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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
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
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
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
Recommended