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Upper GI Disorders

Peptic Ulcer Disease

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PUD Extremely common disorder

4 million people, 350,000 new cases/year>100,000 hospitalizations/year and 3000

deaths/year Ulcer

Disruption in bowel wall extending deep to the muscular mucosa

Resulting from imbalance of mucosal injury, protection and repair

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Stomach and Duodenum: Normal Anatomy and HistologyThe major regions:

Fundus, Cardia,

Body Transitional Zone Antrum, Pylorus,

Sphincter Duodenum

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In the body & fundus region:Deep within the glands – are parietal

cells (oxyntic cells) which secrete HCl, and – chief cells – which secrete pepsinogen

Mucous cells Cells in the Antrum:

Mucous cells, gastrin-releasing cells (no parietal or chief cells)

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Normal Gastric Physiology Human stomach secretes ~ 2L of HCl

every day Parietal (oxyntic) cells in the stomach

mucosaWhen stimulated secrete acid into the gastric

lumen In resting state: secrete intrinsic factor

(carrier protein for Vit B12) Three substances that stimulate parietal

cells: Acetylcholine, Gastrin, Histamine

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Agonist binds to a specific parietal cell receptor Second messenger systems activate the gastric proton pump (H+/K+ -ATPase)

one-to-one exchange of intracellular H+ for luminal K+ ions (terminal step in acid secretion)

Basal Acid Secretion:The usual circadian rhythm – higher acid secretion in afternoon (2 to 11pm)

lower rates in the morning (5 to 11 am)

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Meal Stimulated Acid secretion: 3 Phases Cephalic – Sensory input initiates acid secretion

(vagus nerves stimulate nerves in gut wall →ACh is released, → stimulates acid secretion)

Gastric – Activated by stimuli within the stomach (acid secretion is controlled by distension → change in acidity, & chemical constituents of food activate vagal nerves to stimulate gastrin release)

Intestinal – Amino acids stimulate parietal cells to release acid→ intraluminal acid, fat, and hyperosmolar solutions inhibit acid

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Protective Mechanisms Within the Gut Wall

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Protective Mechanisms Within the Gut Wall

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The protective factors are balanced with the presence of aggressive factors.

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Definitions Peptic Ulcer Disease: A group of

disorders characterized by erosion of the mucosa anywhere in the GI tract that is exposed to the erosive action of acid and pepsin

Erosions (more superficial) may be reepithelialized rapidly by a process called restitution.

Ulcers extend into the deeper layers of the mucosa and require a more complex healing process.

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Cotran: Robbins Pathologic Basis of Disease, 6th ed., Copyright © 1999 W. B. Saunders Company

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Definitions Duodenal

Associated with acid outputusually seen in the proximal duodenum [the

1st few cm past pyloric sphincter] Increased pepsinogen I (parietal cell mass)

Gastric ( in Stomach)Usually not associated with acid outputoccur mainly in the antrum of the stomach

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Helicobacter pylori.-colonizes the gastric mucosa (normally a harsh environment for bacteria)-adapted itself to establish colonization

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Adaptive mechanisms: Uses flagella to hide in mucous layer away from

acid Produces urease – hydrolyzes urea into CO2 &

ammonia (creates an alkaline microenvironment) Produces mucinase – thins viscous mucous &

allows bacteria to burrow into mucous layer Provides a passageway for hydrogen ions to enter

epithelium. Not all people infected with H pylori develop

ulcers. The only relatively absolute requirements are:1) Secretions of acid & pepsin, 2) H. pylori infxn 3) NSAID use

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Types of PUD1-Non ulcer dyspepsia Dyspepsia: an imprecise symptom

complex that includes: epigastric pain or discomfort, Nausea, belching, bloating.

There is over lap between the symptoms reposted by patients diagnosed with peptic ulcer and dyspepsia

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2-NSAID-Induced Ulcers Symptomatic ulcers occur in only 1% of

patients after 3-6 months of NSAIDs This type of ulcer does not correlate with

pain because analgesic action may mask ulcer pain

Mechanisms of Injury: Produce gastric damage by two

mechanismsDirect irritant effectSystemic effect →inhibition of

cyclooxygenase COX-1 → ↓ PG synthesis

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PG protect the GI mucosa by maintaining blood flow & stimulating bicarbonate & mucus

Low PG impair the ability of the gastric mucosa to withstand aggressive factors

COX –2 inhibitions is responsible for anti-inflammatory and analgesic effects

Ulcers occur more frequently in the stomach than in the duodenum.

Many are painless acute, low-dose NSAID-induced lesions

usually heal spontaneously

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Risk factors Age > 60 yrs, High-NSAID dose OR Use of multiple NSAIDs, Hx of ulcer/complication, Co-morbid illness, Concurrent steroid use, GI sx in past 6 mos requiring discontinuation

of the NSAID or the addition of another drug. Patients taking anticoagulants High surgical risk or Debilitated patients

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Association of steroids and PUD is controversial. Steroids may induce ulcers:↑ gastric acid

secretion, ↓ PG production May delay or inhibit healing of ulcers caused by

NSAIDs. Patients taking steroids considered at high risk Recent studies: elderly taking both steroids and

NSAIDs are at much higher risk of PUD than those receiving either agent alone (related to dose & duration of therapy)

3-Adrenocorticosteroids

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Increased basal & postprandial acid secretion Mechanisms:

Enhanced sensitivity of the parietal cell to vagal stimulation,

Impaired acid inhibitory mechanismsZollinger-Ellison Syndrome: caused by a

gastrin-secreting tumor of the duodenum or pancreas → marked gastric acid hypersecretion & recurrent peptic ulceration.

2/3 of tumors are malignant. Found in ~ 0.1% of patients with duodenal

ulcers.

4-Disorders of Acid Hypersecretion

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Etiology and Pathophysiology Develop only in presence of acid

environment Excess of gastric acid not necessary for

ulcer development Person with a gastric ulcer have normal

to less than normal gastric acidity compared with person with a duodenal ulcer.

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Risk Factors for PUD

Cigarette smoking Genetic factors Psychological & physiological stress -

multiple trauma, sepsis, neurosurgical problems, ICU stresses

Dietary factors

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Chief complaint:Pain (25% are painless) doesn’t always correlate

w/presence of acid or ulcer cratersDuodenal Ulcer Gastric Ulcer

Most common symptom Most common symptom

Sharp, burning, or gnawing Less typical & predictable

Occurs 1-3 hrs after meals May occur during a mealRelieved by alkali & food Food offers little/no

relief; may precipitate itUsually located in RUQ May extend over a

wide area of epigastrumNocturnal; awakens patient (1-2am)

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Clinical presentation of ZE Syndrome

Similar to sever PUD More persistent Less responsive to standard therapy Abdominal pain; most common Sx Diarrhea: because gastrin inhibits

sodium and water reabsorption from intestine

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Complications

Three Major Complications Hemorrhage Perforation Gastric outlet obstruction

Initially treated conservativelyMay require surgery at any time

during course of therapy

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Hemorrhage

Most common complication of peptic ulcer disease

Develops from erosion of Granulation tissue found at base of

ulcer during healing Ulcer through a major blood vessel

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Perforation Most lethal complication of peptic ulcer Commonly seen in large penetrating

duodenal ulcers that have not healed and are healed and are

located on posterior mucosal wall Occurs when ulcer penetrates serosal

surface Size of perforation directly proportional

to length of time patient has had ulcer

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Gastric Outlet Obstruction Active ulcer formation is associated with edema,

inflammation Duodenum can predispose to gastric outlet

obstruction ↑ contractile force needed to empty stomach

results in hypertrophic stomach wall Obstruction is not totally due to fibrous scar tissue Short duration or absence of pain indicative of a

malignant obstruction Vomiting and Constipation are a common complaint

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Diagnosis

Visualization of the ulcer defines the disease 1-Barium Upper GI Study (X-rays)Can show obstruction, perforation, or penetrationCannot show bleeding 30-60% of ulcers can be detected

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2-Endoscopy Most often used Superior test for diagnosis More costly & less patient acceptance

Can visualize the ulcer Can visualize any bleeding Can treat bleeding Determines degree of ulcer healing

after treatment Tissue specimens can be obtained to

identify and to rule out gastric cancer

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Indications for Endoscopy: New onset dyspepsia in pts > 45 yrs old

(to rule out gastric cancer) Patients with “alarm” symptoms:

Evidence of GI bleeding, anemia, unexplained weight loss, recurrent

vomiting, decreased appetite, easy fullness, dysphagia, abdominal mass,

lymphadenopathy Patients whose symptoms have failed to

respond to initial therapy Patients with recurrent or difficult to

control disease

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Laboratory tests Guaiac test on stool sample CBC should be done if the patient’s

stool is guaiac positive Acute blood loss:

Red cell indices: RBC, Hct, Hgb, Normocytic (MCV), Normochromic (MCH)

Chronic blood loss: Iron deficiency: RBC, Hct, Hgb, MCV,

MCH

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Tests for GUT Blood Very important tool for

screening in the clinic setting

Hemoccult (stool) Gastroccult (stomach) Both are based on the

catalytic activity of hemoglobin during the conversion of guiac into a blue pigment in the presence of peroxide

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Diagnosis of ZE syndrome

Measurement of gastric acid secretion >15 mmol/hr in patients with no prior

gastric surgery > 5 mmol/hr in patients with prior

gastric surgery fasting gastrin level > 1000 pg/ml secretin provocative test: secretion will cause a marked increase

in serum gastrin

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H. pylori TestingIndications for H. pylori testing: New onset dyspepsia in patients < 45

years old (with no alarm symptoms) Active peptic ulcer disease PMH of documented peptic ulcer, which

has not been tested for H. pylori Gastric lymphoma

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Methods of diagnosis for Helicobacter pylori

Test Relative cost

Advantages Disadvantages

Histology + + + Permits visualization; most sensitive (2+ specimens)

Requires endoscopy; time-consuming

Culture + + + Allows determination of antimicrobial sensitivity

Requires endoscopy; technically demanding

Requires several days for result

Rapid Urease (CLO-test)

+ Rapid (20 min-2hrs); inexpensive; Simple to perform

Requires endoscopy

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13C Breath Test

+ +

Can be used multiple times; noninvasive; Non radioactive

May not be widely available; requires

expensive equipment (cost ~ $300)

14C Breath Test

+ + Good for follow-up; noninvasive; rapid (60 min), Less expensive than 13C test (cost ~ $50)

Small radiation exposure; not able to repeat test multiple times

Serology

+ Noninvasive; least expensive; rapid; simplest Look for IgG antibodies to H. pylori

Not useful for short-term f/u of antimicrobial therapy, preferred when endoscopy not done Not useful for pts s/p H. pylori Tx

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Stool Antigens

A stool antigen enzyme immunoassay has a sensitivity of about 94% and specificity of about 90%.

It should not be used to test for eradication of H. pylori until 6- 8 weeks after therapy.

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Gold Standard: Gastric biopsy The Rapid UreaseTest is the most popular

and recommended because of its excellent sensitivity & low cost.

The labeled C breath tests utilize H pylori’s ability to hydrolyze urea into ammonia.

Urea labeled with carbon isotope is administered orally

If organism is present, urea is hydrolyzed & pt will exhale labeled Co2 which can be quantified.

14C is radioactive – not recommended for children, pregnant women, or for multiple uses in the same person. 13C is non-radioactive

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The Serological Test An excellent initial screen to determine

infection because the result is known in 20 min.

H. pylori infection elicits an immune response with an increase in IgG and IgA antibodies. There are commercially available tests that measure IgG antibody.

All of the tests – with the exception of serological testing – may be falsely negative in pts who have taken antibiotics, bismuth compounds, or omeprazole in the recent past.

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TherapyTherapeutic Objectives Relieve pain; control symptoms Prevent pain recurrence Prevent further irritation while healing occurs Remove or treat cause if possible Promote healing Prevent complications Maintain the healed ulcer condition

Indices of Therapeutic Effect:A.Pain relief/Absence of painB.Frequency of antacid useC. Endoscopy (to confirm healing – if symptom

response is inadequate

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General Treatment Principles: Establish diagnosis with certainty (poor

symptom correlation) Utilize non-drug modalities, removing potential

exacerbating factor

Non-drug Therapy: Avoid alcohol Stop smoking Avoid caffeine Avoid aggravating foods Reduce stress Eliminate drug- induced causes (NSAIDs, ASA)

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H2-blockers MOASelectively and competitively Inhibit the action of histamine on H2 receptors of the parietal cells → reducing basal and stimulated secretion of gastric acid

Efficacy Equally Effective for:Treatment of acute ulcers in the absence of H. pyloriTreatment of NSAID-induced ulcersMaintenance therapy in patients unable to tolerate a course of antimicrobial therapy to eradicate H. pylori

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1-H2-blockers

Efficacy70-95% heal rate in 4-8 weeksStandard doses inhibit 50- 80% of 24-hour acid secretionEqual in efficacy to antacid, and sucralfate therapy Effective as single therapy in pts with no H pylori infection

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Side effectsSafe, Frequency of SE is lowCommon SE:

Diarrhea, constipation, Mental confusion, headache, dizziness, drowsiness, and rashes

Confusion/agitation occurs more frequently in elderly, renal & hepatic dysfxn

Similar profile (reported more frequently with cimetidine)Mental status changes, diarrhea, headache (2-3%)Rare: bone marrow suppression (thrombocytopenia, agranulocytosis)

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Cimetidine: Prolonged use – gynecomastia, erectile dysfxn, sperm ct (anti-androgen)

Ranitidine: Hepatitis Famotidine:CNS, headache Nizatidine: Sweating, itching, hepatic

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Table 27-4Cimetidine inhibits oxidative metabolism CYP450Magnitude of interaction varies from patient to patientGenerally it will reduce clearance of another drug by 20-30%Clinically significant in drugs with narrow therapeutic windowAddition of cimetidine may require ↓ dosage of the object drug to avoid increased serum concentrationlidocaine, valium, propranolol, metoprolol, warfarin, phenytoin, theophylline

Drug Interaction Profile

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Other H2-blockers have lower affinity for p450 system; fewer drug interactions:

Cimetidine > ranitidine, nizatidine > famotidine

Cimetidine and ranitidine inhibit renal tubular secretion of procanamide and its metabolite

All 4 drugs can affects absorption and reduce bioavailability of some drugs by requiring gastric PH

Cimetidine ↑ PH →slows dissolution of ketoconazole → ↓ absorption

Cimetidine, ranitidine, nizatidine ↑ absorption of ethanol

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See Table 27-1 and Table 1Control of night time acid secretion is more effective in healing ulcers

May be given as a single bedtime dose for treatment of DU

For ZES: Not totally effective, require large doses and more frequent dosing

The dose to heal an ulcer – DU=GUThe dose to maintain a healed ulcer –DU=GUMaintenance dose is cut in half, single daily dose

Route of Administration and Dosing

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2-SucralfateMOAProtects ulcerated mucosa from aggressive factors

It binds to damaged tissue forming a physical barrier to injury

Efficacy1 gm 4 times daily as effective as 2 gms twice daily

Requires acid medium to work (don’t combine with H2-blocker)

As effective as H2-blockers in promoting DU healing

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Side effectsNot absorbed systemicallyConstipation, xerostomia, skin eruptions, nausea, indigestion, dizziness

Contains aluminum (Al); accumulates in pts with renal dysfxn;

Neuro toxicity; seizures Drug Interaction profileAl dissociates from sucralfate: absorption of TCN, phenytoin, warfarin

Chelation with other drugs given simultaneously

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Dosing: 1 gram, four times daily, before meals & at bedtime (compliance)

For duodenal ulcer, 2 grams bid (before breakfast & at bedtime) may be as effective

Large tablet size – may be difficult to swallow

Route of Administration and Dosing Frequency

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3-Antacids MOARelive pain and promote healing by providing a cytoprotective effect through stimulation of PG

Neutralizing gastric acidStimulating restitution of the gastric mucosa

EfficacyLow to moderate doses may be as effective in healing duodenal ulcers as H2 blockers if taken multiple times a day

neutralize acid; inhibit pepsinogen to pepsin, bile salts

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Antacids High dose as effective as H2-blockers May provide less symptom relief than H2-

blockers High dose: 30 cc po 1hr before & 3 hrs after

each meal & at bedtime (7 doses) May accelerate healing of GU (lack of data to

confirm it, but likely) Currently used for symptomatic relief in addition

to H2-blockers or sucralfate Primarily used on as PRN for pain Liquid formulation are more rapid acting

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Side EffectsAluminum antacids Reacts with intestinal bicarbonatelow alkalosis risk Constipation, hypophosphatemia, renal accumulationMagnesium antacids :Reacts with intestinal bicarbonate - low alkalosis risk, Diarrhea (dose-related), avoid in CRF Combination (Al/Mg) Less ADRs; lower doses usedSodium bicarb: Patients with poor renal fxn –metabolic alkalosis, Sodium overload – 12 Meq/g (edema, CHF, CRF, HTN)

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Calcium antacidsConstipation, rebound hyperacidity (may

not be clinically signif.) More potent & prolonged neutralization,

Systemicalkalinization, milk alkali syndrome, pH ,

Ca++ kidney stonesMalgaldrate: chemical entity composed of aluminum &

magnesium hydroxides (not a physical mixture & lower neutralizing capacity)

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Drug Interaction ProfileChelation – divalent/trivalent cations bind drugs & absorption e.g ciprofloxacin, TCNGastric pH – interfere w/drugs requiring low pH for absorption e.g digoixn, phenytion, isoniazidUrinary pH – may affect drugs requiring acidic/basic urine for elimination

May reduce absorption of tetracyclines, iron, digoxin, & many other drugs

Can reduce absorption of H2-blockers, may effect of sucralfate

Avoid taking other meds 1-2 hrs before & after taking an antacid

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Route of Administration and Dosing frequency

Tablets: chewed/dissolved, palatable. Suspensions work faster; more surface area

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4-Proton Pump Inhibitors: PPI

MOA:Specific inhibitors of gastric acid secretion by irreversible biding to K+-H+ - ATPase ( enzyme which transports acid across parietal cells)

Inhibit basal and stimulated acid secretion

Indicated for short-term treatment of DUIndicated for long-term treatment of ZES

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PPIEfficacyAbsolute healing rates are similarSuperior to H2-blockers with regard to onset of healing & pain relief

Effective in patients refractory to H2-blockers.

may be more efficacious than H2-blockers for the prevention of recurrent GU and DU in patients who must continue on NSAID therapy.

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PPIEfficacyStandard doses inhibit more than 90% of 24-hour acid secretion.

For DU: Omeprazole 20 mg qd 90 –100% healing in 4 weeks

Lansoprazole 30 mg qd 90 – 100% healing in 4 wks

For GU: As effective as H2-blockers for healing ulcer

Higher doses may provide faster relieof pain, recurrence

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For ZES: Long-term efficacy has been observed Decreases diarrhea, heals ulcers Daily dose of 120 mg (mean daily dose 60-

70mg) controls symptoms in > 90% of ptsSide Effects May cause headache, diarrhea, abdominal

pain, nausea, dizziness. Concern over long-term use & development of

carcinoid tumors Treatment: acid will pH; which gastrin

secretion – possible ECL cell hyperplasia (recommended to check serum

gastrin levels annually in pts on long-term therapy)

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PPI : Drug Interaction ProfileAll agents are extensively metabolized by

cytochrome p450 Omeprazole: Inhibitor of oxidative metabolism by p450

systemMay diazepam, phenytoin, warfarin, etc. Omeprazole and Clarithromycin →

concentration of both drugsLansoprazoleMetabolized through p450 system: may

clearance of theophylline (10%)Sucralfate Reduces absorption of PPIsDrugs whose absorption may be impaired from reduced acidity: Ketoconazole, iron, ampicillin, etc.

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Route of Administration and Dosing

See table 1 & 2Rabeprazole is available as a 20mg enteric-coated tablet; dosed once daily.

Pantoprazole is dosed 40mg po qdFor ZES: Longer duration of action so require less frequent dosing

Large doses are necessaryStart at 60mg lansoprazole or 80mg omeprazole po qd

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5-Prostaglandin E1 Analog

MOAInhibits basal & nocturnal gastric acid secretion;

Enhances mucous & bicarb secretion;Reduces pepsin concentration but does not affect histamine stimulated secretion.

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Prostaglandin E1 AnalogEfficacy For prevention of NSAID-induced gastric

ulcers in patients at high risk. Superior to sucralfate in preventing

NSAID-induced gastric ulcers Superior to H2-blockers in reducing

mucosal injury, but may relieve pain less rapidly (H2-blockers more effective for inhibiting gastric acid output, especially at night)

May be effective in healing H2 blocker-resistant ulcers

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Side Effects: Diarrhea, abdominal pain, nausea,

headache, flatulence, constipation Can GFR and improve renal function Contraindicated in women of childbearing

age unless effective contraceptive measures are used (may cause uterine contractions; abortifacient).

Take with or after meals and at bedtime to reduce ADRs

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Drug Interaction Profile No effect on cytochrome p450 system Use of Mg-containing antacids can worsen

misoprostol-induced diarrhea (use an Al-antacid)

Dosing: 200 g qid If patient unable to tolerate: can be given

100 g qid OR 200 g bid or tid (also a small in effectiveness at lower doses)

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6-Bismuth SubsalicylateMOA Direct mucosal protective effect; anti-infective

actions, weak antacid properties It complexes deposit on the surface of H. pylori,

diminishing its ability to adhere to the gastric epithelium. The end result is lysis of the organism within 30-90 min.

The addition of an antimicrobial agent produces a synergistic effect.

May also stimulate production of prostaglandins & modulate the immune response.

Side Effects Abdominal pain, constipation, headache,

confusion, anxiety, tinnitus, tremor.

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Drug Interaction Profile Anticoagulants (plt fxn), May potentiate hypoglycemic effects of

diabetic agents May displace other drugs from protein binding

sites May form complexes with other drugs (TCN,

quinolones) May effects of uricosuric agents, use with omeprazole may systemic absorption

of bismuth (unknown significance)

Dosing 2 tablets QID (1 tablet = 262mg bismuth

subsalicylate; equiv to 100mg salicylate)

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7-Prokinetic Agents: Metoclopramide

MOA Increases GI motility and peristalsis Increases LES tone Antagonizes dopamine receptors.Side Effects Extrapyramidal symptomsDrug Interaction Profile Increased sedative effect of benzodiazepines or

alcohol.Dosing Metaclopramide 5-15 mg dose, up to 4 times a

day (take 30 min before meals). Single dose of 20 mg may be needed in a

provoking situation

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Treatment of NSAID induced ulcer

1-Stop NSAIDs when possible.2- Treat with low dose H-2 antagonist for 8 weeks

Prophylactic therapy In patients unable to discontinue NSAIDs and

have risk factors for development of ulcer1-PPIs: they are preferred if NSAIDs are to be

continued 2-Misoprostol3-H2 antagonist are more effective in healing

duodenal ulcer than gastric ulcer

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Treatment plan & Monitoring1. Assess risk factors for NSAID-induced

ulcers and ulcer-related complications, and when indicated

2.recommend appropriate strategies for reducing ulcer risk (see Table 35-10).

3. Recommend eradication treatment for H. pylori-positive patients taking NSAIDs.

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Treatment plan & Monitoring4. Monitor patients for signs and

symptoms of NSAID-related upper GI complications.

5. Assess and monitor patients for potential drug interactions and adverse effects (especially misoprostol).

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Treatment plan & Monitoring

6. Provide patient education to patients who are at risk of NSAID-induced ulcers or GI-related complications, including

why cotherapy is used with nonselective NSAIDs; when and how to take medications; adverse effects; alarm symptoms; when to contact their healthcare provider; the importance of adherence to drug treatment.

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Eradication of Helicobacter pylori In the past, PUD was considered a chronic

disorder because the ulcer tended to recur. Eradication of H. pylori dramatically reduces ulcer recurrence & cures many patients of their disease.Advantages of eradication:Inflammatory changes return to normalRestoration of microvilli by 4 monthsDecrease in disease recurrenceProblems:Eradication may be difficult; resistance to antibioticsAdverse reactions to antibiotics

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Who should be treated for H. pylori?All pts with established duodenal ulcers with H.

pylori.All pts with gastric ulcers with H. pylori.First or recurrent H. pylori infectionWho should not be treated for H. pyloriAsymptomatic (H. pylori positive or negative)Non-ulcer dyspepsia* (H. pylori positive or negative)Gastric ulcer (H. pylori negative)Duodenal ulcer (H. pylori negative)Gastroesophageal reflux diseaseGallbladder or pancreatic diseaseIrritable bowel or inflammatory bowel disease

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Disadvantages of Maintenance Treatment:

recurrence despite long-term treatment doesn’t change H. pylori colonization long-term drug exposure increased cost potential for disease complications from

recurrence

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H. pylori Eradication Regimens Monotherapy with antibiotics or acid

suppressants have not been optimal Combination of acid suppressants with antibiotics Should contain one anti-secretory agent & at

least 2 antibiotics)

Dosing Clarithro 500 mg bid, Amoxil 1000mg bid,

Metronidazole 500mg bid, Tetracycline 500mg bid

BMT-1: Bismuth 525mg qid + Metronidazole 500mg tid + Tetracycline 500mg qid

BMT-2: Bismuth 525mg qid + Metronidazole 250mg qid + Tetracycline 500mg qid

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Treatment plan & Monitoring1. Assess patient allergies to determine if

allergic to penicillin (or other antibiotics) so that drug regimens that contain penicillin (or other antibiotics) can be avoided.

2. Assess patient use of alcohol or alcohol-containing products with metronidazole and oral birth control medications with antibiotics and counsel appropriately.

3. Assess likelihood of nonadherence to the drug regimen as a cause of treatment failure.

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Treatment plan & Monitoring4. Recommend a different antibiotic

combination if H. pylori eradication fails and a second treatment is planned.

5. Inform the patient of change in stool color when bismuth salicylate.

6. Assess and monitor patients for potential adverse effects, especially those associated with metronidazole, c1arithromycin, and amoxicillin.

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Treatment plan & Monitoring7. Assess and monitor patients for potential

drug interactions, especially those receiving metronidazole, clarithromycin, or cimetidine.

8.Monitor patients for salicylate toxicity, especially patients receiving cotherapy with other salicylates, anticoagulants, and patients with renal failure.

9.Monitor patients for persistent or recurrent symptoms within 14 days after completion of a course of therapy.

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Treatment plan & Monitoring

10. Provide patient education to patients including why antibiotic and antiulcer combinations are

used; when and how to take medications; adverse effects; the importance of adherence to the entire

course of drug treatment; to contact their healthcare provider if alarm

symptoms develop (e.g., blood in the stools, black tarry stools, vomiting, severe abdominal pain), or if symptoms persist or return.

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Stress ulcer

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They differ from chronic PUD They are not recurring They are not related to pervious

history of ulcer They occur in untreated critically

ill patients in 24-48 hrs Multiple superficial ulcers develop 50% of them bleed Patients who develop GI bleed have a

higher rate of mortality

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Pathogenesis Occur due to impaired protective mechanisms Acid secretion can be high, low or normal

Low in trauma patients High in sepsis, CNS injuries or small bowel resection

Gastric blood flow is decrease in hemorrhagic, cardiogenic and septic shock resulting in ↓ nutrient and oxygen delivery inability of the mucosa to remove or neutralize

gastric acid ↓ bicarbonate

Decrease rate of proliferation and cellular turnover of gastric mucosa

Diffusion of bile salts backwards from duodenum High concentrations of urea in the blood Lack of PG and mucous formation

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Risk factors Shock Burns Multiple organ failure Trauma Sepsis Coagulopathy CNS injury High corticosteroid administration Mechanical ventilation

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TreatmentGoal: ↓morbidity and mortality1-Treat underlying disease state or

condition Early fluid replacement Immediate oxygenation Early hemodynamic stabilization Prevention of infection Effective analgesia and sedation Maintaining adequate nutrition Respiratory support2-Adequate neutralization of acid Very Important Should maintain gastric PH 3.5-4 to ↓ frequency

of bleeding

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A-Aggressive Antacid Therapy 30-60 ml every hour Very effectively maintains PH > 3.5 Inconvenient to administer Associated with accumulation of

Mg, Al, or Ca, and diarrhea

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B- H2Anatgonists

Effectively prevent ulcer Ranitidine and famotidine are better at

controlling PH to < 4 Continues IV infusion most effective in ↑

PH Dosage is adjusted according to severity

of illness, renal function and intragastric PH

Intragastric PH can be measured by indwelling probe or measuring PH of NG aspirate.

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C- PPI

Most potent acid suppressant drugs Used with good success

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D-Sucralfate

Does not alter PH Effective in preventing stress ulcer as

H2 blockers Not ↓ PH so it will not promote

growth of bacteria in stomach →aspiration → nosocomial pneumonia

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