GI Pharmacology

Dr Alia Shatanawi

542018

Z Gastroenterol 1983 Mar21 Suppl111-6

[Effect of antacids on intestinal motility]

[Article in German]

Wienbeck M Erckenbrecht J Strohmeyer G

Abstract

Disturbances of gut motility occur frequently under a highdose antacid regimen

Typical symptoms are diarrhea and constipation

They are due to the cations of the antacids

Aluminum causes constipation magnesium induces diarrhea and calcium has no

definite motor effect

The following mechanisms of action have to be taken into consideration

effects of the cations on the smooth muscle of the gut on the enteric nervous system

and on the release of

gastrointestinal hormones as well as alterations of the physiochemical properties of the

intraluminal contents

Aluminum inhibits the motor activity of the stomach and intestine magnesium

stimulates muscle contractions

however the simultaneous activation of the intrinsic nerves which are predominantly

inhibitory by magnesium may conceal the muscular effects of this cation

The diarrhea under a highdose regimen of antacid combinations appears to be due

predominantly to the

osmotic-secretory effects of the antacids

Z Gastroenterol 1983 Mar21 Suppl111-6

[Effect of antacids on intestinal motility]

[Article in German]

Wienbeck M Erckenbrecht J Strohmeyer G

Abstract

Disturbances of gut motility occur frequently under a highdose antacid regimen

Typical symptoms are diarrhea and constipation

They are due to the cations of the antacids

Aluminum causes constipation magnesium induces diarrhea and calcium has no

definite motor effect

The following mechanisms of action have to be taken into consideration

effects of the cations on the smooth muscle of the gut on the enteric nervous system

and on the release of

gastrointestinal hormones as well as alterations of the physiochemical properties of the

intraluminal contents

Aluminum inhibits the motor activity of the stomach and intestine magnesium

stimulates muscle contractions

however the simultaneous activation of the intrinsic nerves which are predominantly

inhibitory by magnesium may conceal the muscular effects of this cation

The diarrhea under a highdose regimen of antacid combinations appears to be due

predominantly to the

osmotic-secretory effects of the antacids

Three pathways control parietal cell acid secretion

1 Neural stimulation via vagus nerve

2 Endocrine stimulation via secreted gastrin

3 Paracrine stimulation via released histamine

Parietal cell

H+K+ ATPase

(proton pump)

Specificity of PPI

bull Drug absorbed in small intestine and

delivered to parietal cell through the

blood

bull Drug is protonated and ldquotrappedrdquo in

acidic canaliculi

bull Trapping of protonated drug within the

acidic canaliculi next to target

enzyme

bull Irreversible inhibition

bull Full inhibition with 21 ratio of drug

enzyme

Specificity of PPI

bull Drug is stable at neutral pH destroyed at low pH

bull Intestine absorbs drug (past the stomach) as microencapsulation dissolves

bull If microencapsulation disrupted before swallowing then drug will be destroyed in stomach

bull When stop drug treatment requires 4-5 days for enzyme to return to full function

Proton Pump Inhibitors PPI(1990s) Very efficacious and safe drugs

Have a major role in PUD

Omeprazole (oral)

Rabeprazole (oral)

Lanzoprazole (oral and IV)

Pantoprazole (oral and IV)

Esmoprazole (oral and IV)

Formulated as prodrugs which are released in the intestine

Immediate Release Suspension results in rapid response

PPI Pharmacokinetics

They are lipophilic weak bases (pKa 4-5)

After intestinal absorption they diffuse across lipid membranes into acidified compartments such as the parietal cell canaliculus

The prodrug becomes protonated and concentrated more than 1000-fold within the parietal cells

There it undergoes a molecular conversion to the active form which covalently binds the H+K+ ATPase enzyme and inactivates it

PPI

Pharmacokinetics Rabeprazole and immediate release

omeprazole have faster onsets of action

Should be given one hour before meal

Have short half lives but effect lasts for 24

hours due to irreversible inhibition

PPI

Pharmacodynamics

Inhibit both fasting and meal-stimulated

secretion because they block the final

common pathway of acid secretion (90-

98 of 24-hour secretion)

PPI

Clinical Uses

Gastroesophageal Reflux (GERD)

ndash They are the most effective agents in all forms of

GERD and complications

Nonulcer Dyspepsia

ndash Modest activity

ndash 10-20 more beneficial than a placebo

PPI Stress- Related Gastritis

ndash Oral immediate- release omeprazole

administered by nasogastric tube

ndash For patients without a nasoenteric tube IV H2-

antagonists are preferred because of their

proven efficacy

Gastrinoma and other Hypersecretory

Conditions

ndash Usually high doses of omeprazole are used

PPI Peptic Ulcer Disease

ndash They heal more than 90 of cases within 4-6

weeks

ndash Hpylori- associated ulcers

PPI eradicate Hpylori by direct antimicrobial activity

and by lowering MIC of the antibiotics

Triple Therapy

ndash PPI twice daily

ndash Clarithromycin 500mg twice daily

ndash Amoxicillin 1gm twice daily OR Metronidazole 500mg twice

daily

PPI Peptic Ulcer Disease

ndash NSAID-associated ulcers

PPIs promote ulcer healing despite continued NSAID

use

Also used to prevent ulcer complications of NSAIDs

ndash Rebleeding peptic ulcer

Oral or IV

High pH may enhance coagulation and platelet

aggregation

PPI Adverse Effects

General

ndash Diarrhea headache abdominal pain not

teratogenic in animals but not used in

pregnancy

Reduction of cyanocobalamine absorption

Increased risk of GI and pulmonary infection

PPI Adverse Effects

Increased serum gastrin levels

Hyperplasia of ECL cells

Carcinoid tumors in rats

Increase proliferative rate of colonic mucosa

but no cancer developed

Chronic inflammation in gastric body

Atrophic gastritis and intestinal metaplasia

PPI Drug Interactions

ndash May affect absorption of drugs due to decreased

gastric acidity like digoxin and ketoconazole

ndash Omeprazole can inhibit metabolism of

coumadine diazepam and phenytoin

ndash Rabeprazole and pantoprazole have no

significant interaction

PPI Side Effects

bull Generally well tolerated and the incidence of short-term adverse effects is relatively uncommon

bull Headache bull Diarrhea bull abdominal pain nausea bull Dizzinesshelliphellip although in clinical trials the incidence of these

effects with omeprazole was mostly comparable to that found with placebo

bull Long term the risk of a fracture increased with the length of time

taking PPIs Possibly due to reduced amount of Ca2+ dissolved in the stomach or interference with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts

Mucosal Protective Agents

GI mucosal defense mechanisms

Mucus secretion

Cell-cell tight junctions

ndash Restrict back diffusion of acid and pepsin

Epithelial bicarbonate secretion

Restitution

ndash Cellular migration from gland neck cells seals

small erosions to reestablish intact epithelium

Mucosal prostaglandins

ndash Stimulate mucus and bicarbonate secretion

Enhance mucosal protection

1 Bismuth compounds

2 Sucralfate

3 Prostaglandin analogs (misoprostol cytotec)

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Specificity of PPI

bull Drug absorbed in small intestine and

delivered to parietal cell through the

blood

bull Drug is protonated and ldquotrappedrdquo in

acidic canaliculi

bull Trapping of protonated drug within the

acidic canaliculi next to target

enzyme

bull Irreversible inhibition

bull Full inhibition with 21 ratio of drug

enzyme

Specificity of PPI

bull Drug is stable at neutral pH destroyed at low pH

bull Intestine absorbs drug (past the stomach) as microencapsulation dissolves

bull If microencapsulation disrupted before swallowing then drug will be destroyed in stomach

bull When stop drug treatment requires 4-5 days for enzyme to return to full function

Proton Pump Inhibitors PPI(1990s) Very efficacious and safe drugs

Have a major role in PUD

Omeprazole (oral)

Rabeprazole (oral)

Lanzoprazole (oral and IV)

Pantoprazole (oral and IV)

Esmoprazole (oral and IV)

Formulated as prodrugs which are released in the intestine

Immediate Release Suspension results in rapid response

PPI Pharmacokinetics

They are lipophilic weak bases (pKa 4-5)

After intestinal absorption they diffuse across lipid membranes into acidified compartments such as the parietal cell canaliculus

The prodrug becomes protonated and concentrated more than 1000-fold within the parietal cells

There it undergoes a molecular conversion to the active form which covalently binds the H+K+ ATPase enzyme and inactivates it

PPI

Pharmacokinetics Rabeprazole and immediate release

omeprazole have faster onsets of action

Should be given one hour before meal

Have short half lives but effect lasts for 24

hours due to irreversible inhibition

PPI

Pharmacodynamics

Inhibit both fasting and meal-stimulated

secretion because they block the final

common pathway of acid secretion (90-

98 of 24-hour secretion)

PPI

Clinical Uses

Gastroesophageal Reflux (GERD)

ndash They are the most effective agents in all forms of

GERD and complications

Nonulcer Dyspepsia

ndash Modest activity

ndash 10-20 more beneficial than a placebo

PPI Stress- Related Gastritis

ndash Oral immediate- release omeprazole

administered by nasogastric tube

ndash For patients without a nasoenteric tube IV H2-

antagonists are preferred because of their

proven efficacy

Gastrinoma and other Hypersecretory

Conditions

ndash Usually high doses of omeprazole are used

PPI Peptic Ulcer Disease

ndash They heal more than 90 of cases within 4-6

weeks

ndash Hpylori- associated ulcers

PPI eradicate Hpylori by direct antimicrobial activity

and by lowering MIC of the antibiotics

Triple Therapy

ndash PPI twice daily

ndash Clarithromycin 500mg twice daily

ndash Amoxicillin 1gm twice daily OR Metronidazole 500mg twice

daily

PPI Peptic Ulcer Disease

ndash NSAID-associated ulcers

PPIs promote ulcer healing despite continued NSAID

use

Also used to prevent ulcer complications of NSAIDs

ndash Rebleeding peptic ulcer

Oral or IV

High pH may enhance coagulation and platelet

aggregation

PPI Adverse Effects

General

ndash Diarrhea headache abdominal pain not

teratogenic in animals but not used in

pregnancy

Reduction of cyanocobalamine absorption

Increased risk of GI and pulmonary infection

PPI Adverse Effects

Increased serum gastrin levels

Hyperplasia of ECL cells

Carcinoid tumors in rats

Increase proliferative rate of colonic mucosa

but no cancer developed

Chronic inflammation in gastric body

Atrophic gastritis and intestinal metaplasia

PPI Drug Interactions

ndash May affect absorption of drugs due to decreased

gastric acidity like digoxin and ketoconazole

ndash Omeprazole can inhibit metabolism of

coumadine diazepam and phenytoin

ndash Rabeprazole and pantoprazole have no

significant interaction

PPI Side Effects

bull Generally well tolerated and the incidence of short-term adverse effects is relatively uncommon

bull Headache bull Diarrhea bull abdominal pain nausea bull Dizzinesshelliphellip although in clinical trials the incidence of these

effects with omeprazole was mostly comparable to that found with placebo

bull Long term the risk of a fracture increased with the length of time

taking PPIs Possibly due to reduced amount of Ca2+ dissolved in the stomach or interference with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts

Mucosal Protective Agents

GI mucosal defense mechanisms

Mucus secretion

Cell-cell tight junctions

ndash Restrict back diffusion of acid and pepsin

Epithelial bicarbonate secretion

Restitution

ndash Cellular migration from gland neck cells seals

small erosions to reestablish intact epithelium

Mucosal prostaglandins

ndash Stimulate mucus and bicarbonate secretion

Enhance mucosal protection

1 Bismuth compounds

2 Sucralfate

3 Prostaglandin analogs (misoprostol cytotec)

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Specificity of PPI

bull Drug is stable at neutral pH destroyed at low pH

bull Intestine absorbs drug (past the stomach) as microencapsulation dissolves

bull If microencapsulation disrupted before swallowing then drug will be destroyed in stomach

bull When stop drug treatment requires 4-5 days for enzyme to return to full function

Proton Pump Inhibitors PPI(1990s) Very efficacious and safe drugs

Have a major role in PUD

Omeprazole (oral)

Rabeprazole (oral)

Lanzoprazole (oral and IV)

Pantoprazole (oral and IV)

Esmoprazole (oral and IV)

Formulated as prodrugs which are released in the intestine

Immediate Release Suspension results in rapid response

PPI Pharmacokinetics

They are lipophilic weak bases (pKa 4-5)

After intestinal absorption they diffuse across lipid membranes into acidified compartments such as the parietal cell canaliculus

The prodrug becomes protonated and concentrated more than 1000-fold within the parietal cells

There it undergoes a molecular conversion to the active form which covalently binds the H+K+ ATPase enzyme and inactivates it

PPI

Pharmacokinetics Rabeprazole and immediate release

omeprazole have faster onsets of action

Should be given one hour before meal

Have short half lives but effect lasts for 24

hours due to irreversible inhibition

PPI

Pharmacodynamics

Inhibit both fasting and meal-stimulated

secretion because they block the final

common pathway of acid secretion (90-

98 of 24-hour secretion)

PPI

Clinical Uses

Gastroesophageal Reflux (GERD)

ndash They are the most effective agents in all forms of

GERD and complications

Nonulcer Dyspepsia

ndash Modest activity

ndash 10-20 more beneficial than a placebo

PPI Stress- Related Gastritis

ndash Oral immediate- release omeprazole

administered by nasogastric tube

ndash For patients without a nasoenteric tube IV H2-

antagonists are preferred because of their

proven efficacy

Gastrinoma and other Hypersecretory

Conditions

ndash Usually high doses of omeprazole are used

PPI Peptic Ulcer Disease

ndash They heal more than 90 of cases within 4-6

weeks

ndash Hpylori- associated ulcers

PPI eradicate Hpylori by direct antimicrobial activity

and by lowering MIC of the antibiotics

Triple Therapy

ndash PPI twice daily

ndash Clarithromycin 500mg twice daily

ndash Amoxicillin 1gm twice daily OR Metronidazole 500mg twice

daily

PPI Peptic Ulcer Disease

ndash NSAID-associated ulcers

PPIs promote ulcer healing despite continued NSAID

use

Also used to prevent ulcer complications of NSAIDs

ndash Rebleeding peptic ulcer

Oral or IV

High pH may enhance coagulation and platelet

aggregation

PPI Adverse Effects

General

ndash Diarrhea headache abdominal pain not

teratogenic in animals but not used in

pregnancy

Reduction of cyanocobalamine absorption

Increased risk of GI and pulmonary infection

PPI Adverse Effects

Increased serum gastrin levels

Hyperplasia of ECL cells

Carcinoid tumors in rats

Increase proliferative rate of colonic mucosa

but no cancer developed

Chronic inflammation in gastric body

Atrophic gastritis and intestinal metaplasia

PPI Drug Interactions

ndash May affect absorption of drugs due to decreased

gastric acidity like digoxin and ketoconazole

ndash Omeprazole can inhibit metabolism of

coumadine diazepam and phenytoin

ndash Rabeprazole and pantoprazole have no

significant interaction

PPI Side Effects

bull Generally well tolerated and the incidence of short-term adverse effects is relatively uncommon

bull Headache bull Diarrhea bull abdominal pain nausea bull Dizzinesshelliphellip although in clinical trials the incidence of these

effects with omeprazole was mostly comparable to that found with placebo

bull Long term the risk of a fracture increased with the length of time

taking PPIs Possibly due to reduced amount of Ca2+ dissolved in the stomach or interference with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts

Mucosal Protective Agents

GI mucosal defense mechanisms

Mucus secretion

Cell-cell tight junctions

ndash Restrict back diffusion of acid and pepsin

Epithelial bicarbonate secretion

Restitution

ndash Cellular migration from gland neck cells seals

small erosions to reestablish intact epithelium

Mucosal prostaglandins

ndash Stimulate mucus and bicarbonate secretion

Enhance mucosal protection

1 Bismuth compounds

2 Sucralfate

3 Prostaglandin analogs (misoprostol cytotec)

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Proton Pump Inhibitors PPI(1990s) Very efficacious and safe drugs

Have a major role in PUD

Omeprazole (oral)

Rabeprazole (oral)

Lanzoprazole (oral and IV)

Pantoprazole (oral and IV)

Esmoprazole (oral and IV)

Formulated as prodrugs which are released in the intestine

Immediate Release Suspension results in rapid response

PPI Pharmacokinetics

They are lipophilic weak bases (pKa 4-5)

After intestinal absorption they diffuse across lipid membranes into acidified compartments such as the parietal cell canaliculus

The prodrug becomes protonated and concentrated more than 1000-fold within the parietal cells

There it undergoes a molecular conversion to the active form which covalently binds the H+K+ ATPase enzyme and inactivates it

PPI

Pharmacokinetics Rabeprazole and immediate release

omeprazole have faster onsets of action

Should be given one hour before meal

Have short half lives but effect lasts for 24

hours due to irreversible inhibition

PPI

Pharmacodynamics

Inhibit both fasting and meal-stimulated

secretion because they block the final

common pathway of acid secretion (90-

98 of 24-hour secretion)

PPI

Clinical Uses

Gastroesophageal Reflux (GERD)

ndash They are the most effective agents in all forms of

GERD and complications

Nonulcer Dyspepsia

ndash Modest activity

ndash 10-20 more beneficial than a placebo

PPI Stress- Related Gastritis

ndash Oral immediate- release omeprazole

administered by nasogastric tube

ndash For patients without a nasoenteric tube IV H2-

antagonists are preferred because of their

proven efficacy

Gastrinoma and other Hypersecretory

Conditions

ndash Usually high doses of omeprazole are used

PPI Peptic Ulcer Disease

ndash They heal more than 90 of cases within 4-6

weeks

ndash Hpylori- associated ulcers

PPI eradicate Hpylori by direct antimicrobial activity

and by lowering MIC of the antibiotics

Triple Therapy

ndash PPI twice daily

ndash Clarithromycin 500mg twice daily

ndash Amoxicillin 1gm twice daily OR Metronidazole 500mg twice

daily

PPI Peptic Ulcer Disease

ndash NSAID-associated ulcers

PPIs promote ulcer healing despite continued NSAID

use

Also used to prevent ulcer complications of NSAIDs

ndash Rebleeding peptic ulcer

Oral or IV

High pH may enhance coagulation and platelet

aggregation

PPI Adverse Effects

General

ndash Diarrhea headache abdominal pain not

teratogenic in animals but not used in

pregnancy

Reduction of cyanocobalamine absorption

Increased risk of GI and pulmonary infection

PPI Adverse Effects

Increased serum gastrin levels

Hyperplasia of ECL cells

Carcinoid tumors in rats

Increase proliferative rate of colonic mucosa

but no cancer developed

Chronic inflammation in gastric body

Atrophic gastritis and intestinal metaplasia

PPI Drug Interactions

ndash May affect absorption of drugs due to decreased

gastric acidity like digoxin and ketoconazole

ndash Omeprazole can inhibit metabolism of

coumadine diazepam and phenytoin

ndash Rabeprazole and pantoprazole have no

significant interaction

PPI Side Effects

bull Generally well tolerated and the incidence of short-term adverse effects is relatively uncommon

bull Headache bull Diarrhea bull abdominal pain nausea bull Dizzinesshelliphellip although in clinical trials the incidence of these

effects with omeprazole was mostly comparable to that found with placebo

bull Long term the risk of a fracture increased with the length of time

taking PPIs Possibly due to reduced amount of Ca2+ dissolved in the stomach or interference with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts

Mucosal Protective Agents

GI mucosal defense mechanisms

Mucus secretion

Cell-cell tight junctions

ndash Restrict back diffusion of acid and pepsin

Epithelial bicarbonate secretion

Restitution

ndash Cellular migration from gland neck cells seals

small erosions to reestablish intact epithelium

Mucosal prostaglandins

ndash Stimulate mucus and bicarbonate secretion

Enhance mucosal protection

1 Bismuth compounds

2 Sucralfate

3 Prostaglandin analogs (misoprostol cytotec)

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

PPI Pharmacokinetics

They are lipophilic weak bases (pKa 4-5)

After intestinal absorption they diffuse across lipid membranes into acidified compartments such as the parietal cell canaliculus

The prodrug becomes protonated and concentrated more than 1000-fold within the parietal cells

There it undergoes a molecular conversion to the active form which covalently binds the H+K+ ATPase enzyme and inactivates it

PPI

Pharmacokinetics Rabeprazole and immediate release

omeprazole have faster onsets of action

Should be given one hour before meal

Have short half lives but effect lasts for 24

hours due to irreversible inhibition

PPI

Pharmacodynamics

Inhibit both fasting and meal-stimulated

secretion because they block the final

common pathway of acid secretion (90-

98 of 24-hour secretion)

PPI

Clinical Uses

Gastroesophageal Reflux (GERD)

ndash They are the most effective agents in all forms of

GERD and complications

Nonulcer Dyspepsia

ndash Modest activity

ndash 10-20 more beneficial than a placebo

PPI Stress- Related Gastritis

ndash Oral immediate- release omeprazole

administered by nasogastric tube

ndash For patients without a nasoenteric tube IV H2-

antagonists are preferred because of their

proven efficacy

Gastrinoma and other Hypersecretory

Conditions

ndash Usually high doses of omeprazole are used

PPI Peptic Ulcer Disease

ndash They heal more than 90 of cases within 4-6

weeks

ndash Hpylori- associated ulcers

PPI eradicate Hpylori by direct antimicrobial activity

and by lowering MIC of the antibiotics

Triple Therapy

ndash PPI twice daily

ndash Clarithromycin 500mg twice daily

ndash Amoxicillin 1gm twice daily OR Metronidazole 500mg twice

daily

PPI Peptic Ulcer Disease

ndash NSAID-associated ulcers

PPIs promote ulcer healing despite continued NSAID

use

Also used to prevent ulcer complications of NSAIDs

ndash Rebleeding peptic ulcer

Oral or IV

High pH may enhance coagulation and platelet

aggregation

PPI Adverse Effects

General

ndash Diarrhea headache abdominal pain not

teratogenic in animals but not used in

pregnancy

Reduction of cyanocobalamine absorption

Increased risk of GI and pulmonary infection

PPI Adverse Effects

Increased serum gastrin levels

Hyperplasia of ECL cells

Carcinoid tumors in rats

Increase proliferative rate of colonic mucosa

but no cancer developed

Chronic inflammation in gastric body

Atrophic gastritis and intestinal metaplasia

PPI Drug Interactions

ndash May affect absorption of drugs due to decreased

gastric acidity like digoxin and ketoconazole

ndash Omeprazole can inhibit metabolism of

coumadine diazepam and phenytoin

ndash Rabeprazole and pantoprazole have no

significant interaction

PPI Side Effects

bull Generally well tolerated and the incidence of short-term adverse effects is relatively uncommon

bull Headache bull Diarrhea bull abdominal pain nausea bull Dizzinesshelliphellip although in clinical trials the incidence of these

effects with omeprazole was mostly comparable to that found with placebo

bull Long term the risk of a fracture increased with the length of time

taking PPIs Possibly due to reduced amount of Ca2+ dissolved in the stomach or interference with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts

Mucosal Protective Agents

GI mucosal defense mechanisms

Mucus secretion

Cell-cell tight junctions

ndash Restrict back diffusion of acid and pepsin

Epithelial bicarbonate secretion

Restitution

ndash Cellular migration from gland neck cells seals

small erosions to reestablish intact epithelium

Mucosal prostaglandins

ndash Stimulate mucus and bicarbonate secretion

Enhance mucosal protection

1 Bismuth compounds

2 Sucralfate

3 Prostaglandin analogs (misoprostol cytotec)

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

PPI

Pharmacokinetics Rabeprazole and immediate release

omeprazole have faster onsets of action

Should be given one hour before meal

Have short half lives but effect lasts for 24

hours due to irreversible inhibition

PPI

Pharmacodynamics

Inhibit both fasting and meal-stimulated

secretion because they block the final

common pathway of acid secretion (90-

98 of 24-hour secretion)

PPI

Clinical Uses

Gastroesophageal Reflux (GERD)

ndash They are the most effective agents in all forms of

GERD and complications

Nonulcer Dyspepsia

ndash Modest activity

ndash 10-20 more beneficial than a placebo

PPI Stress- Related Gastritis

ndash Oral immediate- release omeprazole

administered by nasogastric tube

ndash For patients without a nasoenteric tube IV H2-

antagonists are preferred because of their

proven efficacy

Gastrinoma and other Hypersecretory

Conditions

ndash Usually high doses of omeprazole are used

PPI Peptic Ulcer Disease

ndash They heal more than 90 of cases within 4-6

weeks

ndash Hpylori- associated ulcers

PPI eradicate Hpylori by direct antimicrobial activity

and by lowering MIC of the antibiotics

Triple Therapy

ndash PPI twice daily

ndash Clarithromycin 500mg twice daily

ndash Amoxicillin 1gm twice daily OR Metronidazole 500mg twice

daily

PPI Peptic Ulcer Disease

ndash NSAID-associated ulcers

PPIs promote ulcer healing despite continued NSAID

use

Also used to prevent ulcer complications of NSAIDs

ndash Rebleeding peptic ulcer

Oral or IV

High pH may enhance coagulation and platelet

aggregation

PPI Adverse Effects

General

ndash Diarrhea headache abdominal pain not

teratogenic in animals but not used in

pregnancy

Reduction of cyanocobalamine absorption

Increased risk of GI and pulmonary infection

PPI Adverse Effects

Increased serum gastrin levels

Hyperplasia of ECL cells

Carcinoid tumors in rats

Increase proliferative rate of colonic mucosa

but no cancer developed

Chronic inflammation in gastric body

Atrophic gastritis and intestinal metaplasia

PPI Drug Interactions

ndash May affect absorption of drugs due to decreased

gastric acidity like digoxin and ketoconazole

ndash Omeprazole can inhibit metabolism of

coumadine diazepam and phenytoin

ndash Rabeprazole and pantoprazole have no

significant interaction

PPI Side Effects

bull Generally well tolerated and the incidence of short-term adverse effects is relatively uncommon

bull Headache bull Diarrhea bull abdominal pain nausea bull Dizzinesshelliphellip although in clinical trials the incidence of these

effects with omeprazole was mostly comparable to that found with placebo

bull Long term the risk of a fracture increased with the length of time

taking PPIs Possibly due to reduced amount of Ca2+ dissolved in the stomach or interference with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts

Mucosal Protective Agents

GI mucosal defense mechanisms

Mucus secretion

Cell-cell tight junctions

ndash Restrict back diffusion of acid and pepsin

Epithelial bicarbonate secretion

Restitution

ndash Cellular migration from gland neck cells seals

small erosions to reestablish intact epithelium

Mucosal prostaglandins

ndash Stimulate mucus and bicarbonate secretion

Enhance mucosal protection

1 Bismuth compounds

2 Sucralfate

3 Prostaglandin analogs (misoprostol cytotec)

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

PPI

Pharmacodynamics

Inhibit both fasting and meal-stimulated

secretion because they block the final

common pathway of acid secretion (90-

98 of 24-hour secretion)

PPI

Clinical Uses

Gastroesophageal Reflux (GERD)

ndash They are the most effective agents in all forms of

GERD and complications

Nonulcer Dyspepsia

ndash Modest activity

ndash 10-20 more beneficial than a placebo

PPI Stress- Related Gastritis

ndash Oral immediate- release omeprazole

administered by nasogastric tube

ndash For patients without a nasoenteric tube IV H2-

antagonists are preferred because of their

proven efficacy

Gastrinoma and other Hypersecretory

Conditions

ndash Usually high doses of omeprazole are used

PPI Peptic Ulcer Disease

ndash They heal more than 90 of cases within 4-6

weeks

ndash Hpylori- associated ulcers

PPI eradicate Hpylori by direct antimicrobial activity

and by lowering MIC of the antibiotics

Triple Therapy

ndash PPI twice daily

ndash Clarithromycin 500mg twice daily

ndash Amoxicillin 1gm twice daily OR Metronidazole 500mg twice

daily

PPI Peptic Ulcer Disease

ndash NSAID-associated ulcers

PPIs promote ulcer healing despite continued NSAID

use

Also used to prevent ulcer complications of NSAIDs

ndash Rebleeding peptic ulcer

Oral or IV

High pH may enhance coagulation and platelet

aggregation

PPI Adverse Effects

General

ndash Diarrhea headache abdominal pain not

teratogenic in animals but not used in

pregnancy

Reduction of cyanocobalamine absorption

Increased risk of GI and pulmonary infection

PPI Adverse Effects

Increased serum gastrin levels

Hyperplasia of ECL cells

Carcinoid tumors in rats

Increase proliferative rate of colonic mucosa

but no cancer developed

Chronic inflammation in gastric body

Atrophic gastritis and intestinal metaplasia

PPI Drug Interactions

ndash May affect absorption of drugs due to decreased

gastric acidity like digoxin and ketoconazole

ndash Omeprazole can inhibit metabolism of

coumadine diazepam and phenytoin

ndash Rabeprazole and pantoprazole have no

significant interaction

PPI Side Effects

bull Generally well tolerated and the incidence of short-term adverse effects is relatively uncommon

bull Headache bull Diarrhea bull abdominal pain nausea bull Dizzinesshelliphellip although in clinical trials the incidence of these

effects with omeprazole was mostly comparable to that found with placebo

bull Long term the risk of a fracture increased with the length of time

taking PPIs Possibly due to reduced amount of Ca2+ dissolved in the stomach or interference with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts

Mucosal Protective Agents

GI mucosal defense mechanisms

Mucus secretion

Cell-cell tight junctions

ndash Restrict back diffusion of acid and pepsin

Epithelial bicarbonate secretion

Restitution

ndash Cellular migration from gland neck cells seals

small erosions to reestablish intact epithelium

Mucosal prostaglandins

ndash Stimulate mucus and bicarbonate secretion

Enhance mucosal protection

1 Bismuth compounds

2 Sucralfate

3 Prostaglandin analogs (misoprostol cytotec)

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

PPI

Clinical Uses

Gastroesophageal Reflux (GERD)

ndash They are the most effective agents in all forms of

GERD and complications

Nonulcer Dyspepsia

ndash Modest activity

ndash 10-20 more beneficial than a placebo

PPI Stress- Related Gastritis

ndash Oral immediate- release omeprazole

administered by nasogastric tube

ndash For patients without a nasoenteric tube IV H2-

antagonists are preferred because of their

proven efficacy

Gastrinoma and other Hypersecretory

Conditions

ndash Usually high doses of omeprazole are used

PPI Peptic Ulcer Disease

ndash They heal more than 90 of cases within 4-6

weeks

ndash Hpylori- associated ulcers

PPI eradicate Hpylori by direct antimicrobial activity

and by lowering MIC of the antibiotics

Triple Therapy

ndash PPI twice daily

ndash Clarithromycin 500mg twice daily

ndash Amoxicillin 1gm twice daily OR Metronidazole 500mg twice

daily

PPI Peptic Ulcer Disease

ndash NSAID-associated ulcers

PPIs promote ulcer healing despite continued NSAID

use

Also used to prevent ulcer complications of NSAIDs

ndash Rebleeding peptic ulcer

Oral or IV

High pH may enhance coagulation and platelet

aggregation

PPI Adverse Effects

General

ndash Diarrhea headache abdominal pain not

teratogenic in animals but not used in

pregnancy

Reduction of cyanocobalamine absorption

Increased risk of GI and pulmonary infection

PPI Adverse Effects

Increased serum gastrin levels

Hyperplasia of ECL cells

Carcinoid tumors in rats

Increase proliferative rate of colonic mucosa

but no cancer developed

Chronic inflammation in gastric body

Atrophic gastritis and intestinal metaplasia

PPI Drug Interactions

ndash May affect absorption of drugs due to decreased

gastric acidity like digoxin and ketoconazole

ndash Omeprazole can inhibit metabolism of

coumadine diazepam and phenytoin

ndash Rabeprazole and pantoprazole have no

significant interaction

PPI Side Effects

bull Generally well tolerated and the incidence of short-term adverse effects is relatively uncommon

bull Headache bull Diarrhea bull abdominal pain nausea bull Dizzinesshelliphellip although in clinical trials the incidence of these

effects with omeprazole was mostly comparable to that found with placebo

bull Long term the risk of a fracture increased with the length of time

taking PPIs Possibly due to reduced amount of Ca2+ dissolved in the stomach or interference with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts

Mucosal Protective Agents

GI mucosal defense mechanisms

Mucus secretion

Cell-cell tight junctions

ndash Restrict back diffusion of acid and pepsin

Epithelial bicarbonate secretion

Restitution

ndash Cellular migration from gland neck cells seals

small erosions to reestablish intact epithelium

Mucosal prostaglandins

ndash Stimulate mucus and bicarbonate secretion

Enhance mucosal protection

1 Bismuth compounds

2 Sucralfate

3 Prostaglandin analogs (misoprostol cytotec)

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

PPI Stress- Related Gastritis

ndash Oral immediate- release omeprazole

administered by nasogastric tube

ndash For patients without a nasoenteric tube IV H2-

antagonists are preferred because of their

proven efficacy

Gastrinoma and other Hypersecretory

Conditions

ndash Usually high doses of omeprazole are used

PPI Peptic Ulcer Disease

ndash They heal more than 90 of cases within 4-6

weeks

ndash Hpylori- associated ulcers

PPI eradicate Hpylori by direct antimicrobial activity

and by lowering MIC of the antibiotics

Triple Therapy

ndash PPI twice daily

ndash Clarithromycin 500mg twice daily

ndash Amoxicillin 1gm twice daily OR Metronidazole 500mg twice

daily

PPI Peptic Ulcer Disease

ndash NSAID-associated ulcers

PPIs promote ulcer healing despite continued NSAID

use

Also used to prevent ulcer complications of NSAIDs

ndash Rebleeding peptic ulcer

Oral or IV

High pH may enhance coagulation and platelet

aggregation

PPI Adverse Effects

General

ndash Diarrhea headache abdominal pain not

teratogenic in animals but not used in

pregnancy

Reduction of cyanocobalamine absorption

Increased risk of GI and pulmonary infection

PPI Adverse Effects

Increased serum gastrin levels

Hyperplasia of ECL cells

Carcinoid tumors in rats

Increase proliferative rate of colonic mucosa

but no cancer developed

Chronic inflammation in gastric body

Atrophic gastritis and intestinal metaplasia

PPI Drug Interactions

ndash May affect absorption of drugs due to decreased

gastric acidity like digoxin and ketoconazole

ndash Omeprazole can inhibit metabolism of

coumadine diazepam and phenytoin

ndash Rabeprazole and pantoprazole have no

significant interaction

PPI Side Effects

bull Generally well tolerated and the incidence of short-term adverse effects is relatively uncommon

bull Headache bull Diarrhea bull abdominal pain nausea bull Dizzinesshelliphellip although in clinical trials the incidence of these

effects with omeprazole was mostly comparable to that found with placebo

bull Long term the risk of a fracture increased with the length of time

taking PPIs Possibly due to reduced amount of Ca2+ dissolved in the stomach or interference with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts

Mucosal Protective Agents

GI mucosal defense mechanisms

Mucus secretion

Cell-cell tight junctions

ndash Restrict back diffusion of acid and pepsin

Epithelial bicarbonate secretion

Restitution

ndash Cellular migration from gland neck cells seals

small erosions to reestablish intact epithelium

Mucosal prostaglandins

ndash Stimulate mucus and bicarbonate secretion

Enhance mucosal protection

1 Bismuth compounds

2 Sucralfate

3 Prostaglandin analogs (misoprostol cytotec)

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

PPI Peptic Ulcer Disease

ndash They heal more than 90 of cases within 4-6

weeks

ndash Hpylori- associated ulcers

PPI eradicate Hpylori by direct antimicrobial activity

and by lowering MIC of the antibiotics

Triple Therapy

ndash PPI twice daily

ndash Clarithromycin 500mg twice daily

ndash Amoxicillin 1gm twice daily OR Metronidazole 500mg twice

daily

PPI Peptic Ulcer Disease

ndash NSAID-associated ulcers

PPIs promote ulcer healing despite continued NSAID

use

Also used to prevent ulcer complications of NSAIDs

ndash Rebleeding peptic ulcer

Oral or IV

High pH may enhance coagulation and platelet

aggregation

PPI Adverse Effects

General

ndash Diarrhea headache abdominal pain not

teratogenic in animals but not used in

pregnancy

Reduction of cyanocobalamine absorption

Increased risk of GI and pulmonary infection

PPI Adverse Effects

Increased serum gastrin levels

Hyperplasia of ECL cells

Carcinoid tumors in rats

Increase proliferative rate of colonic mucosa

but no cancer developed

Chronic inflammation in gastric body

Atrophic gastritis and intestinal metaplasia

PPI Drug Interactions

ndash May affect absorption of drugs due to decreased

gastric acidity like digoxin and ketoconazole

ndash Omeprazole can inhibit metabolism of

coumadine diazepam and phenytoin

ndash Rabeprazole and pantoprazole have no

significant interaction

PPI Side Effects

bull Generally well tolerated and the incidence of short-term adverse effects is relatively uncommon

bull Headache bull Diarrhea bull abdominal pain nausea bull Dizzinesshelliphellip although in clinical trials the incidence of these

effects with omeprazole was mostly comparable to that found with placebo

bull Long term the risk of a fracture increased with the length of time

taking PPIs Possibly due to reduced amount of Ca2+ dissolved in the stomach or interference with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts

Mucosal Protective Agents

GI mucosal defense mechanisms

Mucus secretion

Cell-cell tight junctions

ndash Restrict back diffusion of acid and pepsin

Epithelial bicarbonate secretion

Restitution

ndash Cellular migration from gland neck cells seals

small erosions to reestablish intact epithelium

Mucosal prostaglandins

ndash Stimulate mucus and bicarbonate secretion

Enhance mucosal protection

1 Bismuth compounds

2 Sucralfate

3 Prostaglandin analogs (misoprostol cytotec)

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

PPI Peptic Ulcer Disease

ndash NSAID-associated ulcers

PPIs promote ulcer healing despite continued NSAID

use

Also used to prevent ulcer complications of NSAIDs

ndash Rebleeding peptic ulcer

Oral or IV

High pH may enhance coagulation and platelet

aggregation

PPI Adverse Effects

General

ndash Diarrhea headache abdominal pain not

teratogenic in animals but not used in

pregnancy

Reduction of cyanocobalamine absorption

Increased risk of GI and pulmonary infection

PPI Adverse Effects

Increased serum gastrin levels

Hyperplasia of ECL cells

Carcinoid tumors in rats

Increase proliferative rate of colonic mucosa

but no cancer developed

Chronic inflammation in gastric body

Atrophic gastritis and intestinal metaplasia

PPI Drug Interactions

ndash May affect absorption of drugs due to decreased

gastric acidity like digoxin and ketoconazole

ndash Omeprazole can inhibit metabolism of

coumadine diazepam and phenytoin

ndash Rabeprazole and pantoprazole have no

significant interaction

PPI Side Effects

bull Generally well tolerated and the incidence of short-term adverse effects is relatively uncommon

bull Headache bull Diarrhea bull abdominal pain nausea bull Dizzinesshelliphellip although in clinical trials the incidence of these

effects with omeprazole was mostly comparable to that found with placebo

bull Long term the risk of a fracture increased with the length of time

taking PPIs Possibly due to reduced amount of Ca2+ dissolved in the stomach or interference with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts

Mucosal Protective Agents

GI mucosal defense mechanisms

Mucus secretion

Cell-cell tight junctions

ndash Restrict back diffusion of acid and pepsin

Epithelial bicarbonate secretion

Restitution

ndash Cellular migration from gland neck cells seals

small erosions to reestablish intact epithelium

Mucosal prostaglandins

ndash Stimulate mucus and bicarbonate secretion

Enhance mucosal protection

1 Bismuth compounds

2 Sucralfate

3 Prostaglandin analogs (misoprostol cytotec)

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

PPI Adverse Effects

General

ndash Diarrhea headache abdominal pain not

teratogenic in animals but not used in

pregnancy

Reduction of cyanocobalamine absorption

Increased risk of GI and pulmonary infection

PPI Adverse Effects

Increased serum gastrin levels

Hyperplasia of ECL cells

Carcinoid tumors in rats

Increase proliferative rate of colonic mucosa

but no cancer developed

Chronic inflammation in gastric body

Atrophic gastritis and intestinal metaplasia

PPI Drug Interactions

ndash May affect absorption of drugs due to decreased

gastric acidity like digoxin and ketoconazole

ndash Omeprazole can inhibit metabolism of

coumadine diazepam and phenytoin

ndash Rabeprazole and pantoprazole have no

significant interaction

PPI Side Effects

bull Generally well tolerated and the incidence of short-term adverse effects is relatively uncommon

bull Headache bull Diarrhea bull abdominal pain nausea bull Dizzinesshelliphellip although in clinical trials the incidence of these

effects with omeprazole was mostly comparable to that found with placebo

bull Long term the risk of a fracture increased with the length of time

taking PPIs Possibly due to reduced amount of Ca2+ dissolved in the stomach or interference with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts

Mucosal Protective Agents

GI mucosal defense mechanisms

Mucus secretion

Cell-cell tight junctions

ndash Restrict back diffusion of acid and pepsin

Epithelial bicarbonate secretion

Restitution

ndash Cellular migration from gland neck cells seals

small erosions to reestablish intact epithelium

Mucosal prostaglandins

ndash Stimulate mucus and bicarbonate secretion

Enhance mucosal protection

1 Bismuth compounds

2 Sucralfate

3 Prostaglandin analogs (misoprostol cytotec)

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

PPI Adverse Effects

Increased serum gastrin levels

Hyperplasia of ECL cells

Carcinoid tumors in rats

Increase proliferative rate of colonic mucosa

but no cancer developed

Chronic inflammation in gastric body

Atrophic gastritis and intestinal metaplasia

PPI Drug Interactions

ndash May affect absorption of drugs due to decreased

gastric acidity like digoxin and ketoconazole

ndash Omeprazole can inhibit metabolism of

coumadine diazepam and phenytoin

ndash Rabeprazole and pantoprazole have no

significant interaction

PPI Side Effects

bull Generally well tolerated and the incidence of short-term adverse effects is relatively uncommon

bull Headache bull Diarrhea bull abdominal pain nausea bull Dizzinesshelliphellip although in clinical trials the incidence of these

effects with omeprazole was mostly comparable to that found with placebo

bull Long term the risk of a fracture increased with the length of time

taking PPIs Possibly due to reduced amount of Ca2+ dissolved in the stomach or interference with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts

Mucosal Protective Agents

GI mucosal defense mechanisms

Mucus secretion

Cell-cell tight junctions

ndash Restrict back diffusion of acid and pepsin

Epithelial bicarbonate secretion

Restitution

ndash Cellular migration from gland neck cells seals

small erosions to reestablish intact epithelium

Mucosal prostaglandins

ndash Stimulate mucus and bicarbonate secretion

Enhance mucosal protection

1 Bismuth compounds

2 Sucralfate

3 Prostaglandin analogs (misoprostol cytotec)

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

PPI Drug Interactions

ndash May affect absorption of drugs due to decreased

gastric acidity like digoxin and ketoconazole

ndash Omeprazole can inhibit metabolism of

coumadine diazepam and phenytoin

ndash Rabeprazole and pantoprazole have no

significant interaction

PPI Side Effects

bull Generally well tolerated and the incidence of short-term adverse effects is relatively uncommon

bull Headache bull Diarrhea bull abdominal pain nausea bull Dizzinesshelliphellip although in clinical trials the incidence of these

effects with omeprazole was mostly comparable to that found with placebo

bull Long term the risk of a fracture increased with the length of time

taking PPIs Possibly due to reduced amount of Ca2+ dissolved in the stomach or interference with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts

Mucosal Protective Agents

GI mucosal defense mechanisms

Mucus secretion

Cell-cell tight junctions

ndash Restrict back diffusion of acid and pepsin

Epithelial bicarbonate secretion

Restitution

ndash Cellular migration from gland neck cells seals

small erosions to reestablish intact epithelium

Mucosal prostaglandins

ndash Stimulate mucus and bicarbonate secretion

Enhance mucosal protection

1 Bismuth compounds

2 Sucralfate

3 Prostaglandin analogs (misoprostol cytotec)

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

PPI Side Effects

bull Generally well tolerated and the incidence of short-term adverse effects is relatively uncommon

bull Headache bull Diarrhea bull abdominal pain nausea bull Dizzinesshelliphellip although in clinical trials the incidence of these

effects with omeprazole was mostly comparable to that found with placebo

bull Long term the risk of a fracture increased with the length of time

taking PPIs Possibly due to reduced amount of Ca2+ dissolved in the stomach or interference with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts

Mucosal Protective Agents

GI mucosal defense mechanisms

Mucus secretion

Cell-cell tight junctions

ndash Restrict back diffusion of acid and pepsin

Epithelial bicarbonate secretion

Restitution

ndash Cellular migration from gland neck cells seals

small erosions to reestablish intact epithelium

Mucosal prostaglandins

ndash Stimulate mucus and bicarbonate secretion

Enhance mucosal protection

1 Bismuth compounds

2 Sucralfate

3 Prostaglandin analogs (misoprostol cytotec)

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Mucosal Protective Agents

GI mucosal defense mechanisms

Mucus secretion

Cell-cell tight junctions

ndash Restrict back diffusion of acid and pepsin

Epithelial bicarbonate secretion

Restitution

ndash Cellular migration from gland neck cells seals

small erosions to reestablish intact epithelium

Mucosal prostaglandins

ndash Stimulate mucus and bicarbonate secretion

Enhance mucosal protection

1 Bismuth compounds

2 Sucralfate

3 Prostaglandin analogs (misoprostol cytotec)

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Enhance mucosal protection

1 Bismuth compounds

2 Sucralfate

3 Prostaglandin analogs (misoprostol cytotec)

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Mucosal Protective Agents Sucralfate

Is a salt of sucrose complexed to sulfated aluminum hydroxide

In the stomach it forms a viscous tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcer or erosions forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Sucralfate Clinical Use

1 gm four times daily on an empty stomach

Reduces the incidence of GI bleeding in

critically ill patients

Acid ndashinhibitory therapies may increase the

risk of nosocomial pneumonia

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Sucralfate Adverse Effects

ndash It is not absorbed so devoid of toxicity

ndash Constipation in 2 of patients

ndash Caution in renal insufficiency

Drug Interactions

ndash May bind to other medications thus impairing

their absorption

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Mucosal Protective Agents Misoprostol

Prostaglandin Analog a methyl analog of PGE1

Half life 30 minutes

Given 3-4 times daily

Stimulates mucus and bicarbonate secretion and

enhances mucosal blood flow

Binds to PG receptor on the parietal cells reducing

the histamine- stimulated cAMP production and

causing modest acid inhibition

Also stimulates electrolyte and fluid secretion

motility and uterine contractions

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Mucosal Protective Agents Misoprostol

Reduces NSAIDs-induced peptic ulcers in

high-risk patients

Not widely used for this purpose because of

a- side effects

b need for multiple daily dosing

c PPI may be as effective and better

tolerated

d Cyclooxygenase2-selective NSAIDs are

an option for such patients

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Mucosal Protective Agents Misoprostol

Can cause diarrhea and abdominal cramping

in 10-20 of patients

Should not be used in pregnancy

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Mucosal Protective Agents Colloidal Bismuth Compounds

Bismuth subsalicylate

Bismuth subcitrate

Bismuth dinitrate

Bismuth is minimally absorbed from GIT

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Mucosal Protective Agents Colloidal Bismuth Compounds

Coat ulcers and erosions creating a protective layer against acid and pepsin

May stimulate PG mucus and bicarbonate secretion

Bi subsalicylate inhibits intestinal PG and chloride secretion so useful in infectious diarrhea leading to reduced liquidity and frequency of diarrhea

Have direct antimicrobial effects and binds enterotoxins so useful in Travellersrsquo diarrhea

Have direct activity against Hpylori

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Mucosal Protective Agents Colloidal Bismuth Compounds

Adverse effects

Black stools and tongue

Encephalopathy headaches ataxia confusion

and seizures

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

1 Reduce gastric acid secretion from

parietal cells

2 Neutralize acid in the lumen

3 Protect the mucosa from acid

destruction

4 Antibiotics to eradicate Helicobacter

pylori

Treatment of peptic ulcers

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Helicobacter pylori and ulcer

1 Barry J Marshall and J Robin Warren won Nobel Prize in Physiology or Medicine

in 2005 for their discovery of the bacterium Helicobacter pylori and its role in

gastritis and peptic ulcer disease

2 a helix-shaped Gram-negative bacterium

3 Produces large amounts of the enzyme urease molecules of which are localized

inside and outside of the bacterium Urease breaks down urea (which is normally

secreted into the stomach) to carbon dioxide and ammonia which is toxic to the

mucosal epithelial cells

4 Other enzymes including protease vacuolating cytotoxin A (VacA) and certain

phospholipases damage the mucosal epithelial cells

5 Colonization of the stomach by H pylori results in chronic gastritis an inflammation

of the stomach lining The inflammatory response to the bacteria induces G cells in

the antrum to secrete the hormone gastrin which travels through the bloodstream

to the fundus of stomach

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Clarithromycin

Amoxicillin

Metronidazole

Tetracycline

Antibiotics to eradicate Helicobacter pylori

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Treatment of ulcers American College of Gastroenterology

US Recommended Primary Therapy

Eradication rates of 70-85

bull Clarithromycin-based triple therapy

PPI+ clarithromycin + amoxicillin or metronidazole for 14 days

bull Bismuth quadruple therapy consider for penicillin allergic patients

PPI or H2 Receptor antagonist + bismuth + metronidazole + tetracycline for 10-14 days

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Muscarinic antagonists

bull Atropine

bull Pirenzepine

Side effcets

bull urinary retention

bull xerostomia

bull blurred vision

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

GastroEsophageal Reflux Disease

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

GastroEsophageal Reflux Disease

bull Heartburn Dysphagia chronic

symptoms or mucosal damage produced

by abnormal reflux of gastric contents

into the esophagus

bull Therapy based on decreasing acidity

increasing lower esophageal sphincter

tone enhanced clearance of refluxed

material

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

GastroEsophageal Reflux Disease

Treatment

1 PPIs 2 Coating agents

Sulcralfate (Carafate) coats mucous membranes and sores to provide an additional protective barrier against stomach acid

3 Promotilityprokinetic agents help tighten the lower esophageal

sphincter and promote faster emptying of the stomach ndash Metoclopramide ndash Bethanechol

bull Health care providers often are reluctant to prescribe promotility agents because they have fairly significant side effects

bull Promotility agents also do not work as well as PPIs for most people

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Prokinetic agents

ldquoenhancing motility of the upper GI tractrdquo

bull useful in the treatment of GERD especially when gastric stasis or hypomotility is involved

Metoclopramide (Reglan)

bull increases lower esophageal sphincter (LES) tone

bull accelerates gastric emptying by enhancing motility of the upper GI tract

bull dopamine antagonist

bull Side effects similar to other dopamine antagonists hyperprolactemia extrapyramidal symptoms (parkinsonian effects)

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice

Zollinger-Ellison Syndrome

bull Non-beta cell tumor of pancreatic islets

bull Produces gastrin in large quantities

bull Stimulates gastric acid secretion

bull PPI treatment is the therapy of choice