ahmed mayet pharm.d.,bcps associate professor king saud university

Ahmed Mayet Pharm.D.,BCPSAssociate ProfessorKing Saud University

Upper GI Disorders

Peptic ulcer disease includes duodenal ulcer, gastric ulcer, gastritis, duodenitis, Zollinger Elison syndrome

Gastroesophgeal Reflex Disease (GERD)

Stress ulcer

Peptic Ulcer

Ulcerative disorders of the upper GI tract involving most proximal portion of the duodenum and the stomach

Peptic Ulcer Disease

Peptic Ulcer

What is a peptic ulcer? An ulcer is an erosion of the gut wall, formed in the

presence of gastric acid and pepsin, extending to the sub-mucosa or deeper.

http://endeavor.med.nyu.edu/courses/physiology/courseware/ulcers/intro/intro01.html




Causes of Ulcer

The inside of the stomach is bathed in about 2 liters of gastric juice every day

Gastric juice is composed of digestive enzymes & concentrated hydrochloric acid, which can readily digest the toughest food or microorganism

The gastroduodenal mucosal integrity is determined by protective (defensive) & damaging

(aggressive) factors

Causes of Ulcer

The Defensive Forces

Bicarbonate

Mucus layer

Mucosal blood flow

Prostaglandins

Growth factors

The Aggressive ForcesHelicobacter 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

Causes of Ulcer

Imbalance between aggressive factors and defensive factors resulting in peptic ulcer

Aggressive factors vs. defensive factors Aggressive factors

Hydrochloric acid Pepsin NSAIDS H.Pylori

Defensive factors

Mucus Bicarbonate Epithelial cell

junction Blood flow

Defensive factors mediator Prostaglandins

Mediate production of mucus Mediate secretion of bicarbonate Regulate gastric mucosal blood flow Inhibit acid secretion

Why do all humans develop peptic ulcer?

The normal capacity of gastric and proximal duodenal mucosa to resist the corrosive effects of acid and pepsin is unique.

Parietal Cell

Found along the course of mucosal glands of the body and fundus of the stomach, secrete Hydrochloric acid (HCL)

Pepsin

Pepsinogen produce by chief cell and mucus cell (body) and convert to pepsin by HCL

Pepsin work well if pH is below 2 and inactivated in neutral pH

Pepsin has corrosive effect

Cigarette smoking

Stimulation of gastric acid secretion and bile salt reflex

Alteration in mucosal blood flow Reduction in prostaglandin synthesis Lower bicarbonate secretion

NSAIDS

Direct irritation to GI mucosa causing ulcer

Decrease prostaglandin synthesis lead to decrease blood flow, mucus secretion, decrease bicarbonate secretion

H Pylori

Aggressive factors Major cause of peptic ulcer disease Up to 90% cause of duodenal ulcer Up to 70% cause of gastric ulcer Release toxic substances to cause

ulcer Survive well in gastric mucosa

(antrum)

H Pylori

Cause inflammatory process in GI mucosa

Decrease mucus viscosity Increase acid permeability Increase serum gastrin level Increase parietal cell mass and acid

secretion

Prevalence

Duodenal ulcer is more in men than in women

Gastric ulcer is same as in men and women

Gastric ulcer and duodenal ulcer are increase with age.

Clinical Presentation

Duodenal Ulcer Burning, gnawing, and

aching abdominal pain occur when stomach is empty or just before the meal or at sleep and relieve by food and antacid.

Patients are over weight Patient may or may not

has pain

Gastric ulcer Burning, gnawing, and

aching abdominal pain occur 1 to 3 hours after the meal and relieve by induced vomiting.

Patients are usually thin. Patient may or may not

has pain

Complication

Bleeding ulcer Perforation of the stomach or

duodenum into peritoneal cavity Pyloric outlet obstruction Penetration of the ulcer into

pancreas

Diagnosis

Upper GI endoscope examination Barium examination All gastric ulcer patient’s must be

biopsied to rule out gastric ulcer

Treatment goals

Promote ulcer healing Relieve pain Prevent recurrence Prevent bleeding Prevent perforation Prevent gastric outlet obstruction

TreatmentGeneral Measures Avoid NSAID Avoid smoking Avoid caffeine - containing

beverages if can not tolerate Avoid spicy food if can not tolerate Eat small meals in DU more

frequently Do not eat large meal in GU

Drugs Therapy

H2 receptor antagonists Proton pump inhibitors Cytoprotective agents Prostaglandin agonists Antacids Antibiotics for H Pylori eradication

H2 receptor antagonists

Histamine release from mass cells, bind to H2 receptors and activates adenylate cyclase and increase the levels of Camp and activate the proton pump of the parietal cell hydrogen ions secretion. H2 receptors antagonists block this process.

Very effective in the treatment of PUD. Very easy to administer (use) If administer for 6 to 8 weeks, H2 blocker can

heal duodenal ulcer 75% and 90% respectively. Can be given one single dose at bed time or two

divided dose

H2 receptor antagonists continue

To treat duodenal ulcer or gasrtic ulcer for 6 to 8 weeks

Famotidine 40mg od or 20mg bid Nizatidine 300mg od or 150mg bid Ranitidine 300mg od or 150mg bid Cimetidine 800mg od or 400mg bid


Rapidly absorb (1 to 3 hours to peak) Bioavailability range from 30% to 88%

because of high first pass metabolism Nizatidine is 98%( availability) Ranitidine and cimetidine hepatic

metabolism is the major pathway whereas famotidine and nizatidine is renally excreted. Some dose adjustment is needed in renal and hepatic failure patients


Adverse effects Diarrhea and constipation Mental confusion, dizziness,

headache Rash Cimetidine has antiandrogenic effect

cause gynecomastia and impotence Hepatotoxicity with rinatidine Most adverse effects seen in elderly


Drugs interaction

Increase serum levels of phenytoin, nifedipine, procanamide, theophylline, warfarin, benzodiazepine, carbamazapine, propanonol, qunidine.

Cytochrome P450 inhibition is highest with cimetidine

Nizatidine and famotidine has the least interaction.

Decrease the absorption of iron

Proton Pump Inhibitors

Irreversibly bind to K+ _ H+ ATPase Total shut down of acid secretion Work at late in the acid production

cycle. Very effective in the treatment of PUD. Very easy to administer (use) If administer for 4 to 6 weeks, PPIs can

heal duodenal ulcer and gastric ulcer upto 90% .

Can be given one single dose at bed time or two divided dose

Proton Pump Inhibitors continue

To treat duodenal ulcer or gasrtic ulcer for 4 to 6 weeks

Omeprazole 40 mg od or 20 mg bid Lansoprazole 60 mg od or 30 mg bid Pantaprazole 80 mg od or 40 mg bid


Unstable in acid media and granules are enteric coated

Rapidly absorb (2 to 4 hours to peak) Bioavailability range from 50% to 80% Omeprazole and lansoprazole are

prodrugs All of them work systemically (not locally) All of them are entirely metabolite in liver No dose adjustment is needed in renal

impairment and adjustment may be need in severe liver disease


Adverse effects

Nausea, abdominal discomfort, dizziness, headache

Increase liver enzymes


Drug interactions

PPIs bind to P450 oxidative enzymes Omeprazole decrease the

metabolism of diazepam, pheytoin, warfarin, tobutamide (increase the levels)

Lasoprazole is not shown to be interact with above drugs

Sucalfate cytoproctective drugs

Bind to damaged and ulcerative tissue forming a physical barrier to injury from aggressive forces such as acid and pepsin

Not absorbed systemically Requires acidic media to be dissolve and

coated Can not be given with H2 blockers, PPIs,

Antacids or any acid suppressors Can not be given with food (must be given

one hour before meals or 3 hours after meals.

Very safe in pregnancy


Can be given 1 gram 4 times daily or 2 gram 2 times daily.

As effective as H2 blockers Must be given for 6 to 8 weeks Large tablet and difficultly to swallow


Adverse effects

Constipation, dry mouth, nausea, rashes

Anacids neutralizing agent and cytoproctective

Neutralizing and cytoprotective effects Requires large amount of neutralizing capacity

(30cc one hour and three hours after the meals and bedtimes to heal the ulcers)

Very inconvenience to administer Very unpleasant taste Only use as needed to relieve ulcer pain in

conjunction with other acid suppressors such as H2 blockers and PPIs

Work within 5 to 15 minutes and duration of relieve last for 2 hours.

Liquid form is more effective than tablet form


Anacids contain either sodium bicarbonate, aluminum hydroxide, magnesium hydroxide, calcium carbonate

Sodium bicarbonate fast acting antacid by absorbs systemically and can cause alkalosis if use for long times

Aluminum hydroxide is always combine with magnesium or calcium because it is a weak antacid and cause constipation

Magnesium hydroxide antacid causes diarrhea and therefore need to combine with aluminum hydroxide


Small amount of antacid can be absorbed and not harmful if patient has good renal function

Avoid magnesium containing antacid in renal failure patient

Calcium carbonate containing antacids work rapidly and very effective but large dose may cause gastric acid secretion and calciuria


Antacids alter gastric pH and interfere with the absorption of many drugs. (digoxin and phenytoin, ketoconazole)

Decrease the bioavailability of cimetidine by 50%, ranitidine and famotidine by 30% if take together with antacids.

May dissolve enteric coated tablets at stomach which suppose to be dissolve at somewhere else.

Decrease antibiotics absorption (ciprofloxacin by 50% and tetracycline etc)

Relapse Rate

Duodenal Ulcer

One Year

80% to 90%

Two Year

100%

Gastric Ulcer 70%

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 ulcers

The effects of aspirin & NSAIDs on the gastric mucosa ranges from mucosal hemorrhages to erosions & acute ulcers

NSAIDS

Inhibits the production of Inhibits the production of prostaglandinsprostaglandins

precursor from membrane fatty acids resulting precursor from membrane fatty acids resulting

in:in:

1. Decrease mucus & HCO3 production1. Decrease mucus & HCO3 production

2. Decrease mucosal blood flow2. Decrease mucosal blood flow

3. Reduce cell renewal3. Reduce cell renewal The drugs also generate oxygen-free radicals &

products of the lipoxygenase pathway that may contribute to ulceration

PATHOGENESIS OF NSAID-INDUCED GASTROPATHY

Because most NSAIDs are weak acids, they are present in unionized forms in the acidic environment of the stomach.Presence of the drug in this form facilitates diffusion across the GI epithelial cells, with subsequent ionization within the neutral intracellular environment. The ionized form of the drug is then incapable of diffusing out of the cell, a process known as “ion trapping”. As the drug accumulates within the cell, the osmotic gradient produced results in an influx of water causing swelling and eventually cell lysis.

Pharmacotherapy Self Assessment program, 5th Edition NSAID-induced Gastropathy

PATHOGENESIS OF NSAID-INDUCED GASTROPATHY


RISK FACTORS FOR UPPER GI COMPLICATIONSAIN PATIENTS RECEIVING NSAIDS

RISK FACTORS FOR UPPER GI COMPLICATIONSAIN PATIENTS RECEIVING NSAIDS

Risk Factor Odd ratio

RA (vs. OA) 1.5

Low-dose aspirin use alone (< 160 mg/day) 1.6

Corticosteroids 1.6

Age 50–59 years 2.4

Use of nonaspirin (nonselective) NSAID alone 4.1



Aspirin (75–160 mg/day) 5.6

History of uncomplicated ulcer 5.9

Use of more than nonaspirin NSAID daily 9.0

Age older than 80 years 9.2

Anticoagulation 12.7

History of complicated ulcer 15.4Pharmacotherapy Self Assessment program, 5th Edition NSAID-induced Gastropathy

RISK FACTORSRISK FACTORS

The annual incidence of NSAID-related ulcer complications based on:

the number of risk factors present is about 0.8% in patients with no risk factors.

•2% for one risk factor.

•7.6–8.6% for three risk factors.

•18% for four risk factors.


RISK FACTORSRISK FACTORS

• Low risk (absence of any risk factors).

• Moderate risk (one or two risk factors)

• High risk (more than two risk factors or concurrent use of aspirin, corticosteroids, or warfarin)

• Very high risk (more than three risk factors or a history of recent ulcer complication).


Type of NSAID & Risk of UlcerType of NSAID & Risk of Ulcer

Risk Group Drug Relative Risk

Low Ibuprofen

Diclofenac

2.0

4.2

Medium Naproxen

Indomethacin Piroxicam

9.1

11.3

13.7

High Ketoprofen Azapropazone

23.7 31.5

Recommendations for H.pylori Testing & Eradication in NSAID Users

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 possible to determine whether the ulcer complications were caused by NSAIDs or both.

H. Pylori and Low Dose Aspirin (LDA) H. Pylori and Low Dose Aspirin (LDA)

• Eradication of H. pylori infection lower the risk of ulcer recurrence in patients on LDA or NSAIDs

• Treatment with a PPIs in addition to the eradication of H. pylori can significantly reduce the risk of recurrent ulcer complications if LDA or NSAIDs continue

N Engl J Med 2001 Mar 29;344(13):967-73. N Engl J Med 2002 Jun 27;346(26):2033-8.

Association between Gastric Ulcer and

Pylori

NSAIDS

H Pylori

Cancer

Slice 472%

26%

Association between DU and H Pylori

H Pylori

NSAID

Cancer

Other

92%

5%

Characteristics of H Pylori

Spiral or curve shape gram negative rod with flagella Unique ability to colonize the stomach Located on epithelial cell within the mucus layer

Pathogenic properties of H Pylori

Colonizationfactors

Persistencefactors

Disease inducingfactors

Urease productionSpiral shape (motility adhesions)

LPSUREASE

Vacuolating cytotoxitc Catalise Phospholipase

LMW Chemotactic protein Urea

Risk of developing duodenal ulcer

Cag A

Vac A

65% H Pylori

Mode of Transmission

Fecal Oral Water borne

Oral Oral Spouses Dental plaque endoscope

0

20

40

60

80

100

%

10 20-29

40-49

<60

Age

Age specific prevalence of H Pylori

Prevalence of H Pylori in developed and developing countries

0

20

40

60

80

100

10 20 30 40 50 60 70 80

age

%

rapid acq

low incid

none

Factors associated with H Pylori infection

Low socio-economicstatus

Crowded livingconditions

Geographiclocation/E

thnicgroup

Increasingage

Gastroenterolosist

Dentist

H Pyloriinfection

Effects of socio-economic status

0102030405060708090

%

Low Med High

socio- economic status

H Pylori distribution according to crowding index

0

10

20

30

40

50

60

70

%

High Mid Low

crowding index

East

Available Test For H Pylori Infection

Office test

Tests at endoscope

Serology TestUrea Breath Test

Biopsy urease testHistologyCulture

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


Non-invasive 1. C13 or C14 Urea Breath Test

The best test for the detection

of an active infection

Diagnostic Tests for Helicobacter pylori Noninvasive

Test Sensitivity (%)

Specificity (%)

Usefulness

Urea breath test 95 to 100 91 to 98 Requires separate appointments; sensitivity reduced by PPIs, antibiotics, & bismuth-containing compounds; reliable test for cure.

Best available noninvasive test in children but higher false +ve rates in infants & children younger than six years compared with school-age children & adolescents

ABLES A Z et al. American Family Physician. 2007


Non-invasive 1) Serology for H pylori

a. Serum Antibodies (IgG) to H pylori (Not for active infection)

b. Fecal antigen testing (Test for active HP)


Invasive Upper GI endoscopy

Highly sensitive test Patient needs sedation Has both diagnostic & therapeutic role


Invasive (endoscopy)– Diagnostic: Detect the site and 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


Invasive (endoscopy) Rapid urease test ( RUT)

o Considered the endoscopic diagnostic test of choice

o 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 CCOOLLOORR change


Invasive (endoscopy)* Histopathology

o Done if the rapid urease test result is negative

* Cultureo Used in research studies and is not

available routinely for clinical use

Definition

Eradication H Pylori is undetectable after 4 weeks of treatment.

Recurrent H Pylori is detectable after 4 weeks of stopping the therapy

Management of H pylori InfectionChallenge We Face

Ahmed Mayet, Pharm.D.,BCPSAssociate Professor

KSU

One out of ten Americans suffers from peptic ulcer disease during their lifetime.

Ulcers cause an estimated 1 million hospitalizations and 6500 deaths per year.

Annual health care costs of PUD have been estimated at nearly $6 billion.

Burden of PUD on Heath Care System

Burden of PUD on Heath Care System

$3 billion in hospitalization costs, $2 billion in

physician office visits, and $1 billion in decreased

productivity and days lost from work.

Causes of PUD

H.Pylori as a Cause of PUD

95%70%

H pylori Infection

~ ½ of the world’s population carries the organism.

Prevalence varies widely:

> 80% of adults in Japan & South America

~ 40% in United Kingdom

~ 20% in Scandinavia

Fuccio et al, BMJ 2008; 337: 746-750

Indications based on Maastricht consensus report 2000 :

Peptic ulcer disease

Mucosa-associated tissue lymphoma (MALT)

Atrophic gastritis

Post-gastric cancer resection

First degree relatives of gastric cancer patients

Idiopathic Thrombocytopenic Purpura

Who Need H. Pylori Eradication

Maastricht consensus report 2000

Non-invasive:C13 or C14 Urea Breath Test

Stool antigen test

H. pylori IgG titer (serology)

Invasive: (Gastric mucosal biopsy )Rapid Urease test

Histopathology


Why Treat H pylori Infection ?

Disease or condition Benefit

Peptic ulcer (active or healed)Healing; prevention of recurrence;

prevention of recurrent bleeding

Gastric mucosa associated lymphoid

tissue lymphoma (MALT low grade)Durable remission

Uninvestigated dyspepsiaManagement of dyspepsia

symptoms

Patient at increased risk of gastric cancer (1st degree relative of patient with gastric cancer and after gastric cancer resection)

Prevention of development or

recurrence of non-cardia gastric

cancer

Fuccio et al, BMJ 2008; 337: 746-750

Expected Outcomes of H pylori Therapy

In 1997, the Masstricht conferences defined the breakpoint between acceptable & unacceptable therapy as intention-to-treat eradication rate of > 80%

Expected Outcomes of H pylori Therapy

Grading scale for H pylori therapy

Graham et al, Drugs 2008; 68 (6): 725-736

OR

Eradication Therapy

If FailureSalvage Therapy

H Pylori Treatment Regimens

Traditional Regimens:Triple Therapy

Optimal duration: 7,10,or 14 days (controversial)

A meta analysis found that 10 days 4% in eradication 14 days 5% in eradication

Traditional Regimens:Triple Therapy

Is Triple Therapy Still Effective ?

Results of recent comparative studies with >100 patients that tested the combination of a PPI + amoxicillin + clarithromycin.


A randomized trial in Japan highly effective (>90% eradication rate) for metronidazole sensitive strains

Vakil N, Am J Gastroenterol 2009; 104:26-30

Traditional Regimens: Alternative Triple Therapy

Why Does Eradication Therapy Fail ?



Resistance is one of the main causes


In USA, of 347 clinical H pylori isolates collected b/w Dec. 1998 & 2002:


Antimicrobial susceptibility pattern of H. pylori strains in Saudi Arabia and particularly in the western region (A total of 1104 gastric biopsies)


Clarithromycin resistance is the strongest predictor of treatment failure.

When clarithromycin resistance reaches 15-20% eradication rate will be less than the recommended threshold of 80%.

Resistance


Metronidazole resistance does not significantly affect the outcome of therapy.

A higher dose of metronidazole effectiveness in metronidazole-resistant H pylori.

Eradication Failure Metronidazole Resistance

Study of 92 Pts with H. pylori infection Failed 1st line therapy PPI + Amoxicillin + Clarithromycin, antibiotic sensitivity testing was performed and Metronidazole resistance was present in 26%.

Pts received 2nd line therapy PPI + Amoxicillin + Metronidazole ER was: 97% of those who were Metronidazole sensitive 82% of those who were Metronidazole resistant

American Family Physician. 2007

Eradication Failure Metronidazole Resistance

In vitro resistance to metronidazole may not accurately reflect in vivo resistance

Fuccio et al, BMJ 2008; 337: 746-750

Eradication Failure Clarithromycin Resistance

In a retrospective analysis of antimicrobial resistance 53 pts received clarithromycin-based regimens and 13 had clarithromycin resistance.

ER: 87% of those who were clarithromycin sensitive 23% of those who were clarithromycin resistant


Testing for antimicrobial susceptibility has several limitations:

In vitro resistance to metronidazole may not accurately reflect in vivo resistance

Expensive

Not done routinely in most hospitals

Performed on gastric biopsies

Expensive, not well tolerated ,not indicated in several circumstances

Is antimicrobial susceptibility testing essential to H pylori eradication ?

Fuccio et al, BMJ 2008; 337: 746-750

Sensitivity Testing

Benefit of antibiotic sensitivity testing before 1st-line H. pylori eradication: the studies, results

showed insignificant difference between empirical versus sensitivity testing

groups

Benefit of antibiotic sensitivity testing before 2nd-line H. pylori eradication: the studies, results

showed significant difference between empirical versus sensitivity testing groups

Fuccio et al, BMJ 2008; 337: 746-750

In current clinical practice, the role of antimicrobial susceptibility testing is likely to be marginal or not recommended.

Is antimicrobial susceptibility testing essential to H pylori eradication ?

Fuccio et al, BMJ 2008; 337: 746-750

Sensitivity Testing Before 2nd-line Treatment

Sensitivity Testing Before 2nd-line Treatment

OAC7 = PPI bd+amoxicillin 1 gbd+ clarithromycin 500 mg bd 7 days

OAC14 = PPI bd+amoxicillin 1 g bd+clarithromycin 500 mg bd 14 days

OAM14 = PPI bd,amoxicillin 1 g bd,and metronidazole 500 mg bd for 14 day

STG = Susceptibility testing group.

Recurrence rates worldwide vary but lower in developed countries.

In the primary care setting, physicians should choose an alternative eradication regimen for recurrences infection, depending on risk factors.

It is too early to know whether shorter courses of eradication therapy is associated with a higher resistance rate

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 infection

Higher urea breath test values

Recurrence


Traditional Regimens: Quadruple Therapy

•Efficacy remains above 80% when clarithromycin resistance is between 15-20%

• Eradication rate 93% in Europe and 87.7% in USA for 10-day therapy (ITT).

• Optimal duration: 10-14 days

Type Mild Moderate Severe

Nausea ++++ ++++ +

Vomiting +++ +++ +

Loose stools +++ +++ +

Diarrhea ++ +

Metallic taste ++++ ++++ +

Rash + +

Malaise + +

Headache + +

Side effects from Quadruple Therapy (Bismuth)

Compliance > 60 %

Compliance < 60 %

Effect of compliance on eradication ofH Pylori using Quadruple therapy (Bismuth)

Emerging Initial Treatment Regimens

Amoxicillin 100 mg BID

+ clarithromycin 250 mg BID

+ metronidazole 400 mg BID

+

PPI BID

Non-bismuth quadruple therapy


Emerging Initial Treatment Regimens:Sequential Therapy

11 randomized trials.

Eradication rates (ITT):Sequential vs. 7-day triple therapy 93.5% vs. 76.1%Sequential vs. 10-day triple therapy 92.4% vs. 79.2%

3 abstracts included, but excluding them did not alter conclusions.

Tong et al, J Clin Pharm Ther 2009; 34: 41-53

All the studies come from Italy.

Many studies have limitations (sample size, blinding).

Tong et al, J Clin Pharm Ther 2009; 34: 41-53

Salvage Therapies

Aliment Pharmacol Ther 2006; 23:35-44

Levofloxacin 250 mg BID + Amoxicillin 1 gm BID + PPI BID

8 studies compared levofloxacin-based triple therapy with quadruple therapy for treatment failure.

Salvage Therapies

Gisbert et al, Aliment Pharmacol Ther 2006; 23:35-44

Eradication rate with levofloxacin 81% vs. 70% (OR 1.8, 95% CI= 0.94-3.46) (heterogeneity present).

The difference was statistically significant when a single outlier study was removed (OR 2.2, 95% CI= 1.3-3.9).


10-day regimen more effective than 7-day regimen (81% vs. 73%, P < 0.01)

Levofloxacin regimen was better tolerated than quadruple therapy (adverse effects 19% vs. 44%)

Levofloxacin resistance reached high levels in some areas may no longer be an acceptable salvage regimen in those areas


Salvage Therapies

Salvage Therapies


Leukopenia with rifabutin in 25%, myalgia with levofloxacin in 30%

Resistance to rifabutin-like drugs is still quiet low (<5%)


Salvage Therapies

Salvage Therapies


Low cost

Lack of resistance

Not widely available in Europe & western countries

High doses side effects (diarrhea)

Data on efficacy not consistent no definitive conclusions.

Salvage Therapies

Systematic reviews have concluded that the urea breath test is the test of choice (sensitivity and specificity exceed 95%)

Eradication of H pylori should be confirmed at least four weeks after treatment ends.

How can eradication be confirmed ?

Fuccio et al, BMJ 2008; 337: 746-750

It is unclear whether testing to confirm eradication is worthwhile in all patients.

Patients with H. pylori-associated peptic ulcer bleeding should be tested to confirm eradiation after completion of antibiotic treatment.

Is confirmation of H. pylori after eradiation with antibiotic treatment needed?

Aliment Pharmacol Ther. 2005;22:529-37.

Do we need to screen and eradicate H pylori to prevent

gastric cancer?

Epidemiologic evidence suggests that infection with HP is

associated with >2 fold increase risk of gastric cancer.

However, wide-spread screening for H pylori in

asymptomatic individuals cannot be recommended at this

time

Gastric Cancer and H. pylori

Current recommendation is Persons at high risk for gastric cancer (first degree

relatives) should be screened and eradicate if H pylori is positive.



What shall we do in patient with early gastric cancer and positive for H pylori?

In a large-scale multicenter Japanese study, patients who had received endoscopic treatment (surgery) for early gastric cancer were randomized to H pylori eradication and non-eradication groups for investigation of cancer recurrence.

After 3 years of followed up, cancer recurrence was markedly reduced in the eradication group.


Helicobacter 2010 feb 15 (1) 1-20 Lancet 2008;372:392–7.

It is recommended that H pylori infection must be eradicated after the surgery of gastric cancer or in patient with athrophic gastritis.


Helicobacter 2010 feb 15 (1) 1-20 Lancet 2008;372:392–7.

Do we need to eradicate H pylori in patient with MALT lymphoma?

H pylori eradication leads to histologic and endoscopic improvement, as well as regression of MALT lymphoma in 60–80% of H.pylori-positive patients.

H.pylori eradication therapy should be the treatment of choice in such patients. (Evidence level III)

Gastric MALT lymphoma and H pylori

Lancet 1998;342:568. Lancet 1995;345:1591–4.

MALT= Gastric mucosa associated lymphoid tissue lymphoma

Does H. pylori need to be eradicated in NSAIDs users with history of ulcer complication?

Recommendations:

1- Patients who have a history of ulcer complications (bleeding ulcer) should undergo H. pylori testing and should be eradicated in all infected patients because it is not plausible to determine whether the ulcer complications were caused by NSAIDs (including low dose aspirin) or both.

2- In addition, continuous PPIs prophylaxis is recommended such patients.

. .

H.pylori Testing and eradication in NSAID Users

N Engl J Med 2002 Jun 27;346(26):2033-8

Does H. pylori need to be eradicated in naive NSAIDs users without history of ulcer complication?

There is a benefit from screening for H. pylori in naive NSAID users at the start of therapy and eradicate if it is positive. It will lower the prevalence of ulcer.

When compared with PPIs prophylaxis, the preventative effects of H. pylori eradication is inferior.

H. Pylori and NSAIDs

Lancet 2002 Jan 5;359(9300):9-13. Aliment Pharmacol Ther 2005;21:1411–8.

Recommendations

Eradication of H. pylori infection is not always recommended for patients taking NSAIDs but PPIs prophylaxis is recommended in high risk patient.

H. Pylori and NSAIDs

Lancet 2002 Jan 5;359(9300):9-13. Aliment Pharmacol Ther 2005;21:1411–8.

A meta-analysis of 17 studies revealed a signicant increase of the platelet count after H.pylori eradication therapy and improvement of the platelet count is maintained or increased due to eradication therapy.

H.pylori eradication should be the treatment of choice for H.pylori-positive patients with chronic ITP (Evidence level I)

Idiopathic Thrombocytopenic Purpura

Ann Hematol 2003;82:30–2. Am J Med 2005;118:414–9.

Helicobacter 2004;9:443–52. J Gastroenterol Hepatol 2007;22:2233–7.

Eradication therapy is strongly recommended in the Mastricht III Consensus report for patients with H.pylori positive functional dyspepsia* based on significant efficacy shown by a number of meta-analyses .( Evidence level I)

H.Pylori Eradication for Functional Dyspepsia

Gut 2007;56:772–81 Am J Gastroenterol 2007;102:1808–25.

*Absence of any organic disease that can explain the symptoms.

ahmed mayet pharm.d.,bcps associate professor king saud university

Documents

womengastric ulcer

presence of gastric

peptic ulceraggressive

mucus secretion

mucosal blood flowreduction

corrosive effects of

liters of gastric juice

mucosal damage