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DefinitionsDefinitions
Ulcer:Ulcer:
A lesion on an epithelial surface (skin or mucous A lesion on an epithelial surface (skin or mucous membrane) caused by superficial loss of tissuemembrane) caused by superficial loss of tissue
Greek peptikos "able to digest”Greek peptikos "able to digest”
What is Peptic Ulcer ?What is Peptic Ulcer ?A peptic ulcer disease or PUD is an ulcer (defined as mucosal A peptic ulcer disease or PUD is an ulcer (defined as mucosal erosions equal to or greater than 0.5 cm) of an area of the erosions equal to or greater than 0.5 cm) of an area of the gastrointestinal tract exposed to the acid and pepsin secretiongastrointestinal tract exposed to the acid and pepsin secretion
Gastritis is the precursor to PUD and it is clinically difficult to Gastritis is the precursor to PUD and it is clinically difficult to differentiate the twodifferentiate the two
Stomach (called gastric ulcer)Stomach (called gastric ulcer)Duodenum (called duodenal ulcer)Duodenum (called duodenal ulcer)Esophagus (called Esophageal ulcer)Esophagus (called Esophageal ulcer)Meckel's Diverticulum (called Meckel's Diverticulum Meckel's Diverticulum (called Meckel's Diverticulum ulcer)ulcer)
Gastric Mucosa & SecretionsGastric Mucosa & Secretions
The inside of the stomach is bathed in about 2 liters of The inside of the stomach is bathed in about 2 liters of gastric juice every daygastric juice every day
Gastric juice is composed of digestive enzymes & Gastric juice is composed of digestive enzymes & concentrated hydrochloric acid, which can readily tear concentrated hydrochloric acid, which can readily tear apart the toughest food or microorganismapart the toughest food or microorganism
The gastroduodenal mucosal integrity is determined by protective (defensive) & damaging
(aggressive) factors
Gastric Mucosa & SecretionsGastric Mucosa & Secretions
The Defensive ForcesBicarbonate
Mucus layer
Mucosal blood flow
Prostaglandins
Growth factors
The Aggressive ForcesHelicobacter pylori
HCl acidPepsinsNSAIDs
Bile acidsIschemia and hypoxia. Smoking and alcohol
When the aggressive factors increase or the defensive factors decrease, mucosal damage will result, leading to erosions & ulcerations
Because of ImbalanceBecause of Imbalance
Imbalance primarily between Aggressive factors Imbalance primarily between Aggressive factors and Defensive factors:and Defensive factors:
Aggressive
factors, e,g,
acid, pepsin,
bile etc.
Defensive
factors, e.g.
mucus,
HCO3, PG
Phases of gastric secretionPhases of gastric secretionPhase Stimuli Pathway
Cephalic (stimulate) Sight, smell, taste or thought of food
1) Vagus (M3 receptors)2) Histamine (H2 receptor)3) Gastrin
Gastric (stimulate) Food in the stomach 1) Stretch: local reflex (M3 receptors)
2) Chemical substances in food (gastrin)
3) Increase pH: Inhibition of somatostatin (GHIH) release
Intestinal (inhibit) Chyme in the duodenum
Gastric secretionsGastric secretions
1.1. Pepsinogens Pepsinogens (Chief cells).(Chief cells).
2.2. HCl and intrinsic factor HCl and intrinsic factor (Parietal cells).(Parietal cells).
3.3. Gastrin Gastrin (G-cells).(G-cells).
4.4. Mucus, bicarbonate Mucus, bicarbonate (mucus-secreting cells).(mucus-secreting cells).
Regulation of Gastric secretionsRegulation of Gastric secretions
1.1. Histamine Histamine (local hormone)(local hormone)
2.2. Acetylcholine Acetylcholine (neurotransmitter).(neurotransmitter).
3.3. Gastrin Gastrin (hormone).(hormone).
ProglumideACh
PGE2Histamine Gastrin
Adenyl cyclase
_ +
ATP cAMP
Protein Kinase (Activated)
Ca++
+
Ca++
Proton pump
KK+ H+
Gastric acid
Parietal cellLumen of stomach
AntacidOmeprazole
Ranitidine
H2M3
Misoprostol
_
__
_
+
PGE receptor
+
+
Gastrin receptor+
+
+
What may contribute What may contribute imbalance ?imbalance ?
Helicobacter pyloriHelicobacter pylori
NSAIDsNSAIDs
EthanolEthanol
TobaccoTobacco
Severe physiologic Severe physiologic
stress (Burns, CNS trauma,stress (Burns, CNS trauma,
Surgery, Severe medical illness)Surgery, Severe medical illness)
SteroidsSteroids
Stress induced ulceration after head trauma -CushingStress induced ulceration after head trauma -Cushing’’s ulcers ulcer
Stress induced ulceration after severe burns - Stress induced ulceration after severe burns -
CurlingCurling’’s ulcers ulcer
EtiologyEtiology
Other uncommon causes include:Other uncommon causes include:Gastrinoma (Gastrin secreting tumor)Gastrinoma (Gastrin secreting tumor)Stress ulceration (trauma, burns, critical illness)Stress ulceration (trauma, burns, critical illness)Viral infectionsViral infectionsVascular insufficiencyVascular insufficiency
Who are they ?Who are they ?
Barry J Marshall J. Robin Warren
Nobel Laureates of Medicine – 2005
Discovery of H. pylori & its role in peptic
ulcer
Etiology Etiology
The two most common causes of PUD are:The two most common causes of PUD are:Helicobacter pyloriHelicobacter pylori infection ( 70-80%) infection ( 70-80%)Non-steroidal anti-inflammatory drugs (NSAIDS)Non-steroidal anti-inflammatory drugs (NSAIDS)
H.pyloriH.pylori Epidemiology Epidemiology
One half of worldOne half of world’’s population has s population has H.pylori H.pylori infection, with infection, with an estimated prevalence of 80-90 % in the developing an estimated prevalence of 80-90 % in the developing worldworld
The annual incidence of new The annual incidence of new H. pylori H. pylori infections in infections in industrialized countries is 0.5% of the susceptible industrialized countries is 0.5% of the susceptible population compared with ≥ 3% in developing countriespopulation compared with ≥ 3% in developing countries
Pathogenesis of Pathogenesis of H. pyloriH. pylori infection infection
H. pyloriH. pylori is Gram-negative, spiral & is Gram-negative, spiral & has multiple flagella at one endhas multiple flagella at one end
Transmitted from person-to-person Transmitted from person-to-person by Oro–oral or feco-oral spreadby Oro–oral or feco-oral spread
No reservoir in animal or water No reservoir in animal or water supplysupply
Urease C=O(NH2)2 + H+ + 2H2O HCO3
- + 2 (NH4+)
Urea Bicarbonate Ammonium ions
And then… HCO3-
CO2 + OH-
Urea Hydrolysis
Pathogenesis of Pathogenesis of H. pyloriH. pylori infection infection
The Flagellae make it motile, The Flagellae make it motile, allowing it to live deep beneath allowing it to live deep beneath the mucus layerthe mucus layer
It uses an adhesin molecule to It uses an adhesin molecule to bind to epithelial cells Where the bind to epithelial cells Where the pH there is close to neutralpH there is close to neutral
Pathogenesis of Pathogenesis of H. pyloriH. pylori infection infection
Any acidity is buffered by the Any acidity is buffered by the organism's production of the organism's production of the enzyme urease, which enzyme urease, which catalyzes the production of catalyzes the production of ammonia (NH3) from urea & ammonia (NH3) from urea & raises the pH thereraises the pH thereThe bacterium stimulates The bacterium stimulates chronic gastritis by chronic gastritis by provoking a local provoking a local inflammatory response.inflammatory response.
Pathogenesis of Pathogenesis of H. pyloriH. pylori infection infection
In the cellular level:In the cellular level:
H. pylori H. pylori express express cagAcagA & & vacAvacA genes genes
cagAcagA gene gene signals to the signals to the epithelial cells involving: epithelial cells involving: - Cell replication, - Cell replication, - Apoptosis, & - Apoptosis, & - Morphology- Morphology
Pathogenesis of Pathogenesis of H. pyloriH. pylori infection infection
In the cellular level:In the cellular level:
vacAvacA gene gene producing producing a pore-forming protein, which a pore-forming protein, which has many destructing effect to has many destructing effect to the epithelium like: the epithelium like: --↑Cell permeability & efflux ↑Cell permeability & efflux of micronutrients, of micronutrients, -- Induction of apoptosis, & Induction of apoptosis, & - - Suppression of local cell Suppression of local cell immunityimmunity
Pathogenesis of Pathogenesis of H. pyloriH. pylori infection infection
- ↓ Somatostatin production from antral D-cells due to antral gastritis- Low somatostatin will ↑Gastrin release from G-cell hypergastrinemia- This will stimulate acid production by the parietal cells leading to further duodenal ulceration.
Effects of H. pylori on gastric Hormones
This effect is exaggerated among smokers!
Carcinogenic effect of Carcinogenic effect of H. pylori H. pylori
H. pylori
Host Factors
Other environmental Factors
Antral gastritis Pangastritis
DU GU Gastritis Cancer
Carcinogenic effect of Carcinogenic effect of H. pyloriH. pylori
Epidemiologic evidence suggests that infection with HP is Epidemiologic evidence suggests that infection with HP is associated with >2 fold increase risk of gastric cancerassociated with >2 fold increase risk of gastric cancer
However due to uncertainty regarding the benefit of HP However due to uncertainty regarding the benefit of HP eradication on reducing cancer risk, wide-spread screening eradication on reducing cancer risk, wide-spread screening for HP in asymptomatic individuals cannot be for HP in asymptomatic individuals cannot be recommended at this time recommended at this time
2. Etiology -Non-Steroidal Anti-inflammatory 2. Etiology -Non-Steroidal Anti-inflammatory Drugs (NSAIDS)Drugs (NSAIDS)
NSAIDSNSAIDS
Symptomatic GI ulceration occurs in 2% - 4% of patients Symptomatic GI ulceration occurs in 2% - 4% of patients treated with NSAIDs for 1 yeartreated with NSAIDs for 1 year
In view of the million of people who take NSAIDs annually, In view of the million of people who take NSAIDs annually, these small percentages translate into a large number of these small percentages translate into a large number of symptomatic ulcerssymptomatic ulcers
The effects of aspirin & NSAIDs on the gastric mucosa ranges The effects of aspirin & NSAIDs on the gastric mucosa ranges from mucosal hemorrhages to erosions & acute ulcersfrom mucosal hemorrhages to erosions & acute ulcers
NSAIDSNSAIDS
Inhibits the production of Inhibits the production of prostaglandinsprostaglandins precursor from membrane fatty acids resulting in:precursor from membrane fatty acids resulting in:
1. Decrease mucus & HCO3 production1. Decrease mucus & HCO3 production
2. Decrease mucosal blood flow2. Decrease mucosal blood flow
3. Reduce cell renewal3. Reduce cell renewal The drugs also generate oxygen-free radicals & The drugs also generate oxygen-free radicals &
products of the lipoxygenase pathway that may products of the lipoxygenase pathway that may contribute to ulcerationcontribute to ulceration
NSAIDSNSAIDS
Gastric acid probably aggravates NSAID-induce mucosal Gastric acid probably aggravates NSAID-induce mucosal injury by injury by
- Converting superficial injury to deeper mucosal necrosis,- Converting superficial injury to deeper mucosal necrosis,
- Interfering with haemostasis & platelet aggregation- Interfering with haemostasis & platelet aggregation
- Impairing ulcer healing- Impairing ulcer healing
NSAIDSNSAIDS
Users of NSAIDs are at approximately 3 times greater Users of NSAIDs are at approximately 3 times greater relative risk of serious adverse gastrointestinal events than relative risk of serious adverse gastrointestinal events than nonusersnonusers
NSAIDSNSAIDS Identify risk factors:Identify risk factors:
Age > 65 years (3.5-fold increased risk)Age > 65 years (3.5-fold increased risk)
Smoking Smoking
Previous history of GI event (e.g. ulcer bleeding 4-fold increase Previous history of GI event (e.g. ulcer bleeding 4-fold increase risk)risk)
Concomitant drug use Concomitant drug use
Anticoagulants ( eg, warfarin; 3-fold increase)Anticoagulants ( eg, warfarin; 3-fold increase)
Corticosteroid ( 2-fold increase)Corticosteroid ( 2-fold increase)
Low dose aspirin alone ( 2.5-fold increase)Low dose aspirin alone ( 2.5-fold increase)
Aspirin + NSAIDS (4-fold increase vs aspirin alone) Aspirin + NSAIDS (4-fold increase vs aspirin alone)
Type of NSAID & Risk of UlcerType of NSAID & Risk of Ulcer
Risk Group Drug Relative Risk
Low Ibuprofen
Diclofenac
2.0
4.2
Medium Naproxen
Indomethacin Piroxicam
9.1
11.3
13.7
High Ketoprofen Azapropazone
23.7 31.5
Psychological Stress Psychological Stress UlcersUlcers
Gastric mucosa of body of stomach undergoes a Gastric mucosa of body of stomach undergoes a period of transient ischemia in association withperiod of transient ischemia in association with
HypotensionHypotensionSevere injurySevere injuryExtensive burnsExtensive burnsComplicated surgery Complicated surgery
Psychological Stress Psychological Stress UlcersUlcers
Ischemia due to ↓ capillary blood flow or shunting Ischemia due to ↓ capillary blood flow or shunting of blood away from GI tract so that blood flow of blood away from GI tract so that blood flow bypasses gastric mucosabypasses gastric mucosa
Imbalance between destructive properties of HCl acid Imbalance between destructive properties of HCl acid and pepsin, and protective factors of stomachand pepsin, and protective factors of stomach’’s s mucosal barriermucosal barrier
Two major variants in peptic ulcers are commonly Two major variants in peptic ulcers are commonly encountered in the clinical practice:encountered in the clinical practice:
1)1) Duodenal UlcerDuodenal Ulcer (DU) (DU)
2)2) Gastric UlcerGastric Ulcer (GU) (GU)
TypesTypesAcute Acute
Superficial erosionSuperficial erosionMinimal erosionMinimal erosion
ChronicChronicMuscular wall erosion with formation of fibrous tissue Muscular wall erosion with formation of fibrous tissue Present continuously for many months or Present continuously for many months or intermittentlyintermittently
Recurrence Recurrence Risk factors for recurrence include:Risk factors for recurrence include:
Non-ulcer dyspepsiaNon-ulcer dyspepsiaPersistence of chronic gastritis after eradication therapyPersistence of chronic gastritis after eradication therapyFemale genderFemale genderIntellectual disabilityIntellectual disabilityYounger ageYounger ageHigh rates of primary infectionHigh rates of primary infectionHigher urea breath test valuesHigher urea breath test values
ABLES A Z et al. American Family Physician. 2007
Clinical PresentationClinical PresentationRecurrent epigastric pain (the most common symptom)Recurrent epigastric pain (the most common symptom)
BurningBurning
Occurs 1-3 hours after mealsOccurs 1-3 hours after meals
Relieved by food Relieved by food DUDU
Precipitated by food Precipitated by food GUGU
Relieved by antacidsRelieved by antacids
Radiate to back (consider penetration)Radiate to back (consider penetration)
Pain may be absent or less characteristic in one-third of Pain may be absent or less characteristic in one-third of patients especially in elderly patients on NSAIDspatients especially in elderly patients on NSAIDs
Clinical PresentationClinical Presentation
Nausea, VomitingNausea, Vomiting
Dyspepsia, fatty food intoleranceDyspepsia, fatty food intolerance
Chest discomfortChest discomfort
Anorexia, weight loss especially in GUAnorexia, weight loss especially in GU
Hematemesis or melena resulting from gastrointestinal Hematemesis or melena resulting from gastrointestinal bleedingbleeding
Weight lossWeight loss
Duodenal Vs Gastric Ulcers Duodenal Vs Gastric Ulcers
Duodenal Duodenal
Age: 25-75 yearsAge: 25-75 years
Gnawing or burning upper Gnawing or burning upper abdomen pain relieved by food but abdomen pain relieved by food but reappears 1-3 hrs after mealsreappears 1-3 hrs after meals
Worse pain when stomach emptyWorse pain when stomach empty
Bleeding occurs with deep erosionBleeding occurs with deep erosionHematemesisHematemesisMelena Melena
GastricGastric
Age: 55-65 yearsAge: 55-65 years
Relieved by food but pain may Relieved by food but pain may persist even after eatingpersist even after eating
Anorexia, wt loss, vomitingAnorexia, wt loss, vomiting
Infrequent or absent remissionsInfrequent or absent remissions
Small % become cancerous Small % become cancerous
Severe ulcers may erode through Severe ulcers may erode through stomach wall stomach wall
Differentiating between H. Differentiating between H. pylori and NSAID-induced pylori and NSAID-induced
ulcer ulcer Ulcers associated with H. pyloriUlcers associated with H. pylori
More often in duodenumMore often in duodenum
Often superficialOften superficial
Less severe GI bleedingLess severe GI bleeding
Ulcers associated with NSAIDsUlcers associated with NSAIDs
More often in stomachMore often in stomach
Often deepOften deep
More severe GI bleedingMore severe GI bleeding
Sometimes asymptomaticSometimes asymptomatic
Differential diagnoses for Differential diagnoses for epigastric painepigastric pain
Surgical Surgical Biliary colic, acute cholecystitisBiliary colic, acute cholecystitis PancreatitisPancreatitis Perforation of viscusPerforation of viscus Acute appendicitisAcute appendicitis MalignancyMalignancy Hiatus herniaHiatus hernia
Medical Medical GORDGORD MIMI PEPE Pneumonia Pneumonia
Taking a history Taking a history 55 yr old man presents with a 6-month history of 55 yr old man presents with a 6-month history of worsening epigastric pain described as a burning worsening epigastric pain described as a burning sensation. He notices the pain is worse when he is sensation. He notices the pain is worse when he is hungry. He feels nauseated with the pain but has not hungry. He feels nauseated with the pain but has not vomited. There is no change in his bowel habits and vomited. There is no change in his bowel habits and his weight is more of less stable. He smokes 10 his weight is more of less stable. He smokes 10 cigarettes a day and drinks socially. He has been to cigarettes a day and drinks socially. He has been to see his GP who has suggested ranitidine but this has see his GP who has suggested ranitidine but this has not helped. On examination he is tender in his not helped. On examination he is tender in his epigastrium but examination is otherwise epigastrium but examination is otherwise unremarkable. unremarkable.
Peptic Ulcer DiseasePeptic Ulcer Disease
Diagnosis:Diagnosis:
1)1) Diagnosis of ulcerDiagnosis of ulcer
2)2) Diagnosis of H. pyloriDiagnosis of H. pylori
EndoscopyEndoscopy Barium meal – contrast x-rayBarium meal – contrast x-ray Biopsy – bacteria & malignancyBiopsy – bacteria & malignancy H.Pylori:H.Pylori:
Endoscopy cytologyEndoscopy cytology Biopsy – Special stainsBiopsy – Special stains Culture - difficultCulture - difficult Urease Breath test.Urease Breath test.
PUD - DiagnosisPUD - Diagnosis
• Niche on the lesser Niche on the lesser curve with notch on curve with notch on the greater curvaturethe greater curvature
Diagnosis of PUDDiagnosis of PUD
In most patients routine laboratory tests are usually In most patients routine laboratory tests are usually unhelpfulunhelpful Diagnosis of PUD depends mainly on endoscopic and
radiographic confirmation
EndoscopyEndoscopy
• Most sensitive and specific . Most sensitive and specific . • Direct visualization of the mucosa, Direct visualization of the mucosa, • Biopsy to rule out malignancy or Biopsy to rule out malignancy or Hpylori.Hpylori.
• Identifies lesions too small to detect by Ba exam, for Identifies lesions too small to detect by Ba exam, for evaluation of atypical radiographic abnormalities, or evaluation of atypical radiographic abnormalities, or to determine if an ulcer is a source of blood loss.to determine if an ulcer is a source of blood loss.
Diagnosis of Diagnosis of H. pyloriH. pylori
Non-invasiveNon-invasive
• CC1313 or C or C1414 Urea Breath Test Urea Breath Test
• Stool antigen testStool antigen test
• H. pylori IgG titer (serology)H. pylori IgG titer (serology)
InvasiveInvasive
• Gastric mucosal biopsyGastric mucosal biopsy
• Rapid Urease testRapid Urease test
Diagnosis of Diagnosis of H. pyloriH. pylori
Non-invasive 1. C13 or C14 Urea Breath Test
The best test for the detection
of an active infection
Diagnosis of Diagnosis of H. pyloriH. pylori
Non-invasiveNon-invasive
1)1) Serology for Serology for H pyloriH pyloria.a. Serum Antibodies (IgG) to Serum Antibodies (IgG) to H pylori H pylori (Not for active (Not for active
infection) infection) b.b. Fecal antigen testing (Fecal antigen testing (Test for active HPTest for active HP) )
Diagnosis of Diagnosis of H. pyloriH. pylori
InvasiveInvasive
• Upper GI endoscopyUpper GI endoscopy– Highly sensitive testHighly sensitive test– Patient needs sedationPatient needs sedation– Has both Has both diagnosticdiagnostic & & therapeutictherapeutic role role
Diagnosis of Diagnosis of H. pyloriH. pylori
Invasive (endoscopy)Invasive (endoscopy)– DiagnosticDiagnostic::– Detect the site and the size of the ulcer, even small Detect the site and the size of the ulcer, even small
and superficial ulcer can be detectedand superficial ulcer can be detected– Detect source of bleedingDetect source of bleeding– Biopsies can be taken for Biopsies can be taken for rapid urease testrapid urease test, ,
histopathologyhistopathology && cultureculture
Diagnosis of Diagnosis of H. pyloriH. pylori
Invasive (endoscopy)Invasive (endoscopy)
• Rapid urease test ( RUT)Rapid urease test ( RUT)o Considered the endoscopic Considered the endoscopic diagnostic test of choicediagnostic test of choiceo Gastric biopsy specimens are placed in the rapid Gastric biopsy specimens are placed in the rapid
urease test kit. If urease test kit. If H pyloriH pylori are present, bacterial are present, bacterial urease converts urea to ammonia, which changes urease converts urea to ammonia, which changes pH and produces a pH and produces a CCOOLLOORR changechange
Diagnosis of Diagnosis of H. pyloriH. pylori
Invasive (endoscopy)Invasive (endoscopy)
* Histopathology* Histopathologyo Done if the rapid urease test result is negative Done if the rapid urease test result is negative
* Culture* Cultureo Used in research studies and is not available Used in research studies and is not available
routinely for clinical useroutinely for clinical use
ComplicationsComplications• Complications of Complications of
Gastric UlcerGastric Ulcer• 1. Hour glass 1. Hour glass
contracture: It occurs contracture: It occurs exclusively inexclusively in
• women, is due to women, is due to cicatricial contracture cicatricial contracture of lesser curveof lesser curve
• ulcer.ulcer.• – – Here stomach is Here stomach is
divided into two divided into two compartmentscompartments
• Clinical featuresClinical features• – – Loss of periodicity.Loss of periodicity.• – – Persistent pain.Persistent pain.• – – Vomiting.Vomiting.• – – Loss of appetite and weight.Loss of appetite and weight.
• • DiagnosisDiagnosis• – – Barium meal: It shows filling only in the proximalBarium meal: It shows filling only in the proximal• stomach or double pouched stomach.stomach or double pouched stomach.• – – Gastroscopy.Gastroscopy.
• • TreatmentTreatment• Partial gastrectomy wherein gastric ulcer with lower Partial gastrectomy wherein gastric ulcer with lower
compartment of the stomach is removed and Billroth-I compartment of the stomach is removed and Billroth-I anastomosis is doneanastomosis is done
• 2. Tea-pot deformity: 2. Tea-pot deformity: (Hand-Bag stomach) (Hand-Bag stomach) is due is due to cicatrisation to cicatrisation and shortening of the and shortening of the lesser curvature.lesser curvature.
• – – They present with They present with features of pyloric features of pyloric stenosis.stenosis.
• – – Treatment is partial Treatment is partial gastrectomy with gastrectomy with Billroth-Ianastomosis.Billroth-Ianastomosis.
• 3. Perforation.3. Perforation.• 4. Bleeding by erosion into the left gastric and 4. Bleeding by erosion into the left gastric and
rarely splenic vessels or to vessels in the wall of rarely splenic vessels or to vessels in the wall of ulcer.ulcer.
• 5. Penetration posteriorly into pancreas, anteriorly 5. Penetration posteriorly into pancreas, anteriorly into into liver.liver.
• 6. Malignant transformation usually into 6. Malignant transformation usually into adenocarcinoma of stomach (2-5%).adenocarcinoma of stomach (2-5%).
TreatmentTreatment
• I. General measures: Avoid alcohol, NSAIDs, I. General measures: Avoid alcohol, NSAIDs, smoking,spicy foods. Have more frequent food.smoking,spicy foods. Have more frequent food.
• II. Specific measures:II. Specific measures:
1)1) MedicalMedical
2)2) SurgicalSurgical
ClassificationClassification1.1. Acid Neutralizing agents: (ANTACIDS)Acid Neutralizing agents: (ANTACIDS)
• Systemic: Sodium Bicarbonate and Sod. CitrateSystemic: Sodium Bicarbonate and Sod. Citrate• Nonsystemic: Magnesium hydroxide, Mag. Treisilicate, Aluminium Nonsystemic: Magnesium hydroxide, Mag. Treisilicate, Aluminium
hydroxide gel, Magaldrate and calcium carbonatehydroxide gel, Magaldrate and calcium carbonate
2.2. Reduction in Gastric acid secretion:Reduction in Gastric acid secretion:
• H2 antihistamines: H2 antihistamines: Cimetidine, Ranitidine, Famotidine, Cimetidine, Ranitidine, Famotidine, Nizatidine and RoxatidineNizatidine and Roxatidine
• Proton pump inhibitors: Proton pump inhibitors: Omeprazole, Lansoprazole Omeprazole, Lansoprazole Pantoprazole, Rabeprazole and EsomeprazolePantoprazole, Rabeprazole and Esomeprazole
• Anticholinergics:Anticholinergics: Pirenzepine, Propantheline and Pirenzepine, Propantheline and OxyphenoniumOxyphenonium
• Prostaglandin analogue: Prostaglandin analogue: MisoprostolMisoprostol
Classification – contd.Classification – contd.
3.3. Ulcer protectives: Sucralfate, Colloidal Bismuth sudcitrateUlcer protectives: Sucralfate, Colloidal Bismuth sudcitrate
4.4. Anti-H. pylori Drugs: Amoxicillin, Clarithromycin, Anti-H. pylori Drugs: Amoxicillin, Clarithromycin, metronidazole, tinidazole and tetracycline metronidazole, tinidazole and tetracycline
AntacidsAntacids• Weak bases that neutralize acidWeak bases that neutralize acid
• Also inhibit formation of pepsin Also inhibit formation of pepsin
(As pepsinogen converted to pepsin at acidic pH)(As pepsinogen converted to pepsin at acidic pH)
• Acid Neutralizing Capacity:Acid Neutralizing Capacity: – Potency of AntacidsPotency of Antacids– Expressed in terms of Number ofExpressed in terms of Number of mEq mEq of of 1N HCl1N HCl that are brought that are brought
down to pH 3.5 in 15 minutes by unit dose of a preparation (1 gm)down to pH 3.5 in 15 minutes by unit dose of a preparation (1 gm)
Antacids - The Oldest Antacids - The Oldest RemedyRemedy
• Sodium Bicarbonate:Sodium Bicarbonate:– Potent neutralizing capacity and acts instantlyPotent neutralizing capacity and acts instantly– ANC: 1 gm = 12 mEqANC: 1 gm = 12 mEq
• NOT USED ANYMORE FOR ITS DEMERITS:NOT USED ANYMORE FOR ITS DEMERITS:– Systemic alkalosisSystemic alkalosis– Distension, discomfort and belching – CO2Distension, discomfort and belching – CO2– Rebound acidityRebound acidity– Sodium overloadSodium overload
AntacidsAntacids• Present day antacids :Present day antacids :
– Aluminium Hydroxide (ANC 1-2.5mEq/g)Aluminium Hydroxide (ANC 1-2.5mEq/g)– Magnesium Hydroxide (ANC 30 mEq) – milk of magnesiaMagnesium Hydroxide (ANC 30 mEq) – milk of magnesia– Magnesium trisilicate (ANC 1mEq/g)Magnesium trisilicate (ANC 1mEq/g)
• Duration of action : 30 min when taken in empty stomach and 2 Duration of action : 30 min when taken in empty stomach and 2 hrs when taken after a mealhrs when taken after a meal
• Side effects :Side effects :– Aluminium antacids – Aluminium antacids – constipationconstipation (As they relax gastric smooth (As they relax gastric smooth
muscle & delay gastric emptying) – also hypophosphatemia and muscle & delay gastric emptying) – also hypophosphatemia and osteomalciaosteomalcia
– Mg2+ antacids – Osmotic Mg2+ antacids – Osmotic diarrhoeadiarrhoea
• In renal failure Al3+ antacid – Aluminium toxicity In renal failure Al3+ antacid – Aluminium toxicity & Encephalopathy & Encephalopathy
(Magaldrate – hydrated hydroxy magnesium aluminate)(Magaldrate – hydrated hydroxy magnesium aluminate)
Non Systemic AntacidsNon Systemic Antacids
Not absorbed – no systemic alkalosisNot absorbed – no systemic alkalosis
Stomach – Al(OH)Stomach – Al(OH)33 + 3HCL = AlCl + 3HCL = AlCl33 + 3H2O + 3H2O
Mg(OH)Mg(OH)22 + 2HCL = MgCl + 2HCL = MgCl22 + 2H2O + 2H2O
Intestine – AlClIntestine – AlCl33 + NaHCO + NaHCO33 = AlCO = AlCO33 + NaCl + H + NaCl + H22O + COO + CO22
MgCLMgCL22 + NaHCO + NaHCO33 = MgCO = MgCO33 + NaCl + H + NaCl + H22O + COO + CO22
Excreted in fecesExcreted in feces
Antacids – contd.Antacids – contd.
• SimethiconeSimethicone: Decrease surface tension thereby reduce bubble : Decrease surface tension thereby reduce bubble formation - added to prevent reflux formation - added to prevent reflux
• Alginates:Alginates: Form a layer of foam on top of gastric contents & Form a layer of foam on top of gastric contents & reduce refluxreduce reflux
• Oxethazaine:Oxethazaine: Surface anaesthetic Surface anaesthetic
Therapeutic QuestionsTherapeutic Questions• Is it rational to combine Aluminium hydroxide and magnesium Is it rational to combine Aluminium hydroxide and magnesium
hydroxide in antacid preparations ?hydroxide in antacid preparations ?
• How to avoid formation of insoluble complexes of drugs by How to avoid formation of insoluble complexes of drugs by antacids, that are not absorbed ?antacids, that are not absorbed ?
Answers (!)Answers (!)• Interactions can be avoided by taking antacids 2 hrs before or Interactions can be avoided by taking antacids 2 hrs before or
after ingestion of other drugsafter ingestion of other drugs
• Combination provides a relatively fast and sustained Combination provides a relatively fast and sustained neutralizing capacityneutralizing capacity– (Magnesium Hydroxide – Rapidly acting(Magnesium Hydroxide – Rapidly acting– Aluminium Hydroxide - Slowly acting )Aluminium Hydroxide - Slowly acting )
• Combination preserves normal bowel functionCombination preserves normal bowel function– (Aluminium Hydroxide – constipation(Aluminium Hydroxide – constipation– Magnesium hydroxide – diarrhoea )Magnesium hydroxide – diarrhoea )
The RealityThe Reality• Not part of Physician prescribed regimen – frequency of dosing Not part of Physician prescribed regimen – frequency of dosing
and rebound acidityand rebound acidity
• Over the counter (OTC) drug for symptomatic relief of Over the counter (OTC) drug for symptomatic relief of dyspepsiadyspepsia
• May only be prescribed for very short term:May only be prescribed for very short term:– Non-ulcer dyspepsia and minor episodes of heart burnNon-ulcer dyspepsia and minor episodes of heart burn– As adjuvant in GERD – quick relieveAs adjuvant in GERD – quick relieve
Sucralfate – ulcer protectiveSucralfate – ulcer protective
• Salt of Salt of sucrose sucrose complexed to sulfated aluminium hydroxide complexed to sulfated aluminium hydroxide (basic aluminium salt)(basic aluminium salt)
• MOA:MOA:– In acidic pH In acidic pH polymerisespolymerises to viscous gel that adheres to ulcer crater - to viscous gel that adheres to ulcer crater -
more on duodenal ulcermore on duodenal ulcer– Precipitates protein on surface proteins and acts as physical barrierPrecipitates protein on surface proteins and acts as physical barrier– Dietary proteins get deposited on this layer forming another coatDietary proteins get deposited on this layer forming another coat– Delays gastric emptying and causes gastric PG synthesis – protective Delays gastric emptying and causes gastric PG synthesis – protective
actionaction
Sucralfate – contd.Sucralfate – contd.
• Taken on empty stomach 1 hr. before mealsTaken on empty stomach 1 hr. before meals
• Concurrent antacids, HConcurrent antacids, H22 antagonist avoided (as it needs acid for antagonist avoided (as it needs acid for activation)activation)
• Uses:Uses:– NSAID induced ulcersNSAID induced ulcers– Patients with continued smokingPatients with continued smoking– ICUICU– Topically – burn, bedsore ulcers, excoriated skinsTopically – burn, bedsore ulcers, excoriated skins
• Dose: 1 gm 1 Hr before mealsDose: 1 gm 1 Hr before meals
• ADRs: Constipation, hypophosphatemia ADRs: Constipation, hypophosphatemia
Chemical reactions of antacids with HCl in the Chemical reactions of antacids with HCl in the stomachstomach
AntacidsAntacidsCapsules & Tablets:Capsules & Tablets:
• PowdersPowders
• Chewable tabletsChewable tablets
• SuspensionsSuspensions
• Effervescent granules and tabletsEffervescent granules and tablets
ProglumideACh
PGE2Histamine Gastrin
Adenyl cyclase
_ +
ATP cAMP
Protein Kinase (Activated)
Ca++
+
Ca++
Proton pump
KK+ H+
Gastric acid
Parietal cellLumen of stomach
AntacidOmeprazole
Ranitidine
H2M3
Misoprostol
_
__
_
+
PGE receptor
+
+
Gastrin receptor+
+
+
HH22 Antagonists Antagonists• Cimetidine, Ranitidine, Famotidine, Roxatidine, Nizatidine Cimetidine, Ranitidine, Famotidine, Roxatidine, Nizatidine
andand
• MOA:MOA: – Reversible competitive inhibitors of HReversible competitive inhibitors of H22 receptor receptor– Highly selective, no action on HHighly selective, no action on H11 or H or H33 receptors receptors– All phases of gastric acid secretionAll phases of gastric acid secretion– Very effective in inhibiting nocturnal acid secretion (as it depends Very effective in inhibiting nocturnal acid secretion (as it depends
largely on Histamine )largely on Histamine )– Modest impact on meal stimulated acid secretion (as it depends on Modest impact on meal stimulated acid secretion (as it depends on
gastrin, acetylcholine and histamine)gastrin, acetylcholine and histamine)– Volume of pepsin content and IF are also reducedVolume of pepsin content and IF are also reduced– Volume reduced by 60 – 70% - anti ulcerogenic effectVolume reduced by 60 – 70% - anti ulcerogenic effect– No effect on motilityNo effect on motility
HH22 antagonists antagonists• Kinetics:Kinetics:
– All drugs are absorbed orally adequatelyAll drugs are absorbed orally adequately– Bioavailability upto 80 %Bioavailability upto 80 %– Absorption is not interfered by presence of foodAbsorption is not interfered by presence of food– Can cross placental barrier and reaches milkCan cross placental barrier and reaches milk– Poor CNS penetrationPoor CNS penetration– 2/32/3rdrd of the drugs are excreted unchanged in bile and urine of the drugs are excreted unchanged in bile and urine
• Preparations: available as tablets, injectionsPreparations: available as tablets, injections
HH2 2 antagonists - ADRsantagonists - ADRs• Extremely safe drugs and well toleratedExtremely safe drugs and well tolerated
• Main ADRs are related to Cimetidine:Main ADRs are related to Cimetidine:– Antiandrogenic Antiandrogenic effectseffects– Increases Increases prolactinprolactin secretion and inhibits degradation of secretion and inhibits degradation of estradiol estradiol by by
liverliver– Cytochrome P450 inhibition – theophylline, metronidazole, phenytoin, Cytochrome P450 inhibition – theophylline, metronidazole, phenytoin,
imipramine etc.imipramine etc.– AntacidsAntacids
• Others:Others:– Headache, dizziness, bowel upset, dry mouthHeadache, dizziness, bowel upset, dry mouth– Bolus IV – release histamine – bradycardia, arrhythmia, cardiac arrestBolus IV – release histamine – bradycardia, arrhythmia, cardiac arrest– Elderly - precautionElderly - precaution
HH2 2 antagonists - Usesantagonists - UsesPromote the healing of gastric and duodenal ulcersPromote the healing of gastric and duodenal ulcers• Duodenal ulcer – 70 to 90%Duodenal ulcer – 70 to 90%• Gastric Ulcer – 50 to 75% (NSAID ulcers))Gastric Ulcer – 50 to 75% (NSAID ulcers))• Stress ulcer and gastritisStress ulcer and gastritis• GERDGERD• Zollinger-Ellison syndromeZollinger-Ellison syndrome• Prophylaxis of aspiration pneumoniaProphylaxis of aspiration pneumonia• UrticariaUrticaria
Doses:Doses: • 300 mg/40 mg/150 mg at bed time of R, F, Rox respectively for healing300 mg/40 mg/150 mg at bed time of R, F, Rox respectively for healing• Maintenance: 150/20/150 mg BD of R, F, Rox Maintenance: 150/20/150 mg BD of R, F, Rox
HH22 blockers Tablets in Peptic blockers Tablets in Peptic ulcerulcer
Cimetidine 800mg bedtime /400mgBd 400mg bedtime
Ranitidine 300 mg bedtime/150mg BD 150 mg bedtime
Famotidine 40 mg bedtime 20 mg bedtime
Roxatidine 150 mg bedtime 75 mg bedtime
Proton Pump InhibitorsProton Pump Inhibitors• Most effective drugs in antiulcer therapyMost effective drugs in antiulcer therapy
• Prodrugs Prodrugs requiring activation in acid environmentrequiring activation in acid environment
• Block enzymes responsible for secreting HCl - binds Block enzymes responsible for secreting HCl - binds irreversiblyirreversibly to to H+K+ATPase H+K+ATPase
• Prototype: Prototype: Omeprazole (Prilosec) Omeprazole (Prilosec)
• Examples:Examples:– Lansoprazole Lansoprazole – PantoprazolePantoprazole– Rabeprazole Rabeprazole – Esomeprazole Esomeprazole
Omeprazole
Mechanism of actionMechanism of actionOmeprazoleOmeprazole
Sulfenic acidSulfenic acid
SulfenamideSulfenamide
Irreversible bind enzyme of HIrreversible bind enzyme of H+ + KK+ + ATPaseATPase
Enzyme inhibitory complexEnzyme inhibitory complex
Block final step in Acid productionBlock final step in Acid production
•Provide prolong suppression of acid secretion = 24 to 48 hrsProvide prolong suppression of acid secretion = 24 to 48 hrs
Adenyl cyclase
_ +
ATP cAMP
Protein Kinase (Activated)
Ca++
+
Ca++
Proton pump
K+ H+
Gastric acid
Parietal cell
Lumen of stomach
H2M3
_
++
+
+
+
PGE receptor
Gastrin receptor
QuestionQuestion• Half life of proton pump inhibitors is 1.5 hours only and these Half life of proton pump inhibitors is 1.5 hours only and these
drugs are generally given once daily. How this can be justified ?drugs are generally given once daily. How this can be justified ?
• Answer :Answer :– P.P.I - Irreversible inhibitors of H+K+ATPaseP.P.I - Irreversible inhibitors of H+K+ATPase(Hit and run drugs) (Hit and run drugs)
Pharmacokinetics - PPIPharmacokinetics - PPI Given on an empty stomach because food affects absorptionGiven on an empty stomach because food affects absorption They should be given 30 minutes to 1 hour before food They should be given 30 minutes to 1 hour before food
intake because an acidic pH in the parietal cell acid intake because an acidic pH in the parietal cell acid canaliculi is required for drug activation, and food stimulates canaliculi is required for drug activation, and food stimulates acid production acid production
Concomitant use of other antisecretory drugs - H2 receptor Concomitant use of other antisecretory drugs - H2 receptor antagonists – reduces action antagonists – reduces action
Highly protein bound and rapidly Metabolized by the liver Highly protein bound and rapidly Metabolized by the liver by CYP2C19 and CYP3A4 – dose reduction necessary in by CYP2C19 and CYP3A4 – dose reduction necessary in severe hepatic failuresevere hepatic failure
Excreted in Kidneys minimally (no dose reduction needed in Excreted in Kidneys minimally (no dose reduction needed in renal failure and elderly) renal failure and elderly)
Adverse EffectsAdverse Effects The most common are GIT troubles in the form of nausea, The most common are GIT troubles in the form of nausea,
abdominal pain, constipation, flatulence, and diarrheaabdominal pain, constipation, flatulence, and diarrhea
Subacute myopathy, arthralgias, headaches, and skin rashes Subacute myopathy, arthralgias, headaches, and skin rashes
Prolonged use:Prolonged use: Gynaecomastia, erectile dysfunctionGynaecomastia, erectile dysfunction Leucopenia and hepatic dysfunctionLeucopenia and hepatic dysfunction Vitamin B12 deficiencyVitamin B12 deficiency Hypergastrinemia which may predispose to rebound Hypergastrinemia which may predispose to rebound
hypersecretion of gastric acid upon discontinuation of therapy and hypersecretion of gastric acid upon discontinuation of therapy and may promote the growth of gastrointestinal tumors (carcinoid may promote the growth of gastrointestinal tumors (carcinoid tumors )tumors )
• Therapeutic uses:Therapeutic uses:1.1. Gastroesophageal reflux disease (GERD)Gastroesophageal reflux disease (GERD)2.2. Peptic Ulcer - Gastric and duodenal ulcersPeptic Ulcer - Gastric and duodenal ulcers3.3. Bleeding peptic Ulcer Bleeding peptic Ulcer 4.4. Zollinger ellison SyndromeZollinger ellison Syndrome5.5. Prevention of recurrence of nonsteroidal antiinflammatory drug Prevention of recurrence of nonsteroidal antiinflammatory drug
(NSAID) - associated gastric ulcers in patients who continue (NSAID) - associated gastric ulcers in patients who continue NSAID use.NSAID use.
6.6. Reducing the risk of duodenal ulcer recurrence associated with Reducing the risk of duodenal ulcer recurrence associated with H. pylori infectionsH. pylori infections
7.7. Aspiration PneumoniaAspiration Pneumonia
PPI – Dosage schedulePPI – Dosage schedule
• Omeprazole 20 mg o.d.Omeprazole 20 mg o.d.
• Lansoprazole 30 mg o.d.Lansoprazole 30 mg o.d.
• Pantoprazole 40 mg o.d.Pantoprazole 40 mg o.d.
• Rabeprazole 20 mg o.d.Rabeprazole 20 mg o.d.
• Esomeprazole 20 - 40 mg o.d.Esomeprazole 20 - 40 mg o.d.
Muscarinic antagonistsMuscarinic antagonistsAtropine:Atropine:
– Block the MBlock the M11 class receptors class receptors– Reduce acid productionReduce acid production– Abolish gastrointestinal spasmAbolish gastrointestinal spasm
Pirenzepine and TelenzepinePirenzepine and Telenzepine
Mechanism of action: Mechanism of action: • Reduce meal stimulated HCl secretion by reversible blockade of muscarinic Reduce meal stimulated HCl secretion by reversible blockade of muscarinic
(M1) receptors on the cell bodies of the intramural cholinergic ganglia(M1) receptors on the cell bodies of the intramural cholinergic ganglia
(receptors on parietal cells are M3).(receptors on parietal cells are M3).
• Unpopular as a first choice because of high incidence of Unpopular as a first choice because of high incidence of anticholinergic side effects (dry mouth and blurredanticholinergic side effects (dry mouth and blurred vision) vision)
Prostaglandin analoguesProstaglandin analogues• Inhibit gastric acid secretionInhibit gastric acid secretion
• Exhibit ‘cytoprotective’ activityExhibit ‘cytoprotective’ activity
• Enhance local production of mucus or bicarbonateEnhance local production of mucus or bicarbonate
• Promote local cell regenerationPromote local cell regeneration
• Help to maintain mucosal bloodHelp to maintain mucosal blood
Prostaglandin analogues - Prostaglandin analogues - MisoprostolMisoprostol
Actions:Actions:Inhibit histamine-stimulated gastric acid secretionInhibit histamine-stimulated gastric acid secretionStimulation of mucin and bicarbonate secretionStimulation of mucin and bicarbonate secretionIncrease mucosal blood flowIncrease mucosal blood flow
(Reinforcing of mucous layer buffered by HCO3 (Reinforcing of mucous layer buffered by HCO3 secretion from epithelial cells)secretion from epithelial cells)
Therapeutic uses:Therapeutic uses:
Prevent ion of NSAID-induced mucosal injury Prevent ion of NSAID-induced mucosal injury (rarely used because it needs frequent (rarely used because it needs frequent administration – 4 times daily)administration – 4 times daily)
MisoprostolMisoprostol• Doses: 200 mcg 4 times a day (Misoprost)Doses: 200 mcg 4 times a day (Misoprost)
• ADRs:ADRs:– Diarrhoea and abdominal crampsDiarrhoea and abdominal cramps– Uterine bleedingUterine bleeding– AbortionAbortion– Exacerbations of inflammatory bowel disease and should Exacerbations of inflammatory bowel disease and should
be avoided in patients with this disorderbe avoided in patients with this disorder
Contraindications:Contraindications:
1.1. Inflammatory bowel diseaseInflammatory bowel disease
2.2. Pregnancy (may cause abortion)Pregnancy (may cause abortion)
QuestionQuestion
A patient comes to your clinic at midnight complaining of heart A patient comes to your clinic at midnight complaining of heart burn. You want to relieve his pain immediately. What drug burn. You want to relieve his pain immediately. What drug will you choose?will you choose?
Answer isAnswer is
AntacidsAntacids
• Explanation :Explanation :
Antacids neutralize the already secreted acid in the Antacids neutralize the already secreted acid in the stomach. All other drugs act by stopping acid secretion and so stomach. All other drugs act by stopping acid secretion and so may not relieve symptoms atleast for 45 minmay not relieve symptoms atleast for 45 min
Triple TherapyThe BEST among all the Triple therapy regimen is:
Omeprazole / Lansoprazole - 20 / 30 mg bd
Clarithromycin - 500 mg bd
Amoxycillin / Metronidazole - 1gm / 500 mg bd
Given for 14 days followed by P.P.I for 4 – 6 weeks
Short regimens for 7 – 10 days not very effective
Triple Therapy – cont …
Bismuth subsalicylate – 2 tab qid
Metronidazole - 250 mg qid
Tetracycline - 500 mg qid
Some other Triple Therapy Regimens are
Ranitidine Bismuth citrate - 400 mg bd
Tetracycline - 500 mg bd
Clarithromycin / Metronidazole - 500 mg bd
Bismuth subsalicylateBismuth subsalicylatePharmacological actions:Pharmacological actions:
• Undergoes rapid dissolution in the stomach into bismuth and Undergoes rapid dissolution in the stomach into bismuth and salicylatessalicylates
• Salicylates are absorbed Salicylates are absorbed
• Bismuth coats ulcers and erosions protecting them from acid Bismuth coats ulcers and erosions protecting them from acid and pepsin and increases prostaglandin and bicarbonate and pepsin and increases prostaglandin and bicarbonate productionproduction
• Uses:Uses:• Treatment of dyspepsia and acute diarrhoeaTreatment of dyspepsia and acute diarrhoea
Question
A pregnant lady (first trimester) comes to you with peptic ulcer disease. Which drug will you prescribe for her ?
Answer : Antacids or Sucralfate
Explanation ;
H2 antagonists cross placenta and are also secreted in breast milk. Safety of Proton pump inhibitors not established in pregnancy. Misoprostol causes abortion
Emergency scenario Emergency scenario • A 50 year old man is brought into A+E via ambulance. A 50 year old man is brought into A+E via ambulance.
He is vomiting bright red blood and complaining of He is vomiting bright red blood and complaining of abdominal pain. You get a quick history from his wife abdominal pain. You get a quick history from his wife who explains he suffers with heartburn and is on who explains he suffers with heartburn and is on lansoprazole. He was out with his work mates last lansoprazole. He was out with his work mates last night and drank quite heavily.night and drank quite heavily.
Initial Management I Initial Management I • ABCDE approach ABCDE approach • Call for help Call for help
Initial management IIInitial management II• Airway is clearAirway is clear• Breathing – RR 30 breaths/min, Sats 91% OABreathing – RR 30 breaths/min, Sats 91% OA• Circulation – HR 130 beats/min, BP 80/40 mmHgCirculation – HR 130 beats/min, BP 80/40 mmHg
– Protect airway & keep NBMProtect airway & keep NBM– High flow oxygenHigh flow oxygen– Gain access – 2 large bore cannulae Gain access – 2 large bore cannulae – Bloods- FBC, U&Es, LFTs, glucose, clotting, cross match Bloods- FBC, U&Es, LFTs, glucose, clotting, cross match
6 units6 units– Catheterise to monitor urine output Catheterise to monitor urine output
Initial management IIIInitial management III• If shocked prompt volume replacementIf shocked prompt volume replacement• Either colloid or crystalloid solutionsEither colloid or crystalloid solutions• Red cell transfusion should be considered after loss of Red cell transfusion should be considered after loss of
30% of the circulating volume30% of the circulating volume• Correct any clotting abnormalities Correct any clotting abnormalities • Urgent endoscopy after resuscitation Urgent endoscopy after resuscitation
Acute upper GI bleedAcute upper GI bleed• Common, 10% mortality Common, 10% mortality • Common causes: PUD, varicesCommon causes: PUD, varices• Endoscopy: primary diagnostic investigation & allows Endoscopy: primary diagnostic investigation & allows
for treatmentfor treatment• Assess using the Blatchford score at first assessment Assess using the Blatchford score at first assessment
and full Rockall score after endscopyand full Rockall score after endscopy
Evaluation/Follow-up/Evaluation/Follow-up/
• H. Pylori Positive: retesting for tx efficacyH. Pylori Positive: retesting for tx efficacy• Urea breath test—no sooner than 4 weeks after therapy to avoid false Urea breath test—no sooner than 4 weeks after therapy to avoid false
negative resultsnegative results• Stool antigen test—an 8 week interval must be allowed after therapy.Stool antigen test—an 8 week interval must be allowed after therapy.
• H. Pylori Negative: H. Pylori Negative: • evaluate symptoms after one month. Patients who are controlled evaluate symptoms after one month. Patients who are controlled
should cont. 2-4 more weeks.should cont. 2-4 more weeks.
Summary Summary A peptic ulcer is a break in superficial epithelial cells A peptic ulcer is a break in superficial epithelial cells
penetrating down to muscularis mucosa penetrating down to muscularis mucosa Duodenal > gastric ulcers Duodenal > gastric ulcers Can be asymptomaticCan be asymptomatic H pylori is a predominant risk factorH pylori is a predominant risk factor H pylori diagnosed by c urea breath test, stool antigen or H pylori diagnosed by c urea breath test, stool antigen or
if validated serology, treated with PAC500 or PMC250 if validated serology, treated with PAC500 or PMC250 regimeregime
Complications of PUD can lead to acute emergency of Complications of PUD can lead to acute emergency of upper GI bleedupper GI bleed