of therapy; noninvasive testing with UBT is preferred,

4-8 weeks after completion of therapy
If 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

Diagnosis of H. pylori in patients with bleeding PUIt is limited

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 test
Infection 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

PUD – ComplicationsBleedingPerforationGastric outlet or duodenal obstruction Chronic anemia

anemia


Слайд 64 Complications of PUD on Endoscopy
Bleeding DU

Complications of PUD on Endoscopy Bleeding DU		 Perforated GU    Duodenal stricture

Perforated GU

Duodenal stricture

Слайд 65
PUD Treatment

PUD Treatment

Слайд 66 Treatment Goals
Rapid relief of symptoms
Healing of ulcer
Preventing

Treatment Goals Rapid relief of symptomsHealing of ulcerPreventing ulcer recurrencesReducing ulcer-related

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

General Strategy Treat complications aggressively if presentDetermine the etiology of ulcerDiscontinue

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

General Strategy Smoking cessation should be encouragedIf DU is diagnosed by

is diagnosed by endoscopy, RU testing of endoscopically obtained

gastric biopsy sample, with or without histologic examination should establish presence or absence of H. pylori
If 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

Drugs Therapy H2-Receptors antagonists Proton pump inhibitors Cyto-protective agentsProstaglandin agonistsAntacidsAntibiotics for H. pylori eradication

agents
Prostaglandin agonists
Antacids
Antibiotics for H. pylori eradication


Слайд 70
Management of NSAIDs Ulcers

Management of NSAIDs Ulcers

Слайд 71 Management of NSAIDs Ulcers
This can be considered under

Management of NSAIDs UlcersThis can be considered under two headings: The

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

Healing the Established NSAIDs-Associated UlcerIf possible, NSAID should be stopped, as

be stopped, as healing with a histamine H2-receptor antagonist

(H2-RA) will be faster than if the NSAID is continued
PPI 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

Best Prevention & Treatment for Upper GI Lesions Induced by NSAIDsThere

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 continued

Mearin & Ponce. Drugs, 2005


Слайд 74 The Astronaut Study
Ranitidine 150 mg twice daily Vs.

The Astronaut StudyRanitidine 150 mg twice daily Vs. Omeprazole 20 or

Omeprazole 20 or 40 mg daily
Gastroduodenal ulcer healing rates

at 8weeks
Ranitidine 87% & Omeprazole 20 mg 71%

Слайд 75 Are Better Results Obtained if Additional Inhibition of

Are Better Results Obtained if Additional Inhibition of Gastric Acid Secretion

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 76 Reducing Risk of NSAIDs Ulcers by Choice of

Reducing Risk of NSAIDs Ulcers by Choice of AgentChoose, where possible,

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

Reducing Risk of NSAIDs Ulcers by Choice of AgentUse highly selective

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 78 Reducing Risk of NSAIDs Ulcers by Choice of

Reducing Risk of NSAIDs Ulcers by Choice of AgentIn low-risk patients

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

Preventing NSAIDs Ulcers with Co-Prescribed Gastric ProtectantsPatients who continue to require

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

Drugs Therapy for Treatment of PUD1- H2-Receptors antagonists 2- H+, K+


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 81 Peptic Ulcer Disease - Treatment

Peptic Ulcer Disease - Treatment

Слайд 82 Degree of Acid Inhibition to Heal an Ulcer
It

Degree of Acid Inhibition to Heal an UlcerIt has been reported

has been reported that a sustained increase in pH

> 3 would be sufficient to heal an ulcer
However, 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

The Purpose of Inhibiting Gastric Acid Secretion in cases of Upper

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 possible
Both 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

The Ideal Drug to Achieve Potent Acid inhibitionIdeal drug should be

drug should be able to maintain pH > 4

for ≥ 16 hr/day
Such 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

Drugs Therapy for Treatment of PUD1- H2-Receptors AntagonistsThese agents are capable

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 secretion
Studies 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

Drugs Therapy for Treatment of PUD1- H2-Receptors AntagonistsPrevious recommendations were to

recommendations were to administer these agents at least twice

a day, a single bedtime dose may be just as effective & may elicit better compliance
If 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

Drugs Therapy for Treatment of PUD1- H2-Receptors AntagonistsAgentsCimetidine 800mg OD or

800mg OD or 400mg BID
Ranitidine 300mg OD or 150mg

BID
Famotidine 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

Drugs Therapy for Treatment of PUD1- H2-Receptors AntagonistsPharmacokineticsRapidly absorbed 1-3 hrs

absorbed 1-3 hrs to peak
Ranitidine & Cimetidine hepatically metabolized

whereas Famotidine & Nizatidine are renally excreted
Dose adjustment is needed in some renal & hepatic failure patients

Слайд 89 Drugs Therapy for Treatment of PUD
1- H2-Receptors Antagonists
Side

Drugs Therapy for Treatment of PUD1- H2-Receptors AntagonistsSide EffectsUsually minor; include

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

Drugs Therapy for Treatment of PUD1- H2-Receptors AntagonistsDrug InteractionsCimetidine slows microsomal

Interactions
Cimetidine slows microsomal metabolism of some drugs
Cimetidine causes these

in a dose-dependent but reversible manner
Inhibits 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

Drugs Therapy for Treatment of PUD1- H2-Receptors AntagonistsDrug InteractionsFamotidine & Nizatidine

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 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

Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Same Acid

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-H2

Mearin & Ponce. Drugs, 2005


Слайд 93 Drugs Therapy for Treatment of PUD
2- Proton Pump

Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Same Acid

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

Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)AgentsOmeprazole LansoprazolePantoprazoleRabeprazoleEsomeprazole1st Generation2nd Generation

Inhibitors (PPIs)
Agents
Omeprazole
Lansoprazole
Pantoprazole
Rabeprazole
Esomeprazole

1st Generation

2nd Generation


Слайд 95 Drugs Therapy for Treatment of PUD
2- Proton Pump

Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Pharmacological EffectPPIs

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 pepsin

Mearin & Ponce. Drugs, 2005


Слайд 96 Drugs Therapy for Treatment of PUD
2- Proton Pump

Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Comparative Anti-secretory

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 potency
Rabeprazole 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

Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Side EffectsNo

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

Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)PPIs &

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 absorption
This 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

Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Time of

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

Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)PharmacokineticsHow can

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

Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)PharmacokineticsMetabolismPPIs undergo

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 bile
Metabolized 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

Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)PharmacokineticsWhat is

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 omeprazole

Mearin & Ponce. Drugs, 2005


Слайд 103 Drugs Therapy for Treatment of PUD
2- Proton Pump

Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Dose Adjustment

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 patients

Mearin & Ponce. Drugs, 2005


Слайд 104 Drugs Therapy for Treatment of PUD
2- Proton Pump

Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Drug InteractionsTheoretically,

Inhibitors (PPIs)
Drug Interactions
Theoretically, their influence on phenytoin, carbamazepine, warfarin,

& diazepam should be monitored
However, 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

Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Presence of

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

Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Do PPIs

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 cases

Mearin & Ponce. Drugs, 2005


Слайд 107 Drugs Therapy for Treatment of PUD
2- Proton Pump

Drugs Therapy for Treatment of PUD2- Proton Pump Inhibitors (PPIs)Do PPI

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

Drugs Therapy for Treatment of PUD3- Cyto-Protective Agent ( Sucalfate)Sucralfate =

( 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 109 Drugs Therapy for Treatment of PUD
3- Cyto-Protective Agent

Drugs Therapy for Treatment of PUD3- Cyto-Protective Agent ( Sucalfate)AdministrationShould not

( Sucalfate)
Administration
Should not be given with food, give 1hr

before or 3hr after meal
Dose: 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

Drugs Therapy for Treatment of PUD3- Cyto-Protective Agent ( Sucalfate)Side EffectsConstipation;

( 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

Drugs Therapy for Treatment of PUD4- Prostaglandin Agonists (PGE1) MisoprostolInhibits secretion

(PGE1) Misoprostol
Inhibits secretion of HCl & stimulates secretion of

mucus & bicarbonatemis
It 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

Drugs Therapy for Treatment of PUD4- Prostaglandin Agonists (PGE1) MisoprostolOptimal role

(PGE1) Misoprostol
Optimal role in ulcer treatment is difficult to

define
PPIs 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

Drugs Therapy for Treatment of PUD4- Prostaglandin Agonists (PGE1) MisoprostolAdministrationShould be

(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

Drugs Therapy for Treatment of PUD5- AntacidsWeak bases that react with

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

Drugs Therapy for Treatment of PUD5- AntacidsAntacids contain either Sodium-bicarbonate, Aluminum-hydroxide,

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

Drugs Therapy for Treatment of PUD5- AntacidsVery inconvenient to administerTablet antacids

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

Drugs Therapy for Treatment of PUD5- AntacidsSide EffectsCation absorption (sodium, magnesium,

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

Drugs Therapy for Treatment of PUD5- AntacidsSide EffectsAluminum hydroxide may be

hydroxide may be constipating, Magnesium hydroxide may produce diarrhea

so, they used in combination
Calcium-carbonate containing antacids work rapidly & very effective but large dose may cause calciuria

Слайд 119 The Mechanism & Side Effects of Various Acid

The Mechanism & Side Effects of Various Acid Suppressive Medications

Suppressive Medications


Слайд 120 Drugs Therapy for Treatment of PUD
6- Antibiotics for

Drugs Therapy for Treatment of PUD6- Antibiotics for H. Pylori Eradication

H. Pylori Eradication
H. pylori eradication significantly reduce the

risk of ulcer recurrence & re-bleeding & less expensive than chronic antisecretory therapy
Continuing 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

To Select Therapy for H. pylori Eradication Duration of treatment &

of treatment & adverse effects

should be considered

Слайд 122 Duration of H. Pylori Eradication Therapy
Until recently,

Duration of H. Pylori Eradication Therapy Until recently, the recommended duration

the recommended duration of therapy for H.pylori eradication was

10 -14 days
There 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

Adverse Effects The most commonly reported adverse events were nausea, vomiting,

were nausea, vomiting, & diarrhea
A bitter or metallic

taste in the mouth is associated with eradication regimens containing clarithromycin
Bismuth 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

Selected Long-Duration Regimens for H. pylori Eradication ABLES A Z et al. American Family Physician. 2007

A Z et al. American Family Physician. 2007


Слайд 125 Short-Course Therapy for Eradication of Helicobacter pylori
ABLES

Short-Course Therapy for Eradication of Helicobacter pylori ABLES A Z et al. American Family Physician. 2007

A Z et al. American Family Physician. 2007


Слайд 126 Short-Course Therapy for Eradication of Helicobacter pylori
ABLES

Short-Course Therapy for Eradication of Helicobacter pylori ABLES A Z et al. American Family Physician. 2007

A Z et al. American Family Physician. 2007


Слайд 127 Short-Course Therapy for Eradication of Helicobacter pylori
ABLES

Short-Course Therapy for Eradication of Helicobacter pylori ABLES A Z et al. American Family Physician. 2007

A Z et al. American Family Physician. 2007


Слайд 128 Resistance
Resistant H. pylori has been documented in

Resistance Resistant H. pylori has been documented in cases of failed

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%

Resistance Resistance rate to clarithromycin is currently 2-30% & to metronidazole

& 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

Resistance 70 % of patients failing one or more regimens responded

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

Resistance A meta-analysis of current literature on treatment of resistant H.

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

Recurrence Recurrence of H. pylori infection is defined by:  A

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

Recurrence Risk factors for recurrence include:Non-ulcer dyspepsiaPersistence of chronic gastritis after

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 134 Recurrence
Recurrence rates worldwide vary but lower in

Recurrence Recurrence rates worldwide vary but lower in developed countriesIn the

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 infection
It 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


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